Type 1 diabetes associated with risk of both medically indicated and spontaneous preterm delivery

The likelihood of giving birth before 37 weeks was increased even in women with HbA1c levels below 6.5%, suggesting that tighter control of type 1 diabetes will not eliminate this risk, the authors of the Swedish study said.

Women with type 1 diabetes were more likely to give birth before 37 weeks, even if their HbA1c levels were at recommended targets, a recent study found.

The population-based cohort study included 2,474 infants of women with type 1 diabetes and 1,165,216 reference infants of women without diabetes, all born in Sweden in 2003 to 2014. The women's periconceptional HbA1c levels were compared with a primary outcome of preterm birth (<37 gestational weeks). Results were published by Annals of Internal Medicine on April 23.

Preterm birth occurred in 22.3% of the infants born to mothers with diabetes versus 4.7% of the reference population. Incidence of preterm birth increased with HbA1c level, from 13.2% with HbA1c level below 6.5% (adjusted risk ratio [aRR] vs. women without diabetes, 2.83; 95% CI, 2.28 to 3.52), to 20.6% with a level from 6.5% to less than 7.8% (aRR, 4.22; 95% CI, 3.74 to 4.75), to 28.3% with a level from 7.8% to less than 9.1% (aRR, 5.56; 95% CI, 4.84 to 6.38), to 37.5% with a level of 9.1% or higher (aRR, 6.91; 95% CI, 5.85 to 8.17). This was true for both medically indicated and spontaneous preterm births, with corresponding aRRs of 5.26, 7.42, 11.75, and 17.51 and 1.81, 2.86, 2.88, and 2.80, respectively. The infants' risk for the study's secondary outcomes (large for gestational age, hypoglycemia, respiratory distress, low Apgar score, neonatal death, and stillbirth) also increased progressively with the mother's HbA1c level.

Most of the elevated risk for preterm birth was attributable to medically indicated preterm births, the study authors noted. For the most part, this probably does not represent a direct effect of glycemic control; it's more likely that delivery is induced because of an effect of hyperglycemia, such as large for gestational age, they said. However, hyperglycemia might also induce oxidative stress, leading to preterm birth. The finding that even women with HbA1c levels under 6.5% had increased risk of preterm delivery suggests that type 1 diabetes could be independently linked to preterm birth, the authors said. The results of this study should be considered in development of future guidelines, “but they do not support the idea that further lowering the recommended HbA1c level during early pregnancy (at least not to 6.0%) will eliminate the excess risk for preterm birth,” the authors said.

The study's limitations include that it was observational, so residual confounding cannot be ruled out. It also used periconceptional HbA1c levels, and some other data have suggested that glycemic control later in pregnancy might better predict risk of preterm birth.