Folate intake in pregnancy and psychomotor development at 18 months

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Note: for non-commercial purposes only Folate intake in pregnancy and psychomotor development at 18 months Charlotta Granström Susanne Petersen Marin Strøm Thorhallur I Halldorsson Emily Oken Sjurdur F Olsen

Hypothesis & background Hypothesis Low folate intake in pregnancy is a risk factor for delayed cognitive development in the child Background Several studies have suggested that low folate status in the elderly is associated with early cognitive decline, possibly via vascular mechanisms Studies in rodents have shown associations of maternal folate deficiency with structural brain abnormalities and poor postnatal learning ability in the offspring A recent observational study from South India showed an inverse association between low serum folate in pregnancy and poorer cognitive scores at 9-10 year old offspring (Veena et al. J Nutr 2010)

Objective Study the association between maternal intake of dietary folate during pregnancy and psychomotor development in children at 18 months using the Danish National Birth Cohort (DNBC)

The Danish National Birth Cohort All pregnant women in Denmark 1996-2002 100% 100% Appr. 30 % do not receive an invitation Appr. 60 % receive an invitation Appr. 10% do not fulfill inclusion criteria 100% Appr. 40% choose not to participate Appr. 60 % are enrolled in the study Total: 101.042 participants 1st interview: 92.892 obs. 92% of total FFQ: 66.874 obs. 66 % of total 3rd interview: 70.296 obs. 70 % of total 4th interview: 65.764 obs. 65 % of total 2nd interview: 87.802 obs. 87 % of total

Data material 34649 children born to mothers participating in the DNBC - 360-item Food Frequency Questionnaire in mid-pregnancy (gestation week 25) estimated intake of dietary folate - 4th interview with the mother 18 months after birth child developmental scores Conception Gestational week 12 Gestational week 25 Gestational week 30 Delivery 6 months after delivery 18 months after delivery 1st telephone interview Food Frequency Questionnaire 2nd telephone interview 3rd telephone interview 4th telephone interview Estimated dietary folate intake Information on folic acid intake from supplements Derived Child Developmental Scores

Child development scores (CDS) Remove socks and shoes - (yes/no) Drink from a cup - (yes/no) Be occupied fo 15 min without adult participation - (yes/no) Fetch an object when requested - (yes/no) Write or draw - (yes/no) Orient a book correctly - (yes/no) Use word-like sounds - (yes/no) Put two words together - (yes/no) Say more than 60 words - (yes/no) Yes: 1 point No: 0 points CDS = sum of points Maximum possible CDS: 9

Statistical method Multivariate cumulative ordinal logistic regression Modelling the OR of obtaining a given CDS or higher Adjustment for non-dietary confounders: smoking, physical activity, socioeconomic status, BMI, age at birth, parity

Maternal folate intake deriving from dietary sources (mcg/day) N Mean Median Std Dev Quintile1 (lowest) 6941 265.4 271.7 24.7 Quintile 2 7070 311.1 311.3 9.2 Quintile 3 6967 341.4 341.3 8.7 Quintile 4 6956 375.2 374.5 11.3 Quintile 5 (highest) 6715 448.2 431.5 55.9 Overall 34649 347.5 340.5 67.3

Scores in relation to maternal intake of dietary folate Q1 Q2 Q3 Q4 Q5 (ref) OR (95% CI) for higher CDS 1,10 1,00 0,90 0,80 0,70 0,60 0,50 Crude Adj for fish Adj for breastfeeding Non-dietary covariates; smoking, physical activity, socioeconomic status, BMI, age at birth, parity Adj for nondietary covariates

Scores in relation to maternal intake of folic acid from supplements Q1 Q2 Q3 Q4 Q5 (ref) OR (95% CI) for higher CDS 1,20 1,10 1,00 0,90 0,80 0,70 0,60 0,50 Crude Adj for fish Adj for breastfeeding Non-dietary covariates: smoking, physical activity, socioeconomic status, BMI, age at birth, parity Adj for nondietary covariates

1,20 1,10 1,00 0,90 0,80 0,70 0,60 0,50 Dietary folate from different sources Unadjusted Q1 Q2 Q3 Q4 Q5 (ref) Lowfat Highfat Wholegrain Fruit Eggs Green veg. Onions Cheese Tomatoes OR (95% CI) for higher CDS

1,20 1,10 1,00 0,90 0,80 0,70 0,60 0,50 Dietary folate from different sources Adjusted for all covariates Q1 Q2 Q3 Q4 Q5 (ref) Lowfat Highfat Wholegrain Fruit Eggs Green veg. Onions Cheese Tomatoes OR (95% CI) for higher CDS

Maternal folate intake deriving from green vegetables, onions and tomatoes (mcg/day) Green vegetables Onions Tomatoes N Mean Median Std Dev N Mean Median Std Dev N Mean Median Std Dev Quintile 1 6648 4.6 4.8 2.3 6804 1.2 1.3 0.4 6492 1.1 1.2 0.4 Quintile 2 7024 11.6 11.6 2.0 7022 2.5 2.5 0.3 6980 2.3 2.3 0.3 Quintile 3 7040 19.2 19.0 2.5 7120 3.7 3.7 0.4 7081 3.6 3.6 0.4 Quintile 4 7041 30.2 29.8 4.1 6978 5.5 5.4 0.7 7067 5.5 5.4 0.7 Quintile 5 6896 62.9 53.6 28.9 6725 10.9 9.2 5.4 7029 11.6 9.5 6.0 Overall 34649 25.8 19.2 24.2 34649 4.7 3.7 4.1 34649 4.9 3.7 4.6

Main findings Association between higher maternal dietary folate intake and higher CDSs No association between higher folic acid intake from supplements and higher CDSs Association between higher CDSs and dietary folate intake from onions, tomatoes, and green vegetables No association between higher CDSs and dietary folate intake from whole grain, dairy products, and eggs

Conclusion The associations between maternal dietary folate intake and early psychomotor development may not be due to folate, but may instead be attributed to other nutrients which coexist with folate in specific food groups

Thank you