Maternal obesity, fetal fraction, and non-invasive prenatal testing performance: a large retrospective cohort study

Introduction Maternal obesity is associated with reduced cell‐free DNA fetal fraction (FF) and may affect non-invasive prenatal testing (NIPT) performance. This study evaluated the associations of maternal body mass index (BMI) and gestational age at sampling with FF and NIPT reportability in a population with a high prevalence of overweight and obesity. Methods This retrospective cohort study included singleton and twin pregnancies undergoing NIPT at ≥10 weeks of gestation across three hospitals in Saudi Arabia between 2022 and 2024. Maternal and pregnancy characteristics were analyzed in relation to FF, test reportability, and high-risk screening results for trisomies 13, 18, and 21. Multivariable linear and logistic regression analyses were used to identify factors independently associated with FF and high‐risk screening results. Results Among 2,659 eligible pregnancies, 2,615 yielded reportable results (98.3%), while 44 tests were non-reportable (1.7%). Nearly half of the participants were obese (48.8%). FF measurements were available for 2,612 reportable tests, with a mean of 15% ± 6.1%; only two of 2,612 tests with available FF had FF <4%. Each 1 kg/m 2 increase in BMI was independently associated with a 0.161 percentage-point reduction in FF (95% CI, –0.198 to –0.125; p < 0.001), whereas each additional week of gestation was associated with a 0.309 percentage-point increase (95% CI, 0.277–0.340; p < 0.001). Maternal BMI was not significantly associated with reportability. High‐risk results were identified in 99 of 2,615 reportable tests (3.8%), most commonly for trisomy 21. Maternal age, gestational age and a previous history of trisomy were independently associated with high‐risk results, whereas BMI and pregnancy type were not. Discussion NIPT demonstrated a high overall reportability rate in this cohort despite the high prevalence of overweight and obesity. Higher maternal BMI was independently associated with lower FF but was not significantly associated with reportability. Advancing gestational age was associated with higher FF; however, the present data do not establish that delaying sampling reduces the likelihood of a non-reportable result.