Periconceptional HbA1c levels ‘strongly linked’ to preterm birth risk
medwireNews: The risk for preterm birth among women with type 1 diabetes increases considerably with increasing glycated hemoglobin (HbA1c) levels around the time of conception, study findings indicate.
The team, led by Jonas Ludvigsson from the Karolinska Institutet in Stockholm, Sweden, report that “[m]ost of the elevated risk for preterm birth was attributable to medically indicated preterm births, although spontaneous preterm births also increased with higher HbA1c levels.”
Data collected in Sweden between 2003 and 2014 showed that preterm birth occurred in 22.3% of 2474 infants born to mothers with type 1 diabetes compared with just 4.7% of 1,165,216 infants born to mothers without diabetes.
For women with an HbA1c level below the ADA recommended threshold of 6.5% within 90 days before or after conception, the preterm birth rate was 13.2%. This equated to a significant risk ratio (RR) of 2.83 compared with women without type 1 diabetes, after adjustment for calendar year, maternal age, country of birth, living with a partner, education level, parity, BMI, smoking status, and other autoimmune diseases.
The incidence increased to 20.6% among women with an HbA1c level of between 6.5% and less than 7.8% (adjusted [a]RR=4.22), 28.3% in those with a level from 7.8% to less than 9.1% (aRR=5.56), and 37.5% for women with a level of 9.1% or higher (aRR=6.91).
Further analysis revealed that reducing the cutoff of the lowest HbA1c category to less than 6.0% did not mitigate the risk. Women in this group still had a significant 2.88-fold higher risk for preterm birth than women without type 1 diabetes.
During the study period, 320 of the births were medically indicated (induced birth or labor or planned cesarean section), 223 were spontaneous preterm births, and nine could not be classified.
The risks for both birth types increased with increasing HbA1c category, but to a greater degree for medically indicated preterm birth.
Specifically, the aRRs for medically indicated preterm birth were 5.26, 7.42, 11.75, and 17.51, for women with periconception HbA1c levels of less than 6.5%, 6.5% to less than 7.8%, 7.8% to less than 9.1%, and 9.1% or higher, respectively, relative to women without diabetes.
The corresponding aRRs for spontaneous preterm birth were 1.81, 2.86, 2.88, and 2.80.
Ludvigsson and team found that increasing HbA1c levels were also significantly associated with the risk for having a child large for gestational age and a low Agpar score as well as hypoglycemia and respiratory distress at birth.
Furthermore, there was a significant positive relationship between HbA1c and both stillbirth and neonatal death, but only at levels above 7.8%, where the aRR ranged from 3.95 to 10.92.
The researchers conclude in the Annals of Internal Medicine that “preterm birth among women with [type 1 diabetes] was strongly linked to periconceptional HbA1c levels, although women whose HbA1c levels were consistent with recommended target values also were at increased risk for preterm birth as well as other adverse pregnancy outcomes.”
They add that although the “data are important for developing future guidelines and informing clinicians about the risks associated with poor glycemic control […] 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 among women with [type 1 diabetes].”
By Laura Cowen
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