Biliary atresia due to delayed maturation of the gut hormones' system?--Introducing a new treatment modality.

BACKGROUND: Congenital biliary atresia is suspected to originate from prenatal biliary duct inflammation of unknown etiology. OBJECTIVE: Based on clinical grounds, we aimed to establish a hypothesis on the primary cause of inflammation, and to suggest a causal treatment modality. CASE REPORT: History. A 28 years old Turkish woman had lost her first child aged two years from congenital biliary atresia (parents second degree cousins). After a miscarriage, in her otherwise uneventful third pregnancy sonography at 34 wks revealed echogenic material in the fetal gallbladder. Nine days later the gallbladder was completely filled with sludge. Chemical inflammation was suspected, and birth was induced at 36+3 weeks in order to allow for surgical flushing of the bile duct. Neonatal clinical chemistry was insuspicious. There was no spontaneous resolution of the sludge within the first 24 hours of life. A trial of medical treatment with intermittent i.v. secretin (0.03 CU/kg/h) and i.v. coeruletid (60 ng/kg/h) was started. Within 24 hours, sludge had resolved. CONCLUSIONS: We hypothesize that dysmaturation may lead to insufficient induction/production/activity of intrinsic gut hormones resulting in prenatally impaired bile flow, or even inspissated bile. Familial occurrence suggests a genetic defect. Exogenous hormone therapy might be an appropriate treatment modality.

The left portal vein is the watershed of the fetal venous system.

Critical fetal organs are preferentially supplied with oxygenated blood from the umbilical vein (UV) by way of the ductus venosus (DV). Under normal conditions a significant part of UV-blood flows steadily forward through the left portal vein (LPV). Blood flow through the LPV could reverse, however, in cases of absent or reversed endodiastolic flow in the umbilical arteries. We tested when fetal blood flow reversal occurs by studying 28 cases with pathological flow in the umbilical artery. In the LPV we observed normal nonpulsatile forward flow in 9 cases, pulsatile forward flow in 10 cases, and reversed flow in 9 cases. Reverse flow in the LPV correlated significantly with an elevated resistance index of the umbilical arteries. This reversal could have major physiological implications: Deoxygenated blood may be added via the LPV to the blood shifted through the DV and ultimately reach critical fetal organs. In extremis there could be a waterhose effect, whereby more blood flows through the DV than the UV that supplies it. The LPV is thus the watershed of the venous circulation of the fetus.

Determinants of fetal growth at different periods of pregnancies complicated by gestational diabetes mellitus or impaired glucose tolerance.

OBJECTIVE: To determine maternal parameters with the strongest influence on fetal growth in different periods of pregnancies complicated by an abnormal glucose tolerance test (GTT). RESEARCH DESIGN AND METHODS: Retrospective study of 368 women with gestational diabetes mellitus (GDM; > or = 2 abnormal GTT values, n = 280) and impaired glucose tolerance (IGT; one abnormal value, n = 88) with 869 ultrasound examinations at entry to and during diabetic care. Both groups were managed comparably. Abdominal circumference (AC) > or = 90th percentile defined fetal macrosomia. Maternal historical and clinical parameters, and diagnostic and glycemic values of glucose profiles divided into five categories of 4 weeks of gestational age (GA; <24 weeks, 24 weeks/0 days to 27 weeks/6 days, 28/0-31/6, 32/0-35/6, and 36/0-40/0 [referred to as <24 GA, 24 GA, 28 GA, 32 GA, and 36 GA categories, respectively]) were tested by univariate and multiple logistic regression analysis for their ability to predict an AC > or = 90th percentile at each GA group and large-for-gestational-age (LGA) newborn. Data obtained at entry were also analyzed separately irrespective of the GA. RESULTS: Maternal weight, glycemia after therapy, rates of fetal macrosomia, and LGA were not significantly different between GDM and IGT; thus, both groups were analyzed together. LGA in a previous pregnancy, (odds ratio [OR] 3.6; 95% CI 1.8-7.3) and prepregnancy obesity (BMI > or = 30 kg/m(2); 2.1; 1.2-3.7) independently predicted AC > or = 90th percentile at entry. When data for each GA category were analyzed, no predictors were found for <24 GA. Independent predictors for each subsequent GA category were as follows: at 24 GA, LGA history (OR 9.8); at 28 GA, LGA history (OR 4.2), and obesity (OR 3.3); at 32 GA, fasting glucose of 32 GA (OR 1.6 per 5-mg/dl increase); at 36 GA, fasting glucose of 32 GA (OR 1.6); and for LGA at birth, LGA history (OR 2.7), and obesity (OR 2.4). CONCLUSIONS: In the late second and early third trimester, maternal BMI and LGA in a previous pregnancy appear to have the strongest influence on fetal growth, while later in the third trimester coincident with the period of maximum growth described in diabetic pregnancies, maternal glycemia predominates.

Maternal obesity not maternal glucose values correlates best with high rates of fetal macrosomia in pregnancies complicated by gestational diabetes.

AIM: The current therapeutic strategies to reduce macrosomia rates in gestational diabetes (GDM) have focused on the normalizing of maternal glucose levels. The aim of our study was 1.) to compare maternal glycemic values with the presence of fetal macrosomia at different gestational ages (GA) and with LGA at birth in a cohort of women with glucose intolerance and standard diabetic therapy. METHODS: 306 women with GDM and 97 with impaired glucose tolerance underwent ultrasound examinations at entry and, after initiation of therapy, monthly in addition to standard diabetic therapy. Measurements from the entry diagnostic oGTT, glucose profile and HbA1c and from subsequent glucose profiles obtained within 3 days of the ultrasound at 5 categories of GA age (20-23, 24-27 etc) were retrospectively compared between pregnancies with and without fetal macrosomia, defined as an abdominal circumference (AC) > or = 90th percentile. Maternal prepregnancy BMI was adjusted for and BMI > or = 30 kg/m2 was defined as obesity. RESULTS: At entry, neither the hourly oGTT values, HbA1c, nor the entry glucose profile differed significantly between pregnancies with and without fetal macrosomia. In a total of 919 pairs of ultrasound/glucose profiles there was no significant difference in glucose levels at every GA category neither in lean nor in obese woman except for the fasting glucose of 32-35 GA. The fetal macrosomia rate in each GA category and the rate of LGA were significantly higher in obese women: e.g. 14.5 vs 28% at diagnosis, 15.7 vs 26.7% at 32-35 weeks, 15.5 vs 25.0% at birth (p < 0.05 for each comparison). CONCLUSION: The association of maternal glucose values and fetal macrosomia was limited to the fasting glucose values between 32-35 weeks while maternal obesity appeared to be a strong risk factor for macrosomia throughout pregnancies with GDM. In obese women the high fetal macrosomia rate did not appear be normalized by therapy based on maternal euglycemia.