Inositol for the prevention of neural tube defects: a pilot randomised controlled trial

The British Journal of Nutrition
Q1
Feb 2016
Citations:50
Influential Citations:4
Interventional (Human) Studies
81
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Enhanced Details

Methods
UK-based double-blind randomized controlled pilot trial; participants were women aged 18–40 with a history of a prior neural tube defect (NTD)-affected pregnancy planning to become pregnant again; exclusion criteria included inability to consent or lack of GP/obstetrician, prior child with additional anomalies, epilepsy or anti-epileptic use. Fifty women were randomised (25 per arm) to receive inositol + FA or placebo + FA; an additional non-randomised group (n=52) was followed for peri-conceptional regimens and outcomes.
Intervention
Randomised group: myo-inositol 1 g daily (two 500 mg tablets) plus folic acid 5 mg daily; started preconception and continued until end of the 12th post-menstrual week; unsupervised at home. Control: placebo 1 g daily (two tablets) plus folic acid 5 mg daily; started preconception and continued until end of the 12th post-menstrual week; unsupervised at home. Non-randomised group: peri-conceptional supplementation with inositol + FA at doses from 0.5–1.35 g/day (most 1 g/day), started preconception and continued through early pregnancy; folic acid 5 mg/day; taken as prescribed.
Results
Among randomized pregnancies with outcomes (n=33): 0/14 NTD recurrences in the inositol + FA group vs 1/19 in the placebo + FA group. Across all randomized pregnancies, 1 NTD occurred in the FA-alone arm and none in the inositol arm. Among non-randomised pregnancies (n=23 with inositol + FA; plus 3 with FA alone), there were 2 NTD recurrences (both anencephaly). Overall, 3 NTD recurrences among 57 established pregnancies (5.3%). No safety concerns linked to inositol in pregnancy. Larger, powered trials are warranted, but recruitment willingness to randomize is a major challenge; alternative trial designs (e.g., cluster or sequential designs) may be needed; results suggest potential additional protection from inositol beyond FA for FA-non-responsive NTD.
Limitations
Small sample size; pilot design not powered to detect recurrence differences; recruitment reluctance to randomize led to substantial nonrandomised data; dosing varied in the non-randomised group (0.5–1.35 g/day); reliance on self-reported outcomes; limited generalizability beyond UK high-risk women.

Abstract

Abstract Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach...