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.
To examine preterm birth risk according to periconceptional HbA1c levels in women with T1D.
Population-based cohort study.
Sweden, 2003 to 2014.
2474 singletons born to women with T1D and 1 165 216 reference infants born to women without diabetes.
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.
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.
Because HbA1c levels were registered annually at routine visits, they were not available for all pregnant women with T1D.
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.
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Author, Article, and Disclosure Information
Jonas F. Ludvigsson,
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.)
Karolinska Institutet, Stockholm, Sweden (M.N., J.S., O.S.)
Karolinska Institutet, Stockholm, Sweden; Centre of Registers Västra Götaland and University of Gothenburg, Gothenburg, Sweden (S.G., S.F.)
Centre of Registers Västra Götaland, Gothenburg, Sweden (A.S.)
Karolinska Institutet, Stockholm, Sweden, and Statens Serum Institut, Copenhagen, Denmark (B.P.)
Grant Support: By grants from the Swedish Diabetes Foundation. Dr. Pasternak was supported by an investigator grant from the Strategic Research Area Epidemiology Program at Karolinska Institutet and the Swedish Research Council (2016-01974). Dr. Stephansson was supported by grants from the Swedish Research Council (2013-2429) and the Stockholm County Council (ALF project 20130156) and received financial support from the strategic Research Program in Epidemiology at Karolinska Institutet.
Disclosures: Dr. Neovius reports grants from Pfizer and AstraZeneca and personal fees from Itrim, outside the submitted work. Dr. Pasternak reports grants from the Swedish Diabetes Foundation, Strategic Research Area Epidemiology Program at Karolinska Institutet, and Swedish Research Council during the conduct of the study, and grants from the Novo Nordisk Foundation outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1974.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol: Available from Dr. Ludvigsson (e-mail, jonasludvigsson@yahoo.
Corresponding Author: Jonas F. Ludvigsson, MD, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden; e-mail, jonasludvigsson@yahoo.
Current Author Addresses: Dr. Ludvigsson: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
Drs. Neovius, Söderling, Stephansson, and Pasternak: Clinical Epidemiology Division T2, Department of Medicine Solna, Karolinska Institutet, 17176 Stockholm, Sweden.
Drs. Gudbjörnsdottir, Svensson, and Franzén: The Swedish National Diabetes Register, Västra Götalandsregionen, Medicinaregatan 18G, Gothenburg 413 45, Sweden.
Author Contributions: Conception and design: J.F. Ludvigsson, M. Neovius, J. Söderling, S. Gudbjörnsdottir, A.M. Svensson, S. Franzén, O. Stephansson, B. Pasternak.
Analysis and interpretation of the data: J.F. Ludvigsson, M. Neovius, J. Söderling, B. Pasternak.
Drafting of the article: J.F. Ludvigsson.
Critical revision for important intellectual content. J.F. Ludvigsson, M. Neovius, J. Söderling, S. Gudbjörnsdottir, A.M. Svensson, S. Franzén, O. Stephansson, B. Pasternak.
Final approval of the article: J.F. Ludvigsson, M. Neovius, J. Söderling, S. Gudbjörnsdottir, A.M. Svensson, S. Franzén, O. Stephansson, B. Pasternak.
Provision of study materials or patients: M. Neovius, A.M. Svensson.
Statistical expertise: J.F. Ludvigsson, J. Söderling, S. Franzén.
Obtaining of funding: M. Neovius, B. Pasternak.
Administrative, technical, or logistic support: J.F. Ludvigsson, M. Neovius.
Collection and assembly of data: J.F. Ludvigsson, M. Neovius, A.M. Svensson, O. Stephansson, B. Pasternak.
This article was published at Annals.org on 23 April 2019.