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Am J Perinatol
DOI: 10.1055/a-2781-7471
SMFM Fellowship Series Article

The Impact of Offspring Sex on Pregnancy and Neonatal Outcomes in Individuals with Pregestational Diabetes

Authors

  • Arlin Delgado

    1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts, United States

  • Kaitlyn E. James

    1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts, United States

  • Sarah Hsu

    2   Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts, United States

  • Andrea G. Edlow

    1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts, United States
    3   Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, United States

  • Camille E. Powe

    1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts, United States
    2   Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts, United States
    4   Diabetes Unit, Endocrinology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States
    5   Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States
    6   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States

  • Lydia L. Shook 

    1   Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts, United States
    3   Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, Massachusetts, United States

Funding Information This study was supported by the National Institute of Health/National Institute of Child Health and Human Development and the National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases (to L.L.S.). Funding supporters had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.
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Abstract

Objective

Pregestational diabetes mellitus (PGDM) is increasing in prevalence among pregnant individuals and is associated with adverse outcomes. Prior work suggests that offspring sex influences placental responses and may impact risk for adverse outcomes. We sought to assess the impact of offspring sex on adverse pregnancy and neonatal outcomes in individuals with PGDM.

Study Design

We conducted a retrospective cohort study of 503 pregnant individuals with PGDM and known offspring sex with care at a major urban academic center between 1998 and 2016. We assessed two co-primary composite outcomes: (1) a composite adverse pregnancy outcome of small for gestational age (SGA), hypertensive disorder of pregnancy (HDP), and stillbirth and (2) a composite adverse neonatal outcome of large for gestational age (LGA), hypoglycemia, hyperbilirubinemia, shoulder dystocia, and respiratory distress syndrome (RDS). Secondary outcomes of spontaneous preterm birth (PTB) and admission to the neonatal intensive care unit (NICU) were assessed. Mixed effects logistic regression models, accounting for multiple pregnancies and adjusting for first trimester body mass index (BMI), insurance, parity, and maternal race/ethnicity, were analyzed.

Results

Of the 503 pregnant individuals with PGDM, 67% had a diagnosis of type 2 DM and 33% had type 1 DM. The composite adverse pregnancy outcome occurred in 79 of 258 (31%) pregnancies with a female fetus and 76 of 245 (31%) pregnancies with a male fetus. The composite neonatal outcome occurred in 163 of 245 males (67%) and 154 of 258 females (60%). Male infants had significantly higher odds of requiring admission to the NICU (adjusted odds ratio 1.79 [95% confidence interval: 1.13, 2.80], p = 0.01). There were no observed sex differences in the incidence of spontaneous PTB.

Conclusion

We identified high rates of both composite outcomes in pregnancies with PGDM, regardless of fetal sex. The significantly higher rate of NICU admission among males suggests an increased risk of neonatal morbidity in males exposed to PGDM.

Key Points

  • A high incidence of adverse outcomes was observed in PGDM pregnancies.

  • Male neonates are at greater risk of NICU admission.

  • In individuals with type 2 DM, a trend toward increased risk of LGA was observed in male neonates.

Keywords

offspring sex - pregestational diabetes - adverse pregnancy outcomes - neonatal morbidity

Contributors' Statement

A.D.: conceptualization, formal analysis, methodology, project administration, supervision, writing—original draft, writing—review and editing; K.J.: conceptualization, data curation, formal analysis, methodology, validation, writing—review and editing; S.H.: conceptualization, data curation, formal analysis, methodology, validation, writing—review and editing; A.E.: conceptualization, methodology, writing—review and editing; C.P.: conceptualization, data curation, methodology, writing—review and editing; L.S.: conceptualization, formal analysis, investigation, methodology, project administration, supervision, writing—original draft, writing—review and editing.


Supplementary Material



Publication History

Received: 02 July 2025

Accepted: 02 January 2026

Accepted Manuscript online:
07 January 2026

Article published online:
16 January 2026

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