Congenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysis.
OBJECTIVE
Investigation of the incidence and distribution of congenital structural cardiac malformations among the offspring of mothers with diabetes type 1 and of the influence of periconceptional glycemic control.


METHODS
Multicenter retrospective clinical study, literature review, and meta-analysis. The incidence and pattern of congenital heart disease in the own study population and in the literature on the offspring of type 1 diabetic mothers were compared with the incidence and spectrum of the various cardiovascular defects in the offspring of nondiabetic mothers as registered by EUROCAT Northern Netherlands. Medical records were, in addition, reviewed for HbA(1c) during the 1st trimester.


RESULTS
The distribution of congenital heart anomalies in the own diabetic study population was in accordance with the distribution encountered in the literature. This distribution differed considerably from that in the nondiabetic population. Approximately half the cardiovascular defects were conotruncal anomalies. The authors' study demonstrated a remarkable increase in the likelihood of visceral heterotaxia and variants of single ventricle among these patients. As expected, elevated HbA(1c) values during the 1st trimester were associated with offspring fetal cardiovascular defects.


CONCLUSIONS
This study shows an increased likelihood of specific heart anomalies, namely transposition of the great arteries, persistent truncus arteriosus, visceral heterotaxia and single ventricle, among offspring of diabetic mothers. This suggests a profound teratogenic effect at a very early stage in cardiogenesis. The study emphasizes the frequency with which the offspring of diabetes-complicated pregnancies suffer from complex forms of congenital heart disease. Pregnancies with poor 1st-trimester glycemic control are more prone to the presence of fetal heart disease.
Academic Medical Center, Amsterdam, The Netherlands.
Lukas A
LA
Lisowski
Paul M
PM
Verheijen
Joshua A
JA
Copel
Charles S
CS
Kleinman
Sander
S
Wassink
Gerard H A
GH
Visser
Erik-Jan
EJ
Meijboom
D003431:Cross-Cultural Comparison; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D004200:Diseases in Twins / Q000175:diagnosis / Q000453:epidemiology; D005060:Europe; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use; D009426:Netherlands; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D011272:Pregnancy, Multiple; D012016:Reference Values; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D016216:Ultrasonography, Prenatal; D014481:United States
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human