Utilizing Longitudinal Measures of Fetal Growth to Create a Standard Method to Assess the Impacts of Maternal Disease and Environmental Exposure

Impaired or suboptimal fetal growth is associated with an increased risk of perinatal morbidity and mortality. By utilizing readily available clinical data on the relative size of the fetus at multiple points in pregnancy, including delivery, future epidemiological research can improve our understanding of the impacts of maternal, fetal, and environmental factors on fetal growth at different windows during pregnancy. This study presents mean and standard deviation ultrasound measurements from a clinically representative US population that can be utilized for creating Z-scores to this end. Between 2006 and 2012, 18, 904 non-anomalous pregnancies that received prenatal care, first and second trimester ultrasound evaluations, and ultimately delivered singleton newborns at Brigham and Women's hospital in Boston were used to create the standard population. To illustrate the utility of this standard, we created Z-scores for ultrasound and delivery measurements for a cohort study population and examined associations with factors known to be associated with fetal growth. In addition to cross-sectional regression models, we created linear mixed models and generalized additive mixed models to illustrate how these scores can be utilized longitudinally and for the identification of windows of susceptibility. After adjustment for a priori confounders, maternal BMI was positively associated with increased fetal size beginning in the second trimester in cross-sectional models. Female infants and maternal smoking were associated with consistently reduced fetal size in the longitudinal models. Maternal age had a non-significant association with increased size in the first trimester that was attenuated as gestation progressed. As the growth measurements examined here are widely available in contemporary obstetrical practice, these data may be abstracted from medical records by investigators and standardized with the population means presented here. This will enable easy extension of clinical data to epidemiologic studies investigating novel maternal, fetal, and environmental factors that may impact fetal growth.