Maternal folic acid supplement

use in early pregnancy

and child behavioural problems

Sabine J. Roza, MD PhD

Erasmus MC

Rotterdam, the Netherlands

www.nutrimenthe.eu

� Maternal nutrition and the foetus

� Why studying folate?

� The Generation R Study

� Folic acid supplementation and behaviour

� How does folic acid influence behaviour?

� Conclusions

Overview

www.nutrimenthe.eu

Nutrition in pregnancy

The intrauterine environment ‘programmes’ the fetus forlater life

Nutrition is one of main external factors of the intrauterine

environment

Fetal organ development as well as placental development

in first trimester

www.nutrimenthe.eu

Folates

In leafy vegetables, yeast and animal products (e.g. liver)

Causes of deficiency: alcoholism, anticonvulsant medication use, pregnancy (!)

Consequences of deficiency: neural tube defects

Recommend folic acid supplement use during periconception

www.nutrimenthe.eu

The Generation R Study

� Prospective cohort design

� From early fetal life

� 7,000 mothers and children

� Detailed measures in 1,000 children

� Urban, multi-ethnic population

www.nutrimenthe.eu

Folic acid supplement use

www.nutrimenthe.eu

Folic Acid Supplement Group Mean folate level (nmol/L)

No use or start > 10 weeks (n=1031) 10.7

Start within first 10 weeks (n=1229) 18.7

Preconceptional start (n=1747) 22.7

Behavioural problems at

age 18 months

OR = Odds Ratio, CI = Confidence interval, p = p-value

All models were adjusted for age and gender, and for maternal age, maternal national

origin, maternal educational level, and maternal psychopathology during pregnancy

www.nutrimenthe.eu

Child Behaviour Checklist broadband scales

Internalizing problems Externalizing problems

Folic acid use OR (95% CI) p OR (95% CI) P

Supplement use Reference Reference

No use 1.65 (1.24 – 2.19) 0.001 1.45 (1.17 – 1.80) 0.001

Potential mechanisms

1) Direct effects of folates on brain development

www.nutrimenthe.eu

Potential mechanisms

2) Gene-environment interactions

www.nutrimenthe.eu

Folate Level

ChildBehaviour

Folic Acid Supplementation

MTHFR*

noyes?

yes

yes

?

Potential mechanisms

3) Residual confounding (epiphenomena of folic acid use)

www.nutrimenthe.eu

Conclusions

www.nutrimenthe.eu

Folic acid supplementation is recommended during thepericonceptional period, mostly because of lower risk of

neural tube defects

Folic acid supplementation leads to higher levels of folatein the blood of pregnant women

Conclusions

www.nutrimenthe.eu

Folic acid supplementation is associated to less behavioural problems in 18-month-old children

Folates influence brain growth and development directly

Women who used folic acid supplementation do probably

have healthier lifestyles compared to other women

Questions?

www.nutrimenthe.eu