Birth defects are preventable

Scientific director of the Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary

Birth defects – or by according to the World Health Organization’s term: congenital anomalies – are structural, functional and/or biochemical-molecular defects preset at birth whether detected at that time or not. Among different categories of birth defects, congenital abnormalities (CAs), i.e. structural-morphological defects represent the largest one.

CAs have two main characteristics: (i) defects conditions with a limited chance for complete recovery and (ii) the earliest (fetal or birth) onset. Thus, there is only one optimal medical solution for CAs and it is the prevention. It is worth differentiating three levels of prevention (Table 1), however, the efficacy of primary prevention was limited before 1990 (1).

There was a breakthrough in the primary prevention of CAs in the 1990s and it was connected with the introduction of periconceptional folic acid or folic acid-containing multivitamin supplementation. First the prevention of recurrent neural-tube defects (NTD) by folic acid (0.36 mg) containing multivitamin used during at least one month before and three months (i.e. periconceptional period) was shown in a non-randomized intervention study (Table 2) (2, 3). However, the results of this study were not accepted by some experts due to the possible social selection. Thus, Medical Research Council (UK) organized a multicenter international randomized controlled trial (RCT) in which 43 % of participants came from Hungary which indicated the efficacy of large pharmacological (4 mg) dose of folic acid in the prevention of recurrent NTD (Table 2) (4).

I established the so-called periconceptional care including (i) the check-up of reproductive health, (ii) the 3-month preparation for conception and (iii) a better protection for early pregnancy for potential parents in Hungary on l984 (5). This new health care system offered an opportunity to organize RCT to check the efficacy of a multivitamin (Table 3) containing physiological dose of folic acid (less than 1 mg) for the prevention of the first occurrence of NTD. About 95 % of women with NTD offspring have no previous NTD pregnancies, thus the prevention of first occurrence of NTD has a real public health importance. Our results proved first the efficacy of this multivitamin for the primary prevention of first occurrence of NTD (Table 4) (6). In addition, our study indicated a significant reduction in the rate of total CAs after the exclusion of NDT offspring as well (Table 5) (7) and it was explained by the primary prevention of cardiovascular CAs and CAs of urinary tract, furthermore by some reduction of congenital limb deficiencies and pyloric stenosis (8).

The possible primary prevention of NTD by this new simple method was accepted by the enthusiasm of the scientific community, but the possible prevention of other CAs raised some doubt. Thus we decided to organize another intervention trial and it was the cohort controlled trial (CCT) using the same multivitamin (because it was not possible to continue the RCT due to ethical reason). The supplemented cohort included the participants of periconceptional care, while unsupplemented cohort comprised of participants of early pregnant women from regional antenatal care matched to age, socioeconomic status and region without folic acid or multivitamin use before the 12th week of gestation. Unfortunately a serious methodological problem was detected at the evaluation of CCT data: the proportion of pregnant women at high risk was much larger in the supplemented than in the unsupplemented cohort (Table 6). The explanation was the good reputation of periconceptional care in Hungary, potential pregnant women at high risk preferred this new health care system. On the contrary of this unbalanced study groups, of 3,056 pairs, 1 and 9 had NTD in the supplemented and