The obesity epidemic is unrelenting, especially among women. A study released this week found that more women than men are now affected by the disease, while the reverse was true just two years ago. The condition is associated with a wide variety of health risks, from chronic diseases to reproductive problems — and in a new study published June 7 in PLOS Medicine, researchers from the Karolinska Institutet in Sweden found that gaining weight between pregnancies further complicates mothers’ and infants’ health. 
 
 Already, research suggests that women who are overweight and obese during pregnancy face greater risk of certain complications, including gestational diabetes and preeclampsia. Infants born to obese women, on the other hand, sometimes score lower on the Apgar test, which is given no more than five minutes after babies are born to determine if they have breathing or heart trouble. While low scores can’t predict the future health of a child, they are commonly caused by asphyxia, a slippery slope that leads to additional adverse outcomes. 
 
 Maternal obesity increases newborns' risk for adverse outcomes. Pixabay 
 
 The researchers were interested to learn more about the ways a woman’s body mass index (BMI) could influence these complications and outcomes. They specifically looked at women’s BMI between their first and second pregnancies using data from the Swedish Medical Birth Register and any asphyxia-related outcomes: neonatal seizures and meconium aspiration syndrome, a severe breathing condition. Researchers also analyzed demographic information for more than 500,000 mothers who had their first and second live births between January, 1992, and December, 2012, including Apgar test scores and mothers’ and infants’ measurements and proportions. 
 
 Essentially, lead author Martina Persson and her team calculated weight gain and risks in two ways: one, they looked at low scores and asphyxia-related morbidities; and two, they looked at risks of these outcomes per every unit increase in a mother’s BMI. 
 
 The results showed an increased risk for all adverse outcomes in infants whose mothers’ BMIs increased by 2 units or more between pregnancies; 6 pounds is about one BMI unit for a woman of average height. These risks were more pronounced in women who started their first pregnancy at normal weight — a BMI of less than 25 — and then gained weight. 
 
 On the other hand, the increase in risk was less pronounced in women who were overweight and obese during early pregnancy. Persson and her colleagues speculate this may reflect the ways metabolism adapts to increased fat mass over time, meaning overweight women in early pregnancy might accumulate less fat in pregnancy than underweight and normal weight women. 
 
 To the researchers’ knowledge, this is the first time a study has assessed these particular risks and how they are influenced by change in weight over time. 
 
 It’s a strong study in that it analyzes a large number of births, exposures, and outcomes; however, the authors did not have information on gestational weight gain and do not know when exactly women gained weight between their first and second pregnancies. The distribution of fat may differ if weight is gained during or after pregnancy, they said. 
 
 Even so, they believe the findings are significant and could influence public health initiatives. 
 
 “Given the high prevalence of maternal overweight and the possible long-term consequences of birth asphyxia, our results have substantial public health relevance, as even modest weight increases in normal weight women may impact offspring outcomes on a population level,” the researchers concluded. Encouraging women to normalize BMI before pregnancy and to avoid weight gain between pregnancies, they said, would likely help improve infant health. 
 
 Source: Persson M, Johansson S, Cnattingius S. Interpregnancy Weight Change and Risks of Severe Birth-Asphyxia-Related Outcomes in Singleton Infants Born at Term: A Nationwide Swedish Cohort Study. PLOS Medicine. 2016. 

 Weight gain between pregnancies is linked to pregnancy complications and adverse neonatal outcomes in second born children, according to a study published by Martina Persson and colleagues from the Karolinska Institutet, Stockholm, Sweden, in this week's PLOS Medicine. 
 
 The researchers examined data from the nationwide Swedish Medical Birth Register, including 532,858 second-born infants born at term (greater than or equal to 37 weeks gestation) to mothers having their first and second infants between 1992 and 2012. Compared with mothers with stable weight (-1 to <1 kg/m2 change in BMI between pregnancies), they observed that infants born to mothers who gained 4 kg/m2 or more between pregnancies had a 33% to 78% increased risk of low Apgar score (a measure of newborn health), neonatal seizures, and meconium aspiration. 
 
 While the researchers could not investigate the potential impact of obstetric and neonatal interventions and did not have information when the weight gain occurred or on gestational weight gain, the findings provided suggest that preventing weight gain between pregnancies could reduce the risk of birth asphyxia and improve infant health. 
 
