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Answer the following medical question.	What does research say about The effects of kangaroo mother care on physiological parameters of premature neonates in neonatal intensive care unit: A systematic review.?	The effects of Kangaroo mother care (KMC) on physiological parameters in preterm infants have been reported in the literature by experimental and quasi-experimental studies, and varying findings have been presented. The present study was conducted to determine the effects of KMC on the physiological parameters of premature newborns in the Neonatal Intensive Care Unit. The review was conducted according to the specified keywords by scanning the EBSCO-host, Cochrane Library, Medline, PubMed, ScienceDirect, Web of Science, and TR index databases using the keywords "kangaroo care AND preterm AND vital signs." The pool mean differences (MDs) were calculated, adopting a 95% confidence interval (CIs) using the Stata 16 software for the meta-analysis [PROSPERO: CRD42021283475]. Eleven studies for systematic review and nine studies for meta-analysis, including 634 participants, were found eligible for inclusion. It was determined that the "temperature" (z = 3.21; p = 0.000) and "oxygen saturation" (z = 2.49; p = 0.000) values created a positive effect in general in the kangaroo care group; however, there was no sufficient evidence to state that it affected the "heart rate" (z = -0.60; p = 0.55) and "respiratory rate" (z = -1.45; p = 0.15) values. In the present study, the duration of KMC application had statistically different effects on temperature and oxygen saturation (SpO Our results provided references for clinical implications, and the "temperature" and "oxygen saturation (SpO The goal of the NICU nurse is to improve the infant's well-being. The application of KMC is a unique care for the nurse in maintaining the newborn's well-being. The vital signs of newborns hospitalized in the NICU with critical problems may be out of normal limits. KMC is an essential developmental care practice that ensures that the neonate's vital signs are kept within normal limits by relaxing the neonate, reducing stress, increasing comfort, and supporting interventions and treatments. KMC application is unique for each mother‑neonate pair. Depending on the tolerance of the mother and infant in terms of duration, it is recommended to perform KMC in the NICU under the supervision of a nurse. Neonatal nurses should support mothers in giving KMC in the NICU since KMC has ameliorative effects on the vital signs of premature neonates.
Answer the following medical question.	What does research say about Nursing Care During Neonatal Electroencephalographs.?	Electroencephalography (EEG) enables the precise evaluation of a neonate's condition. Three factors that determine the quality of care during this procedure are knowledge, experience, and attitude. The role of the nurse during EEG recordings was evaluated in this study, and the requirements for successfully performing neonatal EEGs, along with practical suggestions, are presented. Evidence in the literature as well as clinical expertise forms the basis for this review. From our observations and practice during EEGs, we found that the following conditions must be met to successfully perform an EEG examination in a newborn: safety, a period of sleep and calm wakefulness of the neonate, good technical conditions, and no external interferences. Key conditions include the maintenance of safety rules and cooperation between nurses, EEG technicians, and parents. The EEG examinations in neonates weighing less than 1500 g or those requiring respiratory support should only be performed by a trained neonatal intensive care unit nurse.
Answer the following medical question.	What does research say about Making neonatal intensive care: cost effective.?	With the improvement in neonatal care in last two decades, the survival of very low birth weight (VLBW), extremely low birth weight (ELBW), fetus diagnosed with malformations, and congenital heart disease and severe birth asphyxia has increased significantly. These infants when admitted to the neonatal intensive care unit (NICU) need numerous interventions depending upon the severity of sickness and postnatal course like need of mechanical ventilation (MV) or noninvasive ventilation, surfactant administration, placement of central lines, total parenteral nutrition, and numerous medications. The duration of NICU and hospital stay of these high-risk infants varies from few days to few weeks to few months. Long stay in the hospital leads to high hospital bills and increase the cost of neonatal care substantially. The cost of NICU stay varies from 90 USD to 1250-2500 USD per day as per various studies, depending upon the level of care and sickness of the admitted infants. In developed countries, the burden of NICU cost is often taken care by the government or insurance companies but in many developing countries the parents bear the substantial cost of NICU admission of their infants. There are many interventions which when implemented in the NICU will lead to reduction of the cost and will make the NICU cost effective. In this review, we cover various interventions mostly from our own published work which have shown to reduce the NICU cost and make it more cost effective with equivalent and better neonatal outcomes, especially in developing countries like ours.
Answer the following medical question.	What does research say about Prolonged pain in premature neonates hospitalised in neonatal intensive care units: A scoping review.?	Exposure to repetitive pain during the neonatal period has been shown to have important short and long-term effects on the neurodevelopment of the premature neonate and can contribute to experienced prolonged pain. A uniform taxonomy of neonatal prolonged pain is still lacking to this day which contributes to suboptimal prolonged pain management in neonatal intensive care units. Accordingly, a scoping review exploring the state of knowledge about prolonged pain in preterm neonates hospitalised in the neonatal intensive care unit will contribute to the developing field of neonatal prolonged pain and provide recommendations for clinical prolonged pain management. To determine the scope, extent, and nature of the available literature on prolonged pain in premature neonates hospitalised in neonatal intensive care units. Scoping review. An electronic search was conducted from inception to November 2023 in the databases of CINAHL, PubMed, Medline, Web of Science, GeryLit.org and Grey Source Index. Included studies discussed concepts related to neonatal prolonged pain such as definitions of prolonged pain, indicators of prolonged pain, contexts that result in prolonged pain, prolonged pain evaluation tools, consequences of prolonged pain and interventions for prolonged pain management. Key concepts of neonatal prolonged pain were identified in the 86 included articles of this scoping review such as definitions (n = 26), indicators (n = 39), contexts (n = 49), scales (n = 56), consequences of prolonged pain (n = 30) and possible interventions for prolonged pain management (n = 22). Whilst a consensus on a definition has yet to be achieved, no proximate event was shown to cause prolonged pain and a time criterion was identified by authors as being relevant in defining prolonged pain. Interestingly, the context of hospitalisation was identified as being the most indicative of prolonged pain in premature neonates and should guide its evaluation and management, whilst only limited pain management interventions and consequences were discussed. The findings of this scoping review contribute to the foundation of growing knowledge in neonatal prolonged pain and shed light on the ambiguity that currently exists on this topic in the scientific literature. This review summarises knowledge of key concepts necessary for a better understanding of prolonged pain and stresses the importance of considering contexts of hospitalisation for prolonged pain evaluation and management in neonatal intensive care units, with the objective of improving developmental outcomes of premature neonates. A scoping review reveals that the contexts of prolonged pain in premature neonates hospitalised in the neonatal intensive care unit are essential in guiding its evaluation and management.
Answer the following medical question.	What does research say about Neonatal Sepsis: A Review of Pathophysiology and Current Management Strategies.?	Early-onset sepsis, occurring within 72 hours of birth, and late-onset sepsis, occurring after this time period, present serious risks for neonates. While culture-based screening and intrapartum antibiotics have decreased the number of early-onset cases, sepsis remains a top cause of neonatal morbidity and mortality in the United States. To provide a review of neonatal sepsis by identifying its associated risk factors and most common causative pathogens, reviewing features of the term and preterm neonatal immune systems that increase vulnerability to infection, describing previous and the most current management recommendations, and discussing relevant implications for the neonatal nurse and novice neonatal nurse practitioner. An integrative review of literature was conducted using key words in CINAHL, Google Scholar, and PubMed. Group B streptococcus and Escherichia coli are the most common pathogens in early-onset sepsis, while Coagulase-negative staphylococci comprise the majority of cases in late-onset. The neonatal immune system is vulnerable due to characteristics including decreased cellular activity, underdeveloped complement systems, preferential anti-inflammatory responses, and insufficient pathogenic memory. Blood cultures remain the criterion standard of diagnosis, with several other adjunct tests under investigation for clinical use. The recent development of the sepsis calculator has been a useful tool in the management of early-onset cases. It is vital to understand the mechanisms behind the neonate's elevated risk for infection and to implement evidence-based management. Research needs exist for diagnostic methods that deliver timely and sensitive results. A tool similar to the sepsis calculator does not exist for preterm infants or late-onset sepsis, groups for which antibiotic stewardship is not as well practiced.Video Abstract available athttps://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?autoPlay=false&videoId=40.
Answer the following medical question.	What does research say about Neonatal Pain: Perceptions and Current Practice.?	DISCLOSURE STATEMENT : The authors have nothing to disclose. Neonates may experience more than 300 painful procedures and surgeries throughout their hospitalization. Prior to 1980, there was a longstanding misconception that neonates do not experience pain. Current studies demonstrate that not only do neonate’s experience pain, but due to their immature nervous systems, they are hypersensitive to painful stimuli. Poorly treated pain during the neonatal period may lead to negative long-term consequences. Proper assessment of a neonate’s pain is vital. Standardized pain scales allow for consistency between providers and individualized treatment plans for neonates. The use of non-pharmacological treatments such as, nonnutritive sucking, facilitated tucking, kangaroo care, swaddling and heel warming may all be beneficial in alleviating a neonate’s pain. Pharmacological treatments in the neonate have been well established and may include, but are not limited to opioids and non-opioid analgesics. Pharmacological and non-pharmacological interventions can be used in conjunction with each other to increase the efficacy of analgesia. Neonatal Pain: Perceptions and Current Practice
Answer the following medical question.	What does research say about Neonatal red blood cell transfusion.?	Transfusions are more common in premature infants with approximately 40% of low birth weight infants and up to 90% of extremely low birth weight infants requiring red blood cell transfusion. Although red blood cell transfusion can be life-saving in these preterm infants, it has been associated with higher rates of complications including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity and possibly abnormal neurodevelopment. The main objective of this review is to assess current red blood cell transfusion practices in the neonatal intensive care unit, to summarize available neonatal transfusion guidelines published in different countries and to emphasize the wide variation in transfusion thresholds that exists for red blood cell transfusion. This review also addresses certain issues specific to red blood cell processing for the neonatal population including storage time, irradiation, cytomegalovirus (CMV) prevention strategies and patient blood management. Future research avenues are proposed to better define optimal transfusion practice in neonatal intensive care units.
Answer the following medical question.	What does research say about Evidence-based skin care in preterm infants.?	Most guidelines on neonatal skin care emphasize issues pertaining to healthy, term infants. Few address the complex task of skin barrier maintenance in preterm, very preterm, and extremely preterm infants. Here, we provide an evidence-based review of the literature on skin care of preterm neonates. Interestingly, the stratum corneum does not fully develop until late in the third trimester, and as such, the barrier function of preterm skin is significantly compromised. Numerous interventions are available to augment the weak skin barrier of neonates. Plastic wraps reduce the incidence of hypothermia while semipermeable and transparent adhesive dressings improve skin quality and decrease the incidence of electrolyte abnormalities. Tub bathing causes less body temperature variability than sponge bathing and can be performed as infrequently as once every four days without increasing bacterial colonization of the skin. Topical emollients, particularly sunflower seed oil, appear to reduce the incidence of skin infections in premature neonates-but only in developing countries. In developed countries, studies indicate that topical petrolatum ointment increases the risk of candidemia and coagulase-negative Staphylococcus infection in the preterm population, perhaps by creating a milieu similar to occlusive dressings. For preterm infants with catheters, povidone-iodine and chlorhexidine are comparably effective at preventing catheter colonization. Further studies are necessary to examine the safety and efficacy of various skin care interventions in premature infants with an emphasis placed on subclassifying the patient population. In the interim, it may be beneficial to develop guidelines based on the current body of evidence.
Answer the following medical question.	What does research say about Families as partners in neonatal neuro-critical care programs.?	Parents of neonates with neurologic conditions face a specific breadth of emotional, logistical, and social challenges, including difficulties coping with prognostic uncertainty, the need to make complex medical decisions, and navigating new hopes and fears. These challenges place parents in a vulnerable position and at risk of developing mental health issues, which can interfere with bonding and caring for their neonate, as well as compromise their neonate's long-term neurodevelopment. To optimize neurologic and developmental outcomes, emerging neonatal neuro-critical care (NNCC) programs must concurrently attend to the unique needs of the developing newborn brain and of his/her parents. This can only be accomplished by embracing a family-centered care environment-one which prioritizes effective parent-clinician communication, longitudinal parent support, and parents as equitable partners in clinical care. NNCC programs offer a multifaceted approach to critical care for neonates at-risk for neurodevelopmental impairments, integrating expertise in neonatology and neurology. This review highlights evidence-based strategies to guide NNCC programs in developing a family-partnered approach to care, including primary staffing models; staff communication, implicit bias, and cultural competency trainings; comprehensive and tailored caregiver training; single-family rooms; flexible visitation policies; colocalized neonatal and maternal care; uniform mental health screenings; follow-up care referrals; and connections to peer support. IMPACT: Parents of neonates with neurologic conditions are at high-risk for experiencing mental health issues, which can adversely impact the parent-neonate relationship and long-term neurodevelopmental outcomes of their neonates. While guidelines to promote families as partners in the neonatal intensive care unit (NICU) have been developed, no protocols integrate the unique needs of parents in neonatal neurologic populations. A holistic approach that makes families true partners in the care of their neonate with a neurologic condition in the NICU has the potential to improve mental and physical well-being for both parents and neonates.
Answer the following medical question.	What does research say about Proposing a care practice bundle for neonatal encephalopathy during therapeutic hypothermia.?	Neonates with neonatal encephalopathy (NE) often present with multi-organ dysfunction that requires multidisciplinary specialized management. Care of the neonate with NE is thus complex with interaction between the brain and various organ systems. Illness severity during the first days of birth, and not only during the initial hypoxia-ischemia event, is a significant predictor of adverse outcomes in neonates with NE treated with therapeutic hypothermia (TH). We thus propose a care practice bundle dedicated to support the injured neonatal brain that is based on the current best evidence for each organ system. The impact of using such bundle on outcomes in NE remains to be demonstrated.
Answer the following medical question.	What does research say about Neonatal hypertension.?	Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.
Answer the following medical question.	What does research say about Antibiotic stewardship in perinatal and neonatal care.?	The spread of antibiotic resistance due to the use and misuse of antibiotics around the world is now a major health crisis. Neonates are exposed to antibiotics both before and after birth, often empirically because of risk factors for infection, or for non-specific signs which may or may not indicate sepsis. There is increasing evidence that, apart from antibiotic resistance, the use of antibiotics in pregnancy and in the neonatal period alters the microbiome in the fetus and neonate with an increased risk of immediate and long-term adverse effects. Antibiotic stewardship is a co-ordinated program that promotes the appropriate use of antibiotics, improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms. This review addresses some of the controversies in antibiotic use in the perinatal period, examines opportunities for reduction of unnecessary antibiotic exposure in neonates, and provides a framework for antibiotic stewardship in neonatal care.
Answer the following medical question.	What does research say about Emotional Responses of Neonatal Intensive Care Nurses to Neonatal Death.?	The study was planned as a descriptive qualitative study to determine the emotional responses of neonatal intensive care nurses to work in the neonatal unit and to neonatal deaths. The sample of the study consisted of 7 nurses who work at the neonatal intensive care unit since data saturation was achieved. The data were collected using the "Semi-Structured In-Depth Interview Guide for Nurses". The data were analyzed using the content analysis method. Following codes were reached as a result of the study: 'happiness-sadness', 'professional satisfaction-exhaustion', 'empathy', 'responsibility-guilt', 'hope-despair' under the theme of being a nurse at neonatal unit'; 'unforgettable first loss', 'professionalism in intervention-and then: sadness, 'mature-premature difference', 'difficulty in giving hurtful news-inability to associate with death' and 'attachment-burnout' under the theme of experiencing neonatal loss.It was seen that nurses' emotions about working at neonatal intensive care unit were generally positive; however, these emotions changed to negative after neonate's relapsing and death.
Answer the following medical question.	What does research say about How is bioelectrical impedance used in neonatal intensive care? A scoping review.?	Poor growth and nutrition management in the neonatal period can have a negative impact upon both the short- and long-term outcomes for the infant. Improvements in bioelectrical impedance technology and accompanying licencing agreements now make this enhanced device available for use in infants as small as 23 weeks gestational age. An exploration of this technology and its use is now timely. The aim of the scoping review was to answer the following question: in preterm and sick term infants in the neonatal intensive care unit, how is bioelectrical impedance being utilized, in what situations, and when? The scoping review was conducted using Arksey and O'Malley's (Int J Soc Res Methodol 8(1):19-32, 2005) framework. Forty-nine papers were initially identified and 16 were included in the scoping review. Three studies were experimental designs, and 13 were observational studies. The review found that BIA was used in neonatal intensive care in three main ways, for, (1) fluid status evaluation, (2) as a measure of adequate nutrition and growth, (3) to validate the technology as an outcome measure in neonates. There is a paucity of recent robust research papers which investigate the use of bioelectrical impedance in preterm neonates. Available evidence spans a range of 30 years, with technological advancement reducing the application of older studies to the modern neonatal setting. Although this technology may be helpful for decision-making around fluid management and nutrition, in preterm infants, robust evidence is needed to demonstrate the clinical benefit of bioelectrical impedance beyond that of usual care. • Clinical decisions regarding neonatal nutrition and fluid management are currently based upon the interpretation of vital signs, fluid balance, weight trend, biochemical markers, and physical examination. • Bioelectrical Impedance Analysis (BIA) is a non-invasive method of assessing body composition which is now available to be used in infants as small as 23 weeks gestation. • Bioelectrical Impedance has been used in three main ways in the NICU, for fluid status evaluation, for measuring nutrition and growth and to validate BIA as an outcome. • There is a lack of recent robust research data to support the use of the device within clinical decision making in neonatal intensive care.
Answer the following medical question.	What does research say about Overcoming the barriers to using kangaroo care in neonatal settings.?	Skin-to-skin contact, or kangaroo care (KC), has benefits for babies and parents, improving clinical outcomes, temperature control, breastfeeding rates and child-parent bonding; it reduces morbidity and mortality. Barriers to KC for neonates may include a lack of training for nurses, lack of time, maternal or child physical or mental ill health, and inappropriate settings. With education and helpful management, neonatal nurses can advocate for KC for all babies. Parents may need information and encouragement to begin with. Therefore, nurses can improve the experiences of their patients and, in the long run, free time to perform clinical procedures.
Answer the following medical question.	What does research say about Assessment of Pain in the Newborn: An Update.?	Preterm and term neonate pain assessment in neonatal intensive care units is vitally important because of the prevalence of procedural and postoperative pain. Of the 40 plus tools available, a few should be chosen for different populations and contexts (2 have been validated in premature infants). Preterm neonates do not display pain behaviors and physiologic indicators as reliably and specifically as full-term infants, and are vulnerable to long-term sequelae of painful experiences. Brain-oriented approaches may become available in the future; meanwhile, neonatal pain assessment tools must be taught, implemented, and their use optimized for consistent, reproducible, safe, and effective treatment.
Answer the following medical question.	What does research say about Training in neonatal neurocritical care: A case-based interdisciplinary approach.?	Interdisciplinary fetal-neonatal neurology (FNN) training strengthens neonatal neurocritical care (NNCC) clinical decisions. Neonatal neurological phenotypes require immediate followed by sustained neuroprotective care path choices through discharge. Serial assessments during neonatal intensive care unit (NICU) rounds are supplemented by family conferences and didactic interactions. These encounters collectively contribute to optimal interventions yielding more accurate outcome predictions. Maternal-placental-fetal (MPF) triad disease pathways influence postnatal medical complications which potentially reduce effective interventions and negatively impact outcome. The science of uncertainty regarding each neonate's clinical status must consider timing and etiologies that are responsible for fetal and neonatal brain disorders. Shared clinical decisions among all stakeholders' balance "fast" (heuristic) and "slow" (analytic) thinking as more information is assessed regarding etiopathogenetic effects that impair the developmental neuroplasticity process. Two case vignettes stress the importance of FNN perspectives during NNCC that integrates this dual cognitive approach. Clinical care paths evaluations are discussed for an encephalopathic extremely preterm and full-term newborn. Recognition of cognitive errors followed by debiasing strategies can improve clinical decisions during NICU care. Re-evaluations with serial assessments of examination, imaging, placental-cord, and metabolic-genetic information improve clinical decisions that maintain accuracy for interventions and outcome predictions. Discharge planning includes shared decisions among all stakeholders when coordinating primary care, pediatric subspecialty, and early intervention participation. Prioritizing social determinants of healthcare during FNN training strengthens equitable career long NNCC clinical practice, education, and research goals. These perspectives contribute to a life course brain health capital strategy that will benefit all persons across each and successive lifespans.
Answer the following medical question.	What does research say about Caring for Dying Infants: A Systematic Review of Healthcare Providers' Perspectives of Neonatal Palliative Care.?	The palliative and hospice care movement has expanded significantly in the United States since the 1960s. Neonatal end of life care, in particular, is a developing area of practice requiring healthcare providers to support terminally ill newborns and their families, to minimize suffering at the end of the neonate's life. This paper seeks to systematically summarize healthcare providers' perspectives related to end of life, in order to identify needs and inform future directions. Informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically reviewed the literature discussing healthcare provider perspectives of neonatal end of life care ranging from year 2009 to 2020. To be included in the review, articles had to explicitly focus on perspectives of healthcare providers toward neonatal end of life care, be published in academic peer-reviewed sources, and focus on care in the United States. Thirty-three articles were identified meeting all inclusion criteria. The literature covers, broadly, provider personal attitudes, experiences delivering care, practice approaches and barriers, and education and training needs. The experiences of physicians, physician assistants, nurse practitioners, and nurses are highlighted, while less is discussed of other providers involved with this work (e.g., social work, physical therapy). Future research should focus on developing and testing interventions aimed at training and supporting healthcare providers working with neonates at end of life, as well as addressing barriers to the development and implementation of neonatal palliative teams and guidelines across institutions.
Answer the following medical question.	What does research say about Prevention Strategies for Neonatal Skin Injury in the NICU.?	The purpose of this article was to determine specific skin injury prevention interventions for neonates in the NICU. The design was a systematic review. PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Embase, and Scopus were systematically searched to identify quantitative studies identifying skin injury preventions for neonates in the NICU. The outcomes included skin integrity or skin condition. Nineteen studies were included in the review. Twelve studies included a randomized design. Barriers were the main interventions for the prevention of pressure injury, medical adhesive skin injury, diaper dermatitis, and general skin condition. The types of barriers included hydrocolloids, polyurethane-based dressings, film-forming skin protectant, or emollients. Nonbarrier interventions included rotation between a mask and nasal continuous positive airway pressure (NCPAP) interfaces, utilization of prescribed guidelines to decrease pressure injuries, and use of a lower concentration of chlorhexidine gluconate as a disinfectant.
Answer the following medical question.	What does research say about Thrombosis in the Neonatal Intensive Care Unit.?	Neonates have the highest risk for pathologic thrombosis among pediatric patients. A combination of genetic and acquired risk factors significantly contributes to this risk, with the most important risk factor being the use of central venous catheters. Proper imaging is critical for confirming the diagnosis. Despite a significant number of these events being life- and limb-threatening, there is limited evidence on what the appropriate management strategy should be. Evaluation and treatment of any neonate with a clinically significant thrombosis should occur at a tertiary referral center that has proper support.
Answer the following medical question.	What does research say about The difficult neonatal airway.?	Airway management is one of the most crucial aspects of neonatal care. The occurrence of a difficult airway is more common in neonates than in any other age group, and any neonatal intubation can develop into a difficult airway scenario. Understanding the intricacies of the difficult neonatal airway is paramount for healthcare professionals involved in the care of newborns. This chapter explores the multifaceted aspects of the difficult neonatal airway. We begin with a review of the definition and incidence of difficult airway in the neonate. Then, we explore factors contributing to a difficult neonatal airway. We next examine diagnostic considerations specific to the difficult neonatal airway, including prenatal imaging. Finally, we review management strategies. The importance of a multidisciplinary team approach and the role of communication and collaboration in achieving optimal outcomes are emphasized.
Answer the following medical question.	What does research say about Preterm infant mental health in the neonatal intensive care unit: A review of research on NICU parent-infant interactions and maternal sensitivity.?	Caregiving relationships in the postnatal period are critical to an infant's development. Preterm infants and their parents face unique challenges in this regard, with infants experiencing separation from parents, uncomfortable procedures, and increased biologic vulnerability, and parents facing difficulties assuming caregiver roles and increased risk for psychological distress. To better understand the NICU parent-infant relationship, we conducted a review of the literature and identified 52 studies comparing observed maternal, infant, and dyadic interaction behavior in preterm dyads with full-term dyads. Eighteen of 40 studies on maternal behavior found less favorable behavior, including decreased sensitivity and more intrusiveness in mothers of preterm infants, seven studies found the opposite, four studies found mixed results, and 11 studies found no differences. Seventeen of 25 studies on infant behavior found less responsiveness in preterm infants, two studies found the opposite, and the remainder found no difference. Eighteen out of 14 studies on dyad-specific behavior reported less synchrony in preterm dyads and the remainder found no differences. We identify confounding factors that may explain variations in results, present an approach to interpret existing data by framing differences in maternal behavior as potentially adaptive in the context of prematurity, and suggest future areas for exploration. Las relaciones de prestación de cuidados en el período postnatal son críticas para el desarrollo del infante. Los infantes nacidos prematuramente y sus progenitores enfrentan retos únicos a este respecto, con los infantes que experimentan la separación de sus progenitores, procedimientos incómodos, así como un aumento en la vulnerabilidad biológica; y los progenitores enfrentando dificultades al asumir el papel de cuidadores y el aumento de riesgo de angustia sicológica. Para comprender mejor la relación progenitor-infante en la Unidad Neonatal de Cuidados Intensivos (NICU), llevamos a cabo una revisión de la literatura e identificamos 52 estudios que comparan la observada conducta de interacción materna, del infante y de la díada en díadas de infantes prematuros con díadas de infantes de gestación completa. Dieciocho de 40 estudios sobre la conducta materna encontraron una menos favorable conducta, incluyendo una baja en la sensibilidad y más intrusión en el caso de madres de infantes prematuros; 7 estudios encontraron que se daba la situación opuesta; 4 estudios presentaron resultados mixtos; y 11 estudios no encontraron diferencias. Diecisiete de 25 estudios sobre el comportamiento del infante encontraron una menor capacidad de respuesta en infantes prematuros; dos estudios encontraron que se daba la situación opuesta; y el resto de los estudios no encontró ninguna diferencia. Ocho de 14 estudios sobre el comportamiento específico de la díada reportaron menos sincronía en las díadas con infantes prematuros y el resto de los estudios no encontró ninguna diferencia. Identificamos factores confusos que pudieran explicar las variaciones en los resultados, presentamos un acercamiento para interpretar la información existente por medio de enmarcar las diferencias en la conducta materna como potencialmente adaptable en el contexto del nacimiento prematuro, y sugerimos futuras áreas para ser exploradas. Les relations de soin dans la période postnatale sont critiques pour le développement du nourrisson. Les bébés nés avant terme et leurs parents font face à des défis uniques à cet égard, avec les bébés faisant l'expérience de la séparation des parents, des procédures désagréables et difficiles, et une vulnérabilité biologique accrue, et les parents faisant face aux difficultés assumant des rôles de soignants et étant à risque plus élevé de détresse psychologique. Afin de comprendre la relation parent-nourrisson USIN nous avons passé en revue toutes les recherches et identifié 52 études comparant le comportement d'interaction dyadique, maternel et du nourrisson chez des dyades prématurées avec des dyades à plein terme. 18 des 40 études sur le comportement maternel ont trouvé un comportement moins que favorable, y compris une sensibilité décrue et plus d'intrusion chez les mères de nourrissons prématurés, 7 études ont trouvé le contraire, 4 études ont trouvé des résultats mélangés, et 11 études n'ont trouvé aucune différence. 17 études sur 25 sur le comportement du nourrisson ont trouvé une réaction moindre chez les nourrissons prématurés deux études ont trouvé le contraire, et le reste n'a trouvé aucune différence. 8 études sur 14 sur le comportement spécifique à la dyade ont fait état de moins de synchronie chez les dyades avant terme et les autres études n'ont trouvé aucune différence. Nous identifions des facteurs confondants qui pourraient expliquer des variations dans les résultats et nous présentons une approche pour interpréter les données existantes en cadrant des différences dans le comportement maternel comme étant potentiellement adaptatives dans le contexte de la prématurité et nous suggérons des domaines futurs d'exploration. Betreuungsbeziehungen in der postnatalen Phase sind für die Entwicklung eines Säuglings entscheidend. Frühgeborene und ihre Eltern sind in dieser Hinsicht mit besonderen Herausforderungen konfrontiert: Die Säuglinge erleben die Trennung von ihren Eltern, unangenehme Prozeduren und eine erhöhte biologische Anfälligkeit. Die Eltern hingegen haben Schwierigkeiten, die Rolle der Betreuenden einzunehmen, und ein erhöhtes Risiko für psychische Probleme. Um die Eltern-Säuglings-Beziehung auf der Neugeborenen-Intensivstation besser zu verstehen, haben wir Literatur ausgewertet und 52 Studien identifiziert, in denen das beobachtete Mutter-Kind-Interaktionsverhalten bei Frühgeborenen-Dyaden mit dem von Reifgeborenen-Dyaden verglichen wurde. 18 von 40 Studien zum mütterlichen Verhalten ergaben ein ungünstigeres Verhalten der Mütter der Frühgeborenen, einschließlich geringerer Sensibilität und größerer Aufdringlichkeit, 7 Studien ergaben das Gegenteil, 4 Studien zeigten gemischte Ergebnisse und 11 Studien stellten keine Unterschiede fest. 17 von 25 Studien über das Säuglingsverhalten stellten eine geringere Reaktionsfähigkeit bei Frühgeborenen fest, zwei Studien fanden das Gegenteil und in den übrigen wurde kein Unterschied festgestellt. 8 von 14 Studien zum dyadenspezifischen Verhalten berichteten eine geringere Synchronität bei Frühgeborenen-Dyaden, während die übrigen keine Unterschiede feststellten. Wir identifizieren Störfaktoren, die Unterschiede in den Ergebnissen erklären könnten, und stellen einen Ansatz zur Interpretation vorhandener Daten vor, indem wir Unterschiede im mütterlichen Verhalten als potenziell adaptiv im Kontext der Frühgeburtlichkeit betrachten. Außerdem schlagen wir künftige Forschungsbereiche vor. 产后期的护理关系对婴儿的发育至关重要。早产婴儿及其父母在这方面面临着独特的挑战, 婴儿会经历与父母分离、不舒服的治疗过程和生物学脆弱性的增加, 而父母则面临着难以承担看护者角色的困难以及心理困扰的风险增加。为了更好地理解NICU中的母婴关系, 我们进行了文献综述, 并确定了52项研究, 比较了早产婴儿和足月婴儿中观察到的母亲、婴儿和双人互动行为。在40项关于母亲行为的研究中, 有18项发现了不太有利的行为, 包括早产婴儿的母亲表现出较低的敏感性和更多的侵入性, 有7项研究发现相反的结果, 有4项研究发现混合结果, 有11项研究未发现差异。在25项关于婴儿行为的研究中, 有17项发现早产婴儿的反应能力较低, 有2项研究发现相反的结果, 其余研究未发现差异。在14项关于双人特定行为的研究中, 有8项报告称早产母婴组的同步性较低, 其余研究没有发现差异。我们确定了可能解释结果差异的混杂因素, 并提出了一种方法, 通过将母亲行为的差异界定为在早产背景下的潜在适应性来解释现有数据, 我们还提出了未来的研究方向。. تعد علاقات تقديم الرعاية في فترة ما بعد الولادة ذات أهمية محورية لنمو الرضيع. يواجه الخدج وأولياء أمورهم تحديات فريدة في هذا الصدد، حيث يعاني الرضع من الانفصال عن والديهم، وإجراءات غير مريحة، وزيادة الضعف البيولوجي، ويواجه الآباء صعوبات في تولي أدوار مقدمي الرعاية وزيادة خطر الإصابة بالضيق النفسي. لفهم العلاقة بين الوالدين والرضيع بشكل أفضل، أجرينا مراجعة للأدبيات وحددنا 52 دراسة تقارن سلوك التفاعل بين الأمهات والرضيع وسلوكيات تفاعل ثنائيات الخدج مع ثنائيات كاملة المدة. وجدت 18 من 40 دراسة حول سلوك الأمهات سلوكًا أقل إيجابية، بما في ذلك انخفاض الحساسية والمزيد من التدخل لدى أمهات الخدج، بينما وجدت 7 دراسات عكس ذلك، وتوصلت 4 دراسات إلى نتائج مختلطة، ولم تجد 11 دراسة أي فروق. وجدت 17 من 25 دراسة حول سلوك الرضع استجابة أقل عند الخدج، ووجدت دراستان عكس ذلك، ولم تتوصل بقية الدراسات إلى أي فروق. وتوصلت 8 من أصل 14 دراسة حول السلوك الثنائي المحدد إلى وجود تزامن أقل في الثنائيات الخدج ولم تجد بقية الدراسات أي اختلافات. حددت الدراسة العوامل المتضاربة التي قد تفسر الاختلافات في النتائج، ونقدم منهجاً لتفسير البيانات الموجودة من خلال تأطير الاختلافات في سلوك الأم على أنها قابلة للتكيف في سياق الخداج، ونقترح مجالات مستقبلية للاستكشاف.
Answer the following medical question.	What does research say about Pitfalls and Limitations of Platelet Counts and Coagulation Tests in the Neonatal Intensive Care Unit.?	The assessment of hemostasis and the prediction of bleeding risk are of great importance to neonatologists. Premature infants are at an increased risk for bleeding, particularly intra-cranial hemorrhages (most commonly intra-ventricular hemorrhages (IVH)), gastrointestinal hemorrhages, and pulmonary hemorrhages. All severe bleeding, but especially severe IVH, is associated with poor neurodevelopmental outcomes, and other than prenatal steroids, no intervention has reduced the incidence of this serious complication. As a result, there is a need in neonatology to more accurately identify at-risk infants as well as effective interventions to prevent severe bleeding. Unfortunately, the commonly available tests to evaluate the hemostatic system were established using adult physiologic principles and did not consider the neonate's different but developmentally appropriate hemostatic system. This review will describe the changes in the platelet count and tests of hemostasis throughout development, the limitations of these tests to predict neonatal bleeding and the utility of treating abnormal results from these tests with platelet and/or fresh frozen plasma (FFP) transfusions in non-bleeding infants.
Answer the following medical question.	What does research say about Neonatal Gastric Perforation: 14-Year Experience from a Tertiary Neonatal Intensive Care Unit.?	Neonatal gastric perforations (NGPs) are rare and account for 7 to 12% of all gastrointestinal perforations in the neonatal period. The etiology and prognostic factors associated with NGP remain unclear. The aim of this study is to review the cases of NGP in our neonatal intensive care unit (NICU) in the past 14 years and describe the risk factors, clinical presentation, and outcomes associated with it. A retrospective chart review of neonates with gastric perforation admitted to the NICU between June 2006 and December 2020 was performed. Data regarding their antenatal and neonatal characteristics, laboratory and radiological results, intra-operative findings, hospital course, and outcomes were recorded. We identified 350 patients with gastrointestinal perforation at our center during the study period of which 14 (4%; nine males and five females) patients were diagnosed with NGP during surgery. A total of 71% neonates were born preterm (range: 24-39 weeks, median: 34 weeks). Two neonates (14%) were SGA. Only one neonate received cardiopulmonary resuscitation at birth. In all neonates, except two, perforation occurred within the first 10 days of life (median: 4 days, range: 1-22 days). In total, 79% infants received feeds prior to perforation. Ten neonates had a feeding tube, and one neonate had a gastrostomy tube placed prior to perforation. Abdominal distension and pneumoperitoneum were present in all neonates. Majority of the babies had metabolic acidosis (64%) and elevated C-reactive protein (79%). Most (86%) neonates received surgical intervention within 12 hours. Overall survival in our study was 93%. NGP is a rare entity seen mostly in preterm infants within the first 10 days of life. Clinical presentation is similar to perforation anywhere along the gastrointestinal tract and definite diagnosis requires exploratory laparotomy. With prompt recognition and surgical intervention, the overall mortality related to neonatal gastric perforation is low. · Neonatal gastric perforation is a rare but life threatening entity with unclear etiology.. · Prematurity is associated with an increased incidence of gastric perforations in the neonate.. · Laparotomy is required for definitive diagnosis and treatment..
Answer the following medical question.	What does research say about Music therapy for preterm neonates in the neonatal intensive care unit: An overview of systematic reviews.?	To summarise the quantity and quality of evidence for using music therapy for preterm infants in the neonatal intensive care unit (NICU). We performed an overview of evidence for the effectiveness and safety of MT for preterm infants in the NICU. We performed a random-effects meta-analysis of data from studies that fit the definition of MT. We identified 12 eligible systematic reviews and the methodological quality by AMSTAR-2 ranged from moderate to critically low. We identified 14 eligible randomised trials and 7 observational studies where the intervention fits the definition of MT. Meta-analysis of the RCTs showed that MT significantly decreases heart rate, mean difference (MD) (95% CI), -3.21 [-5.22, -1.19], respiratory rate, MD -2.93 [-5.65, -0.22], and maternal anxiety, MD -17.50 [-20.10, -14.90], and increases feeding volume, MD 29.59 [12.79, 46.38]. Long-term neurodevelopmental or safety outcomes were not reported. GRADE assessment of outcomes ranged from low to very low, downgraded for high risk of bias in the included studies, inconsistency and imprecision. Low to very low certainty evidence suggests that MT in preterm infants improves short-term physiological parameters, feeding and maternal anxiety but safety and long-term outcomes were not reported.
Answer the following medical question.	What does research say about Has Quality Improvement Really Improved Outcomes for Babies in the Neonatal Intensive Care Unit??	During the past decade, the emergence of outcome measurement and quality improvement in the neonatal intensive care unit, far more than the introduction of new research approaches or novel therapies, has had a profound effect on improving outcomes for premature neonates. Collection of outcome data, review of those data, and strategies to identify and resolve problems using continuous quality improvement methods can dramatically improve patient outcomes. It is likely that further initiatives in quality improvement will continue to have additional beneficial effects for the neonate.
Answer the following medical question.	What does research say about Neonatal anesthesia.?	The physiology of the preterm and term neonate is characterized by a high metabolic rate, limited pulmonary, cardiac and thermoregulatory reserve, and decreased renal function. Multisystem immaturity creates important developmental differences in drug handling and response when compared to the older child or adult. Neonatal anesthetic management requires an understanding of the pharmacophysiologic limitations of the neonate as well as the pathophysiology of coexisting surgical disease. This review addresses the pertinent aspects of neonatal physiology and pharmacology, general considerations in the anesthetic care of surgical neonates, and concludes with a brief review of the anesthetic management of neonates with necrotizing enterocolitis, diaphragmatic hernia, and tracheoesophageal fistula.
Answer the following medical question.	What does research say about Traditional neonatal care practices in Jordan: A qualitative study.?	Traditional practices during the first months of neonatal life are common in developing countries, such as Jordan. Many international studies and reports have highlighted the fact that traditional neonatal practices are the cause of high neonatal mortality and morbidity rates in some countries. The aim of the present study was to identify neonatal care practices in Jordan. A descriptive, qualitative research design was used across four Jordanian cities across diverse regions. Forty mothers of neonates were interviewed over a period of 6 months (from January to June 2016). Thematic and content analysis was undertaken following Braun and Clarke's six step analysis. The results indicated that in Jordan, home-based neonatal care comprises non-biomedical practices. Rubbing the neonate's skin with salt, swaddling, prelacteal feeding, and other treatment modalities are common. Further studies are necessary to determine and report on the pros and cons of these practices in regard to neonatal health.
Answer the following medical question.	What does research say about Fresh Frozen Plasma Administration in the Neonatal Intensive Care Unit: Evidence-Based Guidelines.?	Neonates receiving fresh frozen plasma (FFP) should do so according to evidence-based guidelines so as to reduce inappropriate use of this life-saving and costly blood product and to minimize associated adverse effects. The consensus-based uses of FFP in neonatology involve neonates with active bleeding and associated coagulopathy. However, because of limited and poor-quality evidence, considerable FFP utilization occurs outside these recommendations. In this review, we describe what we conclude are currently the best practices for the use of FFP in neonates, including interpreting neonatal coagulation tests and strategies for reducing unnecessary FFP transfusions.
Answer the following medical question.	What does research say about Neonatal hypertension: an educational review.?	Hypertension is encountered in up to 3% of neonates and occurs more frequently in neonates requiring hospitalization in the neonatal intensive care unit (NICU) than in neonates in newborn nurseries or outpatient clinics. Former NICU neonates are at higher risk of hypertension secondary to invasive procedures and disease-related comorbidities. Accurate measurement of blood pressure (BP) remains challenging, but new standardized methods result in less measurement error. Multiple factors contribute to the rapidly changing BP of a neonate: gestational age, postmenstrual age (PMA), birth weight, and maternal factors are the most significant contributors. Given the natural evolution of BP as neonates mature, a percentile cutoff of 95% for PMA has been the most common definition used; however, this is not based on outcome data. Common causes of neonatal hypertension are congenital and acquired renal disease, history of umbilical arterial catheter placement, and bronchopulmonary dysplasia. The treatment of neonatal hypertension has mostly been off-label, but as evidence accumulates, the safety of medical management has increased. The prognosis of neonatal hypertension remains largely unknown and thankfully most often resolves unless secondary to renovascular disease, but further research is needed. This review discusses important factors related to neonatal hypertension including BP measurement, determinants of BP, and management of neonatal hypertension.
Answer the following medical question.	What does research say about The hypertensive neonate.?	Hypertension in neonates is increasingly recognized because of improvements in neonatal intensive care that have led to improved survival of premature infants. Although normative data on neonatal blood pressure remain limited, several factors appear to be important in determining blood pressure levels in neonates, especially gestational age, birth weight and maternal factors. Incidence is around 1% in most studies and identification depends on careful blood pressure measurement. Common causes of neonatal hypertension include umbilical catheter associated thrombosis, renal parenchymal disease, and chronic lung disease, and can usually be identified with careful diagnostic evaluation. Given limited data on long-term outcomes and use of antihypertensive medications in these infants, clinical expertise may need to be relied upon to decide the best approach to treatment. This review will discuss these concepts and identify evidence gaps that should be addressed.
Answer the following medical question.	What does research say about Infant-Guided, Co-Regulated Feeding in the Neonatal Intensive Care Unit. Part II: Interventions to Promote Neuroprotection and Safety.?	Feeding skills of preterm neonates in a neonatal intensive care unit are in an emergent phase of development and require careful support to minimize stress. The underpinnings that influence and enhance both neuroprotection and safety were discussed in Part I. An infant-guided, co-regulated approach to feeding can protect the vulnerable neonate's neurologic development, support the parent-infant relationship, and prevent feeding problems that may endure. Contingent interventions are used to maintain subsystem stability and enhance self-regulation, development, and coping skills. This co-regulation between caregiver and neonate forms the foundation for a positive infant-guided feeding experience. Caregivers select evidence-based interventions contingent to the newborn's communication. When these interventions are then titrated from moment to moment, neuroprotection and safety are fostered.
Answer the following medical question.	What does research say about The educational needs of neonatal nurses regarding neonatal palliative care.?	Studies have shown that education can improve the knowledge, attitudes, and beliefs of neonatal nurses regarding neonatal palliative care. However, no study has investigated the need for neonatal nurse education in neonatal palliative care in Taiwan. The purpose of this study was to explore neonatal nurses' experiences in caring for dying neonates and their educational backgrounds regarding palliative care, as well as to assess their educational needs. A cross-sectional survey was used for this research. A research structural questionnaire was used to investigate the research goals. One hundred fifteen nurses participated in this survey. Few participants indicated having received neonatal palliative care education (13%), but most responded that palliative care is necessary in neonatal nursing education (97.4%). Participants also responded that they were often or always exposed to death in NICU (62.6%), but few reported providing pain management to dying neonates (8.7%) and few had experience providing symptomatic care for dying neonates (19.1%). Fifty percent ranked "pain control" as the area in which they most required training. Another high-ranked need was in discussing with parents and families the outcomes of CPR and their neonate's progress. Research indicates that the education currently provided to neonatal nurses does not meet their distinctive needs. Neonatal nurses in Taiwan expressed an urgent desire for training in pain control and communication. Research suggests that the most important topics to trainees are pain management and end-of-life communication. Additionally, non-pharmacological pain control interventions are valuable and should be included in an educational program.
Answer the following medical question.	What does research say about Effects of Kangaroo Care on Neonatal Pain in South Korea.?	Blood sampling for a newborn screening test is necessary for all neonates in South Korea. During the heel stick, an appropriate intervention should be implemented to reduce neonatal pain. This study was conducted to identify the effectiveness of kangaroo care (KC), skin contact with the mother, on pain relief during the neonatal heel stick. Twenty-six neonates undergoing KC and 30 control neonates at a university hospital participated in this study. Physiological responses of neonates, including heart rate, oxygen saturation, duration of crying and Premature Infant Pain Profile (PIPP) scores were measured and compared before, during and 1 min and 2 min after heel sticks. The heart rate of KC neonates was lower at both 1 and 2 min after sampling than those of the control group. Also, PIPP scores of KC neonates were significantly lower both during and after sampling. The duration of crying for KC neonates was around 10% of the duration of the control group. In conclusion, KC might be an effective intervention in a full-term nursery for neonatal pain management.
