Prenatal cerebellar growth trajectories and the impact of periconceptional maternal and fetal factors.

STUDY QUESTION: CAN WE assess human prenatal cerebellar growth from the first until the third trimester of pregnancy and create growth trajectories to investigate associations with periconceptional maternal and fetal characteristics? SUMMARY ANSWER: Prenatal growth trajectories of the human cerebellum between 9 and 32 weeks gestational age (GA) were created using three-dimensional ultrasound (3D-US) and show negative associations with pre-pregnancy and early first trimester BMI calculated from self-reported and standardized measured weight and height, respectively. WHAT IS KNOWN ALREADY: The cerebellum is essential for normal neurodevelopment and abnormal cerebellar development has been associated with neurodevelopmental impairments and psychiatric diseases. Cerebellar development is particularly susceptible to exposures during the prenatal period, including maternal folate status, smoking habit and alcohol consumption. STUDY DESIGN, SIZE, DURATION: From 2013 until 2015, we included 182 singleton pregnancies during the first trimester as a subgroup in a prospective periconception cohort with follow-up until birth. For the statistical analyses, we selected 166 pregnancies ending in live born infants without congenital malformations. PARTICIPANTS/MATERIALS, SETTING,
METHODS: We measured transcerebellar diameter (TCD) at 9, 11, 22, 26 and 32 weeks GA on ultrasound scans. Growth rates were calculated and growth trajectories of the cerebellum were created. Linear mixed models were used to estimate associations between cerebellar growth and maternal age, parity, mode of conception, geographic origin, pre-pregnancy and first trimester BMI, periconceptional smoking, alcohol consumption, timing of folic acid supplement initiation and fetal gender. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 166 pregnancies provided 652 (87%) ultrasound images eligible for TCD measurements. Cerebellar growth rates increased with advancing GA being 0.1691 mm/day in the first trimester, 0.2336 mm/day in the second trimester and 0.2702 mm/day in the third trimester. Pre-pregnancy BMI, calculated from self-reported body weight and height, was significantly associated with decreased cerebellar growth trajectories (β = -0.0331 mm, 95% CI = -0.0638; -0.0024, P = 0.035). A similar association was found between cerebellar growth trajectories and first trimester BMI, calculated from standardized measurements of body weight and height (β = -0.0325, 95% CI = -0.0642; -0.0008, P = 0.045, respectively). LIMITATIONS, REASONS FOR CAUTION: As the study population largely consisted of tertiary hospital patients, external validity should be studied in the general population. Whether small differences in prenatal cerebellar growth due to a higher pre-pregnancy and first trimester BMI have consequences for neurodevelopmental outcome needs further investigation. WIDER IMPLICATIONS OF THE
FINDINGS: Our findings further substantiate previous evidence for the detrimental impact of a higher maternal BMI on neurodevelopmental health of offspring in later life. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Department of Obstetrics and Gynecology, Erasmus MC University Medical Centre and Sophia Children's Hospital Fund, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared.