Cerebral Palsy, Autism Spectrum Disorders, and Developmental Delay in Children Born After Assisted Conception

NANEA, Institute of Public Health, Department of Epidemiology, University of Aarhus, Paludan-Müllers vej 17, 8000 Aarhus C, Denmark.
JAMA Pediatrics (Impact Factor: 5.73). 02/2009; 163(1):72-83. DOI: 10.1001/archpediatrics.2008.507
Source: PubMed


To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay.
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.
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.
Cerebral palsy, ASD, and developmental delay.
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.
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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Available from: Bo Jacobsson, Apr 13, 2014
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    • "Any increase in cerebral palsy must be accounted for in any studies analysing the neurodevelopment of children conceived after IVF and ICSI treatment. With regard to developmental delay, the review by Hvidtjorn et al. (2009) found that most studies demonstrated no differences in the incidence of developmental delay or delayed behavioural development when IVF-conceived children were compared with naturally conceived children. "
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    ABSTRACT: BACKGROUND Limited data exist with regard to longer-term mental health and psychological functioning of children born from IVF treatment. With the known adverse perinatal outcome for children born from IVF treatment, it would be expected that there is a negative impact upon their mental development.METHODSA search strategy restricted to studies relating to the medical condition of children of at least 1 year of age, born from IVF treatment was performed to include case series, data linkage and prospective studies published from 1 January 2000 to 1 April 2012.RESULTSLimited long-term follow-up data suggest that there is an increase in the incidence of cerebral palsy and neurodevelopmental delay related to the confounders of prematurity and low birthweight. Previous reports of associations with autism and attention-deficit disorder are believed to be related to maternal and obstetric factors. There exists a potential increase in the prevalence of early adulthood clinical depression and binge drinking in the offspring of IVF, with the reassuring data of no changes with respect to cognitive development, school performance, social functioning and behaviour. Whether these potential associations are related to the IVF treatment, the adverse obstetric outcomes associated with IVF treatment, the genetic or subsequent environmental influences on the children is yet to be determined.CONCLUSIONS In general, the longer-term mental and emotional health outcome for children born from IVF treatment is reassuring, and is very similar to that of naturally conceived children; however, further studies are required to explore any association with depression, and its causality in more detail.
    Human Reproduction Update 02/2013; 19(3). DOI:10.1093/humupd/dmt002 · 10.17 Impact Factor
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    • "An example is assisted conception. Indeed, while it was shown that in vitro fertilization and ovulation induction can result in abnormal methylation and dysregulation of imprinted genes,77 epidemiologic studies on the use of assisted reproductive technology and the risk of autism found conflicting results.78 "
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    ABSTRACT: The aim of this review is to summarize the key findings from genetic and epidemiological research, which show that autism is a complex disorder resulting from the combination of genetic and environmental factors. Remarkable advances in the knowledge of genetic causes of autism have resulted from the great efforts made in the field of genetics. The identification of specific alleles contributing to the autism spectrum has supplied important pieces for the autism puzzle. However, many questions remain unanswered, and new questions are raised by recent results. Moreover, given the amount of evidence supporting a significant contribution of environmental factors to autism risk, it is now clear that the search for environmental factors should be reinforced. One aspect of this search that has been neglected so far is the study of interactions between genes and environmental factors.
    09/2012; 14(3):281-92.
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    • "locomotor, cognitive, speech and language and behaviour) in ART children showed no differences between ART-conceived and naturally conceived singletons; when adjusted for recognized confounding factors such as low birthweight and prematurity (Koivurova et al., 2003; Place and Englert, 2003; Ponjaert-Kristoffersen et al., 2005; Leunens et al., 2008; Hvidtjørn et al., 2009). Similarly, there is no evidence of an increased risk of autism among ART children (Maimburg and Vaeth, 2007; Hvidtjørn et al., 2009, 2011). Current evidence suggests that the ART process itself does not lead to an increased risk of adverse neuro-cognitive outcomes or autism. "
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    ABSTRACT: There is a large population of children conceived via assisted reproductive technology (ART), which continues to increase worldwide, without a clear understanding of associated long-term outcomes. ART children are more likely to be the result of multiple pregnancies, and thus to be born prematurely or low birthweight. There is growing evidence that ART children are phenotypically and biochemically different from naturally conceived children, but the mechanism(s) leading to these changes have not been elucidated. There is a possible increased risk of rare imprinted gene disorders in these children. However, it remains unclear whether more subtle changes in DNA methylation occur commonly, leading to differences in gene expression and phenotype in ART children. Although an increased risk of cancer among ART children has been reported, the role of ART in the development of cancer has not been demonstrated. Further research and ongoing surveillance of ART children is essential to better understand the possible effects of ART on the long-term health of this population.
    Human Reproduction 06/2011; 26(9):2392-400. DOI:10.1093/humrep/der212 · 4.57 Impact Factor
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