 The authors say: "Encouraging women to normalize BMI before pregnancy and to avoid weight gain between pregnancies is likely to be an important measure to improve infant health." 
 
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 Research Article 
 
 IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER: http://journals. plos. org/ plosmedicine/ article?id= 10. 1371/ journal. pmed. 1002033 
 
 Citation: Persson M, Johansson S, Cnattingius S (2016) Inter-pregnancy Weight Change and Risks of Severe Birth-Asphyxia-Related Outcomes in Singleton Infants Born at Term: A Nationwide Swedish Cohort Study. PLoS Med 13(6): e1002033. doi:10.1371/journal.pmed.1002033 
 
 Funding: This study was supported by the Swedish Research Council for Health, Working Life and Welfare (grant number 2014-0073) and an unrestricted grant from Karolinska Institutet (Distinguished Professor Award to SC). MP was supported by Stockholm City Council (clinical post-doc position). No funding bodies had any role in study design, data collection and analysis, decision to publish or preparation of the manuscript. 
 
 Competing Interests: The authors have declared that no competing interests exist. 

 Risks of low Apgar score, neonatal seizures, and meconium aspiration increased with inter-pregnancy weight gain. Compared with offspring of mothers with stable weight (BMI change of −1 to <1 kg/m 2 ), the adjusted OR for a low Apgar score in the offspring of mothers with a BMI change of 4 kg/m 2 or more was 1.33 (95% CI 1.12–1.58). The corresponding risks for neonatal seizures and meconium aspiration were 1.42 (95% CI 1.00–2.02) and 1.78 (95% CI 1.19–2.68), respectively. The increased risk of neonatal seizures related to weight gain appeared to be restricted to mothers with BMI < 25 kg/m 2 in the first pregnancy. A study limitation was the lack of data on the effects of obstetric interventions and neonatal resuscitation efforts. 
 
 We estimated associations between the difference in maternal BMI between the first and second pregnancy and risks of low Apgar score (0–6) at 5 min, neonatal seizures, and meconium aspiration in the second-born offspring. Odds ratios (ORs) were adjusted for BMI at first pregnancy, maternal height, maternal age at second delivery, smoking, education, mother´s country of birth, inter-pregnancy interval, and year of second delivery. Analyses were also stratified by BMI (<25 versus ≥25 kg/m 2 ) in the first pregnancy. 
 
 Maternal overweight and obesity are associated with increased risks of birth-asphyxia-related outcomes, but the mechanisms are unclear. If a change of exposure (i.e., maternal body mass index [BMI]) over time influences risks, this would be consistent with a causal relationship between maternal BMI and offspring risks. Our objective was to investigate associations between changes in maternal BMI between consecutive pregnancies and risks of birth-asphyxia-related outcomes in the second offspring born at term. 
 
 Funding: This study was supported by the Swedish Research Council for Health, Working Life and Welfare (grant number 2014-0073) and an unrestricted grant from Karolinska Institutet (Distinguished Professor Award to SC). MP was supported by Stockholm City Council (clinical post-doc position). No funding bodies had any role in study design, data collection and analysis, decision to publish or preparation of the manuscript. 
 
 Data Availability: According to Swedish law, we are not allowed to share our data files. Research on national data used in this study is only possible in Sweden given that an ethical approval is obtained. For data acquisition from the Medical Birth Register please see www.socialstyrelsen.se . Contact person: karin.gottvall@socialstyrelsen.se . 
 
 Copyright: © 2016 Persson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 
 
 In this nationwide Swedish cohort study, we examined whether changes in maternal BMI between first and second pregnancies influenced the risks of birth-asphyxia-related outcomes in the second-born offspring, including low Apgar score (0–6) at 5 min, neonatal seizures, and meconium aspiration. 
 
 We have previously demonstrated a linear relationship between maternal BMI in early pregnancy and the risks of low Apgar scores at 5 and 10 min and birth-asphyxia-related neonatal morbidity in infants born at term [ 8 ]. Furthermore, we have found that the risk of asphyxia-related infant mortality in term infants increases with the degree of maternal obesity [ 5 ]. Risks being influenced by a change of exposure (i.e., maternal BMI) over time would be consistent with a causal relationship between maternal BMI and adverse outcomes of the offspring. 
 
 Maternal overweight and obesity during pregnancy increase the risks of severe maternal and infant complications [ 1 – 4 ]. In Sweden, the proportion of women with overweight and obesity (body mass index [BMI] ≥ 25 kg/m 2 ) in early pregnancy increased from 26% in 1992 to 38% in 2010 [ 5 ]. In the US, 58% of women between 20 and 39 y of age were overweight or obese in 2011–2012 [ 6 ]. As recently stated by WHO, the prevalence of maternal obesity must be reduced in order to improve maternal, fetal, and neonatal health [ 7 ]. 
 
 In sensitivity analyses ( S1 Table ), mothers with obesity-related disorders (chronic hypertension, preeclampsia, or any type of diabetes) were excluded from the regression analyses. A sensitivity analysis was also performed to explore whether pregnancies of mothers with missing data on inter-pregnancy weight change differed from those with information on inter-pregnancy weight change ( S2 Table ). To explore any effect modification by first pregnancy BMI on the association between exposure and outcomes, analyses were also stratified by maternal BMI in the first pregnancy (BMI < 25 or BMI ≥ 25 kg/m 2 ). Interaction terms were introduced in the multivariate models, and a p-value of less than 0.05 for the interaction term was considered statistically significant. 
 
 Rates of low Apgar score, meconium aspiration, and neonatal seizures were calculated as the number of infants with these outcomes per 1,000 births. Logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals for all outcomes. Mothers whose first infant had a low Apgar score, meconium aspiration, or neonatal seizures were excluded from the analysis of the respective outcome in the second pregnancy to avoid bias in case of a tendency to repeat adverse pregnancy outcomes. Inter-pregnancy weight change was categorized as presented above in the regression model, but also treated as a continuous variable. Multivariate models were restricted to second births with complete data on inter-pregnancy weight change and covariates. We adjusted for maternal BMI in the first pregnancy, maternal height, maternal age at second delivery, smoking habits in the second pregnancy, inter-pregnancy interval, mother´s education, mother’s country of birth, and year of second birth, categorized according to Table 1 . Given the long study period, spanning over 21 y, we categorized year of second birth (not shown in Table 1 ) into intervals as 1992–1996, 1997–2001, 2002–2006, and 2007–2012. 
 
 We estimated the risks of severe asphyxia-related outcomes, including low Apgar score, meconium aspiration, and neonatal seizures, at the second birth by change in BMI from the first to the second pregnancy. A low Apgar score was defined as a score between 0 and 6 points at 5 min after birth. A diagnosis of neonatal seizures was based on ICD-9 code 779.0 or ICD-10 code P90, and a diagnosis of meconium aspiration was based on ICD-9 code 770.1 or ICD-10 code P24.0. 
 
 The inter-pregnancy interval was calculated as the time difference between the date of birth of the first infant and estimated date of conception of the second infant (i.e., date of birth of the second infant minus gestational age + 14 d). Gestational age was estimated primarily based on early second trimester ultrasound, which is offered to all pregnant women and which 95% of women accept [ 16 ]. When dating from an ultrasonic scan was not available, gestational age was estimated using information on date of last menstrual period. Obesity-related disorders were identified in the Swedish Medical Birth Register based on ICD codes: preeclampsia—ICD-9 codes 642E–642G, ICD-10 codes O14–O15; chronic hypertension—ICD-9 codes 401–405, 642C, 642M, ICD-10 codes O10–O11; gestational diabetes—ICD-9 code 648W, ICD-10 code O244; pregestational diabetes—ICD-9 code 250, ICD-10 codes E10–E14, O241–O243. Covariates were categorized according to Table 1 . 
 
 Maternal BMI (kg/m 2 ) was calculated for each of the two consecutive pregnancies. At the first antenatal visit, which occurs in the first trimester in 90% of pregnancies [ 13 ], the woman´s weight is measured wearing light indoor clothes and barefoot, and data on self-reported height are recorded. Inter-pregnancy change in BMI was calculated as the difference in BMI between the second and first pregnancies. We categorized the inter-pregnancy BMI change as <−2 kg/m 2 (i.e., BMI loss greater than 2 kg/m 2 ), −2 to <−1 kg/m 2 , −1 to <1 kg/m 2 (stable weight), 1 to <2 kg/m 2 , 2 to <4, and ≥4 kg/m 2 . A 1-kg/m 2 change in BMI corresponds to change of 2.8 kg in a woman of average height (167 cm). Based on BMI in the first pregnancy, mothers were categorized as underweight (BMI < 18.5 kg/m 2 ), normal weight (18.5–24.9 kg/m 2 ), overweight (25–29.9 kg/m 2 ), obese grade I (30–34.9 kg/m 2 ), and obese grade II-III (≥35 kg/m 2 ) [ 15 ]. 
 
