In utero teratogen exposure and cardiometabolic risk in 5-year-old children: a prospective pediatric study

Abstract

Background: Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The in utero milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation.

Aim: To explore an association between maternal smoking and alcohol consumption during pregnancy and intima media thickness in 5-year-old children for a low-income setting.

Methods: Data were collected from 500 mother-child pairs at antenatal clinic visit, at birth, and at age 5 years. Anthropometric measurements were collected at birth and again at age 5 years. As well as clinical and ultrasound measurements at age 5 years. Clinical measurements, at age 5 years, included blood pressure, mean arterial pressure, and heart rate. Ultrasound measurements of the aorta and carotid arteries IMT were performed at age 5 years. Main outcome of interest was effect of dual teratogen exposure on the ultrasound measures IMT as indication of cardiometabolic risk.

Results: cIMT was significantly higher in children exposed to both alcohol and nicotine during pregnancy compared to those not exposed (p = .008). In separate linear models, dual in utero exposure (beta = 0.12; p = .01) and male sex (beta = 0.14; p = .01) were associated with higher right cIMT values (F(6,445) = 5.20; R² = 0.07, p < .01); male sex (beta = 0.13; p = .01) and low birth weight (beta = 0.07; p = .01) with higher left cIMT value (F(4,491) = 4.49; R² = 0.04; p = .01); and males sex (beta = 0.11; p = .02) with higher aorta IMT (F(6,459) = 5.63; R² = 0.07; p < .01). Significant positive correlations between maternal measures of adiposity, maternal MUAC (r = 0.10; p = .03), and maternal BMI (r = 0.12; p < .01) and right cIMT measurements adjusted for the BMI of the child at age 5 years as covariate. Blood pressure measurements at age 5 years were not significantly associated with IMT but, instead, correlated significantly and positively with the BMI of the child at age 5 years (p < .01).

Conclusion: Children exposed to both maternal smoking and alcohol consumption during pregnancy presented with cardiometabolic risk factors 5 years after birth. In addition, maternal adiposity, male sex, and low birth weight were associated with higher IMT at age 5 years.

Keywords: Anthropometry; cardiometabolic risk factors; intima media thickness; intrauterine teratogen exposure; pediatrics.

Figure 1.

Mean values for right carotid intima-media thickness (mm) according to the four exposure groups (p < .01) and compared between males and females at age 5 years as measured by ultrasound.

Figure 2.

Mean values for left carotid intima-media thickness (mm) compared between males and females (p< .01) at age 5 years as measured by ultrasound.