Identifying abnormal fetal growth as restriction or overgrowth during an ongoing pregnancy remains a pressing clinical challenge. One promising area of research suggests that changes in fetal soft tissue, including lean mass, fat mass, and organ size, may be the earliest changes that occur in pathologic growth and that soft tissue measures may complement traditional estimates that are based primarily on bone dimensions. Three-dimensional volume assessment of a portion of the arm or thigh where the borders are easier to trace, known as fractional limb volumes, may also detect abnormalities in soft tissue that result from pathologic growth earlier than conventional 2D measures. Despite the fact that most standard ultrasound machines in the U.S. have 3D/4D capability, the available technology has not been widely integrated into routine clinical practice other than for evaluation of fetal malformations. It remains to be determined whether 3D significantly improves prenatal diagnosis over 2D and is worth the extra time and cost. The Government recently completed a multi-site, prospective cohort study, the NICHD Fetal Growth Studies, which was designed to establish a standard for normal fetal growth (velocity) and size for gestational age in the U.S. population, and to improve estimation of abnormal fetal growth for four self-identified race/ethnicity backgrounds in 2,334 low-risk, non-obese gravidas: African American (n=611), Asian (n=460), Caucasian (n=614), and Hispanic (n= 649). Following a detailed sonogram at 10-13 weeks of gestation, each woman was randomized to one of 4 follow-up visit schedules. Each schedule comprised 5 additional sonograms: (16-22, 24-29, 30-33, 34-37 and 38-41 gestational weeks) for fetal biometry plus additional image and 3D volume acquisition for later analysis. An additional 486 obese women were recruited as well as 171 women with dichorionic twin gestations (where each twin has its own chorionic and amniotic sacs). The twin protocol was similar to the singleton protocol, with slight differences undertaken to allow the research ultrasounds to report to the clinical side, recognizing the high risk status of twin pregnancies, and a simplified ultrasound protocol to limit ultrasound time and patient burden. In addition to traditional biometrics, the following volumes were collected in the singleton study if they were able to be obtained: 1st trimester: fetus and gestational sac; 2nd and 3rd trimesters: head, cerebellum, face, chest, heart, abdomen, pelvis, arm and thigh. In twins, the volumes collected were 1st trimester: fetus and gestational sac and in the 2nd and 3rd trimesters the thigh. In addition to body composition, fetal cerebellar and organ sizes may differ in fetuses with growth abnormalities. Fetal cerebellar volumes have been suggested as potentially having better discrimination for fetal growth restriction than one measurement in a 2-D plane. However, there are very few studies on fetal cerebellar volumes. In addition, there may be racial differences, as cerebellar volumes were different in a Taiwan population compared to a Brazilian population. Whether cerebellar volumes vary by pregnancy complication is unknown. Kidney and liver volumes have been studied in association with pregnancy conditions such as small-for-gestational age (SGA) and gestational diabetes. In summary, there is a paucity of data on longitudinal changes in fetal body composition (subcutaneous fat, lean mass) and visceral volumes over the course of pregnancy. This data gaps contrasts sharply with available imaging technology. Knowledge of fetal body composition has the potential for practical scientific and clinical use given that current management of many pregnancy complications is limited because the degree of severity that results in adverse outcomes remains uncertain. Moreover, given reported differences in birth size characteristics by maternal race, we will be able to use data from a prospective pregnancy cohort design with longitudinal measurements (2D and 3D) to assess body composition changes and visceral measurements for the 4 maternal racial groups. Future interventions can also be tested such as increasing periods of maternal rest to increase blood flow to the uterus in instances of decreasing fetal fat deposition as an early signal for fetal growth restriction. The NICHD Fetal Growth Study is an ideal, prospective epidemiologic study well-designed to characterize fetal body composition and organ sizes. Knowledge of these associations could help increase understanding of the etiology of fetal and subsequent neonatal morbidity, and guide future interventions such as improved maternal disease control, individualized pregnancy monitoring and determining timing of delivery.
