Growth charts for use at birth and in the neonatal period: Recommendations of the French Neonatal Society.

INTRODUCTION: The use of different growth charts can lead to confusion in discussions between professionals. There are obstetric charts (of fetal growth) and neonatal charts (of measurements at birth and of postnatal growth). These charts can be descriptive (derived from an unselected population) or prescriptive (derived from of a population at low risk and with optimal conditions for growth). OBJECTIVES: (1) To describe available charts for infants at birth and in the neonatal period and compare them, and (2) to recommend one or more charts for use in neonatology in France. METHODS: Bibliographic research was conducted on MEDLINE and completed by the guidelines of professional societies. RESULTS: Antenatal information about fetal growth restriction (FGR) or fetuses identified as small-for-gestational-age using Intrauterine charts must be integrated into the identification of newborns at risk, but the use of Intrauterine charts to evaluate birthweight is not recommended to allow consistency with postnatal charts used in neonatal practice. Z-score variations using the updated Fenton postnatal charts are the most appropriate for the assessment of birthweight and postnatal growth for infants born preterm. These charts are sex-specific, include the three measurements (length, weight, and head circumference) and enable longitudinal follow-up of growth up to 50 weeks of corrected age and are linked to the WHO charts at term. The French Audipog charts, although are individualized, accessible online and can be used in maternity units to evaluate birthweight for term infants, but do not allow the follow-up of postnatal growth, while Fenton charts may be used to evaluate birthweight and postnatal growth in the first month for hospitalized term infants. CONCLUSION: The updated Fenton charts are the neonatal charts that best suit the objectives of pediatricians in France for monitoring the growth of preterm newborns. The use of the Audipog charts at term remains an alternative in maternity wards, while Fenton charts can be used for hospitalized term newborns.

Validity of a Delphi consensus definition of growth restriction in the newborn for identifying neonatal morbidity.

BACKGROUND: Small for gestational age is defined as a birthweight below a birthweight percentile threshold, usually the 10th percentile, with the third or fifth percentile used to identify severe small for gestational age. Small for gestational age is used as a proxy for growth restriction in the newborn, but small-for-gestational-age newborns can be physiologically small and healthy. In addition, this definition excludes growth-restricted newborns who have weights more than the 10th percentile. To address these limits, a Delphi study developed a new consensus definition of growth restriction in newborns on the basis of neonatal anthropometric and clinical parameters, but it has not been evaluated. OBJECTIVE: To assess the prevalence of growth restriction in the newborn according to the Delphi consensus definition and to investigate associated morbidity risks compared with definitions of Small for gestational age using birthweight percentile thresholds. STUDY DESIGN: Data come from the 2016 and 2021 French National Perinatal Surveys, which include all births ≥22 weeks and/or with birthweights ≥500 g in all maternity units in France over 1 week. Data are collected from medical records and interviews with mothers after the delivery. The study population included 23,897 liveborn singleton births. The Delphi consensus definition of growth restriction was birthweight less than third percentile or at least 3 of the following criteria: birthweight, head circumference or length <10th percentile, antenatal diagnosis of growth restriction, or maternal hypertension. A composite of neonatal morbidity at birth, defined as 5-minute Apgar score <7, cord arterial pH <7.10, resuscitation and/or neonatal admission, was compared using the Delphi definition and usual birthweight percentile thresholds for defining small for gestational age using the following birthweight percentile groups: less than a third, third to fourth, and fifth to ninth percentiles. Relative risks were adjusted for maternal characteristics (age, parity, body mass index, smoking, educational level, preexisting hypertension and diabetes, and study year) and then for the consensus definition and birthweight percentile groups. Multiple imputation by chained equations was used to impute missing data. Analyses were carried out in the overall sample and among term and preterm newborns separately. RESULTS: We identified that 4.9% (95% confidence intervals, 4.6-5.2) of newborns had growth restriction. Of these infants, 29.7% experienced morbidity, yielding an adjusted relative risk of 2.5 (95% confidence intervals, 2.2-2.7) compared with newborns without growth restriction. Compared with birthweight ≥10th percentile, morbidity risks were higher for low birthweight percentiles (less than third percentile: adjusted relative risk, 3.3 [95% confidence intervals, 3.0-3.7]; third to fourth percentile: relative risk, 1.4 [95% confidence intervals, 1.1-1.7]; fifth to ninth percentile: relative risk, 1.4 [95% confidence intervals, 1.2-1.6]). In adjusted models including the definition of growth restriction and birthweight percentile groups and excluding birthweights less than third percentile, which are included in both definitions, morbidity risks remained higher for birthweights at the third to fourth percentile (adjusted relative risk, 1.4 [95% confidence intervals, 1.1-1.7]) and fifth to ninth percentile (adjusted relative risk, 1.4 [95% confidence intervals, 1.2-1.6]), but not for the Delphi definition of growth restriction (adjusted relative risk, 0.9 [95% confidence intervals, 0.7-1.2]). Similar patterns were found for term and preterm newborns. CONCLUSION: The Delphi consensus definition of growth restriction did not identify more newborns with morbidity than definitions of small for gestational age on the basis of birthweight percentiles. These findings illustrate the importance of evaluating the results of Delphi consensus studies before their adoption in clinical practice.

