Evidence map›Paper›PMID 27166384›Full record

ArticleCirculation2016

Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease: A Nationwide Cohort Study.

Nina Øyen, Lars J Diaz, Elisabeth Leirgul, Heather A Boyd, James Priest, Elisabeth R Mathiesen, Thomas Quertermous, Jan Wohlfahrt, Mads Melbye

Open access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 5 pooled it
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

141 citing papers in PubMed, 5 syntheses or guidelines pooled it, 263 citations in OpenAlex.

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  14. Subclinical Changes in Cardiovascular Function During the Neonatal Period in Infants Born to Mothers With Diabetes.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026
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81 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Nina ØyenFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.). noy@ssi.dk.
Lars J DiazFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
Elisabeth LeirgulFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
Heather A BoydFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
James PriestFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
Elisabeth R MathiesenFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
Thomas QuertermousFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
Jan WohlfahrtFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
Mads MelbyeFrom Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark (N.Ø., L.J.D., H.A.B., J.W., M.M.); Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Norway (N.Ø., E.L.); Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway(N.Ø.); Department of Cardiology, Haukeland University Hospital, Bergen, Norway (E.L.); Cardiovascular Institute, Stanford University School of Medicine, CA (J.P., T.Q.); Center for Pregnant Women with Diabetes, Department of Endocrinology, University of Copenhagen, Denmark (E.R.M.); Department of Medicine, Stanford University School of Medicine, CA (M.M.); and Department of Clinical Medicine, University of Copenhagen, Denmark (M.M.).
Stanford University · USUniversity of Copenhagen · DKCardiovascular Institute of the South · US

Funding

Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
Genetic Mechanisms of Congenital Heart DiseaseR00HL130523 · NHLBI · STANFORD UNIVERSITY · PI PRIEST, JAMES R. · 2017 to 2019
$747k
Genetic Mechanisms of Congenital Heart DiseaseK99HL130523 · NHLBI · STANFORD UNIVERSITY · PI PRIEST, JAMES R. · 2016 to 2017
$306k
NHLBI NIH HHS K99 HL130523NHLBI NIH HHS R00 HL130523NICHD NIH HHS K12 HD000850
6 · The paper itself

Abstract

backgroundMaternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort. METHODS AND

resultsIn a national cohort study, we identified 2 025 727 persons born from 1978 to 2011; among them were 7296 (0.36%) persons exposed to maternal pregestational diabetes mellitus. Pregestational diabetes mellitus was identified by using the National Patient Register and individual-level information on all prescriptions filled in Danish pharmacies. Persons with CHD (n=16 325) were assigned to embryologically related cardiac phenotypes. The CHD prevalence in the offspring of mothers with pregestational diabetes mellitus was 318 per 10 000 live births (n=232) in comparison with a baseline risk of 80 per 10 000; the adjusted relative risk for CHD was 4.00 (95% confidence interval, 3.51-4.53). The association was not modified by year of birth, maternal age at diabetes onset, or diabetes duration, and CHD risks associated with type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes mellitus did not differ significantly. Persons born to women with previous acute diabetes complications had a higher CHD risk than those exposed to maternal diabetes mellitus without complications (relative risk, 7.62; 95% confidence interval, 5.23-10.6, and relative risk, 3.49; 95% confidence interval, 2.91-4.13, respectively; P=0.0004). All specific CHD phenotypes were associated with maternal pregestational diabetes mellitus (relative risk range, 2.74-13.8).

conclusionsThe profoundly increased CHD risk conferred by maternal pregestational diabetes mellitus neither changed over time nor differed by diabetes subtype. The association with acute pregestational diabetes complications was particularly strong, suggesting a role for glucose in the causal pathway.

Indexed as

Prenatal Exposure Delayed EffectsAdolescentAdultDenmarkDiabetes, GestationalDiabetes MellitusFemaleHeart Defects, CongenitalHumansHypoglycemic AgentsMalePregnancyPregnancy in DiabeticsPrevalenceRegistriesRisk AssessmentHypoglycemic Agentscongenital abnormalitiesdiabetes mellitusheart defects, congenitalinsulinpregnancy

Identifiers

PMID27166384
PMCPMC4890838
OpenAlexW2372435063

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.