Autism risk in children not heightened by COVID-19 pandemic exposure

Children born during the COVID-19 pandemic or to mothers with history of prenatal SARS-CoV-2 infection are not at increased risk of autism compared with their counterparts who were born before the pandemic or have no exposure to maternal SARS-CoV-2 infection, as reported in a cohort study.

“We evaluated neurodevelopmental risk of children … using the M-CHAT-R, a screening tool widely used for clinical and research purposes, in a demographically diverse sample in New York City, [US],” the investigators said.

In a cohort of 2,049 children from the COVID-19 Mother Baby Outcomes (COMBO) Initiative, M-CHAT-R scores at 16 to 30 months were extracted from electronic health records for 1,664 children (COMBO-EHR cohort). For the remaining 385 children, M-CHAT-R was administered prospectively at 18 months for (COMBO-RSCH cohort).

“We found no increase in positive screening rates for autism for children born during the pandemic,” the investigators said.

M-CHAT-R positive screenings did not significantly differ between children born during and those born before the pandemic both in the COMBO-EHR cohort (23.2 percent vs 22.6 percent; adjusted odds ratio [aOR], 0.75, 95 percent confidence interval [CI], 0.52–1.08; p=0.12) and the COMBO-RSCH cohort (17.0 percent vs 13.5 percent; aOR, 1.40, 95 percent CI, 0.66–3.23; p=0.40). [JAMA Netw Open 2024;7:e2435005]

“Surprisingly, we found that prenatal maternal SARS-CoV-2 infection was associated with lower rates of positive autism screenings,” noted the investigators.

M-CHAT-R positivity rates were significantly lower among children with vs without prenatal exposure to maternal SARS-CoV-2 infection in the COMBO-EHR cohort (12.3 percent vs 24.0 percent; aOR, 0.40, 95 percent CI, 0.22–0.68; p=0.001). However, in the COMBO-RSCH cohort, the difference in M-CHAT-R positivity did not reach statistical significance, although the rates were still lower among the exposed children (12.9 percent vs 19.9 percent; aOR, 0.51, 95 percent CI, 0.24–1.04; p=0.07).

Evidence suggests that SARS-CoV-2 may contribute to maternal immune activation, which has potential implications for child neurodevelopment, through temporary cytokine fluctuations during pregnancy. The findings of the present study are consistent with those of other studies showing null or limited associations between prenatal SARS-CoV-2 exposure and child neurodevelopment, according to the investigators, who nevertheless acknowledged that the said studies, along with the present, mostly involved participants with mild illness. [Front Pediatr 2023;11:1277697; JAMA Netw Open 2023;6:e234415; JAMA Pediatr 2022;176:e215563; JAMA Netw Open 2023;6:e237396; BMC Pediatr 2022;22:319]

“We suspect that having COVID during pregnancy may have influenced parents’ assessment of their child’s behaviours, [while] parents who did not have COVID may have experienced higher stress—due to the constant worry of getting sick and the vigilance around preventing infection—and may have been more likely to report concerning child behaviours,” explained senior investigator Prof Dani Dumitriu from the Columbia University Irving Medical Center, New York, New York, US.

Fears abated

Dumitriu acknowledged the ongoing prevalence of COVID-19 and highlighted the positive implications of the findings, stating that knowing that COVID-19 exposure in utero doesn’t appear to heighten autism risk can be a significant weight off pregnant people’s minds.

“Autism risk is known to increase with virtually any kind of insult to mom during pregnancy, including infection and stress. The scale of the COVID pandemic had paediatricians, researchers, and developmental scientists worried that we would see an uptick in autism rates. But reassuringly, we didn’t find any indication of such an increase in our study,” she said.

Not out of the woods yet

Despite the lack of early indicators of autism, the possibility of other issues emerging later cannot be entirely ruled out, according to Dumitriu and colleagues. For one, the social and economic impact of the COVID-19 pandemic may have long-term effects on the development of pandemic-born children. Furthermore, previous research suggests a link between higher maternal stress during pregnancy and lower educational attainment in children. [Child Dev Perspect 2020;14:236-243; JAMA Psychiatry 2022;79:1040-1045; J Hum Resour 2016;51:523-555]

Also, Dumitriu acknowledged the limitation of using the M-CHAT-R, stating that the study focused on autism risk screening, without follow-up of actual diagnoses. 

“It's too early to have definitive diagnostic numbers. But this [M-CHAT-R] screener is predictive, and it’s not showing that prenatal exposure to COVID or the pandemic increases the likelihood of autism,” she continued. “There has been broad speculation about how the COVID generation is developing, and this study gives us the first glimmer of an answer with respect to autism risk.”