Population-based surveillance of congenital anomalies over 40 years (1981-2020): Results from the Paris Registry of Congenital Malformations (remaPAR).

INTRODUCTION: Registries of congenital anomalies (CAs) play a key role in the epidemiological surveillance of CAs. The objective was to estimate the prevalence of CAs and proportions of prenatal diagnosis, terminations of pregnancy for fetal anomaly (TOPFA) and infant mortality in the Paris Registry of Congenital Malformations (remaPAR) over 40 years, from 1981 to 2020. MATERIAL AND METHODS: remaPAR records all births (live births, stillbirths ≥22 weeks of gestation and TOPFA at any gestational age) with CAs detected prenatally until the early neonatal period. We estimated the prevalence of CAs and proportions of prenatal diagnosis, TOPFA and infant mortality, overall and for a selected group of CAs in 3-year intervals. RESULTS: The prevalence of CAs remained stable during the study period: 2.9 % of total births and 2.1 % of live births. Genetic anomalies were the most frequent subgroup (about 23 %), followed by congenital heart defects (about 22 %) and limb defects (about 20 %). Among non-genetic anomalies, the prevalence per 10,000 births was the highest for hypospadias (about 18 %) and the lowest for bilateral renal agenesis (about 1 %). Prenatal diagnoses increased from about 17 % in the 1980s to approximately 70 % in the most recent period (2018-2020), whereas the proportion of early TOPFA <16 weeks of gestation increased from 0.4 % to 14 %. Infant mortality ranged from 0 % for transverse limb reduction defects to 86 % for hypoplastic left heart syndrome. CONCLUSION: The overall prevalence of CAs was fairly stable in Paris from 1981 to 2020. Prenatal diagnoses substantially increased, accompanied by much smaller increases in TOPFA.

Prevalence and prenatal diagnosis of congenital eye anomalies: A population-based study.

OBJECTIVE: To estimate the prevalence and trend of congenital eye anomalies (CEAs) and the rate of prenatal diagnosis over a 10-year period. DESIGN: Retrospective population-based registry study. SETTING: All maternity units in Paris, France, from 2010 to 2020. POPULATION: A cohort of 115 cases of CEA detected among all live births or stillbirths, after 22 weeks of gestation, and terminations of pregnancy. METHODS: The total prevalence of CEAs and prevalence of each specific CEA were calculated using 95% Poisson exact confidence intervals. MAIN OUTCOME MEASURES: The total prevalence of CEAs and the proportion of prenatal diagnosis of CEAs, and their evolution. RESULTS: The prevalence of CEAs was 4.1 (95% CI 3.4-5.0) cases, ranging between 3.1 and 5.7 cases, per 10 000 births. CEAs were prenatally diagnosed in 23.5% of cases. CEAs were bilateral in 51 cases (44.3%), unilateral in 43 cases (37.4%) and missing or unknown in 21 cases (18.3%). Of those with CEAs, 20.9% had genetic anomalies and 53.0% had at least one other extraocular anomaly. When detected prenatally, CEAs were bilateral in 15 cases (55.6%), unilateral in eight cases (29.6%) and missing in the four remaining cases. The prenatal diagnosis rate of CEAs associated with genetic anomalies, CEA cases with at least one other malformation and isolated CEA cases were 29.2%, 26.2% and 13.3%, respectively. CONCLUSIONS: In total, 115 cases of CEAs were observed during the study period, representing a total prevalence of 4.1 cases per 10 000 births. The overall prenatal detection rate of CEAs in our population was 23.5%, which dropped to 13.3% for isolated cases of CEAs.

