Laterality Spectrum Disorders in the Prenatal Era: Outcomes Across the Severity Spectrum and Associations with Pregestational Diabetes

Objective To describe severity-stratified early outcomes in pregnancies with prenatally suspected laterality spectrum disorders (LSD), defined as abnormalities of left–right body patterning affecting thoracoabdominal situs and associated cardiovascular and visceral structures, and to explore phenotype patterns associated with pregestational diabetes mellitus (PDM). Study Design Retrospective cohort study of pregnancies evaluated at a tertiary fetal care and fetal cardiology referral center (2010–2026). LSD subtype was assigned using a prespecified operational framework. Cardiac severity was classified as major versus non-major congenital heart disease (CHD). Outcomes included termination, intrauterine fetal demise (IUFD), neonatal survival (≤28 days), infant survival (28 days–1 year), cardiac surgery, and gastrointestinal morbidity. Results Seventy-eight pregnancies were included; 16/78 (20.5%) had PDM. Major CHD was present in 49/78 (62.8%). Pregnancy outcomes included live birth in 62/78 (79.5%), IUFD in 5/78 (6.4%), and termination in 11/78 (14.1%); all terminations occurred among major-CHD cases. Among live births, neonatal survival was 59/62 (95.2%), and infant survival among neonatal survivors was 46/53 (86.8%). In major-CHD live births (n=33), neonatal survival was 30/33 (90.9%) and infant survival among neonatal survivors with available follow-up was 20/27 (74.1%). Cardiac surgery occurred in 22/62 (35.5%) and was more common in major versus non-major CHD (63.6% vs 3.4%). Intestinal malrotation occurred in 18/62 (29.0%). Abdominal situs inversus was more frequent in PDM pregnancies (37.5% vs 8.1%). Conclusion In LSD, major CHD drives pregnancy termination, surgical intervention, and early mortality concentrated during infancy. PDM was associated with a higher frequency of abdominal situs phenotypes, supporting deliberate postnatal gastrointestinal surveillance planning.