Gestational diabetes is associated with the risk of offspring's congenital anomalies: a register-based cohort study

Jenni Kinnunen; Hilkka Nikkinen; Elina Keikkala; Sanna Mustaniemi; Mika Gissler; Hannele Laivuori; Johan G Eriksson; Risto Kaaja; Anneli Pouta; Eero Kajantie; Marja Vääräsmäki

doi:10.1186/s12884-023-05996-6

Gestational diabetes is associated with the risk of offspring's congenital anomalies: a register-based cohort study

BMC Pregnancy Childbirth. 2023 Oct 3;23(1):708. doi: 10.1186/s12884-023-05996-6.

Authors

Jenni Kinnunen^{1

2}, Hilkka Nikkinen^{3

4}, Elina Keikkala^{3

4}, Sanna Mustaniemi^{3

4}, Mika Gissler^{5

6}, Hannele Laivuori^{7

8

9}, Johan G Eriksson^{10

11

12}, Risto Kaaja¹³, Anneli Pouta¹⁴, Eero Kajantie^{3

4

15

16}, Marja Vääräsmäki^{3

4}

Affiliations

¹ Wellbeing Services County of North Ostrobothnia, Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, 90029, Finland. jenni.kinnunen@oulu.fi.
² Finnish Institute for Health and Welfare, Population Health, Public Health and Welfare, Helsinki, Oulu, 00271, 90101, Finland. jenni.kinnunen@oulu.fi.
³ Wellbeing Services County of North Ostrobothnia, Department of Obstetrics and Gynecology, Research Unit of Clinical Medicine, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, 90029, Finland.
⁴ Finnish Institute for Health and Welfare, Population Health, Public Health and Welfare, Helsinki, Oulu, 00271, 90101, Finland.
⁵ Department of Knowledge Brokers, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland.
⁶ Academic Primary Health Care Centre, Region Stockholm, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, 17176, Sweden.
⁷ Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology Tampere University Hospital, Tampere University, Tampere, 33100, Finland.
⁸ Medical and Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, 00014, Finland.
⁹ Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, 00014, Finland.
¹⁰ Department of General Practice and Primary Health Care, Helsinki University Hospital, University of Helsinki, Helsinki, 00014, Finland.
¹¹ Folkhälsan Research Center, Helsinki, 00250, Finland.
¹² Department of Obstetrics and Gynecology, Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
¹³ Turku University Hospital, Turku University, Turku, 20521, Finland.
¹⁴ Department of Government Services, Finnish Institute for Health and Welfare, Helsinki, 00271, Finland.
¹⁵ University of Helsinki and Helsinki University Hospital, Children's Hospital, Helsinki, 00290, Finland.
¹⁶ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NO-7491, Norway.

Abstract

Background: Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder and a well-known risk factor for adverse pregnancy outcomes. There are conflicting findings on the association of GDM with the risk of congenital anomalies (CAs) in offspring. In this study, we aimed to determine study whether maternal GDM is associated with an increased risk of major CAs in offspring.

Methods: This Finnish Gestational Diabetes (FinnGeDi) register-based study included 6,597 women with singleton pregnancies and a diagnosis of GDM and 51,981 singleton controls with no diabetes identified from the Finnish Medical Birth Register (MBR) in 2009. Data from MBR were combined in this study with the Register of Congenital Malformations, which includes the data of CAs. We used logistic regression to calculate odds ratios (OR) for CAs, together with their 95% confidence intervals (CIs), adjusting for maternal age, parity, pre-pregnancy body mass index (BMI), and maternal smoking status.

Results: The risk of major CAs was higher in the GDM-exposed (n = 336, 5.09%) than in the non-exposed group (n = 2,255, 4.33%) (OR: 1.18, 95% CI: 1.05-1.33, p = 0.005). The adjusted OR (aOR) was 1.14 (95% CI: 1.00-1.30, p = 0.047). There was a higher overall prevalence of CAs, particularly chromosomal abnormalities (0.52% vs. 0.21%), in the GDM-exposed group (OR: 2.49, 95% Cl: 1.69-3.66, p < 0.001). The aOR was 1.93 (95% Cl: 1.25-2.99, p = 0.003).

Conclusions: Offspring exposed to GDM have a higher prevalence of major CAs. Of note, risk factors other than GDM, such as older maternal age and a higher pre-pregnancy BMI, diminished the between group differences in the prevalence of major CAs. Nevertheless, our findings suggest that offspring exposed to maternal GDM are more likely to be diagnosed with a chromosomal abnormality, independent of maternal age, parity, pre-pregnancy BMI, and smoking.

Keywords: Aneuploidy; Chromosomal abnormalities; GDM; Gestational diabetes; Major congenital anomalies; Non-chromosomal anomalies; Offspring; Pregnancy outcome.

MeSH terms

Body Mass Index
Cohort Studies
Diabetes, Gestational* / epidemiology
Female
Humans
Pregnancy
Pregnancy Complications* / epidemiology
Pregnancy Outcome / epidemiology
Risk Factors