Exposure to methylergonovine maleate as a cause of sirenomelia.

BACKGROUND: Sirenomelia is a rare, but deadly condition characterized by fusion of the lower limbs, lower spinal column defects, severe malformations of the urogenital and lower gastrointestinal tract, and an aberrant abdominal umbilical artery. METHODS: The two main hypotheses, not mutually exclusive, that have been advanced to explain the pathogenesis of sirenomelia are the blastogenetic theory and the vascular disruption theory. RESULTS: We describe a case of sirenomelia, probably associated with the use of methylergonovine maleate, an ergot alkaloid, during the first weeks of pregnancy. CONCLUSION: On the basis of the mechanisms of vascular disruption and early administration of methylergonovine maleate at a critical stage of organogenesis, we conclude that exposure to methylergonovine maleate could be the cause of the development of sirenomelia. Birth Defects Research (Part A) 106:643-647, 2016. © 2016 Wiley Periodicals, Inc.

Ongoing pregnancies in patients with unexplained recurrent pregnancy loss: adverse obstetric outcomes.

To investigate the incidence of adverse pregnancy outcomes in couples with an unexplained Recurrent Pregnancy Loss (RPL) history, a retrospective cohort study was conducted between 2014 and 2015. The study group (A) included couples with an unexplained RPL, and the control group (B) was composed of couples who attended the Low-Risk Antenatal Unit during the same period. On the other hand, 53 couples were included in the study group (A) and on the other hand, 65 in the control group (B). Women with previous unexplained recurrent pregnancies loss had a significantly increased risk of gestational diabetes with 12 cases (22.6%) in the study group and 3 cases (4.6%) in the control (OR: 6.048; 95% CI: 1.607-22.762; p = 0.007). A slight increase in the risk of preterm delivery and hepatic cholestasis was observed in the study group (6 cases, 11.3%, in study group and 1 case, 1.5% in the controls (OR: 8.170; 95% CI: 0.951-70.158; p = 0.0555). Women with a history of RPL delivered more frequently by caesarean section (OR: 3.252; 95% CI: 1.460-7.241; p = 0.0039). Women with a history of RPL were at an increased risk for adverse pregnancy outcomes, mainly gestational diabetes. Therefore, a closer surveillance during the antenatal period is recommended in this group of patients.

Endothelial nitric oxide synthase gene influences the risk of pre-eclampsia, the recurrence of negative pregnancy events, and the maternal-fetal flow.

OBJECTIVES: Pre-eclampsia is associated with vascular endothelial dysfunction, adverse pregnancy outcome and cardiovascular disease in later life. An inadequate nitric oxide availability related to polymorphisms in the endothelial nitric oxide synthase gene (eNOS) might predispose to the disease. METHODS: We investigated the role of eNOS T-786C, G894T and 4a4b polymorphisms in predisposing to both pre-eclampsia and the recurrence of negative pregnancy events, per se and in the presence of angiotensin-converting enzyme (ACE) DD genotype, and investigated their influence on maternal-fetal flow in 106 non-thrombophilic women with a history of pre-eclampsia, compared with 106 women with a history of normal pregnancy. RESULTS: No association between eNOS polymorphisms and predisposition to pre-eclampsia was found; nevertheless, the contemporary presence of eNOS 894TT and -786CC genotypes represented a susceptibility factor to the disease. In 48 out of 106 women, documented complications (pre-eclampsia and fetal growth restriction) were present in the current pregnancy. The eNOS 894TT genotype influenced the risk of recurrence of negative events (odds ratio = 5.45), particularly in contemporary women homozygous for both eNOS 894TT and ACE DD genotypes (odds ratio = 11.4). Throughout the pregnancy, a progressive alteration of maternal-fetal flow indices was found in women carrying the eNOS 894TT genotype, and this effect was strengthened in women with the contemporary presence of the ACE DD genotype. CONCLUSIONS: An original finding is the increased risk of pre-eclampsia and recurrence of pregnancy negative events, probably by modulating the maternal-fetal flow, in women homozygous for the eNOS 894T allele previously analyzed for the ACE I/D polymorphism.

Unusual gastric and pancreatic metastatic renal cell carcinoma presentation 10 years after surgery and immunotherapy: A case report and a review of literature.

Renal cell carcinoma (RCC) is the most common renal tumor, accounting for 2%-3% of all malignancies. Though RCC is known to spread hematogenously, isolated RCC metastasis to the stomach is a rare event. In this article, we describe the clinical course of a patient who developed a pancreatic recurrence of RCC and 1 year later a gastric recurrence of RCC treated 10 years ago with a resection and interleukin-2 (IL-2). Accumulating evidence indicates that metastatic involvement of the pancreas and stomach should be suspected in any patient with a history of RCC who presents with gastrointestinal symptoms even 10 years after RCC resection and immunotherapy.

Recurrent pregnancy losses and gestational age are closely related: an observational cohort study on 759 pregnancy losses.

