title: Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Zwink
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Jenetzky
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schmiedeke
authors.forename: Dominik
authors.initials: D
authors.lastname: Schmidt
authors.forename: Stefanie
authors.initials: S
authors.lastname: Märzheuser
authors.forename: Sabine
authors.initials: S
authors.lastname: Grasshoff-Derr
authors.forename: Stefan
authors.initials: S
authors.lastname: Holland-Cunz
authors.forename: Sandra
authors.initials: S
authors.lastname: Weih
authors.forename: Stuart
authors.initials: S
authors.lastname: Hosie
authors.forename: Peter
authors.initials: P
authors.lastname: Reifferscheid
authors.forename: Helen
authors.initials: H
authors.lastname: Ameis
authors.forename: Christina
authors.initials: C
authors.lastname: Kujath
authors.forename: Anke
authors.initials: A
authors.lastname: Rissmann
authors.forename: Florian
authors.initials: F
authors.lastname: Obermayr
authors.forename: Nicole
authors.initials: N
authors.lastname: Schwarzer
authors.forename: Enrika
authors.initials: E
authors.lastname: Bartels
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D001003:Anal Canal / Q000002:abnormalities*; D016022:Case-Control Studies; D005858:Germany; D006801:Humans; D012007:Rectum / Q000002:abnormalities*