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Introduction: Prenatal choline is a key nutrient, like folic acid and Vitamin D, that influences fetal brain development and subsequent offspring mental function and is being considered as a possible prenatal intervention for mental illness. An earlier double-blind randomized trial of prenatal choline supplementation showed a significant effect of prenatal choline supplementation on parent ratings of children at 40 months of age on the Attention Problems and Withdrawn Syndrome scales of the Child Behavior Checklist/1½-5 (CBCL1½-5). This study assesses whether similar associations between higher maternal choline levels and child outcomes exist in second cohort of mothers not randomized or required to take supplements. Additionally, the present study sought to expand the results of the initial trial to include mothers who had infections or used substances including nicotine and cannabis, whereas they were excluded from the initial trial.
Hypotheses: Higher maternal plasma choline concentrations will be associated with lower scores on the Attention Problems and Withdrawn Syndrome subscales on the CBCL 1 ½-5. For children of mothers who used cannabis or who had infections during pregnancy: (1) scores will be higher when compared to children of mothers without these exposures; (2) higher maternal plasma choline concentrations will be associated with lower scores.
Study population: Expectant mothers were recruited before 16 gestational weeks from an urban safety net hospital prenatal clinic. Of 183 mothers enrolled, 162 complied with gestational assessments and brought their newborns for study at 1 month of age. For assessments through 4 years of age, 83 mothers continued participation.
Method: This was a longitudinal study with participants and researchers blind to plasma choline concentrations measured at 16 weeks gestation. Choline concentrations > 7.07uM, 1 SD below the mean level obtained with choline supplements in the previous trial, were compared to lower levels. The Attention Problems and Withdrawn Syndrome scales of the CBCL 1½-5 were the principal outcomes.
Results: Children whose mothers had higher plasma choline concentrations had lower mean Attention Problems percentiles (58.5, SE 2.4) than children whose mothers had lower concentrations (65.3, SE 1.8; P = 0.050). For male children, the Withdrawn percentile was also lower if mothers had higher choline concentrations (59.2, SE 3.2, versus 68.3, SE 2.5; P = 0.007). For children of mothers who used cannabis in gestation, the Attention Problems percentile was significantly lower if mothers had higher plasma choline concentrations (59.8, SE 8.6) than if mothers had lower concentrations (78.8, SE 3.9; P = 0.024). For children of mothers who had gestational infections, the Attention Problems percentile was also lower if mothers had higher plasma choline concentrations.
Conclusions and Relevance: Prenatal choline’s positive associations with early childhood behaviors are found in a second, more diverse cohort. Increases in attention problem behaviors and social withdrawal in early childhood are associated with later mental illnesses including attention deficit disorder and schizophrenia. However, choline concentrations in the pregnant women in this study replicate other research findings suggesting that the majority of pregnant women do not meet adequate intake levels of choline from their diets.