To assess the accurate dating of the cessation of pregnancy in patients with recurrent pregnancy loss (RPL) and to evaluate the incidence and recurrence rate of pregnancy losses in similar gestational age. In a retrospective cohort study, couples with history of RPL and availability of precise documentation regarding previous pregnancy losses were included. The vast majority of losses occurred within the first trimester. In patients experiencing more than 2 miscarriages in the same gestational stage, a tendency for recurrent losses around the same period of gestation was observed. Overall, the probability of losses at different gestational stages goes down with increasing number of miscarriages at the same stage. The study supports the need to ascertain data regarding the timing of pregnancy loss as accurately as possible for prognosis of future pregnancies and management of couples. A classification for unexplained RPL based on gestational age of miscarriages could help researchers to better investigate RPL.

Ethical issue and consent form in the management of high-risk pregnancy.

Through the description of two high risk unplanned pregnancy cases and the subsequent interview of the patients, a few years after delivery, this article focuses on the following issues: 1. The importance of a planned pregnancy in a woman with diabetes or other chronic disease; 2. The ethical role of counselling and how it should not be influenced by the ethical belief of the obstetrician; 3. The legal aspect related to the knowledge and qualifications of the obstetrician in the management of a high-risk pregnancy to improve both maternal and fetal outcomes. Here, two cases of complicated type 1 diabetes in women with unplanned pregnancies and the importance of counselling in high-risk pregnancy are presented.

Breastfeeding and the basal insulin requirement in type 1 diabetic women.

OBJECTIVE: To evaluate whether breastfeeding in women with type 1 diabetes mellitus is associated with a decreased insulin requirement. METHODS: In this prospective study conducted between September 2006 and August 2008, type 1 diabetic pregnant women were recruited before the third trimester of pregnancy. Eligible women had no evidence of diabetes-related complications and were treated with continuous subcutaneous insulin infusion pump therapy. During pregnancy and in the first 8 weeks of the postpartum period, participants performed daily fingerstick blood glucose monitoring with at least 12 measurements per day; insulin dosages were adjusted to maintain normoglycemia. Participant characteristics, diabetic parameters, and neonatal growth were compared between women who breastfed exclusively and women who did not breastfeed. RESULTS: Of 18 women, 12 breastfed and 6 did not. Compared with nonbreastfeeding mothers, breastfeeding mothers showed a decreased need for total daily basal insulin (0.21 +/- 0.05 units/kg per day vs 0.33 +/- 0.02 units/kg per day). The mean value of total daily basal insulin was significantly lower in the breastfeeding group than in the non-breastfeeding group. The mean number of hyperglycemic episodes in the first 2 weeks post partum and during the third to eighth weeks was not different between the groups. However, the mean number of hypoglycemic episodes in the first 2 weeks post partum in the breastfeeding group was significantly higher than in the nonbreastfeeding group (11.9 +/- 2.6 episodes vs 5.5 +/- 1.6 episodes, P<.001). No differences were observed between the groups in neonatal birth weight or infant weight after 8 weeks of age. CONCLUSIONS: Decreased need in total daily basal insulin is caused by increased glucose use during lactation. We recommend that the starting total daily basal insulin dosage for type 1 diabetic women who breastfeed be calculated as 0.21 units times the weight in kg per day. This regimen results in normoglycemia and minimizes the risk of severe hypoglycemia associated with lactation.

Low-molecular-weight heparin lowers the recurrence rate of preeclampsia and restores the physiological vascular changes in angiotensin-converting enzyme DD women.

Data from literature report that angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the recurrence of preeclampsia and that low-molecular-weight heparin (LMWH) prevents adverse outcomes in thrombophilic women. We investigated the effect of LMWH on the pregnancy outcome, on maternal blood pressure values, and on uteroplacental flow in ACE DD nonthrombophilic women with history of preeclampsia. Eighty nonthrombophilic ACE DD women were randomized in 2 groups: 41 treated with dalteparin 5000 IU/day and 39 untreated (control group). Women underwent 24-hour automated blood pressure monitoring in the preconceptional period and every 2 weeks from weeks 8 to 36 and transabdominal color flow/pulsed Doppler examination at weeks 16, 20, and 24. LMWH reduced the risk of clinical negative outcomes (74.1% reduction of preeclampsia and 77.5% reduction of fetal growth restriction) and the severity (88.3% reduction of early onset of preeclampsia and 86.4% reduction of early onset of fetal growth restriction). In treated women, the relative risk for preeclampsia was 0.26 (P=0.02), and the relative risk for fetal growth restriction was 0.14 (P<0.001). Systolic (P=0.002) and diastolic (P=0.002) blood pressures, as well as awake (P=0.04) and asleep (P=0.01) period values, and the resistance indexes of both uterine arteries (P=0.002) were lower in the treated group. LMWH reduces the recurrence of preeclampsia, of negative outcomes, and the resistance of uteroplacental flow, and also prevents maternal blood pressure increase in ACE DD homozygote women with a previous history of preeclampsia.