Commentary: major defects are overestimated

After reclassification of birth defects according to the system used by the Western Australian Birth Defects Registry, Kurinczuk and Bower's reanalysis of our data suggests that the 420 live born infants conceived by intracytoplasmic sperm injection were twice as likely to have a major birth defect as the general population of Western Australia. This result is considered unlikely to be due to chance.

For the cardiac malformations in particular, we think that the authors overestimate the number of major malformations. They do not take into account the fact that these malformations were found as part of an ultrasound research screening programme for the infants conceived by intracytoplasmic sperm injection. Kurinczuk and Bower made conservative estimates about the patent ductus arteriosus in six children, since we had given insufficient information to determine whether they should be included as major defects according to Australian criteria. In fact, none of the cases of patent ductus arteriosus reported as a minor anomaly was still patent at 3 months of age when the child was born at term or at 6 months of age when the child was born prematurely.

Most of the atrial septal defects were foramen ovale with small shunts, detected very early after birth by routine ultrasound examination, done for the purposes of our study. On further follow up (within several months) there was no evidence of shunt, which begs the question of whether they should even be considered as a minor malformation in the first place. For completeness of our reports, however, we mentioned them in the list of minor malformations, but we cannot agree at all that they might be categorised as major malformations.

With regard to the three ventricular septal defects, these may certainly be considered minor in the two cases where they closed spontaneously before 1 year of age. The third case had regressed at 2 months of age, but an additional examination at 1 year of age will allow a correct classification.

Kurinczuk and Bower conclude that the observation of two out of 420 children with cleft palate suggests that there might be a fivefold excess risk for cleft palate after intracytoplasmic sperm injection. We consider this a premature conclusion. Overall, the authors observed an excess of gastrointestinal defects in the infants born after intracytoplasmic sperm injection compared with the Australian population, including (in their classification) a higher number of cleft palates (two children). These two children were two non-identical twins. No family history of cleft palate was documented. The fact that the two cleft palates occurred in the same pregnancy suggests an environmental or genetic problem rather than a problem related to the procedure itself.

Genitourinary malformations were found in excess in the infants born after intracytoplasmic sperm injection compared with the Australian population; this is what we might expect, since we know that some of the fathers had a genitourinary malformation and that some of these malformations can be transmitted to offspring. In one case the son had, indeed, exactly the same form of hypospadias (with two meatus) as his father.

Recalculating the prevalence of major cardiac defects without the nine cases of atrial septal defects would give a figure of 1.1% (5/420). This is not significantly different from the 0.67% observed in the Western Australian population (odds ratio 1.786 (95% confidence interval 0.74 to 4.33)). Recalculating the prevalence of all major malformations without the cases of atrial septal defects gives a figure of 5.23% (22/420), which is higher than the 3.78% observed in the Western Australian population but is not significantly different (odds ratio 1.406 (0.91 to 2.16)). However, the number of infants born after intracytoplasmic sperm injection that have been studied is still small.

We agree that the comparison of our data with that of another population using exactly the same classification system could be useful. This must, however, be carried out with care. There is, for example, a danger of overestimation if the cohort born after intracytoplasmic sperm injection is approached differently from the general population. Further research is needed on the risks of major malformations, particularly those of the genitourinary and gastrointestinal systems,1 2 in order to prove differences and to find out if specific risk factors can be identified. A controlled study would be the best and probably the only valid scientific approach, but, for obvious reasons, it would be difficult to perform.