Neurodevelopmental outcomes of preterm and growth-restricted neonate with congenital heart defect: a systematic review and meta-analysis.

The purpose of the study is to assess the risks of neurodevelopmental morbidity among preterm and growth restricted youth with congenital heart defects (CHD). This systematic review and meta-analysis included observational studies assessing neurodevelopmental outcomes among children with CHD born preterm (i.e., before 37 weeks of gestation) or growth restricted (small-for-gestational age (SGA) with a birthweight < the 10th percentile or with low birthweight (LBW) < 2500 g). Studies were identified in Medline and Embase databases from inception until May 2022, with data extracted by two blinded reviewers. Risk of bias was assessed using the Critical Appraisal Skills Programme cohort checklist. Meta-analysis involved the use of random-effects models. Main outcome measures were neurodevelopmental outcomes including overall cognitive impairment and intellectual disability, IQ, communication, and motor skills scores. From 3573 reports, we included 19 studies in qualitative synthesis and 6 meta-analysis studies. Risk of bias was low in 8/19 studies. Cognitive impairment and intellectual disability were found in 26% (95% CI 20-32, I2 = 0%) and 19% (95% CI 7-35, I2 = 82%) of preterm children with CHD, respectively. Two studies documented a lower IQ score for SGA children who underwent CHD operations in comparison to non-SGA children who also underwent CHD operations. Two studies have reported lower IQ, communication, and motor skills in children with hypoplastic left heart syndrome (HLHS) and low birth weight compared to those with HLHS and expected birth weight. CONCLUSIONS: Based on a low level of evidence, prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. Further evidence is needed to confirm these findings. TRIAL REGISTRATION: PROSPERO [CRD42020201414]. WHAT IS KNOWN: • Children born with CHD, preterm birth, or growth restriction at birth are independently at higher risk for neurodevelopmental impairment. • The additional effect of preterm birth and/or growth restriction on neurodevelopmental outcomes in children with CHD remains unclear. WHAT IS NEW: • Prematurity and/or growth retardation appear to accentuate specific neurodevelopmental outcomes in certain CHD subgroups. • Children with CHD, particularly those born preterm or with growth restriction, should undergo lifelong systematic comprehensive neurodevelopmental assessment.

Which fetal growth charts should be used in France? Position of the French College of Obstetricians and Gynecologists (CNGOF).

OBJECTIVE: To assess which fetal growth charts best describe intrauterine growth in France defined as the ability to classify 10% of fetuses below the 10th percentile (small for gestational age [SGA]) and above the 90th percentile (large for gestational age [LGA]) in the second and third trimesters. METHODS: We analyzed five studies on fetal ultrasound measurements using three French data sources. Two studies used second and third trimester ultrasound data from a nationwide birth cohort in 2011 (the ELFE study, N = 13 197 and N = 7747); one study used third trimester ultrasound data from on a nationwide cross-sectional study (the 2016 French National Perinatal Survey, N = 9940); and the last two studies were from the "Flash study" 2014 which prospectively collected ultrasound data from routine visits in the second and third trimesters (N = 4858 and N = 3522). For each study, we reported the percentage of measurements below the 10th percentile or above the 90th percentile, using French, Hadlock's, WHO and Intergrowth (IG) charts. RESULTS: WHO classified 4.7% and 16.3% of fetuses as having an estimated fetal weight (EFW) <10th and >90th percentiles in the second trimester compared to 3.3% and 34.7% with IG. The percentage of fetuses in the third trimester with an EFW <10th and >90th percentiles, ranged from 9.1% to 9.4% and from 8.0% to 11.1%, respectively, for WHO, and from 3.9% to 4.1% and from 17.3% to 21.6%, respectively, for IG. The WHO and IG charts for head circumference were very similar and performed well. Compared to the WHO charts, the French and Hadlock's charts deviated more frequently from the target percentiles values for EFW and biometric measures. CONCLUSION: It is recommended to use the WHO charts for the assessment of EFW and ultrasound biometric measurements in France (strong recommendation; low quality of evidence).

Postnatal diagnosis of congenital anomalies despite active systematic prenatal screening policies: a population-based registry study.

