Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study.

OBJECTIVES: To assess the risk of autism spectrum disorders (ASD) in children born after assisted conception compared with children born after natural conception. DESIGN: Population-based follow-up study. SETTING: All children born alive in Denmark 1995-2003. PARTICIPANTS: 588,967 children born in Denmark from January 1995 to December 2003. Assisted conception was defined as in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection and ovulation induction (OI) with or without subsequent insemination. Children exposed to IVF or OI were identified in the IVF Register and in the Danish Drug Prescription Register. MAIN OUTCOME MEASURES: A diagnosis of ASD in the Danish Psychiatric Central Register. RESULTS: 33,139 (5.6%) of all children born in Denmark in 1995-2003 resulted from assisted conception, 225 of whom (0.68%) had a diagnosis of ASD. Of the 555,828 children born in this period after natural conception, 3394 (0.61%) had a diagnosis of ASD. The follow-up time was 4-13 years (median 9 years). In crude analyses, children born after assisted conception had an increased risk of a diagnosis of ASD: crude hazard rate ratio (HRR) 1.25 (95% CI 1.09 to 1.43). In analyses adjusting for maternal age, educational level, parity, smoking, birth weight and multiplicity, the risk disappeared: adjusted HRR 1.13. (95% CI 0.97 to 1.31). However, subgroup analyses that suggest possible associations in women who received follicle stimulating hormone indicate the need for further study. DISCUSSION: This population-based follow-up study found no risk of ASD in children born after assisted conception.

Use of clomiphene citrate and birth defects, National Birth Defects Prevention Study, 1997-2005.

BACKGROUND: Clomiphene citrate (CC) is the first line drug for subfertility treatment. Studies assessing the association between CC and birth defects have been inconclusive. METHODS: We used data from the National Birth Defects Prevention Study, a population-based, multi-site case-control study of major birth defects. Women from 10 US regions with deliveries affected by at least one of >30 birth defects (cases) and mothers of live born infants without a major birth defect (controls) who delivered October 1997-December 2005 were interviewed. The exposure of interest was reported CC use in the period from 2 months before conception through the first month of pregnancy. Women who conceived using assisted reproductive technology were excluded. Thirty-six birth defect categories with at least three exposed cases were studied. Multiple logistic regression was used to control for potential confounders. RESULTS: CC use was reported by 1.4% of control mothers (94/6500). Among 36 case-groups assessed, increased adjusted odds ratios (aOR) were found [all: aOR, 95% confidence interval (CI)] for anencephaly (2.3, 1.1-4.7), Dandy-Walker malformation (4.4, 1.7-11.6), septal heart defects (1.6, 1.1-2.2), muscular ventricular septal defect (4.9, 1.4-16.8), coarctation of aorta (1.8, 1.1-3.0), esophageal atresia (2.3, 1.3-4.0), cloacal exstrophy (5.4, 1.6-19.3), craniosynostosis (1.9, 1.2-3.0) and omphalocele (2.2, 1.1-4.5). CONCLUSIONS: Several associations between CC use and birth defects were observed. However, because of the small number of cases, inconsistency of some findings with previous reports, and the fact that we cannot assess the CC effect separately from that of the subfertility, these associations should be interpreted cautiously.

Assisted reproductive technology and major structural birth defects in the United States.

BACKGROUND: With >1% of US births occurring following use of assisted reproductive technology (ART), it is critical to examine whether ART is associated with birth defects. METHODS: We analyzed data from the National Birth Defects Prevention Study, a population-based, multicenter, case-control study of birth defects. We included mothers of fetuses or live-born infants with a major birth defect (case infants) and mothers who had live-born infants who did not have a major birth defect (control infants), delivered during the period October 1997-December 2003. We compared mothers who reported ART use (IVF or ICSI) with those who had unassisted conceptions. Multiple logistic regression was used to adjust for the following confounders: maternal race/ethnicity, maternal age, smoking and parity; we stratified by plurality. RESULTS: ART was reported by 1.1% of all control mothers, and by 4.5% of control mothers 35 years or older. Among singleton births, ART was associated with septal heart defects (adjusted odds ratio [aOR] = 2.1, 95% confidence intervals [CI] 1.1-4.0), cleft lip with or without cleft palate (aOR = 2.4, 95% CI 1.2-5.1), esophageal atresia (aOR = 4.5, 95% CI 1.9-10.5) and anorectal atresia (aOR = 3.7, 95% CI 1.5-9.1). Among multiple births, ART was not significantly associated with any of the birth defects studied. CONCLUSIONS: These findings suggest that some birth defects occur more often among infants conceived with ART. Although the mechanism is not clear, couples considering ART should be informed of all potential risks and benefits.

Evaluation of internal alpha-particle radiation exposure and subsequent fertility among a cohort of women formerly employed in the radium dial industry.

This study examined the effect of internal exposure to alpha-particle radiation on subsequent fertility among women employed in the radium dial industry prior to 1930, when appreciable amounts of radium were often ingested through the practice of pointing the paint brush with the lips. The analysis was limited to women for whom a radium body burden measurement had been obtained and who were married prior to age 45 (n = 603). Internal radiation dose to the ovary was calculated based on initial intakes of radium-226 and radium-228, average ovarian mass, number and energy of alpha particles emitted, fraction of energy absorbed within the ovary, effective retention integrals and estimated photon irradiation. Time between marriage and pregnancy, number of pregnancies and number of live births served as surrogates for fertility. Radiation appeared to have no effect on fertility at estimated cumulative ovarian dose equivalents below 5 Sv; above this dose, however, statistically significant declines in both number of pregnancies and live births were observed. These trends persisted after multivariable adjustment for potential confounding variables and after exclusion of subjects contributing a potential classification or selection bias to the study. Additionally, the high-dose group experienced fewer live births than would have been expected based on population rates. There were no differences in time to first pregnancy between high- and low-dose groups. These results are consistent with earlier studies of gamma-ray exposures and suggest that exposure to high doses of radiation from internally deposited radium reduces fertility rather than inducing sterility.