Increased risk of multicystic dysplastic kidney among babies of both pre-gestational and gestational diabetic mothers.

Abstract

Pre-gestational maternal diabetes mellitus (DM) is a well-established risk factor for congenital malformations in the offspring [1]. Recent epidemiological studies have shown a significant increase of anomalies also in the offspring of gestational diabetic mothers [3, 5]. Certain malformations have been recognised to be overrepresented, namely cardiovascular, CNS, and musculoskeletal defects, caudal regression in particular [1, 3, 4]. An association between maternal DM and renal and urinary tract malformations has been postulated as well, but reported cases have been mostly anecdotal and rather nonspecific [1, 3, 4]. Multicystic dysplastic kidney (MDK) is generally considered to represent a sporadic form of congenital cystic renal disease. It is thought to arise early (at about 5 to 6 weeks of gestation) due to obstruction of the ureteric bud. Thus MDK is an ideal malformation for studying the possible effects of the imbalance of maternal glucose metabolism on embryonic development of the kidneys and the urinary tract. In the present study the relationship between both pregestational and gestational DM, and MDK in the offspring was investigated in a well-defined population. The study population comprised all infants born with MDK between 1990 and 2001 in the Greater Helsinki area, Finland. During the study period, altogether 209,125 live infants were born in the same area (population data, Greater Helsinki area, Finland). An ultrasound examination was performed routinely in all mothers. Of the mothers studied, 0.38% had pre-gestational DM and 0.50% had gestational DM [2]. Gestational DM was diagnosed using a 75 g 2 h oral glucose tolerance test (OGTT) at 28–32 gestational weeks. For pathological thresholds, mean glucose values +2SD were chosen and at least two out of three had to be abnormal (fasting 4.4 mmol/l, 1 h 9.1 mmol/ l, 2 h 7.4 mmol/l, venous whole blood). An OGTT was performed in all women with any known risk factor for gestational DM. Maternity clinic and obstetric records of all women with MDK in the offspring were carefully reviewed, including not only maternal DM but also other common teratogenic factors (e.g. teratogenic medications, reproductive hormones, alcohol, narcotics, teratogenic infections). None of the infants with MDK had been exposed to any of these other common teratogenic factors during gestation. MDK was defined as a renal tissue conglomerate consisting ultrasonographically of cysts of variable size, with scanty or no identifiable renal parenchyma in between, and with no uptake in the renal isotope scan. For statistical evaluation, the relative risk (RR) was calculated and the Chi squared test used to estimate the statistical significance. In the study population, 51 infants were born with MDK. The prevalence of MDK was thus 1 in 4100 live births. Eight babies with MDK were born to diabetic mothers, comprising 16% of the total. Three mothers had insulin-dependent pre-gestational DM and five had gestational DM. The overall RR for MDK among infants of mothers with pre-gestational (n=795) or gestational (n=1046) DM was as high as 20.95 (P<0.0001) (Table 1). Improved preconceptional, gestational and postnatal care has significantly decreased the incidence of spontaneous abortions and stillbirths in offspring of diabetic mothers. The frequency of congenital malformations has, interestingly, remained constant. Careful examination for congenital anomalies, including the urinary tract and the kidneys in particular, of infants born to diabetic mothers, is recommended. Eur J Pediatr (2002) 161: 634–635 DOI 10.1007/s00431-002-1043-4