Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study
1 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
2 Department for Child and Adolescent Psychiatry, Johannes Gutenberg-University, Mainz, Germany
3 Department of Pediatric Surgery and Urology, Centre for Child and Youth Health, Klinikum Bremen-Mitte, Bremen, Germany
4 Department of Pediatric Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany
5 Department of Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany
6 Department of Pediatric Surgery, University of Heidelberg, Heidelberg, Germany
7 Department of Pediatric Surgery, Klinikum Schwabing, Technical University Munich, Munich, Germany
8 Department of Child and Adolescent Medicine, Westküstenklinikum Heide, Heide, Germany
9 Department of Pediatric Surgery, Altonaer Kinderkrankenhaus, Hamburg, Germany
10 Department of Pediatric Surgery, University Hospital Greifswald, Greifswald, Germany
11 Malformation Monitoring Centre Saxony-Anhalt, Otto-von-Guericke University, Magdeburg, Germany
12 Department of Pediatric Surgery and Urology, University Hospital for Child and Adolescent Medicine Tübingen, Tübingen, Germany
13 SoMA e.V.; Self-help organisation for people with anorectal malformation, Munich, Germany
14 Institute of Human Genetics, University of Bonn, Bonn, Germany
15 Department of Neonatology, Children’s Hospital, University of Bonn, Bonn, Germany
Orphanet Journal of Rare Diseases 2012, 7:65 doi:10.1186/1750-1172-7-65Published: 15 September 2012
The use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births.
In total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982 controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95% confidence interval) of 8.7 (5.9–12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95% CI, 6.2–19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6–12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95% confidence intervals) were 7.7 (4.6–12.7) for singletons and 4.9 (2.4–10.1) for multiple births.
There is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.