Type 1 Diabetes Tied to Increased Risk for Preterm Birth

Veronica Hackethal, MD

April 23, 2019

Pregnant women with type 1 diabetes may be at increased risk for preterm birth, and that risk seems to increase as blood glucose control worsens, according to a study published online on April 22 in Annals of Internal Medicine.

"We found that women with type 1 diabetes are at increased risk of having a preterm born child, even if they adhere to recommended blood sugar levels [HbA1c], but the risks increased substantially when the blood sugar was high," first author Jonas Ludvigsson, MD, PhD, of the Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.

"We also found that, in women with type 1 diabetes, several other adverse pregnancy outcomes increase with high HbA1c," he added.

Infants born to women with type 1 diabetes were at increased risk of being large for gestational age (LGA), as well as increased risk for hypoglycemia, respiratory distress, birth injury, low Apgar scores, and stillbirth.

However, Ludvigsson stressed that most newborns of women with type 1 diabetes are not affected.

"It should be emphasized that most newborns of mothers with type 1 diabetes are fine at birth and do not suffer from any adverse pregnancy outcomes," he continued.

Preterm birth represents the second most common cause of death in children under age 5 years and past studies have suggested that children of women with type 1 diabetes are at increased risk for preterm birth.

The American Diabetes Association, Endocrine Society, and UK National Institute for Health and Care Excellence all recommend keeping HbA1c below 6.5% during early pregnancy in women with type 1 diabetes. But those guidelines are based on research on congenital malformations and LGA. Whether strict glycemic control can affect risk for preterm birth has been less clear.  

The researchers conducted a population-based cohort study using Swedish national registers for 2003 to 2014. The study included 2474 singleton babies born to women with type 1 diabetes who had at least one HbA1c around the time of conception and 1,165,216 babies born to women without diabetes. The primary outcome was risk for preterm birth before 37 weeks' gestation. The analysis adjusted for calendar year, maternal age, country of birth, living with a partner, education, number of past pregnancies, body mass index, smoking, and autoimmune disease.

Among women with type 1 diabetes, 22.3% (552/2474) of babies were born preterm, compared with 4.7% (54,287/1,165,216) of babies born to mothers without diabetes.

Risk for preterm birth was increased even among women with HbA1c levels below the guideline-recommended value of 6.5% around the time of conception, compared with women without type 1 diabetes (13.2% vs 4.7%; adjusted risk ratio [aRR], 2.83).

Additional analyses using a stricter HbA1c cutoff of 6.0% showed a similar risk for preterm birth as for those with an HbA1c < 6.5% (aRR, 2.88).

The risk for preterm birth progressively rose with increasing HbA1c levels. The rates of preterm birth were 20.6% (aRR, 4.22), 28.3% (aRR, 5.56), and 37.5% (aRR, 6.91) for those with HbA1c 6.5% to < 7.8%, 7.8% to 9.1%, and ≥ 9.1%, respectively.

Increased risk for preterm birth was largely associated with medically indicated preterm birth, at 5.26, 7.42, 11.75, and 17.51 for those with HbA1c < 6%, 6.5% to < 7.8%, 7.8% to 9.1%, and ≥ 9.1%, respectively.

However, babies born to mothers with type 1 diabetes also had an increased risk for spontaneous preterm birth compared to mothers without diabetes, at 1.81, 2.86, 2.88, and 1.80 for those with HbA1c < 6%, 6.5% to < 7.8%, 7.8% to 9.1%, and ≥ 9.1%, respectively).

Babies born to women with type 1 diabetes also were at increased risk for worse neonatal outcomes, and these risks increased as HbA1c levels rose. Risks for LGA, macrosomia, hypoglycemia, respiratory distress, and low Apgar scores at 5 minutes seemed to level off around HbA1c 6.5% to < 7.8% and HbA1c 7.8% to 9.1%. Risk for neonatal death and stillbirth only appeared to increase with HbA1c levels ≥ 7.8%.

The exception was birth injury. At all HbA1c levels, infants of mothers with type 1 diabetes were at about three times increased risk for this outcome compared with mothers without type 1 diabetes.  

The authors emphasized that babies born to women with type 1 diabetes were at increased risk for preterm birth even with glycemic control that met guidelines (HbA1c < 6.5%) or exceeded them (HbA1c 6.0%). That suggests type 1 diabetes itself may confer increased risk for preterm birth and risk increases as glycemic control worsens. It may not necessarily mean that guidelines need to recommend even tighter glycemic control.   

"Our results do not suggest that a lower HbA1c cutoff (< 6.0%) would lower the risk of preterm birth. It seems that there is some excess risk of preterm birth in women with type 1 diabetes independent of HbA1c levels," Ludvigsson said.

"I believe that clinicians already work hard to help women with type 1 diabetes achieve the recommended HbA1c levels. Our study underlines the importance of that effort," he concluded.

The study had several limitations. HbA1c values came from annual routine visits and were not available for all women. The study looked only at HbA1c levels around conception, and some evidence suggests HbA1c later in pregnancy may better predict preterm birth. Also, the study lacked information on physical activity, alcoholic beverage consumption, and race/ethnicity. Management of type 1 diabetes may differ according to country of residence, which could affect risks for preterm birth. 

The study was funded by the Swedish Diabetes Foundation, Swedish Research Council, Stockholm County Council, and Karolinska Institutet. One or more authors has reported receiving grants and/or personal fees from one or more of the following: Pfizer, AstraZeneca, Swedish Diabetes Foundation, Strategic Research Area Epidemiology Program at the Karolinska Institutet, Swedish Research Council, and/or Novo Nordisk.

Ann Intern Med. Published online April 22, 2019. Abstract

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