Fetal Growth Standards Research Articles

Should Fetal Growth Charts Be References or Standards?

Fetal growth standards (prescriptive charts derived from low-risk pregnancies) are theoretically better tools to monitor fetal growth than conventional references. We examined how modifying chart inclusion criteria influenced the resulting curves. We summarized estimated fetal weight (EFW) distributions from a hospital's routine 32-week ultrasound in all nonanomalous singleton fetuses (reference) and in those without maternal-fetal conditions affecting fetal growth (standard). We calculated EFWs for the 3rd, 5th, 10th, and 50th percentiles, and the proportion of fetuses each chart classified as small for gestational age. Of 2309 fetuses in our reference, 690 (30%) met the standard's inclusion criteria. There were no meaningful differences between the EFW distributions of the reference and standard curves (50th percentile: 1989 g reference vs. 1968 g standard; 10th percentile: 1711 g reference vs. 1710 g standard), or the proportion of small for gestational age fetuses (both 9.9%). In our study, there was little practical difference between a fetal growth reference and standard for detecting small infants.

OC07.04: Stillbirth risk and small‐for‐gestational‐age rate in subgroups according to maternal size: comparison of GROW, WHO and IG21 fetal growth standards

OC07.04: Stillbirth risk and small‐for‐gestational‐age rate in subgroups according to maternal size: comparison of GROW, WHO and IG21 fetal growth standards

VP40.18: Comparing the new standard chart in Korea to Hadlock fetal growth standard, Tokyo chart, and the INTERGROWTH‐21st: multicentre retrospective cohort study

VP40.18: Comparing the new standard chart in Korea to Hadlock fetal growth standard, Tokyo chart, and the INTERGROWTH‐21st: multicentre retrospective cohort study

Evaluation of the INTERGROWTH-21st Fetal Growth Standards in the United Arab Emirates: A Pilot Study.

Objectives: To evaluate the use of recently published INTERGROWTH-21st (IG-21) fetal growth standards in United Arab Emirates native population. Method: This prospective cohort study analyzed fetal ultrasound measurements of head circumference, abdominal circumference and femur length. Z-scores and percentiles of fetal and neonatal growth measurements were calculated using IG-21 and compared with a standard reference. Results: Measurements were performed in 120 pregnancies at a median gestational age of 25.8 weeks (range, 16 to 35). Thirteen out of 15 mean IG-21 Z-scores for all measurements remained between −0.5 and +0.5 at all gestational-ages. Actual standard deviations (SD) using IG-21 charts gave an acceptable SD (0.8 to 1.2) for 13 out of 15 measurements. The proportions of most antenatal measurements 90th and >97th percentiles were identical between standard and IG-21st charts. The median gestational age was 39 weeks (range, 29 to 41) and 14 (13%) were delivered by cesarean section. The mean z-scores of all biometric measurements were close to zero while the mean percentiles were close to the 50th percentile, thus, describing appropriately the neonatal growth parameters in our population. Conclusions: Fetal size in our population was comparable to the IG-21 standards. The IG-21 neonatal growth standards were more similar to that of the anticipated population distribution than to the standard charts. These preliminary results, if confirmed in a larger study in the UAE, would support use of IG-21 standards in UAE instead of the currently used standard charts.

A cohort study of fetal growth in twin pregnancies by chorionicity: comparison with European and American standards

