Associations of Fetal and Infant Growth Patterns with Early Markers of Arterial Health in School-Aged Children

Importance: Fetal life and infancy might be critical periods for predisposing individuals to develop cardiovascular disease in adulthood. Objective: To examine the associations of fetal and infant weight growth patterns with early markers of arterial health. Design, Setting, and Participants: This population-based prospective cohort study was conducted from early fetal life onward among 4484 offspring of women in Rotterdam, the Netherlands, delivering between April 1, 2002, and January 31, 2006. Statistical analysis was performed between January 1 and August 31, 2021. Exposures: Estimated fetal weight was measured in the second and third trimester. Data on weight and gestational age at birth were collected from midwives. Infant weight was measured at 6, 12, and 24 months. Main Outcomes and Measures: The common carotid intima-media thickness (cIMT) and carotid distensibility were measured as early markers of arterial health. Results: Follow-up measurements were available for 4484 children (2260 girls [50.4%]; median age, 9.7 years [95% range, 9.3-10.5 years]; and 2578 [57.5%] of Dutch ethnicity). Gestational age at birth was not associated with markers of arterial health. A 500-g-higher birth weight was associated with increased cIMT (standard deviation score [SDS], 0.08 mm [95% CI, 0.05-0.10 mm]) and a lower carotid distensibility (SDS, -0.05 × 10-3kPa-1; [95% CI, -0.08 to -0.03 × 10-3kPa-1]). Compared with children with a birth weight of 2500 to 4500 g, those weighing more than 4500 g had the lowest carotid distensibility (difference in SDS, -0.22 × 10-3kPa-1[95% CI, -0.42 to -0.02 × 10-3kPa-1]). Conditional regression analyses showed that higher third-trimester fetal weight and birth weight were associated with increased cIMT (difference in SDS: third-trimester fetal weight, 0.08 mm [95% CI, 0.04-0.12 mm]; birth weight, 0.05 mm [95% CI, 0.01-0.09 mm]) and that higher weight at 6, 12, and 24 months was associated with increased cIMT (difference in SDS: 6 months, 0.05 mm [95% CI, 0.01-0.10 mm]; 12 months, 0.06 mm [95% CI, 0.02-0.10 mm]; and 24 months, 0.07 mm [95% CI, 0.03-0.11 mm]) and lower carotid distensibility (difference in SDS: 6 months, -0.04 × 10-3kPa-1[95% CI, -0.09 to -0.001 × 10-3kPa-1]; 12 months, -0.05 × 10-3kPa-1[95% CI, -0.09 to -0.01 × 10-3kPa-1]; and 24 months, -0.10 × 10-3kPa-1[95% CI, -0.15 to -0.06 × 10-3kPa-1]). Compared with children with normal fetal and infant growth, children with normal fetal growth that was followed by accelerated infant growth had the highest cIMT (SDS, 0.19 mm [95% CI, 0.07-0.31 mm]) and lowest carotid distensibility (SDS, -0.16 × 10-3kPa-1[95% CI, -0.28 to -0.03 × 10-3kPa-1]). The observed associations were largely explained by childhood body mass index. Conclusions and Relevance: In this cohort study of 4484 children aged approximately 10 years, higher fetal and infant weight growth patterns were associated with early markers of impaired arterial health. Childhood body mass index seemed to be involved in the underlying pathways of the observed associations.