The risk for four specific congenital heart defects associated with assisted reproductive techniques: a population-based evaluation

STUDY QUESTION Are the risks of hypoplastic left heart syndrome, transposition of great arteries, tetralogy of Fallot (TOF) and coarctation of the aorta increased in infants conceived by different assisted reproductive techniques (ARTs)? STUDY ANSWER ARTs, and particularly intracytoplasmic sperm inj...

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Published in:Human reproduction (Oxford) 2013-02, Vol.28 (2), p.367-374
Main Authors: Tararbit, Karim, Lelong, Nathalie, Thieulin, Anne-Claire, Houyel, Lucile, Bonnet, Damien, Goffinet, François, Khoshnood, Babak
Format: Article
Language:English
Subjects:
Adult
Aortic Coarctation - etiology
Aortic Coarctation - genetics
Case-Control Studies
Chromosome Aberrations
Cohort Studies
Female
Heart Defects, Congenital - etiology
Heart Defects, Congenital - genetics
Humans
Hypoplastic Left Heart Syndrome - etiology
Hypoplastic Left Heart Syndrome - genetics
Infant, Newborn
Logistic Models
Male
Registries
Reproductive Techniques, Assisted - adverse effects
Risk Assessment
Tetralogy of Fallot - etiology
Tetralogy of Fallot - genetics
Transposition of Great Vessels - etiology
Transposition of Great Vessels - genetics
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Summary:STUDY QUESTION Are the risks of hypoplastic left heart syndrome, transposition of great arteries, tetralogy of Fallot (TOF) and coarctation of the aorta increased in infants conceived by different assisted reproductive techniques (ARTs)? STUDY ANSWER ARTs, and particularly intracytoplasmic sperm injection (ICSI), are specifically associated with a higher risk of TOF. WHAT IS ALREADY KNOWN ARTs are associated with an increase in the overall risk of birth defects. The risk for congenital heart defects (CHDs) associated with ARTs has been evaluated as a whole but there is limited information on the risks for specific CHDs. STUDY DESIGN, MATERIAL AND METHODS We conducted a case–control study using population-based data from the Paris registry of congenital malformations for the period 1987–2009 and a cohort study of CHD (EPICARD) on 1583 cases of CHDs and 4104 malformed controls with no known associations with ARTs. ARTs included ovulation induction only, IVF and ICSI. RESULTS Exposure to ARTs was significantly higher for TOF than controls (6.6 versus 3.5%, P = 0.002); this was not the case for the other three CHDs. ARTs (all methods combined) were associated with a 2.4-fold higher odds of TOF after adjustment for maternal characteristics, paternal age and year of birth [adjusted odds ratios (OR): 2.4, 95% confidence interval (CI): 1.5–3.7] with the highest risk associated with ICSI (adjusted OR: 3.0, 95% CI: 1.0–8.9). No statistically significant associations were found for the other CHDs. LIMITATIONS Our study cannot disentangle to what extent the observed associations between the risk of TOF and ARTs are due to causal effects of ARTs and/or the underlying infertility problems of couples who conceive following ART. IMPLICATIONS The developmental basis of the specific association between the risk of TOF and ARTs need to be further investigated. FUNDING This work was supported by grants from the Agence de Biomédecine (Saint-Denis La Plaine, France) (to B.K.). The Paris Registry of Congenital Malformations received financial support from INSERM (Paris, France) and the Institut de Veille Sanitaire (Saint-Maurice, France). The EPICARD study was supported by three grants from the Ministry of Health (PHRC 2004, 2008 and 2011). Additional funding for the EPICARD study was provided by the AREMCAR Association (Association pour la Recherche et l'Etude des Maladies Cardiovasculaires). COMPETING INTERESTS None.
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/des400