Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study

• Published in: PloS one 2015-10, Vol.10 (10), p.e0141089-e0141089
• Main Authors: Koning, Irene V, Groenenberg, Irene A L, Gotink, Anniek W, Willemsen, Sten P, Gijtenbeek, Manon, Dudink, Jeroen, Go, Attie T J I, Reiss, Irwin K M, Steegers, Eric A P, Steegers-Theunissen, Régine P M
• Format: Article
• Language: English
• Subjects: Acids; Adolescent; Adult; Age; Analysis; Autism; Blood; Brain; Cerebellum; Cerebellum - diagnostic imaging; Cerebellum - embryology; Cerebellum - growth & development; Child & adolescent psychiatry; Children & youth; Congenital diseases; Dietary Supplements; DNA methylation; Embryogenesis; Embryonic development; Embryonic Development - physiology; Erythrocytes; Female; Fetal Development - physiology; Fetuses; Folic acid; Folic Acid - blood; Gestational age; Growth; Gynecology; Humans; Liquid crystal displays; Menstruation; Netherlands; Obstetrics; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Studies; Systematic review; Trajectories; Ultrasonic imaging; Ultrasonography, Prenatal; Ultrasound; Vitamin B; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141089

We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: β = 0.260mm, 95%CI = 0.023-0.491, p