ObjectiveTo develop fetal growth standards for twin gestations by placental chorionicity in a Spanish population and compare them with European and American standards to estimate the suitability of their use in clinical practice. Study designThis was a retrospective cohort study of 518 twin pregnancies, 435 dichorionic-diamniotic and 83 monochorionic-diamniotic, performed between January 2012 and December 2017. A total of 4,783 and 1,455 estimated fetal weights were considered from the 17th to the 37th week of gestation, using multilevel models, to build dichorionic-diamniotic and monochorionic-diamniotic standards, respectively. The percentages of small and large for gestational age were calculated as a model adjustment measure and adjustment to the studied data and the values provided by our model were compared against those of six European and American twin standards and three singleton standards. Correlation analyses between percentile predictions were performed using Cohen kappa coefficient. The predictive ability to detect small for gestational age was also provided by the sensitivity and positive predictive value. ResultsWe found slight differences between standards by chorionicity, being dichorionic-diamniotic percentiles slightly higher than monochorionic-diamniotic ones from the 17th to 37th weeks’ gestation. For dichorionic-diamniotic cases, both our standard (9.8-8.2) and that of Grantz (8.2-10.5) showed good adjustments for the 10th and 90th percentiles while the other compared standards underestimated or overestimated them. For monochorionic-diamniotic cases, both our standard (10.2-8.5) and that of Shivkumar (11.4-6.8) had the most suitable adjustment. The correlation analysis between small and large for gestational age cases provided by standards, showed clear differences among them. Kappa’s coefficient showed a substantial agreement between both Ananth (0.7) and Stirrup (0.69) dichorionic-diamniotic cases and our standard. There was also a substantial agreement between the Shivkumar (0.77) standard and our results for monochorionic-diamniotic cases. The correlation was moderate for all other comparisons. ConclusionsOur model showed a good adjustment to the studied population. There are clear differences among small and large for gestational age cases provided by twin standards in our studied population. The twin growth standards depend on the population characteristics and model structure. We found the use of singleton standards for twin pregnancies inadequate.

Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project

BackgroundHuman growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth.ObjectiveThis study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks’ gestation based on the same cohort that contributed to the INTERGROWTH-21st Fetal Growth Standards.Study DesignThis study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21st Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks’ gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4–7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression.ResultsPeak velocity was observed at a similar gestational age: 16 and 17 weeks’ gestation for head circumference (12.2 mm/wk), and 16 weeks’ gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks’ gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work.ConclusionThe fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21st Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21st tools at https://intergrowth21.tghn.org/standards-tools/.

Validation of Delphi procedure consensus criteria for defining fetal growth restriction.

Recently, a Delphi procedure was used to establish new criteria for defining fetal growth restriction (FGR). These criteria require clinical validation. We sought to validate the Delphi consensus criteria by comparing their performance with that of our current definition (estimated fetal weight (EFW) < 10th percentile) in predicting adverse neonatal outcome (ANO). This was a secondary analysis of data from a prospective cohort study of women referred for fetal growth assessment between 26 and 36 weeks' gestation. The current standard definition of FGR used in our clinical practice is EFW < 10th percentile using Hadlock's fetal growth standard. The Delphi consensus criteria for FGR include either a very small fetus (abdominal circumference (AC) or EFW < 3rd percentile) or a small fetus (AC or EFW < 10th percentile) with additional abnormal Doppler findings or a decrease in AC or EFW by two quartiles or more. The primary outcome was the prediction of a composite of ANO including one or more of: admission to the neonatal intensive care unit, cord pH < 7.1, 5-min Apgar score < 7, respiratory distress syndrome, intraventricular hemorrhage, neonatal seizures or neonatal death. The discriminatory capacities of the two definitions of FGR for composite ANO and delivery of a small-for-gestational-age (SGA) neonate, defined as birth weight < 10th percentile, were compared using area under the receiver-operating-characteristics curve (AUC). The sensitivity, specificity and predictive values of the methods were also compared. Of 1055 pregnancies included in the study, composite ANO occurred in 139 (13.2%). There were only two cases of early FGR (before 32 weeks); therefore, the study focused on late FGR. Our current FGR diagnostic criterion of EFW < 10th percentile was not associated significantly with composite ANO (relative risk (RR), 1.1 (95% CI, 0.6-1.8)), while the Delphi FGR criteria were (RR, 2.0 (95% CI, 1.2-3.3)). Our current definition of FGR showed higher discriminatory ability in the prediction of a SGA neonate (AUC, 0.69 (95% CI, 0.65-0.73)) than did the Delphi definition (AUC, 0.64 (95% CI, 0.60-0.67)) (P = 0.001). The AUCs of both definitions were poor for the prediction of composite ANO, despite slightly improved performance using the Delphi consensus definition of FGR (AUC, 0.53 (95% CI, 0.50-0.55)) compared with that of our current definition (AUC, 0.50 (95% CI, 0.48-0.53)) (P = 0.02). The newly postulated criteria for defining FGR based on a Delphi procedure detects fewer cases of neonatal SGA than does our current definition of EFW < 10th percentile, but is associated with a slight improvement in predicting ANO. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Fetal growth standards for Somali population

