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Centre for Evidence-
Based Medicine

Neural Tube Defects - Vitamin A in pregnancy increases the risk

Clinical Bottom Line

Pregnant women taking supplements of vitamin A > 10,000 UI/d increase their risk of having a child with cranial-neural-crest (CNC) defect by nearly 5 times (NNH=57 with a baseline risk of 0.5%).

Citation

Rothman KJ, Moore LL, Singer MR et al. Teratogenicity of high vitamin A intake. NEJM 1995;333(21):1369-1373. .

Clinical Question

Do pregnant women receiving vitamin A supplementation have a higher risk of having children with birth defects?

Search Terms

'retinoids' and 'abnormalities' and 'pregnancy'

The Study

  1. Cohort study of pregnant women being screened by AFP or amniocentesis (23,491 out of 24,559 gave consent to participate), outcomes known for 22,748 (96.8%).
  2. Exposure assessed between week 15 and week 20 (since last menstruation) by telephone interview performed by nurse (blind to outcome) with detailed questions on diet, medications and illnesses during first trimester, allowing calculation of estimated daily Vit A intake.
  3. Outcome was obtained around expected time of delivery from obstetricians (76.5%) and mothers (23.5%) by questionnaire and then classified by blinded coders. Disagreements were submitted to a third coder.

The Evidence

Outcome EER1 CER2 RR3 (95% CI) ARI NNH (95% CI)
All birth defects 0.031 0.013 2.3 (2.36 to 2.45) 1.8% 55 (30 to 1250)
CNR defects 0.022 0.005 4.8 (2.2 to 10.5) 1.7% 59 (NNT 2044 to infinity; NNH 26 to infinity)
  1. Vit A > 15,000 IU/d
  2. Vit A ≤ 5,000 IU/d
  3. called Prevalence ratio in paper

Comments

  1. The risk is only associated with preformed vitamin A supplement not beta carotene.
  2. There was a dose-response gradient.
  3. There was no statistically significant association between cranial neural crest defects and high Vit A intake from food only.

Appraised By

O.Duperrex and R Gilbert; 05 Mar. 1999

Expiry Date

March 2000