179
population in Northern Ireland with what happened in south-east England. The programme has been in operation since 1976 and the results include those published previously2 together with subsequent deliveries up to July 31, 1989. Women who had one or previous pregnancy complicated by an NTD were given the multivitamin supplement ’Pregnavite Forte F’ (Bencard) for not more
less than 4 weeks before conception and for 6 weeks afterwards. In Northern Ireland there is total ascertainment of all women at
risk for NTD, and the outcomes of all such
who became the are whether known, 13-year study period during again pregnant they had supplements or not. In unsupplemented women there were 353 babies or fetuses, 17 of whom had an NTD, a recurrence of 48%. In women who received vitamin therapy there were 511 babies or fetuses, with 4 NTD (0-8%) (p = 0-00018, Fisher’s exact test). In south-east England there are no comparable figures for unsupplemented at-risk women, but they are at a notional 4% recurrence risk (with one, two, or even three affected pregnancies). In 457 fully supplemented babies or fetuses there were 8 NTD, a recurrence of 1-8%. Thus, in both areas the number of NTD with vitamin therapy was less than expected, but the recurrence rate in south-east England was more than twice that found in Northern Ireland. Although the difference between the two areas is not significant (p=0143), it is a trend which has been consistent right from the first published results of the multicentre trial in 1980.3 Indeed the trend has become more striking since we first commented on it in 1984,4 when recurrence-rates were 0-9% and 1’5%. Northern Ireland (high) and south-east England (low) represent the extremes of birth prevalence of NTD within the UK. Our findings show that vitamin supplementation is very effective in the primary prevention of NTD where the prevalence is high, but less so where the prevalence is lower. This finding accords with the principles of multifactorial causation, in which environmental contribution is greater in high than in low incidence areas. It may be economic not to introduce such a preventive programme into areas of low NTD prevalence, but to restrict it to high prevalence areas. The findings are also relevant to the interpretation of the Medical Research Council trial in which many participants are from countries outside the UK and with NTD prevalences lower than those of south-east England. Department of Medical Genetics, Queen’s University of Belfast, Belfast City Hospital, Belfast BT9 7AB, UK
women
N. C. NEVIN
Paediatric Research Unit,
Guy’s Hospital, London, UK 1. Smithells
MARY J. SELLER
RW, Sheppard S, Wild J, Schorah CJ. Prevention of neural tube defect in Yorkshire: final report. Lancet 1989; ii: 498-99.
recurrences
2. Seller MJ. Periconceptional vitamin supplementation to prevent recurrence of neural tube defects. Lancet 1985; i: 1392-93. 3. Smithells RW, Sheppard S, Schorah CJ, et al. Possible prevention of neural tube defects by periconceptional vitamin supplementation. Lancet 1980; i: 339-40. 4. Seller MJ, Nevin NC. Periconceptional vitamin supplementation and the prevention of neural tube defects in south-east England and Northern Ireland. J Med Genet
1984; 21: 325-30.
hospital). The frequency of hyperbilirubinaemia was significantly higher at the university hospital that at the district hospital (13% vs 3’2%, X2 test, p
population in Northern Ireland with what happened in south-east England. The programme has been in operation since 1976 and the results include those published previously2 together with subsequent deliveries up to July 31, 1989. Women who had one or previous pregnancy complicated by an NTD were given the multivitamin supplement ’Pregnavite Forte F’ (Bencard) for not more
less than 4 weeks before conception and for 6 weeks afterwards. In Northern Ireland there is total ascertainment of all women at
risk for NTD, and the outcomes of all such
who became the are whether known, 13-year study period during again pregnant they had supplements or not. In unsupplemented women there were 353 babies or fetuses, 17 of whom had an NTD, a recurrence of 48%. In women who received vitamin therapy there were 511 babies or fetuses, with 4 NTD (0-8%) (p = 0-00018, Fisher’s exact test). In south-east England there are no comparable figures for unsupplemented at-risk women, but they are at a notional 4% recurrence risk (with one, two, or even three affected pregnancies). In 457 fully supplemented babies or fetuses there were 8 NTD, a recurrence of 1-8%. Thus, in both areas the number of NTD with vitamin therapy was less than expected, but the recurrence rate in south-east England was more than twice that found in Northern Ireland. Although the difference between the two areas is not significant (p=0143), it is a trend which has been consistent right from the first published results of the multicentre trial in 1980.3 Indeed the trend has become more striking since we first commented on it in 1984,4 when recurrence-rates were 0-9% and 1’5%. Northern Ireland (high) and south-east England (low) represent the extremes of birth prevalence of NTD within the UK. Our findings show that vitamin supplementation is very effective in the primary prevention of NTD where the prevalence is high, but less so where the prevalence is lower. This finding accords with the principles of multifactorial causation, in which environmental contribution is greater in high than in low incidence areas. It may be economic not to introduce such a preventive programme into areas of low NTD prevalence, but to restrict it to high prevalence areas. The findings are also relevant to the interpretation of the Medical Research Council trial in which many participants are from countries outside the UK and with NTD prevalences lower than those of south-east England. Department of Medical Genetics, Queen’s University of Belfast, Belfast City Hospital, Belfast BT9 7AB, UK
women
N. C. NEVIN
Paediatric Research Unit,
Guy’s Hospital, London, UK 1. Smithells
MARY J. SELLER
RW, Sheppard S, Wild J, Schorah CJ. Prevention of neural tube defect in Yorkshire: final report. Lancet 1989; ii: 498-99.
recurrences
2. Seller MJ. Periconceptional vitamin supplementation to prevent recurrence of neural tube defects. Lancet 1985; i: 1392-93. 3. Smithells RW, Sheppard S, Schorah CJ, et al. Possible prevention of neural tube defects by periconceptional vitamin supplementation. Lancet 1980; i: 339-40. 4. Seller MJ, Nevin NC. Periconceptional vitamin supplementation and the prevention of neural tube defects in south-east England and Northern Ireland. J Med Genet
1984; 21: 325-30.
hospital). The frequency of hyperbilirubinaemia was significantly higher at the university hospital that at the district hospital (13% vs 3’2%, X2 test, p