Answer the following medical question.	What does research say about Neonatal mortality risk assessment using SNAPPE- II score in a neonatal intensive care unit.?	There are many scoring systems to predict neonatal mortality and morbidity in neonatal intensive care units (NICU). One of the scoring systems is SNAPPE-II (Score for Neonatal Acute Physiology with Perinatal extension-II). This study was carried out to assess the validity of SNAPPE-II score (Score for Neonatal Acute Physiology with Perinatal Extension-II) as a predictor of neonatal mortality and duration of stay in a neonatal intensive care unit (NICU). This prospective, observational study was carried out over a period of 12 months from June 2015 to May 2016. Two hundred fifty five neonates, who met the inclusion criteria admitted to NICU in tertiary care hospital, BPKIHS Hospital, Nepal were enrolled in the study and SNAPPE-II score was calculated. Receiver Operating Characteristic (ROC) curve was constructed to derive the best SNAPPE-II cut-off score for mortality. A total of 305 neonates were admitted to NICU over a period of one year. Among them, 255 neonates fulfilled the inclusion criteria. Out of 255 neonates, 45 neonates (17.6%) died and 210 were discharged. SNAPPE-II score was significantly higher among neonates who died compared to those who survived [median (IQR) 57 (42–64) vs. 22 (14–32), P < 0.001]. SNAPPE II score had discrimination to predict mortality with area under ROC Curve (AUC): 0.917 (95% CI, 0.854–0.980). The best cut - off score for predicting mortality was 38 with sensitivity 84.4%, specificity 91%, positive predictive value 66.7% and negative predictive value 96.5%. SNAPPE II score could not predict the duration of NICU stay ( P = 0.477). SNAPPE- II is a useful tool to predict neonatal mortality in NICU. The score of 38 may be associated with higher mortality. Survival of the newborns admitted to the NICUs does not depend only on birth weight and gestational age, but also on other perinatal factors and physiological parameters, particularly those related with severity of their diseases [ 1 – 6 ]. Scoring systems have been developed and used to assess the severity of the illness and to predict the mortality, morbidity and prognosis of neonates in neonatal intensive care units (NICU). Birth weight, gestational age and APGAR score were the only parameters assessed previously to predict mortality and morbidity. However, the association between mortality prediction and these three factors were not much accurate [ 6 – 8 ]. In 1993, Richardson et al. [ 5 ] had formulated the physiology-based score; score for Neonatal Acute Physiology (SNAP), which contains 34 parameters for neonates of all birth-weights and validated it as a predictor of mortality and morbidity [ 3 – 5 ]. They made this score easier by reducing the number of parameters to six. To this score, three more perinatal variables namely birth weight, APGAR scores and small for gestational age (SGA) status were added and renamed it as SNAP II with Perinatal Extension (SNAPPE-II) score [ 7 ]. Data validating SNAPPE II score from Nepal are lacking. As the clinical profile of neonates and their outcomes may be different in our scenario, we aimed to assess the validity of this score to predict mortality and duration of NICU stay in a resource poor NICU set-up of Nepal. This may help in prioritizing the treatment of sick newborns as well as counselling of their parents about disease severity. This prospective, observational study was carried out during the period from June 2015 to May 2016 at NICU in a tertiary care hospital of eastern Nepal. All newborns admitted to NICU were included in the study. Newborns who died or were discharged in < 24 h after admission, those with congenital malformations incompatible with life, those neonates who did not require ABG (Arterial blood gas analysis) or catheterization, home deliveries with unknown APGAR score and those discharged against medical advice were excluded from our study. Informed consent from parents was taken before conducting this study then participants were enrolled consecutively. This study was approved by the ethical committee of the hospital. The SNAPPE-II score was calculated on the basis of recommended physiological and clinical factors [ 7 ], evaluated prospectively within the first 12 h of admission after stabilization. Noninvasive mean blood pressure in (mmHg) was measured with the use of appropriate cuff size in left or right arm via vital sign monitor (Nihon Kohden Corporation, japan). Temperature was measured in axilla using commercially available mercury thermometer (35 to 42 °C) keeping thermometer for 3 min in axilla. Serum pH and PaO2/FiO2 was calculated by arterial blood gas analysis (ABG) using blood gas and electrolytes analyzer ABL 800 basic (Radiometer, Denmark) available in our NICU. All types of neonatal seizure were included in this score. Birth-weight of inborn neonates was measured by electronic weighing machine (Hardik Meditech, Delhi, India) (±5 g error) without clothing. Birth-weight of outborn neonates was recorded from their details mentioned on referral slips. Urine output (ml/kg/hr) was measured using Pediatric urine collecting bag or by catheterization. Modified Ballard score was used to assess the gestational age. Lubchenco’s [ 9 ] intrauterine growth chart was used for classification as small for gestational age as birth-weight < 10th percentile for gestational age. Neonates were treated as per hospital protocols and they were discharged from NICU as per standard NICU protocol. Data were entered in MS excel and coded where necessary. SPSS version 20.0 was used for data analysis. Comparison between survivors and non-survivors was performed using Mann-Whitney test. Chi-square test was used for qualitative variables. The power of SNAPPE II score to predict the neonatal mortality was evaluated by means of Receiver Operating Characteristics (ROC) curve. Optimal cut-off score to predict mortality was determined by visual inspection of the curve at a level that combined maximum sensitivity and optimal specificity. Positive predictive values and negative predictive values were calculated for different cut-off scores. P values less than 0.05 was considered as statistically significant. A total of 305 neonates were admitted to NICU over a period of one year (June 2015 to May 2016). Among them, 35 neonates were excluded who did not meet the inclusion criteria. Two hundred seventy neonates were enrolled in the study of which 15 neonates left against medical advice (LAMA). Among 255 neonates completing the study, 92 (36.1%) were preterm and 163 (63.9%) were term neonates. Mean (SD) birth-weight was 2422.9 (858.2) g and mean (SD) gestational age was 36.8 (0.2) weeks. Out of 255 neonates, 45 (17.6%) died and 210 were discharged. Neonates with SNAPPE II score 40 to 60, mortality rate was 36.7%, score of ≥40 had mortality rate of 55.1% and score of ≥60 had 100% mortality. General characteristics of neonates admitted to NICU have been shown in Table 1 . The median (IQR) SNAPPE II score was significantly higher in the babies who died in comparison to those who survived [57 (42–64) vs. 22(14–32), P < 0.001]. Average duration of NICU stay was 4 days. There was no significant correlation between SNAPPE II score and duration of NICU stay ( P = 0.477). Table 1 General characteristics of the neonates admitted in NICU Characteristics n = 255 Gender, n (%) Male 175 (69%) Female 80 (31%) Mean Gestational age, mean (SD) week 36.8 (0.2) Gestational age, n (%) Term 163 (63.9%) Preterm 92 (36.1%) Mean Birth weight, mean (SD) gram 2422.9 (858.2) Birth weight n (%) < 1000 g 8 (3.1%) 1000 g to 2500 g 102 (40%) > 2500 g 145 (56.9%) Outcome, n (%) Discharged 210 (82.4%) Expired 45 (17.6%) SNAPPE II score, mortality (%) ≥ 40 55.1% 40–60 36.7% ≥ 60 100% SNAPPE II score ≥ 38 Sensitivity 84.4% Specificity 91% Positive predictive value 66.7% Negative predictive value 96.5% General characteristics of the neonates admitted in NICU Area under curve (AUC) in ROC curve was 0.917 [95% CI 0.854–0.980] as shown in Fig. 1 , which validates the utility of SNAPPE II score to predict neonatal mortality in NICU. The best cut-off SNAPPE II score in predicting overall mortality was 38. Sensitivity, specificity, positive and negative predictive value of score ≥ 38 in estimating overall mortality were 84.4, 91, 66.7 and 96.5% respectively. Fig. 1 Receiver operating characteristics curve (ROC) for SNAPPE-II score for prediction of mortality Receiver operating characteristics curve (ROC) for SNAPPE-II score for prediction of mortality The present study documented that the SNAPPE II score of the neonates who died in the NICU was higher than in those who survived. The higher the score of SNAPPE- II, the higher was the mortality risk of neonates. SNAPPE II score of ≥38 was the best to predict mortality with sensitivity 84.4%, specificity 91%, positive predictive value (PPV) 66.7% and negative predictive value (NPV) of 96.5%. There was no significant correlation between SNAPPE II score and duration of NICU stay. This result supports the study done by original author Richardson et al. (AUC 0.91) [ 10 ], Zupanic et al. (AUC 0.90) [ 11 ] and Mia et al. [ 12 ] in Soetomo Hospital, Indonesia in which AUC was 0.863. In studies conducted in a tertiary care hospital, Indonesia [ 12 ] (score of ≥40), in a general pediatric hospital in Paraguay [ 13 ] (score of ≥40), Niranjan et al. in India [ 14 ] (score of ≥37) & in Indira Gandhi Institute of Child Health, India [ 15 ] (score of ≥37) were all associated with higher mortality which is similar to our results. But in contrast to our results, studies conducted in a hospital of indonesia [ 16 ] (with a score of ≥51), by Ucar et al. [ 17 ], (score of ≥33), Dammann et al. [ 18 ], (a score of ≥30) were associated with high mortality. In two studies done in India by Niranjan et al. [ 14 ] and (Harsha & Archana) [ 15 ] with cut-off score of ≥37 in both studies, Sensitivity (84.4% vs. 76.1% & 76.9%), specificity (91% vs. 87.1% & 87.9%) and NPV (96.5% vs. 52.6%) were higher in our study than these two studies. But positive predictive value in our study was less (66.7 vs. 95. 3%). Variation in the cut-off score and discrimination might be due to the factors affecting the score such as diseases, severity of illness, quality of care in NICU etc. There was no significant correlation between SNAPPE II score and duration of NICU stay ( P = 0.477). But SNAPPE II score had positive correlation with duration of NICU stay as correlation coefficient was r = 0.045 which is similar to a study done by Harsha & Archana [ 15 ] in India where P = 0.255 for duration of NICU stay. Other studies also reported similar findings [ 19 , 20 ]. All newborns who were born at home and those neonates who left NICU against medical advice were excluded from the study. Birth-weight and Apgar score of outborn neonates were taken from referral card. These were the limitations of this study. Thus, SNAPPE II score is a useful tool to asess the severity of illness and prognosis. These findings can be implicated in NICU routinely to know the most critical newborn for prioritizing the management and for the purpose of counselling the parents. This score might also be used to compare the effectiveness of various NICU across the country which will help to improve the facilities provided by different NICUs. SNAPPE II score can be used to predict the severity of diseases and associated mortality and may help in prioritizing the treatment of sick newborns as well as counselling of their parents about disease severity. We conclude that SNAPPE II scoring system may be a useful tool to predict neonatal mortality in resource poor NICU setting. Arterial blood gas analysis Area under ROC Curve Neonatal intensive care unit Receiver Operating Characteristic Score for Neonatal Acute Physiology Score for Neonatal Acute Physiology with Perinatal Extension II Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Mr. Dharanidhar Baral, statistician, BP Koirala institute of Health sciences (BPKIHS). DM: conception and design, acquisition of data, analysis and interpretation of data and drafting of the manuscript. RRS and NKB involved in conception and design of the study and critical analysis of data. DS: interpretation of data and critically reviewed the manuscript for intellectual content. All authors read and approved the final manuscript. None. Available upon reasonable request to corresponding author. Approved by institutional ethical review committee (IRC) B.P. 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SNAPPE-II (score for neonatal acute physiology with perinatal extension) as a predictor of mortality in NICU SNAPPE-II (score for neonatal acute physiology with perinatal extension-II) in predicting mortality and morbidity in NICU Score for Neonatal Acute Physiology Perinatal Extension II (SNAPPE II) as the predictor of neonatal mortality hospitalized in neonatal intensive care unit The efficacy of SNAPPE.II-II in predicting morbidity and mortality in extremely low birth weight infants SNAP-II and SNAPPE-II as predictors of death among infants born before the 28th week of gestation. Inter-institutional variations Profile of neonates admitted in paediatric ICU and validation of score for neonatal acute physiology (SNAP) Role of score for neonatal acute physiology (SNAP) in predicting neonatal mortality
Answer the following medical question.	What does research say about Neonatal hypothermia and associated factors among neonates admitted to neonatal intensive care unit of public hospitals in Addis Ababa, Ethiopia.?	Neonatal hypothermia is a worldwide problem and an important contributing factor for Neonatal morbidity and mortality especially in developing countries. High prevalence of hypothermia has been reported from countries with the highest burden of Neonatal mortality. So the aim of this study was to assess the prevalence of Neonatal hypothermia and associated factors among newborn admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa. An institutional based cross-sectional study was conducted from March 30 to April 30, 2016, in Public Hospitals in Addis Ababa and based on admission rate a total of 356 Neonates with their mother paired were enrolled for the study. Axillary temperate of the newborn was measured by a digital thermometer at the point of admission. Multivariate binary logistic regression, with 95% confidence interval and a p -value < 0.05 was used to identify variables which had a significant association. The prevalence of Neonatal hypothermia in the study area was 64% . Preterm delivery (AOR = 4.81, 95% CI: 2.67, 8.64), age of Neonate ≤24 h old (AOR = 2.26, 95% CI: 1.27, 4.03), no skin to skin contact with their mother immediately after delivery (AOR = 4.39, 95% CI: 2.38, 8.11), delayed initiation of breastfeeding (AOR = 3.72, 95% CI: 2.07, 6.65) and resuscitation at birth (AOR = 3.65, 95%CI: 1.52, 8.78) were significantly associated with hypothermia. The prevalence of Neonatal hypothermia in the study area was high. Preterm delivery, age ≤ 24 h old, no skin to skin contact immediately after delivery, delayed initiation of breastfeeding and resuscitation at birth were independent predictors of Neonatal hypothermia. Therefore attention is needed for thermal care of preterm newborn and use of low-cost thermal protection principles of warm chain especially on early initiation of breastfeeding, skin to skin contact immediately after delivery and warm resuscitation. The online version of this article (10.1186/s12887-018-1238-0) contains supplementary material, which is available to authorized users. World Health Organization (WHO) defined Neonatal hypothermia as an axillary temperature less than 36.5 °c. Reduction of thermal stability has a long-term physiologic effect that leads to, death due to hypoxia, and hypotension [ 1 ]. Globally an estimated of four million newborns die within the first four weeks of life, which accounts 2/3rd of all deaths in the first year of life and 40% of under five deaths. Most Neonatal deaths (99%) arise in low and middle-income countries [ 2 , 3 ]. In Ethiopia also there is high Neonatal mortality, 37 deaths per 1000 live birth [ 4 ]. Hypothermia is one of the important causes for Neonatal death and morbidity in developing countries, which increases mortality by five times, and recent studies showed that every 1 °c decrement of body temperature increases mortality by 80% [ 2 , 5 , 6 ]. The prevalence is high among countries with the highest burden of Neonatal mortality [ 7 ]. It is a problem of both home delivered (32 - 85%) and institutional delivery (11 to 90%) [ 8 ]. A study in Bangladesh reported 34% of Neonates had hypothermia out of NICU admission [ 9 ]. Reports in developing country show that greater than 90% of Neonates were hypothermic (temperature less than 36.5 °C) and 10.7% of the newborn were at less than 35.0 °C [ 10 , 11 ]. In West African sub-region, a prevalence rate of 62% at the point of admission was reported [ 12 ]. In Ethiopia also there was a prevalence of hypothermia ranging from 53 to 69.8% [ 8 , 13 ]. Prematurity is one of the risk factors for Neonatal hypothermia and it is the leading cause of Neonatal mortality which accounts 37% of Neonatal death in Ethiopia [ 4 ]. And the prevalence of preterm birth ranges from 10 - 25.9% [ 14 , 15 ]. Both physical characteristics and environmental factors predispose the preterm infant to hypothermia [ 16 ]. In Ethiopia lack of adequate perinatal care is one of the factors for onset of hypothermia, there is a high prevalence of home delivery which accounts 73% and Institutional deliveries accounts only 26% [ 17 ]. Low socio-economic status, poor kangaroo mother care practice, low birth weight, bathing of a newborn within 24 h, delayed initiation of breastfeeding, a traditional practice of oil massage of Neonates and inadequate knowledge of thermal care among health workers are determinant factors for hypothermia [ 2 , 18 , 19 ]. Although hypothermia is rarely a direct cause of death, it contributes to Neonatal mortality as a comorbidity of severe Neonatal infections, preterm birth, and asphyxia [ 8 ]. Mortality rate was significantly higher among hypothermic babies (RR = 2.26, CI = 1.14–4.48). Even though predisposing factors for hypothermia are easily preventable the problem of hypothermia remains an unanswered question and it is highly prevalent in developing nations including sub-Sahara Africa [ 2 ]. Ethiopia applies thermal care principle which is one of the components of essential newborn care (ENBC) recommended by WHO. Despite this intervention, the problem of hypothermia remains a challenge in Ethiopia [ 1 , 20 ]. And the achievement of sustainable development goal (SDG) 3 of ensuring healthy lives and promote well-being for all at all age requires a remarkable reduction of Neonatal death. Even though reduction of Neonatal hypothermia contributes to the achievement of SDG 3, it sustains as a challenge [ 21 ]. Providing ENBC including thermal care or prevention of Neonatal hypothermia is one part of nursing care, but the problem of Neonatal hypothermia remains a worldwide problem, especially in sub-Saharan Africa. Therefore, the purpose of this study was to determine the prevalence of Neonatal hypothermia and associated factors among Neonates admitted to NICU of Public Hospitals in Addis Ababa. So, this study will provide baseline data on the prevalence of Neonatal hypothermia and identification of possible factors for the onset of Neonatal hypothermia in the area will have greater input to program managers and policy makers for designing, proper implementation and evaluation programs on reduction of Neonatal mortality and improvement of newborn care to achieve SDG 3. In addition, the study will help to improve quality of newborn care in the nursing profession, specifically thermal protection, by low - tech preventive measures and early detection and referral of hypothermia. An institutional based cross -sectional study design was conducted from March 30 to April 30, 2016, to determine the prevalence of Neonatal hypothermia and associated factors among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa. The study was conducted in six Public Hospitals in Addis Ababa, Ethiopia, that have their own NICU; namely; Tikur Anbessa Specialized Teaching Hospital that has its own Neonatal Intensive Care Unit (NICU) with an average NICU admission of 240 Neonates per month, St. Paul’s Hospital Millennium Medical College with an average NICU admission of 210 Neonates per month, Yekatit 12 Hospital Medical College with an average NICU admission of 170 Neonates per month, Gandhi Memorial Specialized Hospital with an average NICU admission of 192 Neonates per month, Zewditu Memorial Hospital with an average NICU admission of 110 Neonates per month and Tirunesh Beijing General Hospital with an average NICU admission of 60 Neonates per month. The study was conducted in all Public Hospitals in Addis Ababa that has their own NICU, because the level of perinatal care given, standards of NICU, and accessibility of thermal prevention materials are somewhat different in each Hospital. The source populations were all Neonates who were admitted to NICU of public Hospitals in Addis Ababa. Randomly Selected Neonates admitted to NICU of public Hospitals in Addis Ababa from March 30 to April 30, 2016, were the study population. All Neonates with their mother admitted to NICU of Public Hospitals in Addis Ababa during the study period were included in the study. Sample size was calculated by using single population proportion formula: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathrm{n}=\frac{\kern0.50em \left(\mathrm{z}a/2\right){2}^{\ast }\ \mathrm{pq}}{d2} $$\end{document} n = z a / 2 2 ∗ pq d 2 By considering 10% none response rate of participants, the final sample size was 356 . Where n = the required sample size. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\displaystyle \begin{array}{l}d=m\arg in\ of\ error\ between\ the\ sample\ and\ population=5\%=0.05\\ {}Z=s\tan dard\ normal\ distribution\ value\ at\ 95\% confidence\ level\\ {}Z\ \alpha /2=1.96\ for\ 95\% confidence \operatorname {int} erval\\ {}p=\Pr evalence\ of\ Neonatal\ hypothermia\ \left(69.8\%\right)\end{array}} $$\end{document} d = m arg in of error between the sample and population = 5 % = 0.05 Z = s tan dard normal distribution value at 95 % confidence level Z α / 2 = 1.96 for 95 % confidence int erval p = Pr evalence of Neonatal hypothermia 69.8 % from the previous study conducted in Gondar University Teaching and Referral Hospital, Northwest Ethiopia [ 13 ]. There were a total of six Public Hospitals in Addis Ababa that have their own organized NICU and they have a total average number of 982 admissions to NICU per month and a total sample size of 356 Neonates were selected from the six Hospitals. Then participants was selected by using systematic random sampling technique, that is every three admission until the required sample size was obtained (K = 2.75, approximately every 3 admissions was taken). The number of Neonates surveyed from each Hospital was allocated proportionally to the total average number of admission per month from all Hospitals. The instrument for data collection was semi-structured pre-tested questionnaire which was adopted and modified from a study conducted in Ethiopia, Gondar University Hospital, Nigeria and Uganda [ 12 , 13 , 19 ]. The questionnaire contains items to assess the temperature of the newborn during admission to NICU and associated factors for the onset of hypothermia (Additional file 1 ). Axillary temperate of the newborn was measured for three minute by using digital thermometer (model of MT-101 MT-111) which can measure from 32.0 ° C to 42.9 °C (89.6 °F to 109.9 °F) that had measurement accuracy of ±0.1 °C for the temperature range of (35.5 °C – 42.0 ° C) and ± 0.2 °C for the temperature range of (32.0 ° C - 35.5 ° C or above 42.0 °C) at point of admission. The thermometer was disinfected by using 70% ethyl alcohol disinfectant with a damp cloth after every measure of axillary temperature of the newborn to prevent infection transmission. And other data such as; medical diagnosis, and CPR history was collected from the chart of the newborn and socio-demographic data and obstetric history was collected from their mother by using semi-structured pre-tested questionnaire. Infrared thermometer (model of Kintrex IRT0421) with a measurement range of (− 60 °C to 50 °C) and measurement accuracy of ±2 ° C was used to measure the room temperature of the NICU. And data collection was done carefully by six BSc nurses. Neonatal hypothermia Neonatal hypothermia Socio-demographic characteristics of the mother Maternal age, parity, residence, ethnicity, educational status, occupation and income. Neonatal, obstetric and environmental factors of the neonate: Socio-demographic characteristics of the mother Maternal age, parity, residence, ethnicity, educational status, occupation and income. Neonatal, obstetric and environmental factors of the neonate: Age of newborn in hour, sex of newborn, low birth weight, mode of delivery, pregnancy type (single / multiple), prematurity, skin to skin contact with mother immediately after delivery, bathing before age of 24 h, CPR, delayed initiation of breastfeeding, room temperature of NICU, place of delivery, application of oil massage, obstetric complication during pregnancy and Medical diagnosis during admission. Hypothermia : an axillary temperature of less than 36.5 °c Cold stress(mild hypothermia) : an axillary temperature of 36.0 to 36.4 °C Moderate hypothermia : an axillary temperature of 32.0 to 35.9 °C Severe hypothermia: an axillary temperature of < 32.0 °C Normothermic: an axillary temperature of 36.5 to 37.5 °C Hyperthermia: an axillary temperature of > 37.5 °C Admission temperature : The first temperature obtained from neonates at admission to NICU Inborn : a new born that was delivered from the study Hospital Out born: a new born that was deliver other than the study Hospital Hypothermia : an axillary temperature of less than 36.5 °c Cold stress(mild hypothermia) : an axillary temperature of 36.0 to 36.4 °C Moderate hypothermia : an axillary temperature of 32.0 to 35.9 °C Severe hypothermia: an axillary temperature of < 32.0 °C Normothermic: an axillary temperature of 36.5 to 37.5 °C Hyperthermia: an axillary temperature of > 37.5 °C Admission temperature : The first temperature obtained from neonates at admission to NICU Inborn : a new born that was delivered from the study Hospital Out born: a new born that was deliver other than the study Hospital The questionnaire was prepared in English and translated to Amharic, and back-translated into English by two language experts to check for consistency of the questionnaire. The data was collected by six BSc. nurse experts. Thermometer calibration was done for the reliability of the thermometer before using the instrument for data collection. Three day training and clear orientation were provided on the process of data collection for data collectors. A pretest was done by 5% of the study population in another Hospital three weeks before the actual data collection to evaluate the clarity of questions and validity of the instrument and reaction of respondents to the questions. Data collectors were closely monitored and guided by two MSc. nurse supervisors during data collection. The data was cleaned manually, coded and entered into Epi info version 3.5 and exported to SPSS version 20 software for further analysis. After coding, and entering the data to the software descriptive statistics were used to calculate the result in proportion, frequencies, cross tabulation, and measure of central tendency. Tables and graphs were used to present the result. A bivariate binary logistic regression was used to identify candidate variables for the final model (multivariate binary logistic regressions) at p - value < 0.20. Finally the independent predictors or variables which had significant association were identified by using multivariate binary logistic regressions. The cut point to declare the presence of an association between the dependent and independent variable was p – value < 0.05 or AOR, 95% CI. A total of 356 mothers with their neonates were included in the study with 100% response rate. The mean age of mothers was 28 years (SD = 5.6) and more than half of the mothers were in the age group between 20 and 29 (51.1%) years of age. One hundred twenty seven (35.7%) were Oromo in ethnicity and majority of the mothers 206 (57.9%) were Orthodox followers. Two hundred seventy six (77.5%) were urban residents. Eighty respondents (22.2%) were unable to read and write and 144 (40.4%) of respondents were housewife. The mean monthly income of the family was 54 US dollar (SD = 11US dollar) and 117 (32.9%) had a monthly income of below average. And 191 respondents (53.7%) were primiparous (Table 1 ). Table 1 Socio-demographic characteristics of mothers of neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Variables Categories Frequency Percentage (%) Age of mother (years) 15–19 17 4.8 20–29 182 51.1 30–39 145 40.7 40–49 12 3.4 Ethnicity Amhara 121 34.0 Tigre 55 15.4 Oromo 127 35.7 Gurage 37 10.4 Other 16 4.5 Religion Orthodox 206 57.9 Protestant 59 16.6 Muslim 88 24.7 Other 3 0.8 Residence Urban 276 77.5 Rural 80 22.5 Educational status Unable to read and write 80 22.5 Primary school 77 21.6 Secondary school 102 28.7 Diploma and above 97 27.2 Occupation House wife 144 40.4 Government employ 79 22.2 Private business 92 25.8 Student 27 7.6 Farmer 14 3.9 Monthly income of the family Below average 117 32.9 Average (43–65 US dollar) 129 36.2 Above average 110 30.9 Parity Primiparous 191 53.7 Multiparous 165 46.3 Socio-demographic characteristics of mothers of neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Majority of Neonates were males 204 (57.3%) and the median age of the newborn was 3 h. And most of the neonates 233 (65.4%) were in the age group of ≤24 h. The mean birth weight was 2440 g (SD 721 g). More than half 183 (51.4%) of the Neonates had birth weight ≥ 2500 g. The mean gestational age (GA) was 36 weeks ±2.8 weeks, most of them, 202 (56.7%) were with GA < 37 weeks. Only 126 (35.4%) of Neonates had early initiation of breastfeeding within one hour after birth. Eighty four (23.6%) had received resuscitation (CPR) during birth (Table 2 ). Table 2 Neonatal characteristics of respondents among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Variables Categories Frequency Percentage (%) Age of Newborn (hour) ≤24 233 65.4 24–72 60 16.9 > 72 63 17.7 Sex of new born Male 204 57.3 Female 152 42.7 Birth weight(grams) < 1000 10 2.8 1000–1499 32 9.0 1500–2499 131 36.8 2500–4000 179 50.3 > 4000 4 1.1 Gestational age (weeks) < 28 weeks 2 0.6 28- < 32 weeks 25 7.0 32- < 37 weeks 175 49.2 37-42 weeks 152 42.7 > 42 weeks 2 .6 Started breast feeding within one hour after birth Yes 126 35.4 No 230 64.6 Received CPR during birth Yes 84 23.6 No 272 76.4 Neonatal characteristics of respondents among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Most of the pregnancies 311 (87.4%) were single and the majority of Neonates 286 (80.3%) were born without any obstetric complication. More than half 213 (59.8%) were delivered through SVD. Sixty five (18.3%) of the newborn were bathed before 24 h old and more than half of Neonates 188 (52.8%) had no skin to skin contact immediately after birth. And 41 (11.5%) had Oil massage of the skin after birth. One hundred seventy (47.8%) were out born neonates and of them, nine (2.5%) delivered at home. More than half 190 (53.4%) deliver during day time. Majority of Neonates 329 (92.4%) were admitted to NICU at room Temperature ≥ 25 ° C (Table 3 ). Table 3 Obstetric and Environmental characteristics of respondents among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Variables Categories Frequency Percentage (%) Obstetric complication during pregnancy Yes 70 19.7 No 286 80.3 pregnancy type Single 311 87.4 Twine 41 11.5 Triple 4 1.1 Mode of delivery SVD 213 59.8 Instrumental 32 9.0 C/S 111 31.2 skin to skin contact immediately after delivery Yes 168 47.2 No 188 52.8 Place of delivery Inborn 186 52.2 Out born 170 47.8 setting for out born delivery Missing (Inborn) 186 52.2 Other Hospital 69 19.4 Health Centre 76 21.3 Private health facility 13 3.7 Traditional birth center 3 0.8 Homes 9 2.5 Oil massage of the skin immediately after birth Yes 41 11.5 No 315 88.5 Bathed the new born before 24 h old Yes 65 18.3 No 291 81.7 Time of delivery Day time 190 53.4 Night time 166 46.6 Room Temperature of NICU < 25 ° C 27 7.6 Obstetric and Environmental characteristics of respondents among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Medical diagnoses during admission were reviewed from medical record of the newborn and 116 (32.6%) were admitted for the reason of respiratory distress, 173 (48.6%) diagnosed as low birth weight and 202 (56.7%) were diagnosed as preterm, and 84 (23.6%) diagnoses as perinatal asphyxia (Table 4 ). Table 4 Medical diagnoses of neonates during admission among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Variable Categories Frequency Percentage (%) Diagnosis during Admission Respiratory distress 116 32.6 Preterm 202 56.7 Jaundice 55 15.4 Sepsis 83 23.3 LBW 173 48.6 Perinatal asphyxia 84 23.6 Congenital anomaly 35 9.8 Meconium aspiration syndrome 22 6.2 Small for gestational age 15 4.2 hypoglycemia 15 4.2 Other 16 4.5 The total cumulative frequency for diagnosis is greater than 100% because the Neonate may have more than one clinical diagnosis during admission. Medical diagnoses of neonates during admission among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] The prevalence of neonatal hypothermia among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa was 228 (64%). Among them, more than half 184 (80.7%) were moderate hypothermic and the remaining 44 (19.3%) were mild hypothermic babies (Fig. 1 ). Fig. 1 Classification of temperature among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Classification of temperature among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] And the prevalence of hypothermia was high among preterm 155 (76.7%), low birth weight 127 (73.4%), age ≤ 24 h 171 (73.4%), and among out born delivery 112 (65.9%) (Fig. 2 ). Fig. 2 Comparison of Hypothermia with gestational age among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Comparison of Hypothermia with gestational age among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] In bivariate logistic regression analysis the following factors were significantly associated with hypothermia; age of newborn ≤24 h old, low birth weight, preterm delivery, no skin to skin contact to their mother immediately after delivery, no early initiation of breastfeeding within one hour, resuscitation at birth (CPR), obstetric complication during pregnancy, multiple Pregnancy and night-time delivery. Then those variables which are significant on bivariate analysis were entered to multiple logistic regressions to see independent predictors. Accordingly, Neonates with the age of ≤24 h old were 2 times more likely to have hypothermia when compared to age greater than 24 h (AOR = 2.26, 95% CI: 1.27, 4.03). Preterm Neonates were 4.8 times more likely to have hypothermia when compared to term delivery (AOR = 4.81, 95% CI: 2.67, 8.64). And newborn who had no skin to skin contact to their mother immediately after delivery were 4.3 times more likely to be hypothermic when compared to those who have skin to skin contact (AOR = 4.39, 95% CI: 2.38, 8.11). Those Neonates who had no early initiation of breastfeeding within one hour after birth were 3.7 times more likely to develop hypothermia when compared to those who have started within one hour after birth (AOR = 3.72, 95% CI: 2.07, 6.65). And Neonates who had resuscitation at birth (CPR) were 3.6 times more likely to be hypothermic when compared to those who had no resuscitation (AOR = 3.65, 95% CI: 1.52, 8.78) (Table 5 ). Table 5 Bivariate and multivariate logistic regression analysis of associated factors among Neonates admitted to Neonatal Intensive Care Unit of Governmental Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] Variables Hypothermic (228) Non Hypothermic (128) COR (95% CI) AOR (95% CI) P - value N (%) N (%) Age of Neonate (hour) ≤ 24 171(73.4) 62(26.6) 3.19(2.02,5.05) 2.26(1.27, 4.03) .005* > 24 57(46.3) 66(53.7) 1.0 1.0 Birth weight (grams) < 2500 127(73.4) 46(26.6) 2.24(1.44,3.5) 1.33(0.75,2.36) 0.331 ≥ 2500 101(55.2) 82(44.8) 1.0 1.0 Gestational age (weeks) < 37 155(76.7) 47(23.3) 3.66(2.32,5.76) 4.81(2.67, 8.64) 0.001* ≥ 37 73(47.4) 81(52.6) 1.0 1.0 skin to skin contact Yes 71(42.3) 97(57.7) 1.0 1.0 0.001* No 157(83.5) 31(16.5) 6.92(4.23,11.32) 4.39(2.38, 8.11) Early initiation of breast feeding Yes 45(35.7) 81(64.3) 1.0 1.0 0.001* No 183(79.6) 47(20.4) 7.0(4.32,11.38) 3.72(2.07, 6.65) CPR received Yes 76(90.5) 8(9.5) 7.5(3.48, 16.15) 3.65(1.52, 8.78) 0.004* No 152(55.9) 120(44.1) 1.0 1.0 Obstetric complication during pregnancy Yes 62(88.6) 8(11.4) 5.6(2.59, 12.13) 1.43(0.57, 3.56) 0.440 No 166(58) 120(42) 1.0 1.0 Pregnancy type Single 190(61.1) 121(38.9) 1.0 1.0 0.145 Multiple 38(84.4) 7(15.6) 3.46(1.45,7.99) 2.14(0.77, 5.97) Time of delivery Day time 108(56.8) 82(43.2) 1.0 1.0 0.352 Night time 120(72.3) 46(27.7) 1.98(1.26, 3.09) 1.32(0.73, 2.37) * Significant at p -value ≤ 0.05 Bivariate and multivariate logistic regression analysis of associated factors among Neonates admitted to Neonatal Intensive Care Unit of Governmental Hospitals in Addis Ababa, Ethiopia, 2016 [ n = 356] * Significant at p -value ≤ 0.05 The prevalence of Neonatal hypothermia among newborn in this study was 64%. This was almost similar with a study conducted in Nigeria (62%) [ 12 ], in Bahir Dar, Ethiopia (67%) [ 22 ] and Gondar, Northwest Ethiopia (69.8%) [ 13 ]. And it was lower than a study conducted in Nepal (92.3%) [ 10 ], Zimbabwe (85%) [ 8 ] and Uganda (83%) [ 19 ]. But it was higher than a study conducted in South Africa (21%) [ 23 ], Bangladesh (34%) [ 9 ] and Pakistan (49.5%) [ 24 ]. This variation might be due to the difference in temperature measurement site, ecological, economic and cultural difference between the study areas. There was high prevalence of hypothermia among out born delivery (65.9%); this might be due to lack of proper thermal care practice during inter-facility transportation. Neonates are transported from ward to ward or to other Hospital without proper wrapping. This finding was higher than a study done in Bangladesh which was 43% for out born and 22% for inborn but lower than Nigeria which was 90.9% for out born and 61.1% for inborn [ 9 , 12 , 23 ]. This might be due to the difference in inter-Hospital transport thermal care services, distance traveled to the hospital and economical difference. This study revealed that Neonates with the age of 24 h old or less were 2 times more likely to have hypothermia than age greater than 24 h (AOR = 2.26, 95%CI: 1.27, 4.03). This could be due to the fact that newborns have no adequate adipose brown tissue and had no shivering thermogenesis so they are not capable for thermoregulation. This is similar to a study conducted in Bangladesh, (AOR = 2.23 95% CI: 1.22, 4.0) [ 9 ]. Preterm Neonates were 4.8 times more likely to have hypothermia when compared to term Neonates (AOR = 4.81, 95% CI: 2.67, 8.64). The possible reason might be preterm Neonates have immature and thin skin that increase heat loss through radiation, underdeveloped hypothalamic control, they lack efficient neural mechanisms for temperature control by shivering, have decreased glycogen stores, have decreased fat for insulation and have less brown adipose tissue, so they have decreased ability to regulate their body temperature, by producing heat through non - shivering thermogenesis [ 2 , 25 , 26 ]. This is almost similar to a study done in Pakistan in which preterm Neonates were 4 times more likely to develop hypothermia when compared to term newborn [ 24 ]. But it is higher than a study conducted in Iran in which preterm Neonates were 1.73 times more likely to be hypothermic than term one [ 27 ]. This variation might be due to the difference in the thermal care of preterm newborn, standard of delivery room and NICU. Neonates who had no skin to skin contact with their mother immediately after delivery were 4.3 times more likely to develop hypothermia when compared with those who have skin to skin contact immediately after delivery (AOR = 4.39, 95% CI: 2.38, 8.11). The possible reason could be in the utero body temperature of the fetus is consistent with maternal temperature; Neonates who had skin to skin contact immediately after delivery with their mother gain heat through conduction which is consistent with their temperature in the womb during exposure of the newborn to extra uterine environment [ 28 ]. This finding is almost similar with a study conducted in Gondar, North west Ethiopia in which those who had no skin to skin contact were 3 times more likely to develop hypothermia [ 13 ]. Putting newborn together with the mother or kangaroo mother care is an important means of prevention of hypothermia [ 29 ]. Those Neonates who had no early initiation of breastfeeding within one hour after birth were 3.7 times more likely to be hypothermic when compared to those who had started breastfeeding within one hour after birth (AOR = 3.72, 95% CI: 2.07, 6.65). This might be due to the reason that breast milk is the source of energy or calories to produce heat for thermoregulation and they have no adequate adipose tissue for glucose breakdown which results in hypothermia [ 25 ]. And it is consistent with a study done in Nigeria but lower than a study done in Gondar, North west Ethiopia in which those who were delayed in initiation of breast feeding were 7.5 times more likely to be hypothermic [ 13 , 18 ]. This difference in magnitude might be due to difference in study setup, knowledge of mothers on good positioning and attachment of breast feeding and difference in place of delivery. Neonates who had resuscitation at birth were 3.6 times more likely to be hypothermic when compared to those who had no resuscitation (AOR = 3.65, 95% CI: 1.52, 8.78). This is due to the fact that Neonates who need resuscitation are those who had birth asphyxia; there is no enough oxygen which is needed for mitochondrial oxidation in the brown adipose tissue, for heat production. And during resuscitation at birth temperature control may not be properly taken care of; during emergency condition resuscitation may be done without wrapping the baby and in cold table. This finding is higher than study done in Bangladesh in which Neonates that had resuscitation were 2 times more likely to be hypothermic(AOR = 2.15, 95% CI:1.4–3.32) [ 9 ] and a study done in Iran in which those who had resuscitation at birth were almost 2 times more likely to be hypothermic (AOR =1.91, p value = 0.001) [ 27 ]. This variation may be due to the difference in thermal care practice during resuscitation, warm resuscitation or not and difference in time of resuscitation. In bivariate analysis, low birth weight was statistically significant with the onset of hypothermia but in multiple logistic regression analysis it was not significant but there was a high prevalence of hypothermia among low birth weight neonates 127 (73.4%) compared with 101 (55.2%) normal birth weight. This is consistent with a study done in Pakistan 58.1%, Nigeria 89.1% and Gondar, Northwest Ethiopia 58 (89.2%) [ 13 , 18 , 24 ]. Even though the study was conducted in multiple Hospitals, it was done with small sample size and it was conducted with short period of time or in one season so factors like climatic changes or seasonal variations were not addressed. The prevalence of Neonatal hypothermia among Neonates admitted to Neonatal Intensive Care Unit of Public hospitals in Addis Ababa was high 228 (64%). Preterm delivery, age of newborn ≤24 h, and absence of skin to skin contact with their mother immediately after delivery, delayed in early initiation of breastfeeding within one hour after birth and resuscitation at birth were factors that had significant association with Neonatal hypothermia. Therefore attention is needed for thermal care of preterm newborn and on the principle of WHO warm chain especially on early initiation of breast feeding, skin to skin contact and warm resuscitation. It is better to increase the practice of skin to skin contact immediately after delivery which is the effective warm chain principle especially in developing countries in which advanced warming instruments and incubators are not present. Additional file 1: English version questionnaire, for the assessment of Neonatal Hypothermia and associated factors among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia. (DOCX 23 kb) English version questionnaire, for the assessment of Neonatal Hypothermia and associated factors among Neonates admitted to Neonatal Intensive Care Unit of Public Hospitals in Addis Ababa, Ethiopia. (DOCX 23 kb) Degree centigrade Degree farhanite Adjusted odds ratio Confidence interval Cardio pulmonary resuscitation Essential newborn care Gestational age Millennium development goal Neonatal Intensive Care Unit Relative risk Sustainable development goal Statistical Package for Social Sciences World Health Organization The authors would like to thank Addis Ababa University for funding this study. Our thanks also goes to for all study participants, supervisors and data collectors for their unreserved efforts and willingness to take part in this study. Addis Ababa University had covered all the costs for data collection instruments, data collection, data entry and payments for supervisors and advisors. The data that support the findings of this study are available from the corresponding authors upon reasonable request. BW was involved in the conception, design, analysis, interpretation, report and manuscript writing; BB and TY were participated in the design, analysis, interpretation and report writing. FH was involved in designing the study, analysis, report and manuscript writing. And all authors have read and approved the final manuscript. Ethical approval was obtained from Institutional Review Board of Addis Ababa University, School of Allied Health Sciences, Department of Nursing and Midwifery and submitted to each Hospital. In addition, Permission was obtained from all hospitals involved in this study, to conduct research on their property: namely; Tikur Anbessa Specialized Teaching Hospital, St. Paul’s Hospital Millennium Medical College, Yekatit Hospital Medical College, Gandhi Memorial Specialized Hospital, Zewditu Memorial Hospital, and Tirunesh Beijing General Hospital. All mothers that were involved in the study were asked for their willingness after they became informed about the purpose of the study and confidentiality of all the data. And an Informed written consent was obtained from all mothers of the newborn that were selected for the study. Mother of the newborns provided consent for them to participate in the study, and also they provided consent on behalf of the newborns to participate in the study. The study participants right to withdraw from the study at any time during data collection was respected. In the event of the mother's child being under the age of providing their own consent, written informed consent was received from the child's grandmother on behalf of the mother and child. Not applicable. The authors declare that they have no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Neonatal hypothermia and associated factors among neonates admitted to neonatal intensive care unit of public hospitals in Addis Ababa, Ethiopia Neonatal hypothermia in sub-Saharan Africa : A review Hypothermia of newborns is associated with excess mortality in the first 2 months of life in Guinea- Bissau, West Africa Risk of mortality associated with neonatal hypothermia in southern Nepal STATE-OF-THE-ART neonatal hypothermia in low resource settings : a review The global burden of neonatal hypothermia: systematic review of a major challenge for newborn survival Admission hypothermia among neonates presented to neonatal intensive care unit Incidence and seasonality of hypothermia among newborns in southern Nepal Luke Incidence and risk factors of neonatal hypothermia at referral hospitals in Tehran, Islamic Republic of Iran Point-of-admission hypothermia among high-risk Nigerian newborns Proportion of neonatal hypothermia and associated factors among newborns at Gondar University teaching and Refferal hospital, Northwest Ethiopia: a hospital based cross sectional study Elimination of admission hypothermia in preterm very low-birth-weight infants by standardization of delivery room management Prevalence and risk factors for hypothermia on admission in Nigerian babies < 72 h of age Neonatal hypothermia in Uganda: prevalence and risk factors Neonatal hypothermia among hospitalized high risk newborns in a developing country Fetal and neonatal thermal physiology Thermal protection of the newborn in resource-limited environments Incidence and risk factors of neonatal hypothermia at referal hospitals in tehran, islamic republic of Iran Kangaroo mother care to prevent neonatal deaths due to preterm birth complications
Answer the following medical question.	What does research say about Neonates as intrinsically worthy recipients of pain management in neonatal intensive care.?	One barrier to optimal pain management in the neonatal intensive care unit (NICU) is how the healthcare community perceives, and therefore manages, neonatal pain. In this paper, we emphasise that healthcare professionals not only have a professional obligation to care for neonates in the NICU, but that these patients are intrinsically worthy of care. We discuss the conditions that make neonates worthy recipients of pain management by highlighting how neonates are (1) vulnerable to pain and harm, and (2) completely dependent on others for pain management. We argue for a relational account of ethical decision-making in the NICU by demonstrating how an increase in vulnerability and dependence may be experienced by the healthcare community and the neonate's family. Finally, an ethical framework for decisions around neonatal pain management is proposed, focussing on surrogate decision-making and the importance of compassionate action through both a reflective and an affective empathy. As empathy can be highly motivating against pain, we propose that, in addition to educational programs that raise awareness and knowledge of neonatal pain and pain management, healthcare professionals must cultivate empathy in a collective manner, where all members of the NICU team, including parents, are compassionate decision-makers.
Answer the following medical question.	What does research say about Modified Pathway to Survival highlights importance of rapid access to quality institutional delivery care to decrease neonatal mortality in Serang and Jember districts, Java, Indonesia.?	Three-quarters of births in Indonesia occur in a health facility, yet the neonatal mortality rate remains high at 15 per 1000 live births. The Pathway to Survival (P-to-S) framework of steps needed to return sick neonates and young children to health focuses on caregiver recognition of and care-seeking for severe illness. In view of increased institutional delivery in Indonesia and other low- and middle-income countries, a modified P-to-S is needed to assess the role of maternal complications in neonatal survival. We conducted a retrospective cross-sectional verbal and social autopsy study of all neonatal deaths from June through December 2018, identified by a proven listing method in two districts of Java, Indonesia. We examined care-seeking for maternal complications, delivery place, and place and timing of neonatal illness onset and death. The fatal illnesses of 189/259 (73%) neonates began in their delivery facility (DF), 114/189 (60%) of whom died before discharge. Mothers whose neonate’s illness started at their delivery hospital and lower-level DF were more than six times (odds ratio (OR) = 6.5; 95% confidence interval (CI) = 3.4-12.5) and twice (OR = 2.0; 95% CI = 1.01-4.02) as likely to experience a maternal complication as those whose neonates fell fatally ill in the community, and illness started earlier (mean = 0.3 vs 3.6 days; P < 0.001) and death came sooner (3.5 vs 5.3 days; P = 0.06) to neonates whose illness started at any DF. Despite going to the same number of providers/facilities, women with a labour and delivery (L/D) complication who sought care from at least one other provider or facility on route to their DF took longer than those without a complication to reach their DF (median = 3.3 vs 1.3 hours; P = 0.01). Neonates’ fatal illness onset in their DF was strongly associated with maternal complications. Mothers with a L/D complication experienced delays in reaching their DF, and nearly half the neonatal deaths occurred in association with a complication, suggesting that mothers with complications first seeking care at a hospital providing emergency maternal and neonatal care might have prevented some deaths. A modified P-to-S highlights the importance of rapid access to quality institutional delivery care in settings where many births occur in facilities and/or there is good care-seeking for L/D complications. Neonatal mortality (NM) in 2018 constituted 47% of the global 5.3 million under-5 years (U5) deaths [ 1 ], and nearly 80% of neonatal deaths occurred during the early neonatal (EN) period of the first seven days of life [ 2 ]. Pregnancy and labour and delivery (L/D) complications are the most important risk factors for perinatal mortality ((PM) = stillbirths plus EN deaths) [ 3 - 8 ], with care provided during L/D affording the greatest reductions in NM [ 9 , 10 ] and prevention of stillbirth [ 10 ]. Delivering in a health facility has been shown to decrease the risk of PM due to intrapartum complications by 43% to 58% [ 8 ], with higher-level facilities capable of providing basic (BEmONC) and comprehensive (CEmONC) emergency obstetric and newborn care best positioned to deliver the intrapartum care needed to contribute to maternal, perinatal, and neonatal survival [ 9 , 10 ]. Over the past three decades, institutional delivery in Indonesia progressively increased from 18% of all live births in 1989-1994 to 40% in 1998-2002, reaching 75% in 2013-2017 [ 11 - 16 ], but with only 32% of births still taking place in hospitals [ 16 ]; now, the government seeks to extend hospital coverage to remote and underserved areas [ 17 ]. During the same time period (1990-2017), Indonesia’s neonatal mortality rate decreased by 52%, from 31 deaths per 1000 live births in 1990 [ 18 ] to 15 per 1000 in 2013-2017 [ 16 ]. By 2017, Indonesia had nearly achieved Sustainable Development Goal 3.2.2, which is to reduce NM in all countries to at least as low as 12 per 1000 by 2030 [ 19 ]. Further NM reduction by Indonesia will depend on its success in decreasing early neonatal mortality (ENM), which fell by 44% from 1990-2017, compared to the 52% decrease in NM during the same period [ 11 , 16 ]. These trends were paralleled globally. Over the two decades prior to 2013-2018, the percentage of institutional deliveries increased by 46% globally, with the largest increases in regions with initially low levels such as West and Central Africa (49%) and South Asia (132%). By 2013-2018, 76% of all births worldwide, including 58% in sub-Saharan Africa and 72% in South Asia, were in a health facility [ 20 ]. Simultaneously, from 1990-2018, NM decreased globally by 51%, from 37 to 18 deaths per 1000 live births, and in all world regions from 35%, from 48 to 31 per 1000, in West and Central Africa to 71%, from 21 to 6 per 1000 in Eastern Europe and Central Asia [ 18 ]. Meanwhile, the share of neonatal deaths due to ENM increased from 71% to 80% during that time [ 2 ]. We conducted the Every Mother and Newborn Counts (EMNC) study of maternal and neonatal deaths in Serang and Jember districts, Java, to inform policy, planning, and intervention selection to combat maternal and neonatal mortality in Indonesia. Estimates of the causes of neonatal deaths in Indonesia are based on statistical models [ 21 ]; and while pregnancy and delivery complications and delivery without a skilled attendant have been identified as risk factors for NM [ 22 , 23 ], we found just one study from Indonesia on care-seeking for severe neonatal illness in the era of increased institutional delivery [ 24 ] and none on care-seeking for maternal complications in the context of neonatal death. To fill these gaps, we aimed to investigate neonatal causes of death and, for the identified deaths, to examine maternal care, care-seeking for maternal complications, and care-seeking for neonatal illness along the Pathway to Survival (P-to-S) framework (Figure S1 in the ) [ Online Supplementary Document 25 ] developed to support the implementation of the WHO/UNICEF Integrated Management of Childhood Illness (IMCI) approach [ 26 ]. The Pathway depicts household and community preventive measures meant to maintain health, and care-seeking needed to return sick young children to health [ 27 ], and has proven to be a useful model in settings where many or most children die at home [ 28 , 29 ]. However, it was not designed to examine preventive maternal care and care-seeking for sick ENs. Given the high rate of institutional delivery, the strong association of maternal complications with PM, and the fact that most neonatal deaths occur during the EN period, we hypothesized that most neonatal deaths are among children whose mothers had a complication and whose fatal illnesses began in their delivery facility (DF). In support of Indonesia’s and global efforts to identify and monitor the impact of appropriate policies and interventions against NM, we sought to develop an extended P-to-S that highlights maternal care and mothers’ response to complications and to examine mothers’ and their fatally ill neonates’ steps along this Pathway. We previously examined care-seeking for sick neonates and neonatal causes of death [ 30 ]. We now focus on maternal complications, mothers’ care-seeking for their complications, delivery place, and association of the complications with newborns’ place of illness onset and severity. We described the study populations and methods extensively elsewhere [ 30 ]. Briefly, this was a retrospective cross-sectional study that examined all neonatal deaths from June to November 2018 in Serang District of Banten Province and July to December 2018 in Jember District of East Java Province, both in Java, Indonesia. We selected the six-month recall period based on the need to minimize this potential source of bias in a study that required detailed information, including on the chronology of care-seeking actions taken by the mother for herself and her newborn. We selected the districts based on the representativeness of their provinces in terms of maternal and neonatal mortality levels, quality of health facilities and local government commitment, population size, and mix of urban, rural, and remote communities [ 31 ]. We used the Neonatal Deaths from Informant/Neonatal Deaths Follow On Review (NODE-IN/NODE-FOR) double capture method adapted from a similar method for maternal deaths [ 32 ] to identify and list possible neonatal deaths. We asked local informants most knowledgeable about vital events in the community to list all known neonatal deaths and stillbirths, together with the parents’ contact information and age at death of neonates. We conducted follow-up interviews with the families to determine which cases met the study eligibility criteria, including that the child was born alive, was of gestational age ≥28 weeks, died on day 0-27 following birth, died during the recall period, and their parents being residents of one of the study districts. We conducted a verbal and social autopsy (VASA) interview with the main caregiver (usually the mother) of each eligible neonate using a questionnaire adapted from the Johns Hopkins Institute for International Programs VASA instrument [ 27 ]. The instrument contains the 2016 World Health Organization verbal autopsy (VA) form [ 33 ], which includes questions on maternal complications, neonatal illness signs and symptoms, and the place of birth and death. Social autopsy questions, including those needed to identify maternal antenatal care (ANC) and care-seeking for maternal complications and neonatal illnesses, are interspersed chronologically with the VA questions throughout the questionnaire. We examined pregnancy (before labour onset) and L/D complications defined by algorithms of illness signs and symptoms ( box 1 ). We defined “Any complication” as having one or more of preeclampsia/eclampsia, prolonged rupture of membranes (PROM), antepartum haemorrhage (APH), fever during labour, prolonged labour, malpresentation or cord complication. We defined care-seeking delays as the time to decide to seek care (“delay 1”) and to reach the DF after deciding to seek care (“delay 2”) for the mother’s L/D symptom(s). We defined delivery place as “delivery hospital” (DH), “lower-level delivery facility” (LLDF) and “community” (home, on route to a health facility, other place). Only hospitals in Indonesia can be accredited as CEmONC facilities, while only the highest level LLDFs (puskesmas: community health centers overseen by the Ministry of Health) can be BEmONC facilities. We were not able to determine which hospitals and LLDFs in our sample were CEmONC- and BEmONC-capable or accredited. Pregnancy complications (start before labour onset) − Maternal anaemia: severe anaemia − Maternal diabetes: diabetes mellitus − Preeclampsia/eclampsia: (high blood pressure during the last three months of pregnancy and blurred vision) or convulsions during pregnancy − Antepartum haemorrhage: Any vaginal bleeding in the last three months of pregnancy Labour/delivery complications (start after labour onset) − Maternal anaemia: same as for pregnancy − Preeclampsia/eclampsia: (High blood pressure during labour/delivery and blurred vision) or (convulsions during labour/delivery and no fever during labour) − Prolonged rupture of membranes: Water broke 24/more hours before baby was born − Fever during labour: fever during labour − Maternal infection: Fever during labour and (foul smelling amniotic fluid or foul-smelling vaginal discharge during delivery) − Prolonged labour: Labour lasted 12/more hours − Malpresentation: newborn delivered not head first − Cord complication: Cord delivered first or around the newborn’s neck more than once We used Fisher’s exact test to assess the association of maternal complications with: providers/facilities where mothers sought care on route to their DF, the timing of neonates’ death before or after discharge from their birth facility, and the likelihood of neonates’ referral from the birth facility. We used the χ 2 test of proportions to examine the association of maternal complications with the place where neonates’ fatal illnesses began and, for neonates delivered in a facility, with the timing of death in relation to discharge from the facility. We used the t test of equivalence of means to evaluate the number of providers/facilities where women sought care for their L/D complications on route to their DF and the Wilcoxon two-sample test with normal approximation of Z to assess their delays 1 and 2, as well as to explore the association of neonates’ age at illness onset and death with place of illness onset. We examined skewness and kurtosis of test samples to assess normality, with acceptable limits from -1 to 1, to determine whether to use the Wilcoxon or t test to evaluate significance (at P < 0.05). We developed logistic regression models to examine variables associated with delivery place (DH, LLDF, community) and delivery place by onset of neonates’ fatal illness. Possible predictor variables included any maternal complication (yes, no), mothers’ education level (primary, secondary, higher), insurance coverage (yes, no), ANC attendance (four or more visits (ANC4+), less than four), and time to reach the nearest health facility in an emergency (less than 30 minutes, 30 minutes or more). Cases with missing data for any variable were excluded from analyses. To account for the finding that many neonates died in their DF before discharge, we modified the P-to-S graphic to incorporate women’s care-seeking for their complications, delivery place, and place of neonates’ illness onset. The NODE-IN/NODE-FOR process yielded 902 potential neonatal deaths or stillbirths, of which 272 (30.2%) were confirmed as study-eligible neonatal deaths. During home visits, 31.2% cases were ineligible due to being stillbirths, 21.9% due to having occurred outside of the study period, 12.5% due to having a gestational age <28 weeks, 2.2% due to being >27 days old at death, and 2.0% due to either being duplicate cases or having unconfirmable eligibility. Just over 95% (259/272) of eligible cases had a complete VASA interview, so we included them in the analysis. Among these, the mean recall period since death was 5.4 (standard deviation (SD) = 2.0) months. To assess the completeness of our study sample, we compared the 272 confirmed neonatal deaths to official health system records. The 272 deaths comprised 1.6 and 2.2 times more neonatal deaths than reported by Serang and Jember district records, respectively; and, in total, the 272 deaths comprised 92.3% of all neonatal deaths captured by NODE-IN/NODE-FOR and the health system records. Almost 80% of the 259 neonatal deaths with a complete VASA interview died within one week of birth ( ). Altogether, 215 (83.0%) and 191 (73.7%) of 259 neonates had been born and had died in a health facility, respectively; 114 (44.0%) had been born and had died in the same facility without leaving, including 91 (75.2%) of 121 hospital births and 23 (24.5%) of 94 lower-level facility (LLF) births. The odds of either a neonate born in a hospital vs a neonate born elsewhere or a neonate born in a LLF vs a neonate born elsewhere dying in their birth facility without leaving were 15.2 (95% confidence interval (CI) = 8.3-27.9) and 0.3 (95% CI = 0.2-0.5), respectively. Table 1 Characteristics of mothers and newborns LLDF – lower-level delivery facility, SD – standard deviation Highest level attended. We found no difference in the ages of the 215 mothers who delivered in a health facility and 44 who delivered in the community (29.1 vs 29.8; P = 0.57), nor in the ages of the 189 mothers whose neonate’s fatal illness started in a health facility and 70 whose neonate’s fatal illness started in the community (29.0 vs 29.9, P = 0.41). We also found no difference in the schooling level of mothers who delivered in a health facility and the community (chi-square (χ 2 ) = 4.27; P = 0.12), nor of mothers whose neonate’s fatal illness began in a health facility and the community (χ 2 = 3.78; P = 0.15). shows the age at illness onset and at death of the 259 neonates, according to their location at onset and when their fatal illness began. Illness onset for groups one through three was in the community, while for groups four and five illness began in the LLDF and DH, respectively. Illness started at a younger age and death occurred earlier for neonates whose illness started at their DF vs in the community. The earlier illness onset of neonates in their LLDF, compared to neonates at their DH, was due to five DH outliers whose illness started at 13 days of age. Table 2 Age at onset of fatal illness and death of neonates, by place of illness onset CI – confidence interval, IQR – interquartile range, SBA – skilled birth attendant, LLDF – lower-level delivery facility, DH – hospital-delivery From Wilcoxon 2-sample test with normal approximation of Z. shows the mothers’ maternal complications by the same categories of neonate’s place of illness onset as displayed in Table 3 . The most common complications were prolonged labour, malpresentation, and PROM. Mothers whose neonate’s fatal illness started in their DF, whether a hospital, LLDF or any facility, had more complications than mothers whose neonate’s illness began in the community; as did mothers whose neonate’s illness started in their DH, compared to those whose neonate’s illness began in their LLDF. Table 2 Maternal complications, by place where fatal neonatal illness began OR – odds ratio, CI – confidence interval, Precl/ecl – preeclampsia/eclampsia during last three months of pregnancy or labour/delivery, PROM – prolonged rupture of membranes, APH – antepartum haemorrhage, SBA – skilled birth attendant, DH – delivery hospital, LLDF – lower-level delivery facility * P < 0.001. † P = 0.046. shows the same complications for mothers of neonates whose illness started in their DF, but additionally categorized by whether the neonate died before leaving the facility or after being discharged alive. Mothers whose neonate died before leaving their DH were 2.8 times more likely to have a complication than mothers whose baby died after discharge. There was no such excess for women whose newborn’s fatal illness began in their LLDF and died there without leaving. There were also differences within and between the two groups of women in complication types, with PROM, preeclampsia/eclampsia, APH and malpresentation more common among women whose neonates died in their DH before discharge than among those whose neonates left alive; and, nearly so, the opposite pattern for LLDF deaths. Table 4 Maternal complications, by delivery facility level where fatal neonatal illness began and timing of death Pre/ecl – preeclampsia/eclampsia during last three months of pregnancy or labour/delivery, PROM – prolonged rupture of membranes, APH – antepartum haemorrhage, OR – odds ratio, CI – confidence interval, LLDF – lower-level delivery facility, DH – delivery hospital By χ 2 test of proportions. †Preeclampsia/eclampsia, prolonged rupture of membranes, antepartum haemorrhage, or malpresentation among women with any complication. ‡ By Fisher’s exact test. Most neonates discharged alive were referred, including 41/51 (80.4%) LLDF deliveries and 16/24 (66.7%) DH deliveries; LLDF neonates were referred more often (70.3% vs 26.1%; P < 0.001) and earlier (mean age 4.0 vs 43.9 hours; P = 0.01). Maternal complications were not associated with neonates’ referral from LLDFs (24/33 (72.7%) with vs 28/41 (68.3%) without a complication; P = 0.68) or DHs (21/83 (25.3%) with vs 9/32 (28.1%) without a complication, P = 0.76). Almost all neonates, equally among those whose mother did and did not have a complication, were referred due to a lack of equipment, medicines, procedures and/or trained providers needed to deliver quality newborn care vs insurance or other matters (LLDFs: 21/24 (87.5%) with vs 24/27 (88.9%) without a complication; P = 1.00; DHs: 20/21 (95.2%) with vs 8/9 (88.9%) without a complication; P = 0.52). All known (26/30) referrals from a DH, and all but four of 50 known referrals from a LLDF, were to a hospital. When adjusted for other potential explanatory factors, DH delivery was strongly associated with having one or more maternal complications and any insurance coverage ( ). Delivery in any facility was associated with the same factors, but the significant factors for LLDF delivery were ANC4+, insurance coverage, and travel time. Analyses of neonates whose illness began in their DF yielded similar results, but with DH delivery even more strongly associated with maternal complications (adjusted odds ratio (aOR) = 4.0; 95% CI = 2.3-6.9); and LLDF delivery no longer significantly related to ANC4+ (aOR = 2.7; 95% CI = 0.8-8.9). Table 5 Unadjusted and logistic regression-adjusted analyses of factors possibly associated with delivering in a hospital and a lower-level facility DH – delivery hospital, OR – odds ratio, CI – confidence interval, aOR – adjusted odds ratio, LLDF – lower-level delivery facility *All factors with univariate P < 0.20 allowed to enter the logistic regression models. †Maternal complications include preeclampsia/eclampsia, prolonged rupture of membranes, antepartum haemorrhage, fever during labour, prolonged labour, foetal malpresentation and/or cord complication. ‡Insurance coverage includes National Health Insurance (NHI), government beneficiaries not covered by NHI, employer-provided and other private insurance. Among 172 women