 The Swedish Medical Birth Register started in 1973 and contains prospectively collected data on more than 98% of all births in Sweden. The quality of data is considered high [ 13 ]. Information on sociodemographic factors, maternal and infant anthropometry, and Apgar scores are collected on standardized forms used in antenatal, obstetric, and neonatal care in Sweden. Maternal and neonatal diagnoses, including pregnancy complications and neonatal morbidities, are classified by physicians according the Swedish version of the International Classification of Diseases (ICD). The ninth version (ICD-9) was used between 1992 and 1996, and the tenth version (ICD-10) thereafter. The standardized forms are forwarded to the Swedish Medical Birth Register when the mother and infant are discharged from hospital. Information on the mother’s country of birth and level of education were obtained from the Swedish Register of Total Population and the Swedish Register of Education, respectively. Individual cross-linkage of registries was possible using the personal identification number [ 14 ], a person-unique identifier assigned to all Swedish citizens at birth or at naturalization. 
 
 Between January 1992 and December 2012, the nationwide Swedish Medical Birth Register included 533,535 mothers with first and second live singleton term births (≥37 completed weeks). We excluded 165 mothers with no information on inter-pregnancy interval and 512 mothers with no information on mothers’ country of birth. In analyses of low Apgar score in the second infant, we excluded another 6,423 mothers (1.2%) where either the first- or the second-born infant had missing information on Apgar score at 1 or 5 min. 
 
 Ethics approval for this study was obtained from the Research Ethics Committee at Karolinska Institutet in Stockholm, Sweden (number 2012/4:9). Informed consent was not required as all data were anonymous. 
 
 Results 
 
 The total number of infants with a low Apgar score (0–6 points) at 5 min was 2,824 (rate 4.08/1,000). Corresponding numbers (rates) for neonatal seizures and meconium aspiration were 658 (1.23/1,000) and 372 (0.70/1,000), respectively (Table 1). Rates of all birth-asphyxia-related outcomes increased with maternal BMI in the first pregnancy, inter-pregnancy interval, smoking, chronic hypertension, preeclampsia, any type of diabetes, and generally also with maternal age at second delivery (Table 1). Maternal education was inversely correlated with all outcomes. There was a U-shaped relationship between birth weight and gestational age and rates of low Apgar score and neonatal seizures, while the rate of meconium aspiration increased with gestational age. Rates of low Apgar score, neonatal seizures, and meconium aspiration in second-born offspring were essentially similar in offspring of mothers with missing data on BMI in the first pregnancy and the total population. 
 
 Rates of low Apgar score, neonatal seizures, and meconium aspiration increased with inter-pregnancy weight gain (Table 2). Compared with mothers with stable weight, the risk of a low Apgar score was 26% increased in offspring of mothers who gained 2 to <4 kg/m2 and 33% increased in offspring of mothers who gained ≥4 kg/m2. Risk of neonatal seizures was increased by more than 40% in offspring of mothers who gained 2 to <4 and ≥4 kg/m2. The risk of meconium aspiration was 78% higher in offspring of mothers who gained ≥4 kg/m2 compared with offspring of mothers with stable weight. 
 
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 larger image TIFF original image Download: Table 2. Maternal inter-pregnancy weight change and risks of low Apgar score (0–6) at 5 min, neonatal seizures, and meconium aspiration: live singleton second term infants of women in Sweden 1992–2012. https://doi.org/10.1371/journal.pmed.1002033.t002 
 
 We investigated whether the effect of weight change on asphyxia-related outcomes differed between offspring of mothers who were underweight/normal weight and overweight/obese in the first pregnancy (BMI <25 and ≥25 kg/m2, respectively) (Table 3). In underweight/normal weight mothers in the first pregnancy, the risk of low Apgar score increased with weight gain, while the corresponding association was less evident in infants of mothers who were overweight/obese in the first pregnancy. However, the test for an interaction between maternal BMI and low Apgar was not significant (p = 0.12). 
 
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 larger image TIFF original image Download: Table 3. Maternal inter-pregnancy weight change and risk of low Apgar score (0–6) at 5 min, neonatal seizures, and meconium aspiration, stratified by maternal BMI in first pregnancy: live singleton second term infants of women in Sweden 1992–2012. https://doi.org/10.1371/journal.pmed.1002033.t003 
 
 The risk of neonatal seizures increased with weight gain in offspring of mothers who were underweight/normal weight in the first pregnancy, but not in offspring of mothers who were overweight/obese in the first pregnancy (test for interaction; p = 0.004). In underweight/normal weight mothers, offspring of mothers with a weight gain of ≥4 kg/m2 had a doubled risk of neonatal seizures compared with offspring of mothers with stable BMI. 
 
 Stratifying the analyses by maternal BMI in the first pregnancy (<25 and ≥25 kg/m2) demonstrated a more than doubled risk of meconium aspiration in offspring of underweight/normal weight mothers who gained ≥4 kg/m2. In contrast, in overweight/obese mothers, weight gain was not associated with increased risk of meconium aspiration in offspring. However, the test for interaction was not significant (p = 0.77). 
 
 In order to investigate whether associations between maternal weight gain and asphyxia-related outcomes were influenced by obesity-related disorders, we repeated the analyses after excluding offspring of mothers with chronic hypertension, preeclampsia, or any type of diabetes. Restricting the analyses to offspring of mothers without obesity-related disorders did not change the risks of low Apgar score, neonatal seizures, or meconium aspiration (S1 Table). 
 
 We also investigated weight gain and the risks of birth-asphyxia-related outcomes in the offspring of mothers who were underweight/normal weight (BMI below 25 kg/m2) in the second pregnancy (S2 Table). Compared with the offspring of mothers with stable weight, the risks of low Apgar score and neonatal seizures were more than doubled in offspring of mothers who were normal weight in the second pregnancy but who had gained ≥4 kg/m2 between pregnancies. 
 
 Finally, we investigated whether mothers with missing information on inter-pregnancy weight gain, and hence not included in the analyses, differed from mothers with information on weight gain with respect to other maternal characteristics or birth outcomes. The proportions of women who were overweight, obesity grade I, and obesity grade II-III in the first pregnancy were 20.5%, 5.2%, and 1.7%, respectively, for mothers with known weight change and 19.3%, 4.9%, and 1.9%, respectively, for mothers with unknown weight change (due to missing data on second pregnancy BMI) (S3 Table). Also, the distributions of maternal covariates (as listed in Table 1) were comparable between mothers with missing data on inter-pregnancy weight change and mothers with an inter-pregnancy weight change of −1 and <1 kg/m2 (the reference group) or an inter-pregnancy weight gain of 1 to <2 kg/m2. The proportions of mothers with obesity-related diseases and rates of birth-asphyxia-related outcomes were similar in mothers with and without data on inter-pregnancy weight change (S3 Table).The proportions of women who were overweight, obesity grade I, and obesity grade II-III in the second pregnancy were 25.3%, 7.6%, and 1.4%, respectively, for mothers with information on inter-pregnancy weight change and 24.2%, 7.1%, and 1.4%, respectively, for mothers with unknown weight change (due to missing data on first pregnancy BMI).
– Not only the sins of the father, but the weight of the mother may well also be laid at the feet of the children. So report researchers out of Sweden in the journal PLoS Medicine in finding that women whose BMI increases by two or more units—amounting to a roughly 12-pound gain in women of average height—between their first and second pregnancies pass on considerable risk to their second-born child. Scientists analyzed data on more than 525,000 second-born babies and found that the risk for all negative outcomes goes up, including seizures, a severe breathing condition involving choking on meconium, and asphyxia. And it all adds up with obesity at "epidemic proportions," including among pregnant women. "Encouraging women to normalize BMI before pregnancy and to avoid weight gain between pregnancies is likely to be an important measure to improve infant health," the researchers note in a press release. In fact, the risk of babies born with a low Apgar score rose sharply by between 33% and 78% when born to a woman who'd gained this much weight between pregnancies, the researchers found. The increase in risk was most pronounced among women who were at a normal weight, or BMI of less than 25, at the start of their first pregnancy and then gained weight between the two, reports Medical Daily. It adds that the study is "strong" in that it analyzes so many births and outcomes, but notes that the authors don't know how much weight was gained during pregnancy or when women gained weight between pregnancies. (Obesity also ups the odds of big babies.)