Prediabetes before conception tied to higher risk for adverse pregnancy outcomes
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Key takeaways:
- Prediabetes before an initial pregnancy more than doubles the risk for gestational diabetes compared with normoglycemia.
- The most optimal HbA1c cutoff for identifying prediabetes before pregnancy is 5.6%.
Adolescent and young adult women who had prediabetes before becoming pregnant had a higher risk for gestational diabetes and adverse maternal outcomes than those with normal glycemic levels, researchers reported.
Few studies have previously explored associations between subclinical diabetes and pregnancy outcomes among younger pregnant women, according to Katharine J. McCarthy, PhD, MPH, assistant professor in the department of population health science and policy and the department of obstetrics, gynecology and reproductive science at the Icahn School of Medicine at Mount Sinai. In findings published in JAMA Network Open, researchers assessed preconception HbA1c and the risk for gestational diabetes and other adverse pregnancy outcomes among women in the A1c in Pregnancy and Postpartum Linkage for Equity (APPLE) cohort.
“We found preconception prediabetes among adolescents and young adults aged 10 to 24 years was associated with more than twice the risk of gestational diabetes at a future first birth, as well as an 18% increased risk of a hypertensive disorder during pregnancy or a preterm birth, respectively,” McCarthy told Healio.
McCarthy and colleagues conducted a retrospective cohort study with data from 14,302 girls and women aged 10 to 24 years who had at least one HbA1c measurement before their first pregnancy and never previously had diabetes or an HbA1c of 6.5% or higher (mean age, 22.1 years; 41% Hispanic; 29% Black; 18.1% white; 10.6% Asian). Participants with an HbA1c of 5.7% to less than 6.5% were considered to have prediabetes before conception, whereas an HbA1c of less than 5.7% was labeled as normoglycemia. Researchers collected diagnoses of gestational diabetes, hypertensive disorders of pregnancy, cesarean delivery, gestational age of less than 37 weeks and macrosomia from hospital and birth records.
Of the study group, 20.2% had prediabetes and 79.7% had a normal HbA1c before conception. Gestational diabetes was diagnosed in 6.6% of women during pregnancy.
Adolescent and young adult women with prediabetes before pregnancy were more likely to have gestational diabetes (adjusted RR = 2.21; 95% CI, 1.91-2.56), hypertensive disorders of pregnancy (aRR = 1.18; 95% CI, 1.03-1.35) and preterm delivery (aRR = 1.18; 95% CI, 1.02-1.37) than those with normoglycemia. The likelihood for cesarean delivery (aRR = 1.09; 95% CI, 0.99-1.2) and macrosomia (aRR = 1.13; 95% CI, 0.93-1.37) was not significantly greater for those with preconception prediabetes compared with normal HbA1c.
“Currently, there is a lack of uniform treatment guidelines for prediabetes care among pregnant individuals without other traditional diabetes risk factors, such as obesity, family history of diabetes, or American Indian, Black, Hispanic and Asian American or Pacific Islander race and ethnicity,” McCarthy said. “Results support the need for clear clinical guidance on how to screen and counsel adolescents and young adults with subclinical hyperglycemia as well as to expand routine testing.”
Researchers also assessed the optimal HbA1c cutoff point for classifying prediabetes in the estimation of gestational diabetes risk. An HbA1c of 5.6% was deemed to be the most optimal cutoff, yielding a sensitivity of 52.5% and a specificity 70.4%. The risk for gestational diabetes using a prediabetes HbA1c cutoff of 5.6% was similar to the main findings, with prediabetes before pregnancy tied to a higher risk for gestational diabetes vs. a normal HbA1c (aRR = 2.14; 95% CI, 1.86-2.46).
“We also found that the threshold was the same among those with and without obesity,” McCarthy said. “These results suggest that weight and elevated blood sugar levels are distinct risk factors for pregnancy health and that health guidelines should emphasize health behaviors outside of weight loss alone.”
An HbA1c of 5.6% was the optimal prediabetes cutoff point for all racial-ethnic groups except for Hispanic participants, where the optimal cutoff point was 5.5%.
McCarthy said more studies are needed to assess the link between prediabetes and adverse pregnancy outcomes in other study populations.
For more information:
Katharine J. McCarthy, PhD, MPH, can be reached at katharine.mccarthy@mountsinai.org.
Perspective
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Linda A. Barbour, MD, MSPH, FACP
In a country in which diabetes now affects about 5% of people of childbearing age and prediabetes affects about 30%, most unaware of these serious cardiometabolic conditions, the JAMA Network Open article by McCarthy and colleagues provides compelling support for universal preconception screening with an HbA1c in individuals as young as age 10 to 24 years. An HbA1c of 5.6% to 6.4% was associated with a more than twofold higher risk for gestational diabetes as well as an increased risk for hypertensive disorders and preterm birth (mean time between HbA1c value and pregnancy was 12.7 months).
Given that the majority of young adults and adolescent pregnancies are unwanted, mistimed or unplanned (between 60% and 75%), and the frequency of preconception counseling is alarmingly low (10% to 20%), the authors make the argument that obtaining an HbA1c preconception identifies a surprisingly high percentage with prediabetes (one in five people with an HbA1c of 5.7% to 6.4%), despite the young age of this cohort. These data are consistent with studies which found that in adult women of childbearing age, a first trimester HbA1c of 5.7% to 6.4%, especially those with an HbA1c of 5.9% to 6.4%, defined as high-risk abnormal glucose metabolism, have twofold to fourfold increased risk for major anomalies, hypertensive disorders, macrosomia and perinatal death (Simmons D, et al. Lancet. 2024;doi:10.1016/S0140-6736(24)00826-2). Furthermore, nearly 50% of these individuals will test positive for early gestational diabetes (Boe B, et al. Am J Obstet Gynecol MFM. 2019;doi:10.1016/j.ajogmf.2019.02.003).
Identifying these individuals preconception allows optimization of metabolic health, including weight loss if appropriate, primary prevention of type 2 diabetes and effective contraception until metabolic health has improved and pregnancy is desired. The ADA provides a long list of risk factors for screening asymptomatic individuals with prediabetes in their 2024 Standards of Care. Although the majority of individuals of childbearing age would qualify, few receive any screening before their first prenatal visit.
In light of the 20% to 40% prevalence of prediabetes in adolescents and young adults, typically unaware of their condition, the effectiveness of new therapeutics to improve metabolic health, and incontrovertible evidence that in utero exposure to maternal metabolic disease results in developmental programming enhancing offspring cardiometabolic risk (Hoffman DJ, et al. Physiol Rev. 2021;doi:10.1152/physrev.00002.2020), the time has come for more widespread HbA1c screening in adolescents and young adults. As supported by this article, universal screening with an HbA1c in all individuals of childbearing age needs to ideally occur preconception in order to reap the greatest benefit from interventions to improve both maternal and infant outcomes. If, unfortunately, this invaluable opportunity is missed, screening is even more critical at the first prenatal visit.
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