# Gestational age and sex interaction and risk for autism spectrum disorder in extremely preterm newborns: an 18‑month follow‑up study

## TL;DR

Extremely preterm newborns are at higher risk for autism symptoms, with females born earlier showing the most severe symptoms at 18 months.

## Contribution

Identifies gestational age and sex as key factors influencing autism risk in extremely preterm infants.

## Key findings

- EPTN children showed significantly higher autistic symptom levels than full-term controls at 18 months.
- Female EPTNs born at lower gestational ages had higher autistic symptom loads at 18 months.
- Gestational age and sex together explained a large portion of symptom variability in EPTNs.

## Abstract

Extremely preterm newborns - EPTN (born ≤28 weeks gestational age) are at increased risk of developing autism spectrum disorders (ASD). Demographic and perinatal risk factors associated with ASD risk in EPTN are understudied.

(i) In EPTN and born at full-term healthy controls (HC), to characterize the emergence of ASD traits and autistic symptom load at age 18 months; (ii) in EPTN, to identify the influence of perinatal characteristics such as sex and gestational age on autistic symptom load at corrected-age 18 months.

Observational, longitudinal, prospective, 18-month follow-up study. We recruited a cohort of n=113 EPTN and n=47 HC (the PremTEA cohort); n=57 EPTN and n=42 HC successfully completed the 18-month follow-up visit. We assessed autistic symptom load & risk at 18 months using the M-CHAT-R/F questionnaire. For all EPTN and HC, we collected demographic and perinatal data. Using GLMs, we assessed, in EPTN, the association between demographic/perinatal variables and 18-month autistic symptom levels.

At 18 months, EPTN children showed higher autistic symptom levels than HC (M-CHAT-R/F score, mean (SD) [range] = 2.21 (3.23) [0-12] in EPTN vs. 0.33 (0.57) [0-2] in HC; d=.873, p=.001. In EPTN, we identified differences by gestational age and sex in autistic symptom levels at 18 months (aR2=0.517, p=.006). In particular, female EPTNs born with lower gestational age showed higher autistic symptom load at age 18 months.

Our findings support the need for early screening of ASD symptomatology in EPTN infants, particularly in higher-risk subgroups, such as female patients born with lower gestational ages.

None Declared