First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study

Objective To examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood. Design Population based prospective cohort study. Setting City of Rotterdam, the Netherlands. Participants 1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle. Main outcomes measures Body mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations. Results One standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (-0.30%, 95% confidence interval -0.57% to -0.03%), android fat mass (-0.07%, -0.12% to -0.02%), android/gynoid fat mass ratio (-0.53, -0.89 to -0.17), diastolic blood pressure (-0.43, -0.84 to -0.01, mm Hg), total cholesterol (-0.05, -0.10 to 0, mmol/L), low density lipoprotein cholesterol (-0.04, -0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown to rump length and lower second and third trimester estimated fetal weight but higher weight growth from the age of 6 months onwards. Conclusions Impaired first trimester fetal growth is associated with an adverse cardiovascular risk profile in school age children. Early fetal life might be a critical period for cardiovascular health in later life.