Intended for healthcare professionals


Risk of congenital malformations in children born after assisted reproduction is higher than previously thought

BMJ 2010; 340 doi: (Published 15 June 2010) Cite this as: BMJ 2010;340:c3191
  1. Susan Mayor
  1. 1London

    Children born as a result of assisted reproductive technology (ART) have a higher risk of major congenital malformation than previously thought, show results from a study presented at the annual conference of the European Society of Human Genetics in Gothenburg, Sweden, on 14 June.

    The survey of all births between 2003 and 2007 at 33 centres in France registered to provide ART followed up 15 162 children, making it one of the largest studies yet to investigate the effects of fertility treatment.

    Questionnaires completed by parents and paediatricians caring for the children showed a prevalence of major congenital malformation of 4.2%, higher than the 2-3% found in previous studies. The results showed that the higher prevalence was due to a higher than expected rate of heart disease and cardiac malformations and malformations of the urogenital system. These were much more common in boys than in girls.

    Among the minor malformations angiomas were five times more common than in national data. These occurred twice as often in girls as in boys.

    Géraldine Viot, a clinical geneticist at the Maternité Port Royal Hospital, Paris, and the study’s lead author, warned that couples contemplating ART treatment should be told about the higher risk of congenital malformation. She is concerned that many doctors discuss these risks only if patients specifically ask.

    Dr Viot noted that the rate of major malformations found in the study was around double that expected from previous studies although lower than the rate of 11% found in some studies. “Given that our study is the largest to date, we think that our data are more likely to be statistically representative of the true picture,” she said.

    “We estimate that in France some 200 000 children have been born after ART, and therefore a malformation rate of this magnitude is a public health issue. At a time when infertility is increasing and more and more couples need to use ART to conceive, it is vitally important that we find out as much as we can about what is causing malformations in these children.”

    The Human Embryology and Fertilisation Authority, the independent regulator of in vitro fertilisation treatment in the United Kingdom, agreed that research into this issue is important and that patients should be informed of the risks. An authority spokesperson said, “The study showed a small but clear increase in risks of congenital abnormalities in children born as a result of IVF or ICSI [intracytoplasmic sperm injection]. The reason for this is not clear, and the risks are still very small. It is important that patients are informed about this but not alarmed by it.”

    The French study also showed that the prevalence of imprinting disorders was higher in children born after ART. These disorders are acquired as a result of a deletion on a maternal or paternal chromosome, by inheriting both chromosomes of a pair from one parent, through mutations in some imprinted genes, or by disruption in the normal pattern of methylation during zygote formation and development. One imprinting disorder, Beckwith-Wiedemann syndrome, was six times more common than in the general population, and the prevalence of retinoblastoma was 4.5 times higher.

    The French group says that the higher rate of malformation and imprinting disorders in children born as a result of ART may have several causes. More research is needed to understand the relation between congenital malformations and embryo culture media, the timing of embryo transfer, the effect of ovarian stimulation, the use of ICSI, and the freezing of gametes and embryos, Dr Viot said.

    Commenting on the need for further follow-up of children conceived after ART, Vic Larcher, consultant in general paediatrics and clinical ethics at Great Ormond Street Hospital for Children NHS Trust, London, said, “The major need is for large studies with sufficient power to link any changes in the ensuing child to the type of ART used and the details the [French] researchers mentioned.” He added: “Proper global research is needed to provide sufficient data quickly so as to counsel putative parents in the most appropriate fashion.”

    In the UK lack of approval to link NHS data on child development to use of ART has made follow-up of babies difficult, said Professor Larcher. “But increasing use of ART in the UK and elsewhere means that we really do need answers to these questions, especially if we take a ‘reasonable outcome’ view of the welfare of the child,” he said.


    Cite this as: BMJ 2010;340:c3191

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