Abstract
Preterm birth and low birth weight are associated with brain developmental and neurocognitive outcomes in childhood; however, not much is known about the specific critical periods in fetal life and infancy for these outcomes. To examine the associations of fetal and infant growth patterns with brain morphology in children at school age. This population-based, prospective cohort study was conducted from February 1 to April 16, 2021, as a part of the Generation R Study in Rotterdam, the Netherlands. The study included 3098 singleton children born between April 1, 2002, and January 31, 2006. Fetal weight was estimated in the second and third trimesters of pregnancy by ultrasonography. Infant weight was measured at birth and at 6, 12, and 24 months. Fetal and infant weight acceleration or deceleration were defined as a change in SD scores greater than 0.67 between time points. Infant measurements also included peak weight velocity, and age and body mass index reached at adiposity peak. Brain structure, including global and regional brain volumes, was quantified by magnetic resonance imaging at age 10 years. The study evaluated 3098 children (mean [SD] age at follow-up, 10.1 [0.6] years; 1557 girls [50.3%]; and 1753 Dutch [57.8%]). One SD score-higher weight gain until the second and third trimesters, birth, and 6, 12, and 24 months was associated with larger total brain volume independently of growth during any other age windows (second trimester: 5.7 cm3; 95% CI, 1.2-10.2 cm3; third trimester: 15.3 cm3; 95% CI, 11.0-19.6 cm3; birth: 20.8 cm3; 95% CI, 16.4-25.1 cm3; 6 months: 15.6 cm3; 95% CI, 11.2-19.9 cm3; 12 months: 11.3 cm3; 95% CI, 7.0-15.6 cm3; and 24 months: 11.1 cm3; 95% CI, 6.8-15.4 cm3). Compared with children with normal fetal and infant growth, those with fetal and infant growth deceleration had the smallest total brain volume (-32.5 cm3; 95% CI, -53.2 to -11.9 cm3). Children with fetal weight deceleration followed by infant catch-up growth had similar brain volumes as children with normal growth. Higher peak weight velocity and body mass index reached at adiposity peak were associated with larger brain volumes. Similar results were observed for cerebral and cerebellar gray and white matter volumes. This cohort study's findings suggest that both fetal and infant weight growth might be critical for cerebral and cerebellar brain volumes during childhood. Whether these associations link to neurocognitive outcomes should be further studied.
Highlights
Fetal life and infancy are critical periods for human brain development.[1,2] During fetal life, and especially in the third trimester of gestation, there is an important growth in brain size
One SD score–higher weight gain until the second and third trimesters, birth, and 6, 12, and 24 months was associated with larger total brain volume independently of growth during any other age windows
Children with fetal weight deceleration followed by infant catch-up growth had similar brain volumes as children with normal growth
Summary
Fetal life and infancy are critical periods for human brain development.[1,2] During fetal life, and especially in the third trimester of gestation, there is an important growth in brain size. Fetal life and infancy are critical periods for human brain development.[1,2]. Especially in the third trimester of gestation, there is an important growth in brain size. Gestational age and weight at birth are merely the end point of fetal development and the starting point for infancy. Children born small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA) have different growth patterns.[20]. Observational studies suggest that rapid weight gain in infancy is associated with benefits to later neurocognitive functioning, especially among those born preterm or SGA; little is known about its association with brain morphology.[22-24]. Population-based studies on the associations of fetal and infant growth patterns with brain structure enable identification of windows of vulnerability for brain development
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