Background Accurate assessment of fetal size is essential in providing optimal prenatal care. National Institute of Child Health and Human Development (NICHD) study from 2015 demonstrated that estimated fetal weight (EFW) differed significantly by race/ethnicity after 20 weeks. There is a large Somali population residing in Minnesota, many of whom are cared for at our maternal fetal medicine practice at the University of Minnesota. Anecdotally, we noticed an increased proportion of small-for-gestational age diagnoses within this population. We sought to use our ultrasound data to create a reference standard specific for this population and compare to currently applied references. Purpose We aimed to model fetal growth standards within a healthy Somali population between 16 and 40 weeks gestation, and address possible differences in the growth patterns compared with standards for non-Hispanic White, non-Hispanic Black, Hispanic, and Asian singleton fetuses published by the NICHD in the Fetal Growth Study. Materials and methods This is a retrospective cohort study using ultrasound data from 527 low risk pregnancies of Somali ethnicity at single tertiary care center between 2011 and 2017. A total of 1107 scans were identified for these pregnancies and maternal and obstetrical data were reviewed. Women 18–40 years of age with low-risk pregnancies and established dating consistent with first trimester ultrasound scan were included. Exclusion criteria were any maternal, fetal or obstetrical conditions known to affect fetal growth. Results Estimated fetal weight among Somali pregnancies differed significantly at some time points from the NICHD four ethnic groups, but generally the EFW graph curves crossed over at most time points between the study groups. At week 18, EFW was significantly larger than all other four ethnic groups (all p<.001), it was also significantly larger from the Hispanic, Black, and Asian ethnic groups at some time points between 18 and 27 weeks gestation (p < .05). Additionally, EFW among Somali pregnancies was significantly smaller than the Black and Asian ethnicity at 32 and 35–36 weeks and smaller than the White ethnicity at 30 and 38–39 weeks (p < .05). Abdominal circumference (AC) for the Somali population was significantly smaller than the other ethnic groups, especially than the White ethnicity at various time points across 16–40 weeks (p < .05). Femur and humerus length were significantly longer when compared to all other ethnic groups at most time points from 16 to 40 weeks of gestation (p < .05). Biparietal diameter (BPD) was significantly smaller than all other ethnic groups specifically at time of fetal survey (18 weeks) and at time of fetal growth assessment (32 weeks) (p < .05). Conclusions Significant differences in fetal growth standards were found between the Somali ethnicity and other ethnic groups (White, Black, Asian, and Hispanic) at various time points from 16 to 40 weeks of gestation. Racial/ethnic-specific standards improve the precision for evaluating fetal growth and may decrease the proportion of fetuses of Somali ethnicity labeled as small-for-gestational age.

SMFM Fetal Anomalies Consult Series #2: Extremities

SMFM Fetal Anomalies Consult Series #2: Extremities

Obstetric and pediatric growth charts for the detection of fetal growth restriction and neonatal adverse outcomes in preterm newborns before 34 weeks of gestation

