Maternal Diabetes and Infant Malformations

Abstract & Commentary

Synopsis: Women with pregestational diabetes or gestational diabetes plus fasting hyperglycemia have a 3- to 4-fold increased risk of infant malformations, whereas women with mild gestational diabetes have malformation rates no different than the general nondiabetic obstetric population.

Source: Sheffield JS, et al. Obstet Gynecol. 2002;100: 925-930.

Sheffield and colleagues recently reviewed data from Parkland Hospital between 1991 and 2000 during which time pregnant patients were compulsively screened for diabetes. The institution’s computerized database allowed Sheffield et al to track outcome in each of the 145,196 patients delivering during this period. Pregestational diabetics were diagnosed before pregnancy. Gestational diabetics were broken down into those with elevated fasting blood sugars (A2) and those with normal fasting levels (A1).

About 2% of the population screened was diagnosed to have gestational diabetes, 10% of which had elevated fasting glucoses. Pregestational diabetes was noted in 0.3% of the study group.

The incidence of all malformations in the pregestational diabetes was 6.1%, 4.8% in the A2 diabetics, and 1.2% in the A1 diabetics, compared with 1.5% in the nondiabetic population. The odds ratio was 4.4 (CI, 2.9- 6.6) for pregestational diabetes, 3.4 (CI, 1.9-6.2) for A2 diabetics, and 0.8 (CI, 0.5-1.2) for A1 diabetics, compared with nondiabetics. The overwhelming majority of the anomalies involved the central nervous system and heart.

Comment by John C. Hobbins, MD

The prevalence rate of anomalies in the study of only 1.5% suggests incomplete ascertainment of anomalies at birth (this rate is usually well above 2%). Nevertheless, the message is quite clear. Pregestational diabetics have a very high rate of anomalies and those gestational diabetics with elevated fasting blood sugars have an anomaly rate that almost equals those diagnosed before pregnancy. Most importantly, a normal fasting glucose level during organogenesis assures the patient of a risk that is no greater than found in the overall normal glycemic population.

Although this makes intuitive sense, this study backs up, with large numbers implications, made from past observations. Glycosolated hemoglobin (Hb A1C) has been used to assess the status of glucose tolerance many weeks before the test is drawn, and if sampled in the second trimester, can give the clinician an indirect idea of glucose levels in the first trimester, when the neural tube is closing (20-29 days postconception) and the heart is being formed. Those with normal fasting glucoses can be reassured that their risk of anomalies is no greater than the overall population (from conception until 8 ½ menstrual weeks). Many studies have shown that the higher the Hb A1C, the greater the chance of fetal anomalies.

Although every patient with any type of diabetes should have a very detailed second trimester ultrasound evaluation to rule out fetal anomalies, an enlightened regimen might now include a first trimester ultrasound evaluation in all diabetics and a later fetal echocardiogram in some.

The recent thrust of early prenatal diagnosis has been centered around the assessment of fetal nuchal translucency (NT) in screening for Down syndrome. There has been important fallout information regarding fetal heart anomalies. Six to 7% of fetuses with an increased NT will have a cardiac defect. Approximately 40% of fetuses with cardiac anomalies will have an NT above the 95th percentile. Also, the larger the NT, the greater the chance of a cardiac abnormality.

If the NT is normal, the chances of a cardiac anomaly diminishes appreciably and the patient can be reassured but not to the point of excluding a detailed fetal evaluation later in pregnancy. If the NT is increased, then diagnostic scrutiny should be heightened and particular attention should be paid to the heart in the second trimester. Reports are emerging regarding very early (first trimester) and somewhat later (14-16 weeks) diagnosis of fetal heart anomalies. However, in general, based on the general experience of ultrasound practitioners in the United States, the bigger the target the better the accuracy of the diagnosis of cardiac defects.

Regarding central nervous system defects, an early maternal serum triple screen (MSAFP), combined with a detailed ultrasound examination in the second trimester by a very experienced operator, should allow the exclusion of spina bifida in virtually 100% of cases. (Anencephaly will have been excluded in the 11-13 week scan.) Caudal regression syndrome is almost pathognomonic for diabetes, but fortunately is very rare in diabetics and this should be identified in either the early or second-trimester scan.

Last, the full fetal echocardiogram can be booked for pregestational and A2 diabetics after 18-20 weeks of gestation, when accuracy is optimized. Many of the most troublesome cardiac anomalies should be picked up during the earlier scan, and the full fetal echocardiogram should add the necessary icing on the cake to identify the odd major anomaly missed earlier and to aid in the management of a fetus with a more subtle problem requiring special attention after birth.

Dr. Hobbins is Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver.

Reference

1. Hyett JA. Prenat Diagn. 2002;22:864-868.