Preterm, early term birth increases risk for autism, large study finds
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Preterm and early term birth were associated with a significantly increased risk for autism spectrum disorder in both boys and girls in a study that included more than 4 million children born over a 40-year period in Sweden.
According to the study, which was published in Pediatrics, the prevalence of ASD was 2.1% for all preterm births, 1.6% for early term births and in 1.4% for term births.
In a related editorial, Elisabeth C. McGowan, MD, and Stephen J. Sheinkopf, PhD, both associate professors of pediatrics at Brown University, said the findings were consistent with previous research “suggesting a dose response-type relationship between degree of prematurity and ASD risk.”
They called the new study “in many ways a definitive accounting of the elevated rates of ASD in preterm infants.”
“And although the impact of prematurity on brain development may be part of the causal chain resulting in ASD (or other neurodevelopmental outcomes), these factors are operating in a complex biological landscape, with pathways to ASD outcomes that can be expected to be heterogeneous,” they wrote.
For the study, Casey Crump, MD, PhD, vice chair for research in the department of family medicine and community health at the Icahn School of Medicine at Mount Sinai in New York, and colleagues included 4,061,795 singleton infants born in Sweden from 1973 through 2013 who survived to the age of 1 year, were followed up for ASD and were diagnosed by 2015.
They categorized participants by gestational age at birth: extremely preterm (22 to 27 weeks), very to moderate preterm (28 to 33 weeks), late preterm (34 to 36 weeks), early term (37 to 38 weeks), term (39 to 41 weeks) and post term (at or more than 42 weeks). The first three groups were combined for summary estimates of preterm births (at or less than 37 weeks).
The prevalence ratios, when adjusted for covariates, were significantly elevated among extremely preterm (3.87; 95% CI, 3.48-4.31), all preterm (1.40; 95% CI, 1.36-1.45) and early term births (1.12; 95% CI, 1.10-1.14), Crump and colleagues reported.
According to the authors, an estimated 83.7% of ASD cases among participants born extremely preterm, 37.7% of cases among those born any preterm and 18.9% of cases among those born early term were attributed to gestational age at birth.
“In this large population-based cohort, preterm and early term birth were associated with significantly increased risks of ASD in boys and girls,” Crum and colleagues wrote. “These findings were largely independent of measured covariates and unmeasured shared familial factors, consistent with a potential causal relationship.”
McGowan and Sheinkopf said other investigations have shown “higher incidences of early cognitive, language motor and impairment, and school problems, social-emotional problems, and psychiatric disorders, some of which may extend to adulthood,” among late preterm infants.
They said, “careful attention should be paid to biological vulnerabilities at later gestational ages.”
“For example, between 34 and 40 weeks, brain weight increases nearly one-third, cortical volume increases nearly 50%, and absolute myelinated white matter volume increases fivefold,” they wrote.
References:
Crump C, et al. Pediatrics. 2021;doi:10.1542/peds.2020-032300.
McGowan EC, Sheinkopf SJ. Pediatrics. 2021;doi:10.1542/peds.2021-051978.
Perspective
Back to TopSusan L. Hyman, MD, FAAP
This well-designed population study examines the prevalence of ASD in singleton pregnancies in the Swedish Medical Birth Registry (1973-2013). Although the minority of individuals identified with ASD had a history of preterm birth, the data provide strong support for significantly increased rates of ASD in individuals born preterm, with an inverse relationship with weeks of prematurity from early preterm (22-27 weeks) through late preterm (34-36 weeks).
This is true for both males and females independent of other risk factors for prematurity and for ASD included in this registry (eg, paternal age, maternal obesity) and is only slightly impacted by having a parent or sibling with ASD. The accompanying editorial reinforces points made in the discussion regarding the potential for common immunologic risk factors for both prematurity and ASD.
In addition to providing support for continued research examining immunology and brain development, the editorial calls for studying interactions with genetic predisposition. The findings of this article also support the critical importance of public health and social programs that address health equity and the prevention of prematurity, as well as the necessity of screening for ASD and developmental delays in all children as recommended by the AAP with ongoing surveillance for children at higher risk, such as those born preterm, whether it is by 1 week or 18 weeks.
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