Introduction Identification of fetal growth-restricted (FGR) infants depends on the fetal or newborn charts used to identify them. We aimed to compare the prenatal and postnatal diagnosis of FGR and their ability to predict adverse perinatal outcomes. Methods Observational retrospective cohort study of 95 consecutive mother–infant pairs with preterm birth between 24 and 34 weeks (study period: January 2014 to December 2015). Prenatal sonographic diagnosis of FGR, based on customized fetal growth standards and fetal Doppler, was compared with the postnatal diagnosis of FGR based on a birthweight < 3rd percentile according to newborn charts (International Newborn size references for the Intergrowth twenty-first century program, and Olsen’s charts). Neonatal mortality and adverse neonatal outcomes were compared among groups. Results In 23/95 (24%) cases a prenatal diagnosis of early FGR was made. Postnatal FGR was confirmed in 11/23 (48%) cases using Olsen’s charts and 8/23 (35%) using Intergrowth 21st charts. One postnatal FGR case was missed by prenatal ultrasound. Bronchopulmonary dysplasia, sepsis and hypoglycemia were more frequent in pre- and postnatal FGR versus non-FGR. After adjusting for gestational age and sex, only an increased relative risk of hypoglycemia (2.0, 95%CI 1.0–2.8) was observed in infants with pre- and postnatal FGR diagnosis. Nonsignificant differences on neonatal outcomes were identified between prenatal FGR cases with normal birthweight and the non-FGR group. Conclusion Only prenatal FGR cases in which a birthweight below the third percentile is confirmed by means of postnatal charts (Olsen or Intergrowth standard) are at higher risk of adverse postnatal outcome.

Assessing the role of maternal race on the prediction of NICU admission by three growth charts: a cross-sectional study

Background The National Institutes of Health (NIH) race-specific and Intergrowth 21st race-independent fetal growth standards have recently been developed to assess fetal growth although the Alexander reference has been commonly used for over two decades. Societies are becoming increasingly stratified by race, and thus fetal growth effects are increasingly socially-derived. Relatedly, there is discussion surrounding the utility of classifying fetal growth on the basis of ideal growth versus typical growth. Therefore, we aimed to evaluate the classification discrepancies for small for gestational age (SGA) or large for gestational age (LGA) infants between growth charts, stratified by maternal race; and to determine which chart most accurately identifies vulnerable infants requiring NICU (Neonatal Intensive Care Unit) admission. Methods This cross-sectional study examined singleton liveborn infants born between 33 and 42 weeks of gestation with a self-identified White, Black, Hispanic, or Asian mother. Data were obtained from the 2014 National Centre of Health Statistics’ Vital Statistics Natality files. SGA infants were considered those <10th percentile and LGA were those >90th percentile, for each growth chart. SGA and LGA classification by maternal race was evaluated using stratified analysis and logistic regression. Odds ratios and goodness of fit characteristics were assessed to determine which chart best predicted NICU admission. Results In our sample of 3,782,660 singleton infants, significantly different proportions of infants were classified SGA/LGA using the Alexander (SGA: 4.6%, LGA:19.4%), Intergrowth 21st (SGA: 4.0%, LGA:19.6%), and NIH (SGA: 9.8%, LGA: 8.5%) charts. Race-specific classification of SGA differed by race and chart; there was an 8.4% difference in white infants considered SGA by Intergrowth (3.3; 95% CI, 3.2–3.3) compared to NIH (11.7%; 95% CI, 11.6–11.7). The NIH and Intergrowth 21st charts were typically in agreement for both SGA and LGA, differing substantially from the Alexander reference; however, there were significant differences between Intergrowth and NIH for proportions of SGA (NIH: 10.2%, CI 95%, 10.1–10.2; Intergrowth: 4.0%, CI 95%, 3.9–4.0) and LGA (NIH: 6.3%, CI 95%, 6.3–6.4; Intergrowth: 19.6%, CI 95%, 19.5–19.6) infants. Overall, 11.1% of Black infants were considered SGA by NIH and 6.8% by Intergrowth—more often than other races. Intergrowth classified the fewest infants as SGA and Alexander classified the most as SGA for all races. While NIH was better at discriminating LGA (OR: 2.72) and SGA-associated (OR: 1.71) NICU admissions compared to other charts, no standard was a significantly better predictor of NICU admission. Conclusion Since the NIH standard identified the fewest LGA infants and the Intergrowth 21st standard identified the fewest SGA infants, these charts may have been better identifiers of infants on either extreme of growth. The agreement between NIH and Intergrowth 21st charts suggest their interchangeable use for healthy populations, but the NIH may be more applicable given its racial stratification. However, the differences in proportions of SGA/LGA infants among the three charts according to maternal race introduce significant clinical ambiguity when identifying vulnerable infants. Additionally, no chart was able to accurately identify vulnerable infants and the dataset did not permit differentiation between growth-restricted and constitutionally small infants. Further work is necessary before selecting a true gold standard for use in routine clinical practice.

