Jonas F Ludvigsson1, Martin Neovius2, Jonas Söderling2, Soffia Gudbjörnsdottir3, Ann-Marie Svensson4, Stefan Franzén3, Olof Stephansson2, Björn Pasternak5. 1. Karolinska Institutet, Stockholm, Sweden, Örebro University Hospital, Örebro, Sweden, University of Nottingham, Nottingham, United Kingdom, and Columbia University College of Physicians and Surgeons, New York, New York (J.F.L.). 2. Karolinska Institutet, Stockholm, Sweden (M.N., J.S., O.S.). 3. Karolinska Institutet, Stockholm, Sweden; Centre of Registers Västra Götaland and University of Gothenburg, Gothenburg, Sweden (S.G., S.F.). 4. Centre of Registers Västra Götaland, Gothenburg, Sweden (A.S.). 5. Karolinska Institutet, Stockholm, Sweden, and Statens Serum Institut, Copenhagen, Denmark (B.P.).
Abstract
Background: Maternal type 1 diabetes (T1D) has been linked to preterm birth and other adverse pregnancy outcomes. How these risks vary with glycated hemoglobin (or hemoglobin A1c [HbA1c]) levels is unclear. Objective: To examine preterm birth risk according to periconceptional HbA1c levels in women with T1D. Design: Population-based cohort study. Setting: Sweden, 2003 to 2014. Patients: 2474 singletons born to women with T1D and 1 165 216 reference infants born to women without diabetes. Measurements: Risk for preterm birth (<37 gestational weeks). Secondary outcomes were neonatal death, large for gestational age, macrosomia, infant birth injury, hypoglycemia, respiratory distress, 5-minute Apgar score less than 7, and stillbirth. Results: Preterm birth occurred in 552 (22.3%) of 2474 infants born to mothers with T1D versus 54 287 (4.7%) in 1 165 216 infants born to mothers without diabetes. The incidence of preterm birth was 13.2% in women with a periconceptional HbA1c level below 6.5% (adjusted risk ratio [aRR] vs. women without T1D, 2.83 [95% CI, 2.28 to 3.52]), 20.6% in those with a level from 6.5% to less than 7.8% (aRR, 4.22 [CI, 3.74 to 4.75]), 28.3% in those with a level from 7.8% to less than 9.1% (aRR, 5.56 [CI, 4.84 to 6.38]), and 37.5% in those with a level of 9.1% or higher (aRR, 6.91 [CI, 5.85 to 8.17]). The corresponding aRRs for medically indicated preterm birth (n = 320) were 5.26 (CI, 3.83 to 7.22), 7.42 (CI, 6.21 to 8.86), 11.75 (CI, 9.72 to 14.20), and 17.51 (CI, 14.14 to 21.69), respectively. The corresponding aRRs for spontaneous preterm birth (n = 223) were 1.81 (CI, 1.31 to 2.52), 2.86 (CI, 2.38 to 3.44), 2.88 (CI, 2.23 to 3.71), and 2.80 (CI, 1.94 to 4.03), respectively. Increasing HbA1c levels were associated with the study's secondary outcomes: large for gestational age, hypoglycemia, respiratory distress, low Apgar score, neonatal death, and stillbirth. Limitation: Because HbA1c levels were registered annually at routine visits, they were not available for all pregnant women with T1D. Conclusion: The risk for preterm birth was strongly linked to periconceptional HbA1c levels. Women with HbA1c levels consistent with recommended target levels also were at increased risk. Primary Funding Source: Swedish Diabetes Foundation.
Background: Maternal type 1 diabetes (T1D) has been linked to preterm birth and other adverse pregnancy outcomes. How these risks vary with glycated hemoglobin (or hemoglobin A1c [HbA1c]) levels is unclear. Objective: To examine preterm birth risk according to periconceptional HbA1c levels in women with T1D. Design: Population-based cohort study. Setting: Sweden, 2003 to 2014. Patients: 2474 singletons born to women with T1D and 1 165 216 reference infants born to women without diabetes. Measurements: Risk for preterm birth (<37 gestational weeks). Secondary outcomes were neonatal death, large for gestational age, macrosomia, infantbirth injury, hypoglycemia, respiratory distress, 5-minute Apgar score less than 7, and stillbirth. Results:Preterm birth occurred in 552 (22.3%) of 2474 infants born to mothers with T1D versus 54 287 (4.7%) in 1 165 216 infants born to mothers without diabetes. The incidence of preterm birth was 13.2% in women with a periconceptional HbA1c level below 6.5% (adjusted risk ratio [aRR] vs. women without T1D, 2.83 [95% CI, 2.28 to 3.52]), 20.6% in those with a level from 6.5% to less than 7.8% (aRR, 4.22 [CI, 3.74 to 4.75]), 28.3% in those with a level from 7.8% to less than 9.1% (aRR, 5.56 [CI, 4.84 to 6.38]), and 37.5% in those with a level of 9.1% or higher (aRR, 6.91 [CI, 5.85 to 8.17]). The corresponding aRRs for medically indicated preterm birth (n = 320) were 5.26 (CI, 3.83 to 7.22), 7.42 (CI, 6.21 to 8.86), 11.75 (CI, 9.72 to 14.20), and 17.51 (CI, 14.14 to 21.69), respectively. The corresponding aRRs for spontaneous preterm birth (n = 223) were 1.81 (CI, 1.31 to 2.52), 2.86 (CI, 2.38 to 3.44), 2.88 (CI, 2.23 to 3.71), and 2.80 (CI, 1.94 to 4.03), respectively. Increasing HbA1c levels were associated with the study's secondary outcomes: large for gestational age, hypoglycemia, respiratory distress, low Apgar score, neonatal death, and stillbirth. Limitation: Because HbA1c levels were registered annually at routine visits, they were not available for all pregnant women with T1D. Conclusion: The risk for preterm birth was strongly linked to periconceptional HbA1c levels. Women with HbA1c levels consistent with recommended target levels also were at increased risk. Primary Funding Source: Swedish Diabetes Foundation.
Authors: Mukkesh Kumar; Li Ting Ang; Hang Png; Maisie Ng; Karen Tan; See Ling Loy; Kok Hian Tan; Jerry Kok Yen Chan; Keith M Godfrey; Shiao-Yng Chan; Yap Seng Chong; Johan G Eriksson; Mengling Feng; Neerja Karnani Journal: Int J Environ Res Public Health Date: 2022-06-01 Impact factor: 4.614