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Original Investigation
September 21, 2020

Association of Gestational Age at Birth With Brain Morphometry

Author Affiliations
  • 1Department of Child and Adolescent Psychiatry, University Medical Center Rotterdam, Erasmus Medical Center, Rotterdam, the Netherlands
  • 2Department of Pediatrics, University Medical Center Rotterdam, Erasmus Medical Center, Rotterdam, the Netherlands
  • 3Department of Psychology, Education and Child Studies, Erasmus School of Social and Behavioral Sciences, Erasmus University, Rotterdam, the Netherlands
  • 4Department of Obstetrics and Gynaecology, University Medical Center Rotterdam, Erasmus Medical Center, Rotterdam, the Netherlands
  • 5Department of Pediatrics, Division of Neonatology, University Medical Center Rotterdam, Erasmus Medical Center, Rotterdam, the Netherlands
  • 6Department of Psychiatry, University Medical Center Rotterdam, Erasmus Medical Center, Rotterdam, the Netherlands
  • 7Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
JAMA Pediatr. Published online September 21, 2020. doi:10.1001/jamapediatrics.2020.2991
Key Points

Question  Is there an association of gestational age at birth with structural brain morphometry in childhood?

Findings  In this population-based cohort study of 3079 singleton children, gestational duration was associated with global and regional brain volumes 10 years after birth and these linear associations persisted when the sample was restricted to term-born children. Consistent with the rapid expansion of brain volume during the third trimester, gestational age at birth was associated with more gyrification and cortical surface area.

Meaning  Gestational duration may be important for long-term neurodevelopment and should be considered a continuum of development throughout pregnancy.

Abstract

Importance  Preterm and postterm births are associated with adverse neuropsychiatric outcomes. However, it remains unclear whether variation of gestational age within the 37- to 42-week range of term deliveries is associated with neurodevelopment.

Objective  To investigate the association of gestational age at birth (GAB) with structural brain morphometry in children aged 10 years.

Design, Setting, and Participants  This population-based cohort study included pregnant women living in Rotterdam, the Netherlands, with an expected delivery date between April 1, 2002, and January 31, 2006. The study evaluated 3079 singleton children with GAB ranging from 26.3 to 43.3 weeks and structural neuroimaging at 10 years of age from the Generation R Study, a longitudinal, population-based prospective birth cohort from early pregnancy onward in Rotterdam. Data analysis was performed from March 1, 2019, to February 28, 2020, and at the time of the revision based on reviewer suggestions.

Exposures  The GAB was calculated based on ultrasonographic assessment of crown-rump length (<12 weeks 5 days) or biparietal diameter (≥12 weeks 5 days) in dedicated research centers.

Main Outcomes and Measures  Brain structure, including global and regional brain volumes and surface-based cortical measures (thickness, surface area, and gyrification), was quantified by magnetic resonance imaging.

Results  In the 3079 children (1546 [50.2%] female) evaluated at 10 years of age, GAB was linearly associated with global and regional brain volumes. Longer gestational duration was associated with larger brain volumes; for example, every 1-week-longer gestational duration corresponded to an additional 4.5 cm3/wk (95% CI, 2.7-6.3 cm3/wk) larger total brain volume. These associations persisted when the sample was restricted to children born at term (GAB of 37-42 weeks: 4.8 cm3/wk; 95% CI, 1.8-7.7 cm3/wk). No evidence of nonlinear associations between GA and brain morphometry was observed.

Conclusions and Relevance  In this cohort study, gestational duration was linearly associated with brain morphometry during childhood, including within the window of term delivery. These findings may have marked clinical importance, particularly given the prevalence of elective cesarean deliveries.

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