BACKGROUND: Prenatal screening for congenital anomalies is an important component of maternity care, with continual advances in screening technology. However, few recent studies have investigated the overall effectiveness of a systematic policy of prenatal screening for congenital anomalies, such as in France where an ultrasound per trimester is recommended for all pregnant individuals. OBJECTIVE: This study aimed to assess the proportion and the type of congenital anomalies that are not detected during pregnancy. STUDY DESIGN: The study population included all singleton fetuses and newborns with congenital anomalies from the Paris Registry of Congenital Malformations (remaPAR) from 2001 to 2021. The registry includes all live births and stillbirths at ≥22 weeks of gestation and terminations of pregnancy for fetal anomaly at any gestational age with congenital anomalies diagnosed from the prenatal period until discharge home from hospital after birth. The prevalence of postnatally detected congenital anomalies was estimated overall and for 5-year intervals within the study period. We also reported the proportion of postnatal detection by subgroups of congenital anomalies according to the EUROCAT classification. RESULTS: Of the 16,602 malformed singleton fetuses and newborns, 32.7% were detected postnatally. Of those with severe anomalies, 11.9% were detected postnatally. The postnatal detection rate decreased from 34.3% from 2001 to 2005, to 27.8% from 2016 to 2021 (P<.001). Anomalies most frequently detected postnatally were genital anomalies (n=969; 87.0%), followed by ear, neck, and face anomalies (n=71; 78.0%), eye anomalies (n=154; 74.0%), and limb anomalies (n=1802; 68.4%). Anomalies of the kidneys and the urinary tract (n=219; 7.1%) and the abdominal wall (n=37; 8.7%) were least likely to be detected after birth. Among the anomalies classified as severe, postnatal detection rates were highest for limb reduction defects (n=142; 40.6%), complete transposition of the great arteries (n=31; 17.6%), and diaphragmatic hernia (n=26; 17.2%). CONCLUSION: Despite improvement of prenatal screening over a 20-year period, our results show that there is still a margin for improvement in prenatal diagnosis of congenital anomalies.

Serial plotting of symphysis-fundal height and estimated fetal weight to improve the antenatal detection of infants small for gestational age: A cluster randomised trial.

OBJECTIVE: To assess whether standardised longitudinal reporting of growth monitoring information improves antenatal detection of infants who are small for gestational age (SGA), compared with usual care. DESIGN: Cluster-randomised controlled trial. SETTING: Sixteen French level-3 units in 2018-2019. POPULATION: Singleton pregnancies. METHODS: The intervention consisted of the serial plotting of symphysis-fundal height (SFH) and estimated fetal weight (EFW) measurements on customised growth charts using a software program, compared with standard antenatal care. We estimated relative risks (RR) adjusted for known risk factors for fetal growth restriction (FGR). MAIN OUTCOME MEASURES: The primary outcome was antenatal detection of FGR among SGA births (with birthweights below the tenth centile of French customised curves), defined as the mention of suspected FGR in medical records and either referral ultrasounds for growth monitoring or indicated delivery for FGR. Secondary outcomes were false-positive rates, mode of delivery, perinatal morbidity and mortality, and number of antenatal visits and ultrasounds. RESULTS: In total, seven intervention clusters (n = 4349) and eight control clusters (n = 4943) were analysed, after the exclusion of one intervention centre for a major deviation in protocol. SGA births represented 613 (14.1%) and 626 (12.7%) of all births, respectively. The rates of antenatal detection of FGR among SGA births were 40.0% in the intervention arm versus 37.1% in the control arm (crude RR 1.08, 95% CI 0.87-1.34; adj RR 1.09, 95% CI 0.88-1.35). No benefits of the intervention were detected in the analyses of secondary outcomes. CONCLUSIONS: Serial plotting of SFH and EFW measurements on customised growth charts did not improve the antenatal detection of FGR among SGA births.

Perinatal survival among very preterm singletons born after detection of early-onset fetal growth restriction with or without maternal hypertensive disorders: A population-based study in France.

