Congenital abnormalities in the offspring of pregnant women with type 1, type 2 and gestational diabetes mellitus: A population‐based case‐control study

To estimate the risk of structural birth defects (i.e. congenital abnormalities [CA]) in the offspring of pregnant women with type 1 (DM‐1), type 2 (DM‐2) and gestational diabetes mellitus (GDM) and to check the efficacy of recent specific care of diabetic pregnant women in the reduction of DM‐related CA. Comparison was made of the occurrence of medically recorded types of diabetes mellitus in pregnant women who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population‐based Hungarian Case‐Control Surveillance System of Congenital Abnormalities, 1980–1996. In the case group, which included 22 843 offspring, there were 79 (0.35%) pregnant women with DM‐1, 77 (0.34%) pregnant women with DM‐2 and 120 (0.53%) pregnant women with GDM. The control group comprised 38 151 newborns, and 88 (0.23%), 141 (0.37%) and 229 (0.60%) pregnant women with DM‐1, DM‐2 and GDM, respectively. The total rate of cases with CA was higher only in the DM‐1 group (adjusted OR with 95% CI: 1.5, 1.1–2.0) and within four specific types/groups: isolated renal a/dysgenesis, obstructive CA of the urinary tract, cardiovascular CA and multiple CA; namely, caudal dysplasia sequence. The risk of total CA was lower in the present study compared to the risk in previous studies and the DM‐1‐related spectrum of CA was also different. There was no higher risk of total CA in the offspring of pregnant women with DM‐2 and GDM. The certain part of maternal teratogenic effect of DM‐1 is preventable with appropriate periconceptional and prenatal care of diabetic women.

[1]  E. Reece,et al.  Gestational diabetes: the need for a common ground , 2009, The Lancet.

[2]  R. D'Agostino,et al.  Genotype score in addition to common risk factors for prediction of type 2 diabetes. , 2008, The New England journal of medicine.

[3]  A. Czeizel,et al.  Use of specified critical periods of different congenital abnormalities instead of the first trimester concept. , 2008, Birth defects research. Part A, Clinical and molecular teratology.

[4]  A. Czeizel,et al.  No association between periconceptional multivitamin supplementation and risk of multiple congenital abnormalities: A population‐based case‐control study , 2006, American journal of medical genetics. Part A.

[5]  A. Czeizel,et al.  MATERNAL EMPLOYMENT STATUS AND ISOLATED OROFACIAL CLEFTS IN HUNGARY , 2008 .

[6]  K. Rothman,et al.  Risk of specific congenital abnormalities in offspring of women with diabetes , 2005, Diabetic medicine : a journal of the British Diabetic Association.

[7]  A. Czeizel,et al.  Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital abnormalities. , 2004, Birth defects research. Part A, Clinical and molecular teratology.

[8]  A. Czeizel,et al.  Periconceptional folic acid/multivitamin supplementation and twin pregnancy. , 2004, American journal of obstetrics and gynecology.

[9]  M. Hod,et al.  Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes , 2004, Diabetic medicine : a journal of the British Diabetic Association.

[10]  A. Czeizel,et al.  Periconceptional Multivitamin Supplementation and Multimalformed Offspring , 2003, Obstetrics and gynecology.

[11]  A. Czeizel,et al.  Validation studies of drug exposures in pregnant women , 2003, Pharmacoepidemiology and drug safety.

[12]  H. Kalter Maternal diabetes mellitus and infant malformations. , 2003, Obstetrics and gynecology.

[13]  K. Leveno,et al.  Maternal Diabetes Mellitus and Infant Malformations , 2002, Obstetrics and gynecology.

[14]  M. Lucas,et al.  Diabetes complicating pregnancy. , 2001, Obstetrics and gynecology clinics of North America.

[15]  C. Loffredo,et al.  Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants. , 2001, Teratology.

[16]  Erika Varga,et al.  Description and mission evaluation of the Hungarian case-control surveillance of congenital abnormalities, 1980-1996. , 2001, Teratology.

[17]  B. Källén,et al.  Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes. , 2001, Early human development.

[18]  T. Buchanan,et al.  Patterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetes. , 2000, American journal of obstetrics and gynecology.

[19]  A. Czeizel,et al.  Dose-dependent effect of folic acid on the prevention of orofacial clefts. , 1999, Pediatrics.

[20]  A. Czeizel Ten years of experience in periconceptional care. , 1999, European journal of obstetrics, gynecology, and reproductive biology.

[21]  E. Bermejo,et al.  Epidemiological analysis of outcomes of pregnancy in gestational diabetic mothers. , 1998, American journal of medical genetics.

[22]  A. Czeizel First 25 years of the Hungarian congenital abnormality registry. , 1997, Teratology.

[23]  A. Czeizel Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. , 1996, American journal of medical genetics.

[24]  M. Baraitser Congenital Limb Deficiencies in Hungary , 1995 .

[25]  A. Czeizel,et al.  What proportion of congenital abnormalities can be prevented? , 1993, BMJ.

[26]  A. Czeizel,et al.  Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. , 1992, The New England journal of medicine.

[27]  M. Gnant,et al.  Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study , 1991, The Lancet.

[28]  R. McCarter,et al.  Maternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosus. , 1990, Teratology.

[29]  M. Khoury,et al.  Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. , 1990, Pediatrics.

[30]  E. Barrett-Connor,et al.  The effect of parity on the later development of non-insulin-dependent diabetes mellitus or impaired glucose tolerance. , 1989, The New England journal of medicine.

[31]  J. Kitzmiller,et al.  Prenatal diagnosis of neural tube defects. VIII. The importance of serum alpha-fetoprotein screening in diabetic pregnant women. , 1982, American journal of obstetrics and gynecology.

[32]  E. Passarge,et al.  Syndrome of caudal regression in infants of diabetic mothers: observations of further cases. , 1966, Pediatrics.

[33]  S. Driscoll,et al.  CONGENITAL SPINAL ANOMALIES IN INFANTS OF DIABETIC MOTHERS. , 1965, Pediatrics.

[34]  W. Maier,et al.  Mißbildungen der Beine und der kaudalen Wirbelsäule bei Kindern diabetischer Mütter , 1965 .

[35]  J. Kucera,et al.  [MALFORMATION OF THE LEGS AND CAUDAL SECTION OF THE SPINE IN INFANTS BORN TO DIABETIC MOTHERS]. , 1965, Deutsche medizinische Wochenschrift.

[36]  I. Tygstrup,et al.  CONGENITAL MALFORMATIONS IN NEWBORN INFANTS OF DIABETIC WOMEN. CORRELATION WITH MATERNAL DIABETIC VASCULAR COMPLICATIONS. , 1964, Lancet.

[37]  Catherine Kim,et al.  Recurrence of gestational diabetes: a systematic review , 2007 .

[38]  M. Greene,et al.  Spontaneous Abortions and Major Malformations in Women with Diabetes Mellitus , 1999, Seminars in reproductive endocrinology.

[39]  E. Reece,et al.  Pregnancy outcomes among women with and without diabetic microvascular disease (White's classes B to FR) versus non-diabetic controls. , 1998, American journal of perinatology.

[40]  B. Brambati,et al.  [Prenatal diagnosis of neural tube defects]. , 1982, La Pediatria medica e chirurgica : Medical and surgical pediatrics.

[41]  R. Jackson,et al.  Diabetes in pregnancy. , 1965, The Journal of the Indiana State Medical Association.