with one or more L/D symptoms who delivered in a facility, 100 sought care from at least one other provider or facility on route to their DF. There was no difference in delay 1 (0.08 vs 0.03 hours; P = 0.62) for the 74/100 women with a L/D complication and 26 with symptom(s) that did not meet the box 1 criteria for a complication. However, while the 100 women went to the same number of providers/facilities, those with a complication took significantly longer to reach their DF than those without a complication ( ). The symptoms of 89 of these 100 women started in the community without a skilled birth attendant (SBA). Providers/facilities they visited most often before reaching their DF included hospitals (28.4% of women with a complication vs 0.0% without; Figure 1 P = 0.003) (all of whom delivered at a hospital), puskesmas (25.4% vs 18.2%; P = 0.57) and private midwives (20.9% vs 18.2%; P = 1.00). In contrast to these 100 women, there was no difference in arrival time between the 22 women with and 50 without a complication (median = 0.3 vs 0.2 hours; P = 0.59) who went directly to their DF. 100 women who sought care from at least one other provider/facility on route to their delivery facility. L/D Sxs – labour/delivery symptoms not meeting the criteria for a complication, L/D Cmps – labour/delivery complications, IQR – interquartile range, CI – confidence interval. One hundred ten of the 172 women delivered in a hospital and drove the findings for the total 172 women: of the 110 women, 79 sought care from at least one other provider/facility on route to their DH, of whom the 62 with a L/D complication took the same 3.3 hours to reach their DH as all 74 women with a complication took to reach their DF. These 62 women and the 17 without a complication went to the same number of providers/facilities on route to their DH (mean = 2.6 vs 2.4; P = 0.41), and there was some indication that those with a complication took almost one hour longer to reach their DH, but this was not statistically significant (median = 3.3 vs 2.5 hours; P = 0.12). There was no difference in delay 1 (median = 0.08 vs 0.17 hours; P = 0.28) for these 62 and 17 women. Of the 31/110 women who went directly to their DH, 23 with and eight without a complication took the same time (0.0 vs 0.02 hours; P = 0.74) to reach it. Among the 62 women who delivered in a LLDF, 12 with and nine without a complication who sought care from at least one provider/facility on route to their LLDF went to 2.3 and 2.0 facilities ( P = 0.19) and reached their LLDF in 0.9 and 0.5 hours ( P = 0.29), respectively, while the 27 women with and 14 without a complication who went directly to their LLDF arrived in 0.3 and 0.4 hours ( P = 0.72), respectively. In total, the 110 women who delivered at DH went to more facilities than the 62 women who delivered at LLDF (mean = 2.1 vs 1.4; P < 0.001), and they took longer to reach their DF (median = 2.0 vs 0.5 hours; P < 0.001). Having National Health Insurance (NHI) coverage did not affect whether women with and without a L/D complication sought delivery care at multiple providers/facilities (NHI: 35/54 (64.8%) with vs 12/23 (56.5%) without a complication, P = 0.49; no NHI: 39/70 (55.7%) with vs 13/25 (52.0%) without a complication, P = 0.75). presents our modified P-to-S, which adds maternal antenatal and delivery care to the left side of the original Pathway, and recognition and care-seeking for maternal complications and emergency neonatal care to the right side. Figure 2 Modified Pathway to Survival. Colour and shape key: orange diamond = health condition/outcome; blue rectangle/oval = inside-the-home preventive care, illness recognition and care provision; purple rectangle/oval = outside-the-home preventive care, care-seeking and health care provision; yellow rectangle = informal care; light green rectangle = mixed informal and formal health care providers/facilities; bright green rectangle/diamond = formal health care provider/facility. B/CEmOC – Basic and Comprehensive Emergency Obstetric Care (to prevent neonatal illness), B/CEmNC – Basic and Comprehensive Emergency Neonatal Care (to treat neonatal illness). Our companion study [ 30 ] focused on care-seeking for sick neonates, including those whose illnesses started in the community. Following the modified Pathway’s maternal care steps provides a summary of the findings discussed in detail above. Nearly all (90%) of the 259 women achieved ANC4+, including 109 (91%) who delivered at DH, 88 (94%) who delivered at LLDF, and 35 (81%) women who delivered in the community. One hundred thirty-six (53%) of the women had a maternal complication that they were able to report at interview; 85 (63%) delivered at DH, 39 (29%) at LLDF, and 3 (1%) and 9 (3%) delivered with and without an SBA in the community. Of 85 babies delivered at a hospital whose mother had a complication, the fatal illnesses of 83 (98%) began in a hospital and two (2%) went home healthy; 70 (84%) of the 83 died before discharge, and 13 (16%) left alive, 10 (77%) of whom were referred to another hospital (n = 9/10) or unknown facility (n = 1/10). Of 39 babies delivered at LLDF whose mother had a complication, the fatal illnesses of 33 (85%) began in the LLDF and six (15%) went home healthy; 10 (30%) of the 33 died before discharge and 23 (70%) left alive, 20 (87%) of whom were referred to a hospital (n = 17/20) or other LLDF (n = 3/20). Two (67%) of the three babies delivered by an SBA in the community whose mother had a complication were sick at birth; one was referred to a hospital and the other one to a LLDF. We did not collect referral data for babies of women who delivered without an SBA. Indonesia’s roadmap to attaining and exceeding its Countdown to 2030 maternal and neonatal mortality reduction targets [ 34 ] lies in ensuring that all births take place in a BEmONC- or CEmONC-capable facility and that, in line with Indonesian government policy, all women with complications deliver in a CEmONC facility [ 35 ]. Indeed, we found a strong connection between maternal complications and delivery place, especially hospital delivery. More than 70% of neonates’ fatal illnesses began in their birth facility, and more than 60% of these neonates’ mothers had one or more complications, more than twice the rate of mothers who delivered at home and nearly twice as great in DH- vs LLDF-deliveries. However, this was most often associated with EN illness onset, on average at several hours of age for facility deliveries that were ill at birth vs nearly four days for neonates whose illnesses began in the community; and facility onset led to death in three and a half days compared to more than five days for community-onset illnesses. While most women with a complication delivered at a hospital, delays related to visiting multiple providers and facilities before reaching the DH may have contributed to the deaths. Nearly 80% of the deaths identified by the EMNC study were of ENs, the deaths most likely to have a maternal underlying cause [ 3 , 7 ]. Also, nearly 80% of neonates whose illness started in their DH and 30% of those whose illness started in their LLDF died before leaving; mothers of neonates who died in their DH were more likely to have a complication than those whose neonates left their DH alive, and their complications were also more likely to differ, with preeclampsia, PROM, APH, and malpresentation being most problematic. These findings again suggest a strong connection between maternal complications, as well as the types of complications, and neonatal illness severity. Other studies in low- and middle-income countries (LMIC) have also found malpresentation [ 7 , 36 ], hypertensive disorders [ 7 , 37 ] and APH [ 37 , 38 ] to be strongly associated with EN death. Among LLDF-delivered neonates, these complications were nearly significantly more common among those discharged alive, although we did not find an association between maternal complications and neonatal referral either from LLDF or DH. Nevertheless, the higher referral rate and earlier referral of neonates from LLDF suggest a decreased capability of LLDFs to care for these sick newborns. Hospitals and LLDFs faced the same shortcomings in quality of care indicators that mothers, both those with and without complications, reported necessitated referral of their newborns, although, given their higher referral rate, apparently at greater levels in LLDFs. These findings suggest that many women delivered at facilities incapable of providing emergency obstetric and neonatal care. Multivariable analysis of delivery place confirmed the strong association of maternal complications with hospital delivery, and a weaker association with LLDF delivery of sick neonates. Women’s knowledge of intrapartum danger signs [ 39 ] and the presence of complications during labour [ 40 ] have previously been shown to increase institutional delivery. Insurance coverage and travel time were stronger predictors of facility delivery for women who delivered a sick neonate in an LLDF; while insurance coverage also promoted hospital delivery for all women and women whose neonate’s illness began in the DH. Other studies have shown a positive effect of NHI coverage on institutional delivery in Indonesia [ 41 , 42 ]. To our best knowledge, this is the first study to examine the effect of any insurance coverage, including private insurance and government assistance to beneficiaries not covered by NHI, on facility delivery. ANC4+ has also been previously shown to increase institutional delivery in Indonesia [ 16 , 41 ] and elsewhere [ 43 , 44 ]. We found ANC4+ to be associated with LLDF- but not DH-delivery, and not in women whose neonate’s fatal illness began in the LLDF. These findings suggest that rapid access, including distance and cost considerations, took precedence over the benefit incurred from ANC visitation in women with maternal complications. Rapid access to delivery care is especially critical in the case of a woman in labour with a complication. Women in the EMNC study with and without L/D complications took the same amount of time to decide to seek care and went to the same number of providers/facilities before reaching their DF, yet those with complications more frequently went to a hospital on route and took on average up to two hours longer to reach their DF. Such delays were greater in women who delivered at a hospital, suggesting their need for more care before being discharged or referred and potentially more severe outcomes as the result of any delay in accessing definitive care. Although having any insurance coverage increased facility delivery, NHI coverage did not decrease women’s seeking care for their L/D complications at multiple providers/facilities on route to their DF, despite NHI policy that women with emergency complications should go directly to a hospital without a need for referral [ 45 ]. An increased delay in reaching appropriate care for maternal complications and neonatal illnesses due to multiple referrals has also been found in other settings [ 46 ]. This study and a companion study of care-seeking for 259 neonatal deaths along the P-to-S identified the need for a modified Pathway that recognizes the importance of rapid access to quality institutional delivery care in settings where many births occur in facilities and/or there is good care-seeking for L/D complications. This is the case in many LMICs, as other studies have found an increase in institutional births accompanied by shifting of high-risk births with maternal complications to facilities [ 47 , 48 ]. The original P-to-S (Figure S1 in the ) was designed more than a quarter century ago as a program development and evaluation tool in support of the WHO/UNICEF IMCI approach of promoting wellness, illness recognition and care-seeking for one-week to 59-month-old children whose illnesses started at home [ Online Supplementary Document 25 ]. The IMCI chart booklet was updated in 2014 to include care of ENs [ 49 ], but the Pathway has not been updated accordingly. With the epidemiological transition to neonatal death as the main driver of U5 mortality, a modified P-to-S is needed that examines inadequate access to quality BEmONC and CEmONC for all parturient women and especially those with maternal complications. Other authors have depicted pathways aimed at newborn survival [ 50 , 51 ], but none that incorporate all the elements of the original P-to-S. The modified Pathway that we present preserves and builds on the original, and should prove a useful supporting tool in the development and monitoring of interventions against neonatal and child mortality that recognize the importance of antenatal and delivery care, care-seeking for maternal complications, and provision of quality BEmONC and CEmONC for women and newborns. The modified Pathway includes steps at which delays in deciding to seek health care and reaching appropriate care both for women with complications and sick children can be assessed. The Three Delays model for examining the contribution to maternal mortality of these two delay types plus the delay in the provision of quality care once reaching an appropriate facility was formulated nearly three decades ago [ 52 ], and has since been used in multiple studies of maternal death and adapted to assess delays contributing to NM [ 53 ]. However, the model has seldom (and, to our knowledge, never before in Indonesia) been applied to evaluate the impact of delays in care-seeking for maternal complications on neonatal death [ 28 ] or stillbirth [ 54 ]. Assessment of, and determining the reasons for, these delays at key steps in the Pathway will make it an even more powerful supporting tool in the fight against NM. All the study data are from interview reports, mainly of the mothers of the deceased neonates, so are subject to possible recall and reporting biases. However, the recall period was shorter than for many VASA studies, which should have minimized recall bias. We defined algorithms of maternal complications based on reports of individual obstetric illness signs and symptoms in the 2016 WHO VA questionnaire, which for some conditions are somewhat limited. For example, hypertension, blurred vision, and convulsions are the only symptoms available with which to construct an algorithm for preeclampsia/eclampsia. Therefore, we may have underestimated the proportion of women with some complications, but this should not have affected the relative levels estimated for women who delivered at a facility and in the community. Small sample size for some sub-group analyses limits our definitiveness in drawing certain conclusions, for example, that neonates whose mothers had particular complications were more likely than those whose mothers had other complications to be discharged alive from their LLDF. The VASA study was not designed to assess the quality of care provided by delivery facilities, and we could not determine which facilities were capable of providing BEmONC and CEmONC. Increased access to institutional delivery by itself, in the absence of improvements in the quality of care, will not decrease NM and in some instances may even have a detrimental effect [ 48 ]. Our findings, that a major portion of neonatal deaths were related to maternal complications and subsequent newborn illnesses cared for in delivery facilities, call for a follow-up study to directly assess the quality of care provided for L/D complications and neonatal illnesses. Most neonatal deaths in two districts of Java, Indonesia were of infants whose fatal illnesses started on the day of birth at their DF. Most of these newborns’ mothers had one or more maternal complications, and many mothers with a L/D complication visited multiple providers/facilities before reaching their DF, leading to delays that might have contributed to their newborn’s death. Given the global trend toward increasing institutional delivery, especially in LMICs, and the increased share of neonatal deaths due to ENM, ANC providers should instruct women about complications for which they should go directly to a CEmONC-capable hospital for delivery; and governmental and institutional policy should support women in following these instructions. A modified Pathway to Survival highlights the increased importance of rapid access to quality institutional delivery care in settings where many births occur in facilities and/or there is good health care-seeking for L/D complications. Health systems in LMICs should consider incorporating use of the modified P-to-S into their ongoing maternal, neonatal and child health program development and monitoring activities. The authors would like to acknowledge the support from: the governments and health offices of East Java Province and Jember District, Banten Province and Serang District; puskesmas (community health centers), heads of sub-districts, heads of villages, and all respondents in the study areas. We would like to thank our colleagues from the Ministry of Health who provided substantial support especially in the initial phase of the study. We also would like to thank all the members of the EMNC study team, especially Ms. Akhir Rianty for assistance with the training, Ms. Nancy Kosasih, Ms. Yenny Fitrianingsih, the data collectors, and data entry team too numerous to mention all by name here; USAID Jalin project staff, especially Dr Luna M. Mehrain, and the Center for Family Welfare at the University of Indonesia (CFW UI) management team who were instrumental in the implementation of the study. We thank Dr Massee Bateman (deceased) of USAID for promoting funding of the EMNC study and Dr Anhari Achadi of the CFW UI for helping to secure the funding, and Dr Sigit Sulistyo of USAID for providing support to the conduct of the study. We would like to also thank Mr. Omair Azam and Mr. Ali Zazri from Vital Strategies for their support in managing the implementation of the study. Ethics statement: The EMNC study was approved by the Ethics Committee for Research and Community Services, Faculty of Public Health, University of Indonesia (Approval letter Number: 633/UN2.F10/PPM.00.02/2018) and the Biomedical Research Alliance of New York (BRANY) IRB (Approval for Investigator-Initiated Protocol 1003214-S-17-30460-00). All respondents provided written informed consent prior to being interviewed. Data availability: The dataset and dictionaries used for this study are available in USAID’s Development Data Library ( https://www.usaid.gov/data ). Questions about data access can be addressed to [email protected] . Funding: This study was made possible by the support of the American people through the United States Agency for International Development (USAID) under the terms of Contract Number: AID-497-C-17-00001. Information about the funder can be accessed at https://www.usaid.gov . The contents of this article are the sole responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authorship contributions: ELA and PWS provided high-level oversight and ELA led and guided conduct of the EMNC study. EHW and HDK facilitated adaptation of the JHU/IIP VASA questionnaire for the EMNC study and training of the VASA interviewers. ELA, KL, TR, FN and TA provided input for adaptation of the VASA tool and implementation guidelines based on their knowledge of the local Indonesian context. ELA and TA adapted the MADE-IN/MADE-FOR method of identifying maternal deaths to the NODE-IN/NODE-FOR method to identify neonatal deaths. HDK, PWS, ELA, and EHW, with input provided by SAN and SS, developed the VASA study methodology. KL, TR, FN and TA set up field aspects of the study, maintained communication with local stakeholders, and together with SAN and SS supervised field activities during conduct of the study. PED monitored data quality, including supervising data entry in the field and working closely with field coordinators to resolve any data-related issues; and organized, integrated and managed the NODE-IN/NODE-FOR and VASA data sets. HDK recognized the need for an updated Pathway to Survival; and HDK, ELA, PWS and EHW contributed to the development of the Pathway. HDK developed and conducted the data analysis and drafted and revised the manuscript. All authors reviewed and provided inputs to subsequent drafts of the manuscript and approved the final version. Disclosure of interest : The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: HDK, PWS, PED, SAN, SS, EHW, KL, TR, FN, TA and ELA report that USAID supported their work on the EMNC study under sub-agreements with Vital Strategies and Center for Family Welfare, Faculty of Public Health, University of Indonesia (PUSKA). HDK and EHW report that Vital Strategies covered their travel expenses to the study site to provide consultative services. HDK reports receiving salary support for work on other studies through grants from the Bill and Melinda Gates Foundation. EHW reports working on a separate USAID contract; and receiving a consulting fee from Johns Hopkins University for work on a different project funded by the Bill and Melinda Gates Foundation. Vital Strategies funded the article processing charges. Modified Pathway to Survival highlights importance of rapid access to quality institutional delivery care to decrease neonatal mortality in Serang and Jember districts, Java, Indonesia Labour complications remain the most important risk factors for perinatal mortality in rural Kenya. Maternal health during pregnancy and perinatal mortality in Bangladesh: evidence from a large-scale community-based clinical trial. Prospective community-based cluster census and case-control study of stillbirths and neonatal deaths in the West Bank and Gaza Strip. 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