Detection of Adverse Perinatal Outcomes at Term Delivery Using Ultrasound Estimated Percentile Weight at 35 Weeks of Gestation: Comparison of Five Fetal Growth Standards

Objective: To assess the predictive ability of the ultrasound estimated percentile weight (EPW) at 35 weeks of pregnancy to predict adverse perinatal outcomes (APOs) at term delivery according to 5 fetal growth standards, including population, population-customized, and international references. Methods: This was a retrospective cohort study of 9,585 singleton pregnancies. Maternal clinical characteristics, fetal ultrasound data obtained at 35 weeks and pregnancy and perinatal outcomes were used to calculate EPWs to predict APOs according to: the customized and noncustomized (NC) Miguel Servet University Hospital (MSUH), the customized Figueras, the NC INTERGROWTH-21st, and the NC World Health Organization (WHO) international standards. APOs were defined as the occurrence of cesarean or instrumental delivery for nonreassuring fetal status, 5-min Apgar score < 7, arterial cord blood pH <7.10, or stillbirth. The predictive ability of EPW for APOs was analyzed using the area under the curve (AUC), and sensitivities were calculated for different false-positive rates (FPRs). Results: For a 10% FPR, detection rates for total APOs ranged between 12.7% with the customized MSUH (AUC 0.52; 95% CI 0.50–0.55) and 14.4% with the NC MSUH standard (AUC 0.55; 95% CI 0.53–0.57) for EPW by ultrasound; and from 22.0% with the customized MSUH standard (AUC 0.60; 95% CI 0.58–0.63) to 27.8% with the NC WHO (AUC 0.65; 95% CI 0.63–0.68) for EPW at delivery. Conclusions: The predictive capacity of the EPW for APOS is limited and similar, by both ultrasound and at delivery, for the 5 growth standards, without significant differences between customized and NC standards.

Comparing INTERGROWTH-21st Century and Hadlock growth standards to predict small for gestational age and short-term neonatal outcomes

Objective: To compare the INTERGROWTH-21st Century growth standard to the Hadlock standard in predicting small for gestational age (SGA) and adverse neonatal outcomes.Method: This is a prospective cohort study on women with singleton gestations referred for fetal growth ultrasound between 26.0 and 36.6 weeks gestational age (GA). The primary outcome is prediction of neonatal SGA. Neonatal SGA was defined as birthweight <10th percentile for GA by Alexander chart. The discriminatory ability of the growth standards was compared using area under receiver operating characteristic curves (AUC).Results: Among 1054 patients who met inclusion criteria, 139 (13.2%) had neonatal SGA. The mean interval between estimated fetal weight and birthweight was 6.7 ± 3.1 weeks. Composite adverse neonatal outcome was seen in 300 (28.4%) patients. The sensitivity for identifying SGA neonates was higher for Hadlock compared with INTERGROWTH-21st standard (41.7 vs. 24.5%); AUC (95% CI) were 0.69 (0.65–0.73) and 0.62 (0.58–0.65), respectively. Both standards were comparable in predicting the composite adverse neonatal outcomes; AUC (95% CI) were 0.52 (0.50–0.53) and 0.52 (0.50–0.54), respectively; p = .28.Conclusions: The Hadlock standard had a moderate but higher discriminatory ability for predicting neonatal SGA compared to the INTERGROWTH-21st project standard. However, the two standards were poor predictors of early adverse neonatal outcomes.Rationale: The Intergrowth-21st project was recently introduced with the goal of providing a universal benchmark for comparing growth across different ethnicity. We performed a prospective cohort study to compare the Intergrowth-21st standard with the commonly used Hadlock standard for predicting pregnancies at risk for neonatal SGA and adverse outcomes. Hadlock fetal growth standard is moderately superior at predicting neonatal SGA compared to the Intergrowth-21st standard. Both standards are poor at predicting adverse neonatal outcomes. These findings, however, need further validation.

