Risk Factors and Outcomes Associated With First-Trimester Fetal Growth Restriction

Abstract

ABSTRACT Exposure of the fetus to an adverse environment may result in developmental adaptations that lead to fetal growth restriction. It has been suggested that fetal growth restriction may increase the risk of metabolic and cardiovascular diseases and other adverse outcomes in adulthood. Previous studies have shown that first trimester fetal growth restriction increased the risks of low birth weight and small size for gestational age. The effects of maternal lifestyle habits and physical characteristics on first trimester growth and postnatal outcomes are not known. This population-based prospective cohort study investigated the associations of first trimester growth restriction with adverse birth outcomes and postnatal outcomes in early childhood. The effect of several maternal physical characteristics and lifestyle habits on postnatal outcomes was also investigated. A self-administered questionnaire was completed by the mothers at enrollment. First trimester fetal growth in singleton mothers was assessed sonographically by measuring fetal crown rump length between the gestational age of 10 weeks 0 days and 13 weeks 6 days, and then performing follow-up growth scans in the second and third trimesters. The primary birth outcomes examined were preterm birth, low birth weight, and small size for gestational age at birth. Postnatal outcomes were studied up to the age of 2 years. Multivariate analysis showed that maternal age was positively associated with fetal crown rump length; the difference was 0.79 mm (95% confidence interval [CI]: 0.41–1.18) per 1 standard deviation (4.68 maternal years of age) increase. Both diastolic blood pressure and the hematocrit were negatively associated with first trimester crown to rump growth (shorter length) (differences, −0.40 mm; 95% CI: −0.74 to −0.06, and −0.52 mm; 95% CI: −0.90 to −0.14 per standard deviation increase, respectively). Mothers who smoked and did not use folic acid supplements had shorter crown rump lengths than nonsmoking mothers who used folic acid supplements; the difference was 3.84 mm; 95% CI: −5.71 to −1.98. In comparison to normal first trimester growth, restricted first trimester growth was associated with increased risks of prematurity (4.0% vs. 7.2%; adjusted odds ratio [OR]: 2.12; 95% CI: 1.24–3.61), small size for the gestational age at birth (4.0% vs.10.6%; OR: 2.64; 95% CI: 1.64–4.25), and low birth weight (3.5% vs. 7.5%; OR: 2.42; 95% CI: 1.41–4.16). Over the first 2 years of postnatal growth, each standard deviation decrease in first trimester fetal crown rump length was associated with an accelerated growth rate in weight and height; the increase in the standard deviation score was 0.139 per 2 years; 95% CI: 0.097 to 0.181. These findings demonstrate that first trimester fetal growth is independently associated with a number of maternal physical characteristics and lifestyle habits. Early fetal growth restriction is also associated with an increased risk of adverse birth outcomes and accelerated growth rates in early childhood.