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Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a
Dorte Hvidtjørn1, Laura Schieve, Diana Schendel
1NANEA, Institute of Public Health, Department of Epidemiology, University of Aarhus, Paludan-Müllers vej 17, 8000 Aarhus C, Denmark. dh@soci.au.dk
Insights
Children born via in vitro fertilization (IVF) have an increased risk of cerebral palsy (CP). More research is needed on assisted conception and autism spectrum disorders (ASD) or developmental delay.
Area of Science:
- Reproductive Medicine
- Developmental Pediatrics
- Epidemiology
Background:
- Assisted conception techniques are increasingly utilized globally.
- Potential neurodevelopmental risks in children born after assisted conception require thorough investigation.
- Existing evidence linking assisted conception to cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay is fragmented.
Purpose of the Study:
- To systematically review and synthesize evidence on the association between assisted conception and neurodevelopmental outcomes.
- To assess risks of CP, ASD, and developmental delay in children conceived via assisted reproductive technologies.
- To identify gaps in current research regarding long-term outcomes of assisted conception.
Main Methods:
- Systematic literature search of PubMed and EMBASE databases (1996-2008).
- Inclusion of 41 studies comparing children born after assisted conception (e.g., in vitro fertilization (IVF), ovulation induction) with those conceived naturally.
- Studies focused on CP, ASD, and developmental delay with a minimum 1-year follow-up.
Main Results:
- Meta-analysis of 9 CP studies revealed an increased risk of CP in children born after IVF, particularly associated with preterm delivery (OR 2.18).
- Evidence regarding associations between assisted conception and ASD or developmental delay was inconsistent across 8 and 30 studies, respectively.
- No studies specifically evaluated risks of CP, ASD, or developmental delay following ovulation induction alone.
Conclusions:
- Methodological limitations in current studies hinder definitive conclusions.
- Significant knowledge gaps exist regarding the long-term neurodevelopmental outcomes of assisted conception, especially concerning ovulation induction.
- Further large-scale studies are recommended to clarify associations with ASD and developmental delay, and to investigate CP risks outside Scandinavia with detailed clinical data.
Objective:
To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay.
Data Sources:
Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008.
Study Selection:
Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more. Main Exposures In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination.
Main Outcome Measures:
Cerebral palsy, ASD, and developmental delay.
Results:
Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively.
Conclusions:
Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.
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