Fetal aneuploidy linked to severe preeclampsia but not overall maternal morbidity

Pregnancies affected by fetal aneuploidy carry a higher risk of preeclampsia with severe features, but do not appear to face elevated risks of overall severe maternal morbidity or hypertensive disorders of pregnancy in general, according to a cross-sectional analysis of United States national hospitalization data published in Archives of Gynecology and Obstetrics.

Researchers led by Keiko Fox used the National Inpatient Sample, a large administrative database of US hospital stays, to identify delivery admissions between 2016 and 2022. Pregnancies with fetal aneuploidy were identified using ICD-10 codes capturing trisomy 21, trisomy 18, and trisomy 13, and were compared with non-aneuploid pregnancies. Severe maternal morbidity was defined using indicators from the Centers for Disease Control and Prevention, and a total comorbidity index was applied to account for pre-existing health conditions.

The unweighted analytic sample included 5,027,079 deliveries, of which 6,144 involved fetal aneuploidy. Because the National Inpatient Sample is survey-weighted to represent the full population of US hospitalizations, the team applied multivariable survey-weighted logistic regression to estimate the independent association between fetal aneuploidy and each maternal outcome, adjusting for maternal age and comorbidity burden.

Rates were statistically similar between the two groups, at 2.2 percent in aneuploid pregnancies versus 1.9 percent in non-aneuploid ones, a difference that did not reach significance in the unadjusted comparison. In the fully adjusted weighted models, fetal aneuploidy was not associated with severe maternal morbidity, with an odds ratio of 0.900 and a 95 percent confidence interval of 0.756 to 1.073, a range that crosses 1.0 and therefore indicates no detectable association.

Hypertensive disorders of pregnancy as a whole told a similar story once confounders were addressed. These disorders were more common in aneuploid pregnancies in raw numbers, 14.8 percent versus 12.9 percent, but after adjustment for maternal age and comorbidities the association disappeared, with an odds ratio of 1.022 and a confidence interval of 0.950 to 1.100. This suggests that the apparent excess of hypertension in aneuploid pregnancies can be explained by the older ages and higher comorbidity burdens typical of these patients rather than by the chromosomal condition itself.

Preeclampsia with severe features, analyzed as a secondary outcome, followed a different pattern. It occurred in 4.4 percent of aneuploid pregnancies versus 2.9 percent of others, and unlike the broader outcomes it remained significantly elevated after adjustment, with an odds ratio of 1.259 and a confidence interval of 1.105 to 1.435. In other words, even after accounting for age and comorbidity, fetuses with trisomy 21, 18, or 13 were associated with roughly a 26 percent higher odds of the mother developing this severe form of preeclampsia.

The authors note that prior studies of pregnancies complicated by fetal aneuploidy have focused primarily on fetal and neonatal outcomes, leaving maternal outcomes comparatively underexplored. Clarifying these associations, they argue, may inform risk stratification and counseling for patients carrying aneuploid fetuses. The new findings refine that picture: counseling conversations may need to weigh a specific elevated risk of severe preeclampsia, while general fears of life-threatening maternal morbidity are not supported by these population-level data.

Several limitations deserve emphasis. The study is cross-sectional and relies on administrative coding, so aneuploidy and outcomes are identified by ICD-10 codes rather than clinical review, which can introduce misclassification. The aneuploidy group was small relative to the total sample, and the analysis captures delivery admissions only, meaning earlier pregnancy events are outside its scope. As an observational database study, it can identify associations but cannot establish causal mechanisms, and residual confounding cannot be excluded even with adjustment.

The takeaway for clinicians and patients is measured. In this large US analysis of delivery hospitalizations, fetal aneuploidy was not associated with severe maternal morbidity or with hypertensive disorders of pregnancy overall after adjustment, but it was independently associated with preeclampsia with severe features. That specific signal may justify heightened surveillance for severe preeclampsia in aneuploid pregnancies, while the broader maternal risk profile appears largely driven by maternal age and comorbidity rather than fetal karyotype.

Subject of Research: Association between fetal aneuploidy and severe maternal morbidity and hypertensive disorders of pregnancy in US delivery hospitalizations

Article Title: Evaluating the relationship between fetal aneuploidy, severe maternal morbidity, and hypertensive disorders of pregnancy: an NIS database analysis

Article References: Fox, K., Enthoven, L. F., Vincent, H., Mass, H., Hopkins, M., & Putra, M. (2026). Evaluating the relationship between fetal aneuploidy, severe maternal morbidity, and hypertensive disorders of pregnancy: an NIS database analysis. Archives of Gynecology and Obstetrics. https://doi.org/10.1007/s00404-026-08580-3

Image Credits: AI Generated

DOI: 10.1007/s00404-026-08580-3

Keywords: fetal aneuploidy, severe maternal morbidity, hypertensive disorders of pregnancy, preeclampsia with severe features, National Inpatient Sample, trisomy 21, trisomy 18, trisomy 13, maternal outcomes, cross-sectional study, obstetrics, Evaluating