Elevated FPG, not post-load glucose, raises risk for large for gestational age outcomes
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Elevated fasting plasma glucose, but not post-load glucose, is associated with increased risk for large for gestational age infants, according to study findings published in Diabetic Medicine.
In a retrospective cohort study of women who had a singleton pregnancy in the province of Alberta, Canada, and oral glucose tolerance test data available from October 2008 to December 2018, large for gestational age rates increased as FPG, 1-hour glucose and 2-hour glucose levels increased. However, only FPG was significantly associated with an increased risk for large for gestational age outcomes, with no increased risk observed for women with only elevated post-load glucose.
“Among pregnancies with elevated 1-hour and 2-hour post-load glucose levels, large for gestational age rates differed markedly between pregnancies with and without FPG elevations,” Padma Kaul, PhD, professor of medicine and co-director of the Canadian VIGOUR Centre at the University of Alberta in Edmonton, Canada, and colleagues wrote. “Despite higher rates of pharmaceutical intervention, often introduced when diet and exercise therapy are insufficient, large for gestational age rates in pregnancies with elevated FPG were much higher than those among pregnancies with only post-load glucose elevations.”
Researchers collected data from 84,534 pregnant women (mean age, 31.7 years) with a singleton pregnancy who underwent an OGTT. The cohort was grouped into seven categories based on their level of FPG, 1-hour post-load glucose and 2-hour post-load glucose. The categories for each glucose type were the same as those observed in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, which examined associations between increasing maternal glucose and adverse pregnancy outcomes. Study data were compared with findings from HAPO.
Large for gestational age risk climbs with glucose
The study cohort had similar FPG levels to the HAPO cohort, but 1-hour post-load glucose (8.8 mmol/L vs. 7.4 mmol/L) and 2-hour post-load glucose (7.4 mmol/L vs. 6.2 mmol/L) were higher than in HAPO.
The rate of large for gestational age increased from 7.6% for women with FPG of less than 4.2 mmol/L to 21.4% for those with an FPG of 5.6 mmol/L to 5.8 mmol/L. Large for gestation age rates increased from 5.7% with a 1-hour glucose level of 5.5 mmol/L or less to 12.5% for with a 1-hour post-load glucose of 11.8 mmol/L or higher. Large for gestational age rates climbed from 7.5% with a 2-hour post-load glucose of 5 mmol/L or less to 9.2% with 2-hour post-load glucose between 9.9 mmol/L and 11.1 mmol/L. All three measures showed a trend of increasing large for gestational age rates with increasing glycemia (P < .01 for all).
FPG predicts large for gestational age
Large for gestational age rates were higher among women with elevated FPG than women who only had elevated post-load glucose. Women with elevated FPG, 1-hour post-load glucose and 2-hour post-load glucose were most likely to have large for gestational age babies (adjusted OR = 2.41; 95% CI, 2.18-2.66) compared with those with normal glucose levels. Researchers wrote that the increased risk was primarily due to elevated FPG. Women who had only elevated post-load glucose had a lower risk for large for gestational age outcomes (aOR = 0.81; 95% CI, 0.77-0.86) than those with normal glucose.
The researchers said there are several possible reasons why FPG more strongly predicts large for gestational age outcomes, all of which should be investigated in future studies.
“First, FPG elevation may be a marker of more severe disease, which requires early identification and treatment,” the researchers wrote. “Second, FPG may be less amenable to treatment. Prospective studies are needed to examine whether more aggressive treatment to lower glucose thresholds would impact large for gestational age rates in pregnancies with elevated FPG. Third, maternal obesity may be an unmeasured confounder of the association between FPG and large for gestational age, and thus not amenable to change by treatment. And lastly, it may be that, along the diabetes spectrum, FPG identifies a different type of diabetes in pregnancy.”
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