Association of Gestational Age at Birth With Brain Morphometry

Abstract

estational age at birth (GAB) is an important determinant of child health and development. Worldwide, approximately 13 million newborns are born preterm (GAB<37 weeks) annually. 1 Prematurity is associated with morbidity and mortality, 2,3 including neurodevelopmental problems, such as cerebral palsy, intellectual disability, learning disability, and poor motor development. [4][5][6] Preterm birth is reportedly associated with increased risks of attention-deficit/ hyperactivity disorder (ADHD), autism spectrum disorder, [7][8][9] and psychiatric disorders in adulthood. 10 In some countries, postterm birth (GAB≥42 weeks) accounts for up to 10% of births 11 and is associated with adverse birth outcomes, in-creased neonatal mortality, cognitive impairment, and increased risk of ADHD. 12 Few studies 13,14 have investigated the associations of GAB with brain structures despite the dynamic neurodevelopment that occurs during early life. During the third trimester of gestation, there is a 4-fold increase in brain size accompanied by marked growth of brain surface area, resulting in the emergence of sulci and gyri. 15,16 Thus, birth before the presumed optimal gestational duration (approximately 40 weeks) may be associated with disruption of neurodevelopmental processes in late pregnancy that persist during postnatal life. 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 PARTICIPANTSThis 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. EXPOSURESThe GAB was calculated based on ultrasonographic assessment of crown-rump length (<12 weeks 5 days) or biparietal diameter (Ն12 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. RESULTSIn 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 cm 3 /wk (95% CI, 2.7-6.3 cm 3 /wk) larger total...

Neurodevelopmental impairment is associated with altered white matter development in a cohort of school-aged children born very preterm

“…However, the difference in subcortical grey matter between the two groups was not robust enough to survive corrections for multiple comparisons, nor did it remain following adjustment for total brain volume. It is possible that we observed fewer volumetric differences between those with and without NDI among children who were all born < 30 weeks gestation than may have been detected had we included a full-term control group, as throughout childhood and adolescence those born preterm consistently have smaller brain volumes than those born at term ( de Kieviet et al, 2012 , El Marroun et al, 2020 ). Nonetheless, brain tissue volumes have been positively associated with IQ and motor function in VPT children in other cohorts ( Monson et al, 2016 , Loh et al, 2017 ), although these associations were not robust to multiple comparison correction in the current investigation.…”

“…Children born before 32 weeks’ gestation (very preterm, VPT) have higher rates of neurodevelopmental disability ( Blencowe et al, 2013 ) and greater individual estimated cost of care through the childhood years ( Petrou and Khan, 2012 ) than those born preterm at more mature gestations, and higher rates of cerebral palsy, cognitive delay, motor delay ( Pascal et al, 2018 ), psychiatric symptoms ( Botellero et al, 2017 ) and social difficulties ( Lund et al, 2012 ) than those born at term. Magnetic resonance imaging (MRI) studies show those born VPT have altered brain maturation, including brain volume ( de Kieviet et al, 2012 , Lax et al, 2013 , El Marroun et al, 2020 ) and white matter microstructure. ( Li et al, 2015 , Travis et al, 2015 ) However, it is unclear which specific brain regions have altered maturation in the 30 percent of VPT children with neurodevelopmental impairment (NDI).…”

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

“…Consistent with this, lower GA at birth, birthweight Z-score, longer requirement for respiratory support and TPN were related to reduced TTV and enlarged CSF/ventricles in both preterm cohorts. Longitudinal studies suggest that these effects are not only evident at TEA but might persist to childhood and later life (Nosarti 2002; Allin et al 2004; Ment et al 2009; de Kieviet et al 2012; El Marroun et al 2020). Not all extremely preterm infants had TTV deviations significantly below the model mean, which could explain the discrepancies found between previous group analyses studying the association between preterm birth and reduced brain volume.…”

Effects of gestational age at birth on perinatal structural brain development in healthy term-born babies

“…These studies all report similar results, namely lower fractional anisotropy (FA) and higher mean diffusivity (MD) in infants born earlier in the term period. Associations of gestational age at birth (GAAB) with MRI features in term only populations have also been reported in later childhood, including lower total brain volume in a cohort of 10 year old children (El Marroun et al, 2020), and a positive association of GAAB with functional connectivity in a cohort of 6-10 year olds (Kim et al, 2014).…”