To determine whether subsequent births after short and long interpregnancy intervals (IPIs) are associated with risk of autism spectrum disorder (ASD).
We assessed the association between IPI and ASD risk in a cohort of 45 261 children born at Kaiser Permanente Northern California (KPNC) between 2000 and 2009. Children with ASD were identified from International Classification of Diseases, Revision 9 diagnostic codes 299.0, 299.8, and 299.9 recorded in KPNC electronic medical records. IPI was defined as the time from the birth of the first child to the conception of the second child. Survival analysis and logistic regression models were used to evaluate the association between IPI and risk of ASD in second-born children.
Children born after an IPI of <12 months or ≥72 months had a 2- to 3-fold increased ASD risk compared with children born after an interval of 36 to 47 months. Respective adjusted hazard ratios (95% confidence intervals) were as follows: <6 months, 3.0 (1.9–4.7); 6 to 8 months, 2.1 (1.4–3.3); 9 to 11 months, 1.9 (1.3–2.1); 12 to 23 months, 1.5 (1.1–2.1); and ≥72 months, 2.4 (1.5–3.7). The results are not explained by maternal BMI or change in BMI between pregnancies or by parental age, maternal antidepressant medication use, or unfavorable events occurring during the first or second pregnancy.
Children born after interpregnancy intervals <2 years or >6 years may be at increased risk of ASD. The mechanism explaining this association is unknown, and more research is needed.
Comments
DHA: An Undervalued yet Possibly Pivotal Nutrient in the Etiology of Autism
To the Editor:
Thank you for the excellent study on interpregnancy interval (IPI)and autism. [1] It supports previous studies linking both short and long intervals to increased risk, and includes important controls to rule out confounding factors like mothers' ages and gestational ages at birth. The short-interval risk could indeed be explained by nutritional deficiencies from the first pregnancy not adequately restored prior to the second pregnancy. As important as folic acid and iron are in normal development, a more plausible nutritional factor in the etiology of autism is docosahexaenoic acid (DHA). Its deficits and repletion rates have been well studied; good repletion with adequate IPIs and breastfeeding may be the reason that second-born sons are generally at lower risk for autism than first-born sons even though their parents are older. [2] DHA is an essential functional component of synapses where genes of known function associated with autism are frequently expressed. [3,4] Most known risk factors for autism, including male predominance, parental migration from places of high fish consumption, prematurity, multiplicity, gestational diabetes, oxidative stress, and formula not supplemented with DHA can be explained in terms of DHA supplies or function. [2,4] The risk of IPIs greater than five years for autism on the second child could be due to less supportive uteri and breasts (out of condition) in supplying DHA. [2] That obviously needs to be studied, but autism researchers need to be aware of the multiple lines of evidence that DHA is a neurocomponent nutrient that could be pivotal in the etiology of autism.
References:
1. Zerbo O, Yoshida C, Gunderson EP, Dorward K, Croen LA. Interpregnancy interval and risk of autism spectrum disorders. Pediatrics. 2015;136(4):651-657 2. Field SS. Interaction of genes and nutritional factors in the etiology of autism and attention deficit/hyperactivity disorders: a case control study. Med Hypotheses. 2014;82:654-661 3. Sanders SJ, He X, Willsey AJ, et al. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron. 2015;87:1215-1233 4. Field SS. How do genes and environment cause autism? Austin J Nutr Metab. 2015;2(2):1017
Conflict of Interest:
I have no conflicts of interests.