NICHD Fetal Growth Studies

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications & trials

Abstract

Overview The primary goal of this study was to establish a standard for normal fetal growth (velocity) and size for gestational age in the U.S. population. Additional goals were to create an individualized standard for fetal growth potential and to improve accuracy of fetal weight estimation. The primary NICHD Fetal Growth Studies Singletons found significant differences in fetal growth and individual fetal dimensions by self-reported maternal race/ethnicity with some differences occurring earlier than others but remaining throughout gestation (Buck Louis et al. American Journal of Obstetrics and Gynecology 2015). These findings suggest that assessment of fetal growth by ultrasound needs to be evaluated clinically using racial/ethnic-specific standards for early identification of potential abnormalities and to minimize misdiagnosis of intrauterine growth restriction and unnecessary clinical interventions. Two online calculators, an EFW calculator, https://www.nichd.nih.gov/fetalgrowthcalculator, and an EFW Fetal Growth velocity calculator, https://www.nichd.nih.gov/fetalvelocitycalculator, provide more accurate estimates compared to conventional growth charts. Given the recognition that inclusion of self-reported race/ethnicity in clinical algorithms may create unintended consequences for diagnosis and intervention, our team followed up this original work and created a unified, multi-ethnic fetal growth and fetal growth velocity standards, weighted using 2011 U.S. births. (Grantz KL et al. American Journal of Obstetrics and Gynecology, 2021 and Grantz KL et al. American Journal of Obstetrics and Gynecology, 2022) Obese Cohort Obesity is common among women of reproductive age and is known to increase the risk for maternal and fetal pregnancy complications. The NICHD Fetal Growth Studies enrolled 468 obese women with singleton pregnancies with the goal of comparing fetal growth patterns between women with obesity and non-obese women. Furthermore, because pregnancy complications such as GDM and preeclampsia are more common in women with obesity, this additional cohort offers the opportunity to examine how fetal growth is impacted by such complications. The researchers found that as early as 32 weeks' gestation, fetuses of obese women had higher weights than fetuses of nonobese women (Zhang et al. JAMA Pediatrics 2018). The team followed up the work and further investigated whether maternal obesity status may modify the effect of maternal glycemia status on fetal growth (Li et al. Lancet Diabetes Endocrinology 2020). Laboratory measurement of persistent organic pollutants (POPs) in the obese cohort has been completed. The team is in the process of evaluating the influences of POPs on longitudinal fetal growth trajectories. Dichorionic Twin Cohort Twin gestations represented 3.4% of U.S. births in 2013, yet there is limited contemporary data on the estimation of fetal growth trajectories in twins. The NICHD Fetal Growth Studies enrolled 171 dichorionic twin pregnancies. The primary objective was to empirically define the trajectory of fetal growth in dichorionic twins using longitudinal two-dimensional ultrasonography and to compare the fetal growth trajectories for dichorionic twins with those based on a growth standard developed by our group for singletons. (Grantz et al. AJOG 2016) Compared with singleton fetuses, the mean abdominal circumference and estimated fetal weight trajectories of dichorionic twin fetuses diverged significantly beginning at 32 weeks. The team followed up this work and found that dichorionic inter-twin estimated weight differences increased across gestation, with a larger percentage of pregnancies exceeding a fixed percent discordance cut-off as gestation advanced, suggesting that a percentile cut-point (e.g., 90th) may be more clinically useful than a fixed cut-point for defining discordance. (Amyx et al AJOG 2020) These findings suggest some part of this increase in twin discordance across pregnancy may be physiologic, and the current definition of twin discordance may need to be reconsidered for clinical practice. Biomedical Markers and Modifiable Risk Factors in Relation to Gestational Diabetes and Fetal Growth The NICHD Fetal Growth Studies is the basis for studying risk factors and the pathogenesis of gestational diabetes (GDM) and fetal growth and to identify factors that can inform the understanding of the etiology of GDM and improve early prediction of GDM. This work is grounded within an evolving body of research suggestive of important roles of maternal metabolism and nutrition in the development of GDM and in fetal growth. Pathway specific biomedical markers, and non-targeted metabolomics and lipidomics were measured longitudinally in 107 GDM cases and 214 non-GDM controls in the NICHD Fetal Growth Studies-Singleton Cohort (c.f. Gestational Diabetes Mellitus: Epidemiology, Etiology, and Health Consequences).