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

Abstract

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.

Fig 1 First trimester fetal growth and cardiovascular risk factors in childhood (n=1184). Values are linear regression coefficients (95% CI) that reflect the difference in childhood outcomes, expressed as standard deviation scores (SDS) between first trimester fetal crown to rump length fifths, and reference group (highest fifth). Estimates are based on multiple imputed data. Models were adjusted for child’s sex and age at measurement and for maternal duration of last menstrual cycle, age, educational level, ethnicity, parity, pre-pregnancy body mass index, diastolic blood pressure, smoking during pregnancy, folic acid supplement use, and duration of breast feeding. Models for total fat mass and android/gynoid fat mass ratio were additionally adjusted for current childhood height. Trend lines are given only when P for linear trend <0.05

Fig 2 First trimester fetal growth and clustering of cardiovascular risk factors (n=745). Values are relative risks (95% CI) from generalised linear models that reflect risk of childhood clustering of cardiovascular risk factors for fifths of first trimester fetal crown to rump length, compared with reference group (lowest fifth). Estimates are based on multiple imputed data. Clustering of cardiovascular risk factors was defined as having three or more of android fat mass percentage ≥75th centile, systolic or diastolic blood pressure ≥75th centile, high density lipoprotein cholesterol ≤25th centile or triglycerides ≥75th centile, and insulin concentration ≥75th centile. Model was adjusted for child’s sex and age at measurement and for maternal duration of last menstrual cycle, age, educational level, ethnicity, parity, pre-pregnancy body mass index, diastolic blood pressure, smoking during pregnancy, folic acid supplement use, and duration of breast feeding

Fig 3 Fetal and childhood length and weight growth from first trimester onwards in children with clustering of cardiovascular risk factors (n=745). Values are regression coefficients (95% confidence interval) that reflect the difference in length and weight standard deviation score from first trimester onwards for children with clustering of cardiovascular risk factors, compared with children without such clustering. Models were adjusted for maternal duration of last menstrual cycle and child’s sex and age at outcome measurements. Length and weight growth characteristics used in the models were: fetal period—first trimester crown to rump length as both length and weight measure (starting point), second and third trimester femur length and estimated fetal weight; at birth—length and weight; during childhood—length and weight. Clustering of cardiovascular risk factors was defined as having three or more of android fat mass percentage ≥75th centile, systolic or diastolic blood pressure ≥75th centile, high density lipoprotein cholesterol ≤25th centile or triglycerides ≥75th centile, and insulin concentration ≥75th centile