Are selection criteria for healthy pregnancies responsible for the gap between fetal growth in the French national Elfe birth cohort and the Intergrowth-21st fetal growth standards?

The Intergrowth-21st (IG) project proposed prescriptive fetal growth standards for global use based on ultrasound measurements from a multicounty study of low-risk pregnancies selected using strict criteria. We examined whether the IG standards are appropriate for fetal growth monitoring in France and whether potential differences could be due to IG criteria for "healthy" pregnancies. We analysed data on femur length and abdominal circumference at the second and/or the third recommended ultrasound examination from 14607 singleton pregnancies from the Elfe national birth cohort. We compared concordance of centile thresholds using the IG standards and current French references and used restricted cubic splines to plot z-scores by gestational age. A "healthy pregnancy" sub-sample was created based on maternal and pregnancy selection criteria, as specified by IG. Mean gestational age-specific z-scores for femur length and abdominal circumference using French references fluctuated around 0 (-0.2 to 0.1), while those based on IG standards were higher (0.3-0.8). Using IG standards, 2.5% and 5.2% of fetuses at the third ultrasound were <10th centile for femur length and abdominal circumference, respectively, and 31.5% and 16.7% were >90th. Only 34% of pregnancies fulfilled IG low-risk criteria, but sub-analyses yielded very similar results. Intergrowth standards differed from fetal biometric measures in France, including among low-risk pregnancies selected to replicate IG's healthy pregnancy sample. These results challenge the project's assumption that careful constitution of a low-risk population makes it possible to describe normative fetal growth across populations.

Intrapartum magnesium sulfate is associated with neuroprotection in growth-restricted fetuses

Intrapartum magnesium sulfate administration is recommended for fetal neuroprotection in women with imminent very preterm birth. However, previous studies have not included or separately analyzed the outcomes of pregnancies with fetal growth restriction that were treated with intrapartum magnesium sulfate. We sought to evaluate the neonatal and neurodevelopmental outcomes of growth-restricted fetuses born <29 weeks' gestation and exposed to maternal intrapartum magnesium sulfate. We conducted a retrospective cohort study of infants born <29 weeks' gestation from 2010 through 2011, admitted to participating Canadian Neonatal Network units, and followed by the Canadian Neonatal Follow-up Network centers. Growth restriction was defined either as estimated fetal or actual neonatal birthweight <10th percentile according to fetal or neonatal growth standards for gestational age and sex, respectively. Infants exposed to intrapartum magnesium sulfate were compared with unexposed infants. The primary outcome was composite of death or significant neurodevelopmental impairment at 18-36 months' corrected age. Secondary outcomes were death or any neurodevelopmental impairment at 18-36 months' corrected age. Neonatal morbidities were also compared. Of the 336 growth-restricted fetuses, 112 (33%) received magnesium sulfate and of the 177 growth-restricted infants, 61 (34%) received magnesium sulfate. Administration of magnesium sulfate was at the discretion of the treating physician. Intrapartum magnesium sulfate was associated with reduced odds of composite of death or significant neurodevelopmental impairment for infants classified according to both fetal standards (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.80) and neonatal standards (adjusted odds ratio, 0.44; 95% confidence interval, 0.20-0.98). Intrapartum administration of magnesium sulfate to women with growth-restricted fetuses born <29 weeks' gestation was associated with reduced odds of composite of death or significant neurodevelopmental impairment.

Comparison of the INTERGROWTH-21st, National Institute of Child Health and Human Development, and WHO fetal growth standards.