OBJECTIVE: To investigate the management and survival of very preterm singletons born because of fetal growth restriction (FGR) with or without maternal hypertensive disorders in France. STUDY DESIGN: From a population-based cohort of very preterm births between 22 and 31 weeks in France in 2011, the study population included all non-anomalous singleton pregnancies delivered because of detected FGR with or without maternal hypertensive disorders. Antenatal detection of FGR was defined as an estimated fetal weight <10th percentile with or without fetal Doppler abnormalities or growth arrest. All fetuses were alive at the time of detection of FGR. Indicators of active perinatal management (antenatal steroids, pre-labor cesarean and birth in level 3 maternity unit) and fetal/neonatal outcomes (terminations of pregnancy (TOP), stillbirths, neonatal deaths and survival to discharge) were compared by gestational age between FGR associated with maternal hypertensive disorders and isolated FGR. RESULTS: Overall, 398 pregnancies delivered before 32 weeks for FGR associated with hypertensive disorders and 234 for isolated FGR. Active perinatal care was rare before 26 weeks in both groups and about one in five cases associated with maternal hypertensive disorders received steroids and was born by prelabor cesarean compared to none for isolated FGR. Before 25 weeks of gestation age, more pregnancies resulted in TOP when FGR was associated with hypertensive disorders compared to isolated FGR (respectively, 76.2 % vs 28.0 % at 22-23 weeks, P = 0.002 and 57.9 % vs 21.1 % at 24 weeks, P = 0.028) whereas stillbirths were more common among isolated FGR (respectively, 23.8 % vs 72.0 % at 22-23 weeks, P = 0.002 and 36.8 % vs 73.7 % at 24 weeks, P = 0.030). Survival to discharge was higher at any gestational age when the cause of birth was FGR associated with hypertensive disorders compared to isolated FGR. CONCLUSION: The management and pregnancy outcomes differed when FGR was associated with maternal hypertensive disorders or isolated. The proportion of TOP was higher when FGR was associated with hypertensive disorders and the proportion of stillbirths was higher in isolated FGR.

Testing the assumptions of customized intrauterine growth charts using national birth studies.

INTRODUCTION: Customized intrauterine growth charts are widely used for growth monitoring and research. They are based on three assumptions: (1) estimated fetal weight (EFW) has a normal distribution with a constant coefficient of variation at all gestational ages; (2) Hadlock's growth curve accurately describes the relation between EFW and gestational ages; (3) associations between EFW and the fetal and maternal characteristics included in the customization model (fetal sex, pre-pregnancy weight, height, parity) are proportional throughout pregnancy. The aim of this study was to test whether these underlying assumptions are verified. MATERIAL AND METHODS: Data came from (1) the French Longitudinal Study of Children (ELFE) cohort, which recruited births after 32 weeks' gestation in 349 maternity hospitals in France in 2011, and (2) the National Perinatal Survey, which included births from all French maternity hospitals in 2016. The study population included, respectively, 6 920 and 8 969 singleton non-malformed term live births with data on customization characteristics and EFW. We computed the coefficient of variation by gestational age and then modeled the association of gestational age, maternal and fetal characteristics with EFW at the second and third trimester ultrasound and with birthweight using linear regression. To assess the proportionality of the impact of maternal and fetal characteristics, we computed the percent change in weight associated with these characteristics at these three time points. RESULTS: The coefficient of variation was close to 12% at each gestational age, but EFW was not normally distributed, leading to small but systematic underestimation of fetuses under the 10th percentile. Weights representing the 50th and 10th percentiles based on Hadlock's growth trajectory were lower than observed or predicted weights. Most characteristics more strongly impacted weight at birth than during pregnancy. In the French Longitudinal study of Children (ELFE) cohort, boys were 1.8% (95% confidence interval [CI] 1.3-2.4) heavier than girls in the third trimester, whereas this percentage was 4.6% (95% CI 4.0-5.2) at birth. In the National Perinatal Survey, these percentages were 2.3% (95% CI 1.8-2.8) and 4.3% (95% CI 3.8-4.8). CONCLUSIONS: These results from two independent sources revealed discrepancies between routine clinical EFW data used for growth monitoring and the customized growth model's assumptions.

World Health Organization fetal growth charts applied in a French birth cohort.

OBJECTIVE: To evaluate the applicability of World Health Organization (WHO) fetal growth charts for abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW) at the second and third trimester ultrasounds in a French birth cohort. MATERIALS AND METHODS: Using the ELFE cohort of live births after 33 weeks' gestation in France in 2011, we selected 7747 singletons with fetal biometric measurements at the second (20-25 weeks) and third (30-35 weeks) trimester routine ultrasounds. We calculated proportions of fetuses <3rd and <10th percentiles and >90th and >97th percentiles for AC, FL and EFW using WHO charts and two international (Intergrowth and Hadlock) and two national (Salomon and CFEF) charts. Analyses were also carried out in a subsample of 4427 low-risk births. RESULTS: WHO charts classified 2,3% and 8-10% of fetuses <3rd and <10th percentiles respectively, for AC and FL in the second and third trimesters and EFW in the third trimester. Similarly, about 3 and 10% of fetuses had AC, FL and EFW >97th and >90th percentile in both trimesters. Hadlock and CFEF charts also provided a good fit for third-trimester EFW <10th percentile. For most measures, Intergrowth yielded low proportions <3rd and <10th percentile, and high proportions >90th and >97th percentiles. Proportions were slightly lower for low-risk pregnancies. CONCLUSION: WHO charts provided a good description of the distribution of French fetal biometric measures. Further research is needed to assess the impact of using WHO charts on obstetrical management and perinatal outcomes.

Unisex vs sex-specific estimated fetal weight charts for fetal growth monitoring: a population-based study.

BACKGROUND: In contrast with birthweight or other growth charts, a feature of most intrauterine charts is that they are not differentiated by sex. Differences in weight by sex during pregnancy are considered to be relatively minor; however, small systematic differences may affect the sensitivity and specificity of screening for fetuses with growth restriction. OBJECTIVE: To assess differences between unisex and sex-specific estimated fetal weight charts at the third-trimester ultrasound with regard to the sex ratio of fetuses detected with an estimated fetal weight <10th percentile and subsequent detection of small-for-gestational-age newborns with morbidity at birth. STUDY DESIGN: The study included 9940 singleton live births from a French population-based study in 2016. Main outcomes were an estimated fetal weight <10th percentile at the routine third-trimester ultrasound between 30 and 35 weeks of gestation, and small for gestational age infants (birthweight <10th percentile) with neonatal morbidity (Apgar score <7 at 5 minutes and/or resuscitation in delivery room and/or admission to a neonatal unit). We used 2 charts with unisex and sex-specific options: the World Health Organization international standard chart and a customized chart for fetal sex based on Gardosi's gestation-related optimal weight model adapted to the French population (Epopé). Hadlock's unisex chart, commonly used in clinical care and research, was also included to provide an external reference. We compared the proportions of female and male fetuses with an estimated fetal weight <10th percentile and the sensitivity and specificity of such estimated fetal weight for predicting small-for-gestational-age newborns with morbidity when using unisex vs sex-specific charts, overall and by sex. RESULTS: Among all singleton births, there were 51.6% males and 48.4% females. Males faced higher risks of being small-for-gestational-age with morbidity at birth (2.4% vs 1.8%; P=.031). Using the World Health Organization unisex chart, 6.9% of males and 9.9% of females had an estimated fetal weight <10th percentile vs 9.9% of males and 7.1% of females with the sex-specific chart; these proportions were 3.5% and 4.6% and 4.3% and 2.7%, respectively, for the Epopé. Proportions of estimated fetal weight <10th percentile using Hadlock's chart were slightly higher than those obtained using the unisex World Health Organization chart (7.5% of males and 10.6% of females), but the difference of about 3% was the same. The sensitivity of an estimated fetal weight <10th percentile for identifying small-for-gestational-age newborns with morbidity differed for males and females by type of chart; unisex charts detected more small-for-gestational-age females with morbidity and sex-specific charts detected more small-for-gestational-age males with morbidity, but the overall sensitivity was the same (49.1% for the World Health Organization chart and Hadlock's chart and 34.9% for the Epopé chart). CONCLUSION: This study suggests that the use of sex-specific charts instead of unisex charts would reduce sex bias in intrauterine growth screening during the third trimester of pregnancy. Prospective studies are needed to assess the effects of using sex-specific charts rather than unisex charts on obstetrical management and outcomes.

Should prenatal chromosomal microarray analysis be offered for isolated fetal growth restriction? A French multicenter study.

BACKGROUND: Compared with standard karyotype, chromosomal microarray analysis improves the detection of genetic anomalies and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of chromosomal microarray analysis in cases of isolated fetal growth restriction. OBJECTIVE: This study aimed to estimate the proportion of copy number variants detected by chromosomal microarray analysis and the incremental yield of chromosomal microarray analysis compared with karyotype in the detection of genetic abnormalities in fetuses with isolated fetal growth restriction. STUDY DESIGN: This retrospective study included all singleton fetuses diagnosed with fetal growth restriction and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over 1 year in 2016. Fetal growth restriction was defined as an estimated fetal weight of

Maternal and neonatal outcomes associated with induction of labor after one previous cesarean delivery: A French retrospective study.

BACKGROUND: The safety of methods of labor induction in women with previous cesarean deliveries is still debated. We investigated perinatal outcomes associated with labor induction among women with a trial of labor after one cesarean delivery. METHODS: This retrospective study included 339 women with a trial of labor after one prior cesarean and a singleton term fetus in cephalic presentation in 2013-2016 in a French maternity unit. Labor induction was performed with oxytocin, artificial rupture of membranes and/or prostaglandin E2, according to the Bishop score. The primary outcome was a composite of uterine rupture, low Apgar score, neonatal resuscitation or admission to a neonatal unit. The secondary outcomes included cesarean delivery after onset of labor, postpartum hemorrhage and maternal hospital stay after delivery. We used logistic regression to estimate odds ratios adjusted (aOR) for potential confounders. RESULTS: In our sample, 67.3% of women had spontaneous labor and 32.7% were induced. More than half of the women received oxytocin during labor regardless of the mode of labor. The proportions of the composite outcome and of cesarean after onset of labor were higher in the induced group compared to the spontaneous group (26.1% vs 15.8%, p = 0.02 and 45.0% vs 27.6%, p<0.01, respectively). There were 9 uterine ruptures (2.6%) and this proportion was higher in the induced group compared to the spontaneous group, although this difference was not statistically significant (3.6% vs 2.2%, p = 0.48). After adjustment, labor induction was associated with higher risks of the composite outcome (aOR = 2.45, 95% CI: 1.29-4.65), cesarean after onset of labor (aOR = 2.06, 95% CI: 1.15-3.68) and maternal hospital stay after delivery ≥6 days (aOR = 6.20, 95% CI: 3.25-11.81). No association was found with postpartum hemorrhage. CONCLUSION: Labor induction after one prior cesarean was associated with a higher risk of adverse perinatal outcome. Nevertheless, the higher proportion of uterine rupture did not differ significantly from that in the spontaneous labor group.

Vitamin D and pregnancy outcomes: Overall results of the FEPED study.

Vitamin D insufficiency is highly prevalent in children and adults including pregnant women. During pregnancy, maternal vitamin D insufficiency could increase risks of several pregnancy complications and adverse birth outcomes. The FEPED study was designed to assess the effects of maternal vitamin D status in the first trimester during pregnancy on risks of preeclampsia, gestational diabetes mellitus (GDM), preterm birth and small-for-gestational age (SGA) at birth. This observational prospective cohort included 3129 women with a singleton pregnancy between April 2012 and July 2014 in six maternity units in France and Belgium. The aim of this review is to summarize the results of the FEPED study. At the first trimester the mean 25(OH)D concentration was 21.9 ± 10.4 ng/mL and 25(OH)D concentration was <20 ng/mL in 46.5 % of patients. After matching 83 cases of preeclampsia with 319 controls, a significant decrease in the risk of preeclampsia was associated with maternal vitamin D levels ≥ 30 ng/mL in the third trimesters (OR = 0.34; 95 % CI: 0.13-0.86. P = 0.023). In the first trimester, the risk for preeclampsia was decreased in these patients, but did not achieve statistical significance (OR = 0.57 95 % CI, 0.30-1.01; p = 0.09). For the 250 cases with GDM matched with 941 controls, no linear relationship was found between GDM and 25OHD levels in the first trimester of pregnancy. Finally, 2813 pregnant women were included in analyses of risks of preterm and SGA birth. No association was found between low maternal vitamin D levels in the first trimester and the risks of preterm birth (aOR = 1.53; 95 % CI: 0.97-2.43) or SGA (aOR = 1.07; 95 % CI: 0.75-1.54). Further investigation is needed to understand the mechanisms behind the association between vitamin D and birth outcomes.

First Trimester Maternal Vitamin D Status and Risks of Preterm Birth and Small-For-Gestational Age.

