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.

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.

Assessing fetal growth in Africa: Application of the international WHO and INTERGROWTH-21st standards in a Beninese pregnancy cohort.

BACKGROUND: Fetal growth restriction is a major complication of pregnancy and is associated with stillbirth, infant death and child morbidity. Ultrasound monitoring of pregnancy is becoming more common in Africa for fetal growth monitoring in clinical care and research, but many countries have no national growth charts. We evaluated the new international fetal growth standards from INTERGROWTH-21st and WHO in a cohort from southern Benin. METHODS: Repeated ultrasound and clinical data were collected in women from the preconceptional RECIPAL cohort (241 women with singleton pregnancies, 964 ultrasounds). We modelled fetal biometric parameters including abdominal circumference (AC) and estimated fetal weight (EFW) and compared centiles to INTERGROWTH-21st and WHO standards, using the Bland and Altman method to assess agreement. For EFW, we used INTERGROWTH-21st standards based on their EFW formula (IG21st) as well as a recent update using Hadlock's EFW formula (IG21hl). Proportions of fetuses with measurements under the 10th percentile were compared. RESULTS: Maternal malaria and anaemia prevalence was 43% and 69% respectively and 11% of women were primigravid. Overall, the centiles in the RECIPAL cohort were higher than that of INTERGROWTH-21st and closer to that of WHO. Consequently, the proportion of fetuses under 10th percentile thresholds was systematically lower when applying IG21st compared to WHO standards. At 27-31 weeks and 33-38 weeks, respectively, 7.4% and 5.6% of fetuses had EFW <10th percentile using IG21hl standards versus 10.7% and 11.6% using WHO standards. CONCLUSION: Despite high anemia and malaria prevalence in the cohort, IG21st and WHO standards did not identify higher than expected proportions of fetuses under the 10th percentiles of ultrasound parameters or EFW. The proportions of fetuses under the 10th percentile threshold for IG21st charts were particularly low, raising questions about its use to identify growth-restricted fetuses in Africa.

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.

International versus national growth charts for identifying small and large-for-gestational age newborns: A population-based study in 15 European countries.

BACKGROUND: To inform the on-going debate about the use of universal prescriptive versus national intrauterine growth charts, we compared perinatal mortality for small and large-for-gestational-age (SGA/LGA) infants according to international and national charts in Europe. METHODS: We classified singleton births from 33 to 42 weeks of gestation in 2010 and 2014 from 15 countries (N = 1,475,457) as SGA (birthweight <10th percentile) and LGA (>90th percentile) using the international Intergrowth-21st newborn standards and national charts based on the customised charts methodology. We computed sex-adjusted odds ratios (aOR) for stillbirth, neonatal and extended perinatal mortality by this classification using multilevel models. FINDINGS: SGA and LGA prevalence using national charts were near 10% in all countries, but varied according to international charts with a north to south gradient (3.0% to 10.1% and 24.9% to 8.0%, respectively). Compared with appropriate for gestational age (AGA) infants by both charts, risk of perinatal mortality was increased for SGA by both charts (aOR[95% confidence interval (CI)]=6.1 [5.6-6.7]) and infants reclassified by international charts from SGA to AGA (2.7 [2.3-3.1]), but decreased for those reclassified from AGA to LGA (0.6 [0.4-0.7]). Results were similar for stillbirth and neonatal death. INTERPRETATION: Using international instead of national charts in Europe could lead to growth restricted infants being reclassified as having normal growth, while infants with low risks of mortality could be reclassified as having excessive growth. FUNDING: InfAct Joint Action, CHAFEA Grant n°801,553 and EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking ConcePTION grant n°821,520. AH received a PhD grant from EHESP.