Are Children Born After Assisted Reproductive Technology at Increased Risk of Developing An Autism Spectrum Disorder?

Background:  In the United States, assisted reproductive technology (ART) accounts for an estimated 1% of total births. In the last decade, a number of reports have suggested an increased risk of an autism spectrum disorder (ASD) in children conceived by ART. 

Objectives:  To determine the rate of infertility and ART in parents of children with an ASD in a clinical practice.

Methods: All new consultations for ASD (n=1117) from 2008-2010 for children ages 2-21 were reviewed and the rates of infertility, the use/type of assisted reproduction, and parental age were recorded. 

Results:  

A total of 159 (13.1%) parents of children with an ASD had experienced infertility, with 122 (10.0%) requiring some form of ART to conceive. This represents an 8-fold increase over the expected 1.2%. Interestingly, 21 (13.2%) parents reported prior infertility (i.e. required ART to conceive previous children) but their child in the ASD sample was conceived naturally.

Within the ART sample, 57 (46.7%) underwent ovarian stimulation alone; 51 (41.8%) underwent in vitro fertilization or intracytoplasmic sperm injection; and 14 (11.5%) underwent intrauterine insemination. In addition, 5 (4.1%) mothers reported endometriosis; 4 (3.3%) Polycystic Ovarian Syndrome; and 2 (1.6) Antiphospholipid Antibody Syndrome.

There were more multiple births within the ART sample: 31 (25.4%) sets of twins and 10 (8.2%) sets of triplets compared with the ASD sample as a whole: 76 (6.5%) sets of twins and 10 (0.8%) sets of triplets (Chi-square = 179.59, p<0.001).

The ratio of males to females in the ART sample was 6.18:1 compared with 4.74:1 in the total ASD sample. There was not a significant association between ART and Sex (Chi-square = 1.15, p = 0.28).

Parental age at conception was statistically higher for both mothers (33.6 versus 30.9 yrs) and fathers (35.5 versus 33.9 yrs) of ART/ASD children versus non-ART/ASD children, respectively (♀: t =  5.74, p < 0.001; ♂: t =  3.90, p < 0.001).

Conclusions:  While the rates of infertility in this clinical sample were not higher than what is expected in the general population, there was a significant association between ART and ASD, with an 8-fold increase of ART compared to the general population. This finding confirms a previous report by Filipek et al (2008). As expected multiple births were highly associated with ART procedures; and both maternal and paternal age was higher in the ART sample. As the use of ART increases worldwide, it is important to consider the possible risks involved, as well as the unknown potential long-term consequences for the offspring. For example, it is possible that ART procedures, including ovarian stimulation and the manipulation of gametes and preimplantation embryos, may be associated with unanticipated epigenetic changes. Large prospective studies are needed to better understand the risks associated with autism and ART.