To compare the ability of the INTERGROWTH-21st, National Institute of Child Health and Human Development, and WHO fetal growth standards to identify fetuses at risk of adverse perinatal outcomes. A retrospective analysis was performed among women enrolled in a multicenter randomized controlled trial (Routine Antenatal Diagnostic Imaging with Ultrasound) that was conducted in six states in the USA between November 1987 and May 1991. The predictive capability of various biometric indicators (biparietal diameter, femur length, abdominal circumference, head circumference, estimated fetal weight, and birthweight) was evaluated. Adverse outcomes included severe morbidity and perinatal death. There were 9409 women included. Biometric indicators measured at a gestational age of 18-24 weeks had insufficient predictive sensitivity (range, 4%-47%). By contrast, measurements taken at 28-34 weeks predicted statistically significant relative risk (range 1.5-10.2; P<0.05 for 27/30 relative risk values) and area under the receiver operating characteristic curve (range, 0.50-0.59; P<0.05 for 8/15 curves). Nonetheless, differences in accuracy between standards for predicting adverse perinatal outcomes were subtle (P>0.05 for differences in area under the curve values). Although useful to monitor fetal growth trajectory and the level of risk, all three fetal growth standards provided limited accuracy for identifying fetuses at risk of adverse perinatal outcomes.

Neonatal and fetal growth charts to identify preterm infants

It is unclear whether a neonatal or a fetal growth standard is a better predictor of adverse in-hospital newborn infant outcomes. We aimed to evaluate and compare the power of birthweight for gestational age to predict adverse neonatal outcomes using neonatal and fetal growth charts. Gestational age-specific birthweight was examined either as a percentile score or as a binary indicator for birthweight <10th percentile (small for gestational age) with the use of 3 fetal growth charts (National Institute of Child Health and Human Development, World Health Organization, and Intergrowth-21st) and 1 neonatal sex-specific birthweight chart. Inborn singleton infants from 2006-2014 with gestational age between 22 and 29 weeks and who were enrolled at 1 of the 852 US centers that were participating in the Vermont Oxford Network were studied. Outcomes included death, necrotizing enterocolitis, severe intraventricular hemorrhage, severe retinopathy of prematurity, and chronic lung disease. Receiver operating characteristic curve analysis was used to assess the predictive power of birthweight for gestational age, either as a score or as a small-for-gestational-age indicator, with the use of the 4 charts. We also examined the relative risks of the outcomes by comparing small-for-gestational-age and non-small-for-gestational-age infants with the use of the 4 charts. The percentage of small-for-gestational-age newborn infants ranged from 25.9-29.7% when with used the fetal growth charts. In contrast, the percentage was 10% when we used the neonatal charts. The areas under the receiver operating characteristic curves were similar across the 4 classification methods and were all <0.60, which suggests a poor predictive power. Small-for-gestational-age status, as classified by the neonatal chart, showed stronger associations with death, necrotizing enterocolitis, severe retinopathy of prematurity, and chronic lung disease, compared with those associations that were based on the other classification methods. Neither the neonatal nor the fetal growth charts are predictive of adverse infant in-hospital outcomes. In contrast to fetalcharts, the use of the neonatal charts results in stronger associationsbetween small-for-gestational-age and adverse outcomes.

Skin thickness as a potential marker of gestational age at birth despite different fetal growth profiles: A feasibility study.

BackgroundNew methodologies to estimate gestational age (GA) at birth are demanded to face the limited access to obstetric ultrasonography and imprecision of postnatal scores. The study analyzed the correlation between neonatal skin thickness and pregnancy duration. Secondarily, it investigated the influence of fetal growth profiles on tissue layer dimensions.Methods and findingsIn a feasibility study, 222 infants selected at a term-to-preterm ratio of 1:1 were assessed. Reliable information on GA was based on the early ultrasonography-based reference. The thicknesses of the epidermal and dermal skin layers were examined using high-frequency ultrasonography. We scanned the skin over the forearm and foot plantar surface of the newborns. A multivariate regression model was adjusted to determine the correlation of GA with skin layer dimensions. The best model to correlate skin thickness with GA was fitted using the epidermal layer on the forearm site, adjusted to cofactors, as follows: Gestational age (weeks) = −28.0 + 12.8 Ln (Thickness) − 4.4 Incubator staying; R2 = 0.604 (P<0.001). In this model, the constant value for the standard of fetal growth was statistically null. The dermal layer thickness on the forearm and plantar surfaces had a negative moderate linear correlation with GA (R = −0.370, P<0.001 and R = −0.421, P<0.001, respectively). The univariate statistical analyses revealed the influence of underweight and overweight profiles on neonatal skin thickness at birth. Of the 222 infants, 53 (23.9%) had inappropriate fetal growths expected for their GA. Epidermal thickness was not fetal growth standard dependent as follows: 172.2 (19.8) μm for adequate for GA, 171.4 (20.6) μm for SGA, and 177.7 (15.2) μm for LGA (P = 0.525, mean [SD] on the forearm).ConclusionsThe analysis highlights a new opportunity to relate GA at birth to neonatal skin layer thickness. As this parameter was not influenced by the standard of fetal growth, skin maturity can contribute to clinical applications.