Maternal 25-hydroxyvitamin D (25-OHD) deficiency during pregnancy may increase the risk of preterm and small-for-gestational age (SGA) birth, but studies report conflicting results. We used a multicenter prospective cohort of 2813 pregnant women assessed for 25-OHD levels in the first trimester of pregnancy to investigate the association between maternal 25-OHD concentrations and risks of preterm birth (<37 weeks) and SGA (birthweight <10th percentile). Odds ratios were adjusted (aOR) for potential cofounders overall and among women with light and dark skin separately, based on the Fitzpatrick scale. 25-OHD concentrations were <20 ng/mL for 45.1% of the cohort. A total of 6.7% of women had a preterm birth. The aOR for preterm birth associated with the 1st quartile of 25-OHD concentrations compared to the 4th quartile was 1.53 (95% confidence interval (CI): 0.97-2.43). In stratified analyses, an association was observed for women with darker skin (aOR = 2.89 (95% CI: 1.02-8.18)), and no association with lighter skin. A total of 11.9% of births were SGA and there was no association overall or by skin color. Our results do not provide support for an association between maternal first trimester 25-OHD deficiency and risk of preterm or SGA birth overall; the association with preterm birth risk among women with darker skin requires further investigation.

Indications leading to termination of pregnancy between 22+0 and 31+6 weeks of gestational age in France: A population-based cohort study.

OBJECTIVE: To estimate the prevalence and indications of terminations of pregnancy (TOP) between 22+0 and 31+6 weeks of gestational age in France and to examine the characteristics of women by indication of TOP. STUDY DESIGN: From the EPIPAGE 2 population-based cohort study of preterm births in France in 2011, we selected 5009 singleton live births, stillbirths and TOP that occurred between 22 and 31 weeks. We estimated the proportion of TOP by gestational age. We then classified terminations by indications into 4 categories: fetal anomalies (TOPFA), preterm premature rupture of the membranes (PPROM), maternal conditions and fetal growth restriction (FGR). We also classified TOPFA by type of anomaly. Maternal characteristics were compared between TOPFA and TOP for maternal or fetal conditions without congenital anomaly. RESULTS: 23.1% of all births and 54.3% of stillbirths were terminations. The proportion of terminations was 36.9% of all births at 22 weeks, 50.2% at 24 weeks and <10% at 30-31 weeks. 85.8% of terminations were for fetal anomaly, 4.4% for PPROM, 6.1% for maternal complications and 3.7% for severe FGR. Compared to women with a TOPFA, those with a termination for maternal or fetal conditions were more often nulliparous, single, African, obese, smokers and covered by non-standard insurance for women in socially deprived circumstances. CONCLUSION: In France, there is a high proportion of TOP of which 14% are for indications other than congenital anomalies. Because rates of terminations have an impact on very preterm birth and perinatal mortality rates, studies on pregnancy outcome should report all terminations, not only those for congenital anomalies.

Comparison of the Hadlock and INTERGROWTH formulas for calculating estimated fetal weight in a preterm population in France.

BACKGROUND: Accurate estimation of fetal weight is needed for growth monitoring and decision-making in obstetrics; the INTERGROWTH project developed an estimated fetal weight formula to construct new intrauterine growth standards. OBJECTIVE: We sought to compare the accuracy of the Hadlock and INTERGROWTH formulas for the estimation of fetal weight among preterm infants. STUDY DESIGN: Using the EPIPAGE 2 population-based study of births between 22-34 weeks of gestation, we included 578 nonanomalous singleton fetuses with an ultrasound-to-delivery interval <2 days. We used abdominal circumference, head circumference, and femur length to calculate estimated fetal weight with Hadlock formula and abdominal and head circumferences to calculate estimated fetal weight according to INTERGROWTH. The mean percentage errors and the proportions of estimated fetal weight measures within ±10% of birthweight were compared between the 2 methods. RESULTS: Mean (SD) gestational age and birthweight were 29.1 (SD 2.7) weeks and 1219 (SD 489) g. Mean (SD) percentage errors for Hadlock and INTERGROWTH were significantly different: -0.7 (SD 10.1) and -3.5 (SD 11.6), respectively (P < .001), and more infants were classified within ±10% of their birthweight with Hadlock compared to INTERGROWTH (68.7% vs 57.8%, P < .001). The INTERGROWTH formula overestimated birthweight at 22-23 weeks compared to Hadlock [mean errors of 18.8 (SD 13.6) vs 5.5 (SD 10.2)] and underestimated birthweight >28 weeks: at 29-31 weeks, mean errors were -5.8 (SD 10.9) for INTERGROWTH and -0.6 (SD 10.4) for Hadlock. CONCLUSION: Hadlock estimated fetal weight formula was more accurate than INTERGROWTH formula for fetuses delivered between 22-34 weeks of gestation. Our results support continued use of Hadlock formula in France and raise questions about the applicability of INTERGROWTH intrauterine growth standards.