<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03758092</url>
  </required_header>
  <id_info>
    <org_study_id>CE 106/18</org_study_id>
    <nct_id>NCT03758092</nct_id>
  </id_info>
  <brief_title>Cardiovascular Screening in Infants Born Small for Gestational Age</brief_title>
  <acronym>CardioSGA</acronym>
  <official_title>Cardiovascular Screening in 2-year Old Infants Born Small for Gestational Age Compared With Infants Born Adequate for Gestational Age</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliero Universitaria Maggiore della Carita</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliero Universitaria Maggiore della Carita</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aims of this study were 1) to evaluate early CV abnormalities in infants born small for&#xD;
      gestational age (SGA) at 24 months of age compared with age and sex-matched subjects that&#xD;
      were born adequate for gestational age (AGA) 2) to investigate the effect of catch-up growth&#xD;
      and the role of breastfeeding on CV risk.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We consecutively enrolled 20 SGA infants, born at term (37+0/41+3 week gestation), aged 24&#xD;
      months, and 20 AGA, age- and sex-matched controls. SGA was defined as a birth weight &lt;10th&#xD;
      percentile for sex, gestational age and birth order, and AGA as a birth weight between the&#xD;
      10th and the 90th percentile, according to Italian neonatal anthropometric charts.&#xD;
&#xD;
      Clinical and anthropometric variables The infants' prenatal and neonatal data were&#xD;
      retrospectively recorded, namely a history of gestational diabetes and hypertension, the&#xD;
      presence of intrauterine growth restriction, maternal weight gain during pregnancy, Apgar&#xD;
      score, gestational age and birth weight, length, and head circumference. All subjects'&#xD;
      parents completed a questionnaire including family history, maternal smoking during&#xD;
      pregnancy, breastfeeding duration. At the time of enrollment (24 months), anthropometric data&#xD;
      were evaluated by trained physicians according to standard procedures and based on the WHO&#xD;
      growth charts. Height, weight, systolic (SBP) and diastolic (DBP) blood pressure were&#xD;
      measured. Body mass index (BMI) was calculated as weight (kg)/height(cm)2 and weight gain in&#xD;
      the first 2 years of life was calculated as the delta between birth weight and weight at 24&#xD;
      months.&#xD;
&#xD;
      Echocardiographic assessment Transthoracic echocardiogram using a Vivid 7 Pro ultrasound&#xD;
      scanner (General Electric Healthcare, USA) was performed by an expert pediatric cardiologist,&#xD;
      blinded to patients' clinical data. Measurements of left ventricle (LV end-diastolic&#xD;
      diameter, LVEDD; LV end-systolic diameter, LVESD; interventricular septum at end diastole,&#xD;
      IVSD; LV posterior wall at end diastole, LVPWD), relative wall thickness (RWT), left atrium&#xD;
      diameter (LAD), the maximum LA volume, LV ejection fraction, and tricuspid annular plane&#xD;
      systolic excursion (TAPSE) were obtained according to established standards. LV mass (LVM)&#xD;
      was derived from the Devereux formula and indexed to body surface area (left ventricular mass&#xD;
      index, LVMI). Left ventricular output (LVO) was obtained with the velocity time integral&#xD;
      (VTI) from a 5-chamber view and calculated as follows LVO=[(VTI)x(heart&#xD;
      rate)x(cross-sectional area)] and indexed to body weight.&#xD;
&#xD;
      Using pulsed wave Doppler, mitral inflow velocities, peak early diastolic velocity (E), peak&#xD;
      late diastolic velocity (A), and E/A ratio, were measured. Pulsed wave tissue Doppler of the&#xD;
      lateral mitral annulus was used for the measurement of early peak diastolic mitral annular&#xD;
      velocity (E'). The E/E' ratio was calculated. End-diastolic pressure (EDP) was calculated&#xD;
      from the E/E' ratio with the formula EDP=1.91+1.24xE/E' (14) and the pressure-volume curve&#xD;
      during diastole with the formula EDP = αxEDVβ (end-diastolic volume, EDV). Volume parameters&#xD;
      were corrected to fixed values of EDP (V30 mmHg). The coefficient &quot;β&quot; (Beta), indicating the&#xD;
      slope of the end-diastolic pressure-volume relationship (EDPVR), was calculated with the&#xD;
      formula β=[Log10(EDP/30)]/[Log10(EDV/V30mmHg)].&#xD;
&#xD;
      Vascular assessment Vascular measurements were performed with a high-resolution&#xD;
      ultrasonography (Esaote MyLab25TM Gold, Esaote, Italy) using a 8 mHz linear transducer and a&#xD;
      5 mHz convex transducer for the abdominal aorta, by an expert vascular surgeon blinded to&#xD;
      patients' clinical status. CIMT, abdominal aortic diameter at maximum systolic expansion (Ds)&#xD;
      and minimum diastolic expansion (Dd), brachial artery diameters, brachial artery peak&#xD;
      systolic velocity (PSV) and end diastolic velocity (EDV) were measured as previously&#xD;
      described and aortic strain (S), pressure strain elastic modulus (Ep), pressure strain&#xD;
      normalized by diastolic pressure (Ep*) and brachial artery flow-mediated dilation (FMD) were&#xD;
      calculated. While S is the mean strain of the aortic wall, Ep and Ep* are the mean stiffness&#xD;
      (16). Arterial wall stiffness index (β index) was calculated with the formula: β&#xD;
      index=ln(SBP/DBP)/[(Ds-Dd) /Dd)] (17) and systemic vascular resistance (dynes/s/cm2) with the&#xD;
      formula: SVR=(mean BP- right atrial pressure)/LVO, with an estimated right atrial pressure of&#xD;
      5 mmHg. The brachial artery maximum diameter recorded following reactive hyperemia was&#xD;
      reported as a percentage change of resting diameter (FMD = peak diameter - baseline&#xD;
      diameter/baseline diameter).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">July 1, 2018</completion_date>
  <primary_completion_date type="Actual">March 1, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiovascular structure</measure>
    <time_frame>24 months</time_frame>
    <description>Heart structure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular function</measure>
    <time_frame>24 months</time_frame>
    <description>Heart function</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>catch-up growth</measure>
    <time_frame>24 months</time_frame>
    <description>delta between body weight at 24 months and birth weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>breastfeeding duration</measure>
    <time_frame>24 months</time_frame>
    <description>breastfeeding duration</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">40</enrollment>
  <condition>Cardiovascular Abnormalities</condition>
  <condition>Small-for-gestational Age</condition>
  <arm_group>
    <arm_group_label>SGA vs AGA infants</arm_group_label>
    <description>infants, born at term (37+0/41+3 week gestation), aged 24 months, with a birth weight &lt;10th percentile or between 10th and 90th percentile for sex, gestational age, and birth order, according to Italian neonatal anthropometric charts</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        We consecutively enrolled 20 SGA infants, born at term (37+0-41+3 weeks gestation), aged 24&#xD;
        months, and 20 AGA, age- and sex-matched controls. SGA was defined as a birth weight &lt;10th&#xD;
        percentile for sex, gestational age and birth order, and AGA as a birth weight between the&#xD;
        10th and the 90th percentile, according to Italian neonatal anthropometric charts&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  infants, 24-month old, born at term SGA or AGA&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  heart, respiratory, liver and kidney diseases, congenital malformations, genetic&#xD;
             diseases, neonatal asphyxia, parenteral nutrition, congenital inborn errors of&#xD;
             metabolism, and preterm and twin birth.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>24 Months</minimum_age>
    <maximum_age>24 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>AOU Maggiore della Carità - Clinica Pediatrica - Ambulatorio di Auxologia ed Endocrinologia Pediatrica</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989 Mar 4;298(6673):564-7. doi: 10.1136/bmj.298.6673.564.</citation>
    <PMID>2495113</PMID>
  </reference>
  <reference>
    <citation>Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ. 2000 Apr 8;320(7240):967-71. doi: 10.1136/bmj.320.7240.967. Erratum In: BMJ 2000 May 6;320(7244):1244.</citation>
    <PMID>10753147</PMID>
  </reference>
  <reference>
    <citation>Faienza MF, Brunetti G, Delvecchio M, Zito A, De Palma F, Cortese F, Nitti A, Massari E, Gesualdo M, Ricci G, Carbonara S, Giordano P, Cavallo L, Scicchitano P, Ciccone MM. Vascular Function and Myocardial Performance Indices in Children Born Small for Gestational Age. Circ J. 2016;80(4):958-63. doi: 10.1253/circj.CJ-15-1038. Epub 2016 Feb 10.</citation>
    <PMID>26861187</PMID>
  </reference>
  <reference>
    <citation>Iruretagoyena JI, Gonzalez-Tendero A, Garcia-Canadilla P, Amat-Roldan I, Torre I, Nadal A, Crispi F, Gratacos E. Cardiac dysfunction is associated with altered sarcomere ultrastructure in intrauterine growth restriction. Am J Obstet Gynecol. 2014 Jun;210(6):550.e1-7. doi: 10.1016/j.ajog.2014.01.023. Epub 2014 Jan 16.</citation>
    <PMID>24440565</PMID>
  </reference>
  <reference>
    <citation>Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, Le Noble F, Ahmed A, Gratacos E. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010 Jun 8;121(22):2427-36. doi: 10.1161/CIRCULATIONAHA.110.937995. Epub 2010 May 24.</citation>
    <PMID>20497977</PMID>
  </reference>
  <reference>
    <citation>Dratva J, Breton CV, Hodis HN, Mack WJ, Salam MT, Zemp E, Gilliland F, Kuenzli N, Avol E. Birth weight and carotid artery intima-media thickness. J Pediatr. 2013 May;162(5):906-11.e1-2. doi: 10.1016/j.jpeds.2012.10.060. Epub 2012 Dec 20.</citation>
    <PMID>23260106</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>November 28, 2018</last_update_submitted>
  <last_update_submitted_qc>November 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliero Universitaria Maggiore della Carita</investigator_affiliation>
    <investigator_full_name>Flavia Prodam</investigator_full_name>
    <investigator_title>Prof</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Abnormalities</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03758092
org study id: CE 106/18
nct id: NCT03758092
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Aims of this study were 1) to evaluate early CV abnormalities in infants born small for
      gestational age (SGA) at 24 months of age compared with age and sex-matched subjects that
      were born adequate for gestational age (AGA) 2) to investigate the effect of catch-up growth
      and the role of breastfeeding on CV risk.
We consecutively enrolled 20 SGA infants, born at term (37+0/41+3 week gestation), aged 24
      months, and 20 AGA, age- and sex-matched controls. SGA was defined as a birth weight <10th
      percentile for sex, gestational age and birth order, and AGA as a birth weight between the
      10th and the 90th percentile, according to Italian neonatal anthropometric charts.

      Clinical and anthropometric variables The infants' prenatal and neonatal data were
      retrospectively recorded, namely a history of gestational diabetes and hypertension, the
      presence of intrauterine growth restriction, maternal weight gain during pregnancy, Apgar
      score, gestational age and birth weight, length, and head circumference. All subjects'
      parents completed a questionnaire including family history, maternal smoking during
      pregnancy, breastfeeding duration. At the time of enrollment (24 months), anthropometric data
      were evaluated by trained physicians according to standard procedures and based on the WHO
      growth charts. Height, weight, systolic (SBP) and diastolic (DBP) blood pressure were
      measured. Body mass index (BMI) was calculated as weight (kg)/height(cm)2 and weight gain in
      the first 2 years of life was calculated as the delta between birth weight and weight at 24
      months.

      Echocardiographic assessment Transthoracic echocardiogram using a Vivid 7 Pro ultrasound
      scanner (General Electric Healthcare, USA) was performed by an expert pediatric cardiologist,
      blinded to patients' clinical data. Measurements of left ventricle (LV end-diastolic
      diameter, LVEDD; LV end-systolic diameter, LVESD; interventricular septum at end diastole,
      IVSD; LV posterior wall at end diastole, LVPWD), relative wall thickness (RWT), left atrium
      diameter (LAD), the maximum LA volume, LV ejection fraction, and tricuspid annular plane
      systolic excursion (TAPSE) were obtained according to established standards. LV mass (LVM)
      was derived from the Devereux formula and indexed to body surface area (left ventricular mass
      index, LVMI). Left ventricular output (LVO) was obtained with the velocity time integral
      (VTI) from a 5-chamber view and calculated as follows LVO=[(VTI)x(heart
      rate)x(cross-sectional area)] and indexed to body weight.

      Using pulsed wave Doppler, mitral inflow velocities, peak early diastolic velocity (E), peak
      late diastolic velocity (A), and E/A ratio, were measured. Pulsed wave tissue Doppler of the
      lateral mitral annulus was used for the measurement of early peak diastolic mitral annular
      velocity (E'). The E/E' ratio was calculated. End-diastolic pressure (EDP) was calculated
      from the E/E' ratio with the formula EDP=1.91+1.24xE/E' (14) and the pressure-volume curve
      during diastole with the formula EDP = αxEDVβ (end-diastolic volume, EDV). Volume parameters
      were corrected to fixed values of EDP (V30 mmHg). The coefficient "β" (Beta), indicating the
      slope of the end-diastolic pressure-volume relationship (EDPVR), was calculated with the
      formula β=[Log10(EDP/30)]/[Log10(EDV/V30mmHg)].

      Vascular assessment Vascular measurements were performed with a high-resolution
      ultrasonography (Esaote MyLab25TM Gold, Esaote, Italy) using a 8 mHz linear transducer and a
      5 mHz convex transducer for the abdominal aorta, by an expert vascular surgeon blinded to
      patients' clinical status. CIMT, abdominal aortic diameter at maximum systolic expansion (Ds)
      and minimum diastolic expansion (Dd), brachial artery diameters, brachial artery peak
      systolic velocity (PSV) and end diastolic velocity (EDV) were measured as previously
      described and aortic strain (S), pressure strain elastic modulus (Ep), pressure strain
      normalized by diastolic pressure (Ep*) and brachial artery flow-mediated dilation (FMD) were
      calculated. While S is the mean strain of the aortic wall, Ep and Ep* are the mean stiffness
      (16). Arterial wall stiffness index (β index) was calculated with the formula: β
      index=ln(SBP/DBP)/[(Ds-Dd) /Dd)] (17) and systemic vascular resistance (dynes/s/cm2) with the
      formula: SVR=(mean BP- right atrial pressure)/LVO, with an estimated right atrial pressure of
      5 mmHg. The brachial artery maximum diameter recorded following reactive hyperemia was
      reported as a percentage change of resting diameter (FMD = peak diameter - baseline
      diameter/baseline diameter).
observational model: Case-Control
time perspective: Retrospective
measure: Cardiovascular structure
time frame: 24 months
description: Heart structure
measure: Cardiovascular function
time frame: 24 months
description: Heart function
measure: catch-up growth
time frame: 24 months
description: delta between body weight at 24 months and birth weight
measure: breastfeeding duration
time frame: 24 months
description: breastfeeding duration
arm group label: SGA vs AGA infants
description: infants, born at term (37+0/41+3 week gestation), aged 24 months, with a birth weight <10th percentile or between 10th and 90th percentile for sex, gestational age, and birth order, according to Italian neonatal anthropometric charts
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 24 Months
maximum age: 24 Months
healthy volunteers: No
facility: 
country: Italy
citation: Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989 Mar 4;298(6673):564-7. doi: 10.1136/bmj.298.6673.564.
PMID: 2495113
citation: Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ. 2000 Apr 8;320(7240):967-71. doi: 10.1136/bmj.320.7240.967. Erratum In: BMJ 2000 May 6;320(7244):1244.
PMID: 10753147
citation: Faienza MF, Brunetti G, Delvecchio M, Zito A, De Palma F, Cortese F, Nitti A, Massari E, Gesualdo M, Ricci G, Carbonara S, Giordano P, Cavallo L, Scicchitano P, Ciccone MM. Vascular Function and Myocardial Performance Indices in Children Born Small for Gestational Age. Circ J. 2016;80(4):958-63. doi: 10.1253/circj.CJ-15-1038. Epub 2016 Feb 10.
PMID: 26861187
citation: Iruretagoyena JI, Gonzalez-Tendero A, Garcia-Canadilla P, Amat-Roldan I, Torre I, Nadal A, Crispi F, Gratacos E. Cardiac dysfunction is associated with altered sarcomere ultrastructure in intrauterine growth restriction. Am J Obstet Gynecol. 2014 Jun;210(6):550.e1-7. doi: 10.1016/j.ajog.2014.01.023. Epub 2014 Jan 16.
PMID: 24440565
citation: Crispi F, Bijnens B, Figueras F, Bartrons J, Eixarch E, Le Noble F, Ahmed A, Gratacos E. Fetal growth restriction results in remodeled and less efficient hearts in children. Circulation. 2010 Jun 8;121(22):2427-36. doi: 10.1161/CIRCULATIONAHA.110.937995. Epub 2010 May 24.
PMID: 20497977
citation: Dratva J, Breton CV, Hodis HN, Mack WJ, Salam MT, Zemp E, Gilliland F, Kuenzli N, Avol E. Birth weight and carotid artery intima-media thickness. J Pediatr. 2013 May;162(5):906-11.e1-2. doi: 10.1016/j.jpeds.2012.10.060. Epub 2012 Dec 20.
PMID: 23260106
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliero Universitaria Maggiore della Carita
investigator full name: Flavia Prodam
investigator title: Prof
mesh term: Cardiovascular Abnormalities
sharing ipd: No