Fetal growth standards: the NICHD fetal growth study approach in context with INTERGROWTH-21st and the World Health Organization Multicentre Growth Reference Study.

Three recently completed longitudinal cohort studies have developed intrauterine fetal growth charts, one in the United States and two international. This expert review compares and contrasts the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies, INTERGROWTH-21st and World Health Organization Multicentre Growth Reference Study conclusions in light of differences in aims, sampling frames, and analytical approaches. An area of controversy is whether a single growth reference is representative of growth, regardless of ethnic or country origin. The INTERGROWTH and World Health Organization Fetal studies used a similar approach as the World Health Organization Multicentre Growth Reference Study for infants and children, the aim of which was to create a single international reference for the best physiological growth for children aged 0-5 years. INTERGROWTH made the same assumption (ie, that there would be no differences internationally among countries or racial/ethnic groups in fetal growth when conditions were optimal). INTERGROWTH found differences in crown-rump length and head circumference among countries but interpreted the differences as not meaningful and presented a pooled standard. The World Health Organization Multicentre Growth Reference Study was designed to create a pooled reference, although they evaluated for and presented country differences, along with discussion of the implications. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Study was designed to assess whether racial/ethnic-specific fetal growth standards were needed, in recognition of the fact that fetal size is commonly estimated from dimensions (head circumference, abdominal circumference, and femur length) in which there are known differences in children and adults of differing racial/ethnic groups. A pooled standard would be derived if no racial/ethnic differences were found. Highly statistically significant racial/ethnic differences in fetal growth were found resulting in the publication of racial/ethnic-specific derived standards. Despite all 3 studies including low-risk status women, the percentiles for fetal dimensions and estimated fetal weight varied among the studies. Specifically, at 39 weeks, the 50th percentile for estimated fetal weight was 3502 g for whites, 3330 g for Hispanics, 3263 g for Asians, and 3256 for blacks in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study, compared with 3186 g for INTERGROWTH and 3403 g for World Health Organization Multicentre Growth Reference Study. When applying these standards to a clinical population, it is important to be aware that different percentages of small- and large-for-gestational-age fetuses will be identified. Also, it may be necessary to use more restrictive cut points, such as the 2.5th or 97.5th, for small-for-gestational-age or large-for-gestational-age fetuses, respectively. Ideally, a comparison of diagnostic accuracy, or misclassification rates, of small-for-gestational-age and large-for-gestational-age fetuses in relation to morbidity and mortality using different criteria is necessary to make recommendations and remains an important data gap. Identification of the appropriate percentile cutoffs in relation to neonatal morbidity and mortality is needed in local populations, depending on which fetal growth chart is used. On a final point, assessment of fetal growth with a one-time measurement remains standard clinical practice, despite recognition that a single measurement can indicate only size. Ultimately, it is knowledge about fetal growth in addition to other factors and clinical judgment that should trigger intervention.

The satisfactory growth and development at 2 years of age of theINTERGROWTH-21st Fetal Growth Standards cohort support itsappropriateness for constructing international standards.

BackgroundThe World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age.ObjectiveThe purpose of this study was to determine whether the babies in the INTERGROWTH-21st Project maintained optimal growth and development in childhood.Study DesignIn the Infant Follow-up Study of the INTERGROWTH-21st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites.ResultsThere were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions.ConclusionThe cohort enrolled in the INTERGROWTH-21st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards.