title: Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.
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 to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.
authors: 1Newlife Birth Defects Research Centre,Institute of Child Health,University College London,London WC1N 1EH,UK.
authors: Nicholas D E
authors: ND
authors: Greene
authors: 1Newlife Birth Defects Research Centre,Institute of Child Health,University College London,London WC1N 1EH,UK.
authors: Kit-Yi
authors: KY
authors: Leung
authors: 1Newlife Birth Defects Research Centre,Institute of Child Health,University College London,London WC1N 1EH,UK.
authors: Victoria
authors: V
authors: Gay
authors: 1Newlife Birth Defects Research Centre,Institute of Child Health,University College London,London WC1N 1EH,UK.
authors: Katie
authors: K
authors: Burren
authors: 2Genetics, Genomics and Metabolism Programme,Institute of Child Health,University College London,London WC1N 1EH,UK.
authors: Kevin
authors: K
authors: Mills
authors: 2Genetics, Genomics and Metabolism Programme,Institute of Child Health,University College London,London WC1N 1EH,UK.
authors: Lyn S
authors: LS
authors: Chitty
authors: 1Newlife Birth Defects Research Centre,Institute of Child Health,University College London,London WC1N 1EH,UK.
authors: Andrew J
authors: AJ
authors: Copp
mesh_terms: D000328:Adult; D015331:Cohort Studies; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007294:Inositol / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use* / Q000652:urine; D039382:Maternal Nutritional Physiological Phenomena; D009436:Neural Tube Defects / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control* / Q000652:urine; D010349:Patient Compliance; D010865:Pilot Projects; D016742:Preconception Care; D011247:Pregnancy; D012008:Recurrence; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007294:Inositol; D005492:Folic Acid
keywords: FA folic acid; Folic acid supplementation; Inositol; MRC Medical Research Council; NTD neural tube defects; Neural tube defects; PONTI Prevention of Neural Tube Defects by Inositol; Pregnancy supplements