Patterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetes.

OBJECTIVES: We sought to determine the types of congenital anomalies affecting infants of women with gestational diabetes mellitus or type 2 diabetes and to examine the relationship between those malformation types and measures of initial glycemia of women at entry into prenatal care with type 2 diabetes or at time of diagnosis in women with gestational diabetes mellitus. STUDY DESIGN: A total of 4,180 pregnancies complicated by gestational diabetes mellitus (n = 3764) or type 2 diabetes (n = 416) that were delivered after 20 weeks of gestation were reviewed for the presence of congenital malformations diagnosed before hospital discharge. Anomalies were categorized as being absent, minor, major, genetic syndromes, or aneuploidies. Major anomalies were further categorized by the number and type of affected organ systems. In addition to maternal clinical and historical parameters, the initial fasting serum glucose either from the diagnostic glucose tolerance test (gestational diabetes mellitus) or at entry to prenatal care (type 2 diabetes) and the initial glycosylated hemoglobin before insulin therapy were examined for a relationship to anomalies. RESULTS: The initial fasting serum glucose and glycosylated hemoglobin levels were significantly higher in pregnancies with major (n = 143) and minor (n = 112) anomalies and genetic syndromes (n = 9) compared with pregnancies with no anomalies (n = 3895). Of those pregnancies with major anomalies, the most commonly affected organ systems were the cardiac (37.6%), musculoskeletal (14.7%), and central nervous systems (9.8%) and anomalies involving multiple organ systems (16%). There was no increased predominance of any specific organ system involvement seen with increasing fasting serum glucose levels in pregnancies with major congenital anomalies. Pregnancies with major anomalies affecting multiple organ systems had significantly higher initial fasting serum glucose levels (166 +/- 64 mg/dL) compared with pregnancies in which one organ system was affected (141 +/- 55 mg/dL, P <.04) or no organ systems were affected (115 +/- 38 mg/dL, P <.0001). CONCLUSION: Congenital anomalies in offspring of women with gestational and type 2 diabetes affect the same organ systems that have been previously described in pregnancies complicated by type 1 diabetes. Increasing hyperglycemia at diagnosis or presentation for care was associated with an increasing risk of anomalies in general and with anomalies involving multiple organ systems without a preferential increase in involvement of specific organ system.

La hipoglucemia como factor de riesgo sobre el desarrollo embrionario en diabetes mellitus. Revisión bibliográfica / Hypoglycemia as a risk factor on the embrionary development in diabetes mellitus

La hipoglucemia, o disminución de la concentración normal de glucosa en sangre, es una secuela importante en el control estricto en pacientes diabéticos tipo 1. En mujeres diabéticas embarazadas, la hipoglucemia al parecer no afecta en gran medida el desarrollo embrionario o fetal; mientras que en roedores, es una importante causa de teratogénesis y/o embriotoxicidad, cuando se presenta durante la organogénesis. A pesar de las diferencias metabólicas, endocrinas y temporales de la gestación en humano y roedor, debe considerarse un posible daño al producto por la hipoglucemia durante el embarazo diabético en humanos

Aphallia as part of urorectal septum malformation sequence in an infant of a diabetic mother.

A male patient with aphallia, anal stenosis, tetralogy of Fallot, multiple vertebral anomalies including sacral agenesis and central nervous system (CNS) malformations was born after a pregnancy complicated by poorly controlled maternal diabetes. Aphallia is an extremely rare abnormality and can be part of the urorectal septum malformation sequence (URSMS). While aphallia has not been reported in infants of diabetic mothers, urogenital malformations are known to occur with increased frequency. Two female products of pregnancies complicated by diabetes presented with multiple malformations including anal atresia and recto-vaginal fistula consistent with the diagnosis of URSMS. The three patients share CNS, cardiac, and vertebral anomalies, abnormalities secondary to abnormal blastogenesis and characteristic of diabetic embryopathy. URSMS is also caused by abnormal blastogenesis. Therefore, this particular malformation should be viewed in the context of the multiple blastogenetic abnormalities in the cases reported here. The overlap of findings of URSMS in our cases with other abnormalities of blastogenesis, such as VATER association or sacral agenesis is not surprising, as these associations are known to lack clear diagnostic boundaries.

Prostanoid production in the umbilicoplacental arterial tree relative to impaired glucose tolerance.

The purpose of this study was to investigate prostanoid synthesis in different segments of the umbilicoplacental vascular tree and its relationship to impaired maternal glucose tolerance. Segments from the umbilical artery and vein, allantochorionic artery branches, and the cotyledon artery from 21 women with diabetes or impaired glucose tolerance and 10 healthy women were studied. Production of prostacyclin (PGI2) and thromboxane (TxA2) metabolites was determined. The Mann-Whitney U test, Wilcoxon signed-ranks matched-pairs test, Kruskal-Wallis test, analysis of variance, and simple linear regression analysis were used. A two-tailed P value of < 0.05 was considered statistically significant. From the umbilical artery distal to the cotyledon artery, the PGI2 synthesis decreased and the TxA2 synthesis increased gradually towards the periphery in normal pregnancy. The PGI2/TxA2 ratio was more than 200 times higher in the umbilical artery than in the cotyledon artery. The TxA2 production tended in general to be higher in the diabetic group than in the control group, resulting in significantly lower PGI2/TxA2 ratios in some vessels. The prostanoid production was not significantly correlated to maternal HbA1c or cord C-peptide concentrations. The balance between vascular prostacyclin and thromboxane synthesis in the umbilicoplacental arterial tree changed gradually towards the periphery: the more peripheral, the lower the prostacyclin and the higher the thromboxane production. The physiological role of this phenomenon is unknown, but may be of importance for the equilibration of vascular tone between arteries of different calibers. The altered prostanoid balance found in diabetic pregnancy was not directly attributable to the degree of maternal glycemic control, but may reflect increased free radical activity and peroxide production in diabetes.