Assisted reproductive technologies and children's neurodevelopmental status

Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland. Electronic address: .
Fertility and sterility (Impact Factor: 4.59). 02/2013; 99(2):311-7. DOI: 10.1016/j.fertnstert.2012.12.013
Source: PubMed


Initial reports suggested that children conceived with assisted reproductive technologies (ART) may be at increased risk for a spectrum of developmental disabilities. Evolving evidence suggests that some of the early risks may have been overstated when not taking plurality of birth or gestational age at delivery into consideration, as both are independent risk factors for neurodevelopmental disabilities arising from alterations in structure and function or limitations in activities. Continued research is needed to overcome lingering data gaps in light of the equivocal literature for many neurodevelopmental disabilities relative to ART, increasing utilization of services, and changes in the clinical management of infecund couples such as the adoption of natural cycles or in vitro maturation treatment options. Population-based cohorts with longitudinal assessment of the multifaceted nature of neurodevelopment across critical and sensitive windows is paramount for the development of empirically based guidance for clinical and population health.

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Available from: Germaine M. Buck Louis, Oct 02, 2014
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    • "Thirty full-text papers were evaluated further and only seven were found to meet the inclusion criteria (Table I). Of the 23 eliminated papers, six were excluded because the diagnosis of autism was not performed according to standardized criteria (ICD-10 or DSM IV-TR), or was included into broader categories of behavioural disorders (Lidegaard et al., 2005; Klemetti et al., 2006; Knoester et al., 2007; Middelburg et al., 2011; Sanchez-Albisua et al., 2011; Lyall et al., 2012), eight were excluded as they were review papers (Ludwig et al., 2006; Middelburg et al., 2008; Hvidtjorn et al., 2009b; Arpino et al., 2010; Schieve et al., 2011; Eisenberg, 2012; Wiener-Megnazi et al., 2012; Hediger et al., 2013), two as they were commentaries (Bhandari et al., 2011; Szatmari, 2011) and one conference proceedings (Rao, 2008); six papers were excluded because autism was not included in the outcome measures (Agarwal et al., 2005; Sanchez-Albisua et al., 2007; Basatemur and Sutcliffe, 2008; Steel and Sutcliffe, 2009; Pinborg et al., 2010; Kondapalli et al., 2011). Two independent blinded reviewers (E.C. and S.M.) assessed the quality of the seven selected studies utilizing the NOS scoring system both for case control and cohort studies (Table II ). "
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    ABSTRACT: Are children born after assisted reproductive technology (ART) at increased risk of autism spectrum disorders (ASD)? There is no evidence that ART significantly increases the risk of ASD in the offspring. A few systematic reviews have explored the correlation between assisted conception and ASD with inconclusive results, partly due to the heterogeneity of diagnostic criteria and methodology in the different studies. Systematic review of 7 observational studies (2 cohort and 5 case-control) encompassing 9216 subjects diagnosed with ASD published since 2000. Literature searches were conducted to retrieve observational studies on the risk of ASD in ART population. Databases searched included PubMed, EMBASE and PsycINFO. In order to obtain more consistent results, we only included the studies in which (i) subjects with either infantile autism or ASD could be identified according to international classification systems and (ii) the diagnosis was obtained from hospital records. Seven studies matched the inclusion criteria. Four out of seven studies, including the two with the best quality scores, did not show an association between ART and ASD. The two papers supporting an increased risk of autism following ART had the lowest quality scores, due to major methodological limitations. Only one paper showed a protective role of ART. In spite of the strict inclusion criteria applied as to the diagnosis of ASD, the papers selected are heterogeneous in many aspects including study design, definitions of ART, data source and analysed confounders. At present, there is no evidence that ART is significantly associated with ASD and hence that current health policies should be modified. The divergent results of some of the studies suggest that further prospective, large and high-quality studies are still needed. This work was supported, in part, by the Italian Ministry of Health and by Tuscany Region. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.
    Preview · Article · Oct 2013 · Human Reproduction
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    ABSTRACT: Interrogating the association between assisted reproductive technologies (ART) and perinatal outcome is complicated but very important. This is an introduction to a series of articles that review this potential association with an eye toward etiology of risk, and what aspects of in vitro fertilization (IVF) can be modified to reduce this risk. When an association is not due to chance (i.e., statistically significant), one must also consider how the association may be affected due to bias or confounding. Despite lack of the perfect study, perinatal consequences of ART are apparent, even though the vast majority of children conceived with ART are healthy. Pregnancy after IVF is altered as evidenced by risk of preterm delivery, low birth weight among infants, and an alerted prevalence of preeclampsia. The long-term clinical implications of ART, such as childhood development and metabolism, have not been established and ongoing study is proceeding. The risk attributed to multiple births is iatrogenic and needs to be minimized. Optimizing the environment at the time a woman conceives will likely have an effect on gestation as well as the health of children. Reproduction effects health and health effects reproduction.
    No preview · Article · Feb 2013 · Fertility and sterility
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    ABSTRACT: Critical data gaps remain regarding infertility treatment and child development. We assessed the utility of a birth certificate registry for developing a population cohort aimed at answering such questions. We utilised the Upstate New York livebirth registry (n = 201 063) to select births conceived with (n = 4024) infertility treatment or exposed infants, who were then frequency-matched by residence to a random sample of infants conceived without (n = 14 455) treatment or unexposed infants, 2008-10. Mothers were recruited at 2-4 months postpartum and queried about their reproductive histories, including infertility treatment for comparison with birth certificate data. Overall, 1297 (32%) mothers of exposed and 3692 of unexposed (26%) infants enrolled. Twins represented 22% of each infant group. The percentage of infants conceived with/without infertility treatment was similar whether derived from the birth registry or maternal report: 71% none, 16% drugs or intrauterine insemination, and 14% assisted reproductive technologies (ART). Concordant reporting between the two data sources was 93% for no treatment, 88% for ART, and 83% for fertility drugs, but differed by plurality. Exposed infants had slightly (P < 0.01) earlier gestations than unexposed infants (38.3 ± 2.8 and 38.7 ± 2.7 weeks, respectively) based upon birth certificates but not maternal report (38.7 ± 2.7 and 38.7 ± 2.9, respectively). Conversely, mean birthweight was comparable using birth certificates (3157 ± 704 and 3194 ± 679 g, respectively), but differed using maternal report (3167 ± 692 and 3224 ± 661, respectively P < 0.05). The birth certificate registry is a suitable sampling framework as measured by concordance with maternally reported infertility treatment. Future efforts should address the impact of factors associated with discordant reporting on research findings.
    Full-text · Article · Mar 2014 · Paediatric and Perinatal Epidemiology
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