Irish research puts low folic acid link to cleft palate beyond all doubt

By Muiris Houston

ANALYSIS: A large study on 11,000 infants will raise international interest and stimulate debates on how best to respond

THE FINDING of a significant link between poor folic acid intake and the development of cleft lip and palate (CLP) underlines the value of long-term health research in the Republic.

The Growing Up in Ireland study, a national project led by Trinity College Dublin and the Economic and Social Research Institute (ESRI), is collecting data on more than 11,000 babies and follows them as they grow older. It is producing a rich vein of original data which can be mined and explored by various researchers.

While it had been thought likely that folic acid had a role beyond that of the developing neural tube and the risk of spina bifida, previous research had failed to establish any significant linkage.

Indeed, a recent Cochrane review of the effect of folic acid on cleft lip or cleft palate found insufficient evidence to support the protective effect of folic acid. This was largely owing to insufficient numbers of cases of the defect occurring in the trials.

There is a higher than normal prevalence of CLP among pregnant women taking drugs that work against folic acid in the body, such as the anti-epilepsy agents phenytoin and phenobarbitone – an association which has long hinted at folic acid having a role in preventing CLP.

But now this large study, to be published in the British Journal of General Practice, has put the issue beyond doubt. The results will cause a ripple internationally and are likely to stimulate debate among public health specialists and general practitioners about how best to respond.

It’s a major coup for TCD’s department of public health and primary care. And the substantial long-term funding provided by the Department of Health, through the Office of the Minister for Children, must be acknowledged.

By mining the data, research student Dervla Kelly and her colleagues hit a rich seam of information connecting expectant mothers’ folic acid intake and the prevalence of CLP.

A cleft lip is a separation in the upper lip, while a cleft palate is an opening in the roof of the mouth.

Clefts result from incomplete development of the lip and/or palate in the early weeks of pregnancy. A cleft lip and palate occurs in approximately one in 700 live births. Cleft lip, with or without cleft palate, is most frequent in boys and isolated cleft palate is most common in girls.

The condition causes significant morbidity: the effects on an individual’s speech, hearing and appearance, along with psychological effects, can lead to long-lasting adverse outcomes for health and wellbeing.

Even when repaired, complications such as persistent ear infections, speech impairments, facial deformities and dental problems often persist.

Now there is an opportunity to prevent at least some cases of CLP. A daily folic acid tablet of 0.4mg taken four weeks before conception and in the first 12 weeks of pregnancy will reduce the risk of CLP by a factor of four, representing a major reduction in future morbidity.

However, there are a number of challenges to be overcome. It is estimated that up to 50 per cent of pregnancies in Ireland are unplanned, thereby denying these women the opportunity to take supplements pre-conceptually. In addition, for those planning pregnancy, it is not unusual for a baby to reach six weeks of gestation before the pregnancy is confirmed.

This opens up the old chestnut of food supplementation for the wider population. Fortifying bread with folic acid has been mooted here before.

With this new evidence of the additional benefits of folic acid, we can expect a public debate on the pros and cons of mandatory food additives. As water fluoridation has proved, these debates are rarely boring.