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ABSTRACT: To assess the risk of autism spectrum disorders (ASD) in children born after assisted conception compared with children born after natural conception.
Population-based follow-up study.
All children born alive in Denmark 1995-2003.
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.
A diagnosis of ASD in the Danish Psychiatric Central Register.
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.
This population-based follow-up study found no risk of ASD in children born after assisted conception.
Journal of epidemiology and community health 06/2011; 65(6):497-502. · 3.04 Impact Factor
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ABSTRACT: This paper assesses the risk of cerebral palsy (CP) in children born after assisted conception compared with children born after natural conception (NC).
This population based follow-up study included all 588,967 children born in Denmark from 1995 to 2003. Assisted conception was defined as IVF, with or without ICSI, and ovulation induction (OI), with or without subsequent insemination.
There were 33 139 (5.6%) children born in Denmark from 1995 to 2003 as a result of assisted conception and through to June 2009, 1146 (0.19%) children received a CP diagnosis. Children born after assisted conception had an increased risk of a CP diagnosis, crude hazard rate ratio (HRR) 1.90 (95% CI: 1.57-2.31) compared with NC children. Divided into IVF and OI children compared with NC children, the risk was HRR 2.34 (95% CI: 1.81-3.01) and HRR 1.55 (95% CI: 1.17-2.06), respectively. When we included the intermediate factors multiplicity and gestational age in multivariate models, the risk of CP in assisted conception disappeared. In general, children with CP born after assisted conception had similar CP subtypes and co-morbidities as children with CP born after NC.
The risk of CP is increased after both IVF and OI. The increased risk of CP in children born after assisted conception, and in particular IVF, is strongly associated with the high proportion of multiplicity and preterm delivery in these pregnancies. A more widespread use of single embryo transfer warrants consideration to enhance the long-term health of children born after IVF.
Human Reproduction 08/2010; 25(8):2115-23. · 4.47 Impact Factor
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ABSTRACT: An increasing number of children are born after assisted conception and in surveillance programmes information on mode of conception is often achieved via maternal self-report. We assessed the validity of self-reported assisted conception in The Danish National Birth Cohort (DNBC), a prospective pregnancy cohort. Here, the term assisted conception refers to IVF, ICSI, ovulation induction and insemination.
We compared self-reported assisted conception in the DNBC to corresponding data from Danish national registers; the IVF Register and Danish Drug Prescription Register, providing method of conception in the entire population. In the DNBC, 101,042 women accepted the invitation in early pregnancy from 1996 to 2002. Our final study population comprised 88,151 DNBC women aged 20 years and older who participated in the first DNBC interview with a pregnancy resulting in a live born child.
In the DNBC, assisted conception was reported with a sensitivity of 83% and positive predictive value of 88%. Misclassification was largely explained by ambiguous phrasing of the DNBC interview question and interview skip patterns. Women with false negative reporting were more often multipara (P < 0.001) and older (P = 0.027 for IVF/ICSI and P = 0.002 for ovulation induction). The risk ratio (RR) for being born preterm in IVF/ICSI children was lower for children identified via the DNBC, RR 3.61 (95% confidence interval (CI) 3.31-3.94), than the IVF Register, RR 4.36 (95% CI 4.02-4.74).
There was a high positive predictive value of self-reported assisted conception in the DNBC, but the structure of the DNBC interview represented a problem and misclassification could introduce bias.
Human Reproduction 06/2009; 24(9):2332-40. · 4.47 Impact Factor
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ABSTRACT: To investigate the association of asphyxia-related conditions (reducing blood flow or blood oxygen levels in the fetus) with spastic cerebral palsy (CP) considering different gestational age groups and the timing of risk.
Population-based case-control study.
Danish Cerebral Palsy Register in eastern Denmark and Danish Medical Birth Register.
271 singletons with spastic CP and 217 singleton controls, frequency matched by gestational age group, born 1982-1990 in eastern Denmark.
Data were abstracted from medical records, and a priori asphyxia-related conditions and other risk factors were selected for analysis. Each factor was classified according to the time at which it was likely to first be present.
Spastic CP.
Placental and cord complications accounted for the majority of asphyxia conditions. In multivariate analysis, placental infarction was significantly associated with a four-fold increased risk for spastic quadriplegia and cord around the neck was significantly associated with a three-fold increased risk for spastic CP overall. The combination of placental infarction and being small for gestational age (SGA) afforded an especially high risk for spastic quadriplegia. Placental and cord complications were present in 21% of cases and 12% of controls.
The risk for spastic quadriplegia from placental infarction may be linked in some cases with abnormal fetal growth (17% of all children with spastic quadriplegia and 3% of control children both had an infarction and were SGA) -- suggesting an aetiologic pathway that encompasses both factors. The risk for spastic CP from cord around the neck is not accounted for by other prepartum or intrapartum factors we examined. Considering the relative timing of risk factors provides a useful framework for studies of CP aetiology.
BJOG An International Journal of Obstetrics & Gynaecology 12/2008; 115(12):1518-28. · 3.41 Impact Factor
