Giuseppe Chiossi

Hyperemesis gravidarum complicated by Wernicke encephalopathy: Background, case report, and review of the literature

Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (±standard deviation) patients’ age was 26.7 ± 4.9 years, the mean gestational age when WE manifested was 14.3 ± 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 ± 2.8 weeks. Wernicke’s classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to list the signs and symptoms of Wernicke encephalpathy associated with hyperemesis gravidarum, outline the methods to make a clinical diagnosis, and recall the importance of thiamine supplementation in patients with prolonged hyperemesis gravidarum.

Timing of Delivery and Adverse Outcomes in Term Singleton Repeat Cesarean Deliveries

OBJECTIVE: To compare the maternal and neonatal risks of elective repeat cesarean delivery compared with pregnancy continuation at different gestational ages, starting from 37 weeks. METHODS: We analyzed the composite maternal and neonatal outcomes of repeat cesarean deliveries studied prospectively over 4 years at 19 U.S. centers. Maternal outcome was a composite of pulmonary edema, cesarean hysterectomy, pelvic abscess, thromboembolism, pneumonia, transfusion, or death. Composite neonatal outcome consisted of respiratory distress, transient tachypnea, necrotizing enterocolitis, sepsis, ventilation, seizure, hypoxic–ischemic encephalopathy, neonatal intensive care unit admission, 5-minute Apgar of 3 or lower, or death. Outcomes after elective repeat cesarean delivery without labor at each specific gestational age were compared with outcomes for all who were delivered later as a result of labor onset, specific obstetric indications, or both. RESULTS: Twenty-three thousand seven hundred ninety-four repeat cesarean deliveries were included. Elective delivery at 37 weeks of gestation had significantly higher risks of adverse maternal outcome (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.06–2.31), whereas elective delivery at 39 weeks of gestation was associated with better maternal outcome when compared with pregnancy continuation (OR 0.51, 95% CI 0.36–0.72). Elective repeat cesarean deliveries at 37 and 38 weeks of gestation had significantly higher risks of adverse neonatal outcome (37 weeks OR 2.02, 95% CI 1.73–2.36; 38 weeks OR 1.39 95% CI 1.24–1.56), whereas delivery at 39 and 40 weeks of gestation presented better neonatal outcome as opposed to pregnancy continuation (39 weeks OR 0.79, 95% CI 0.68–0.92; 40 weeks OR 0.57, 95% CI 0.43–0.75). CONCLUSION: In women with prior cesarean delivery, 39 weeks of gestation is the optimal time for repeat cesarean delivery for both mother and neonate. LEVEL OF EVIDENCE: II

Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets.

The present study explored the possible relationships between immune cell subsets and interleukin (IL)-12 or IL-13 levels in the peritoneal fluid of patients with and without endometriosis. Peritoneal fluid samples were obtained from 80 women while they were undergoing laparoscopy for pain, infertility, tubal ligation or reanastomosis. The American Fertility Society scoring system was used to determine the extension of endometriosis. The peritoneal fluid mononuclear cells were analyzed for immunophenotyping using cytometry, whereas peritoneal fluid concentrations of interleukins were measured using two ultrasensitive commercially available enzyme-linked immunosorbent assay kits. Significantly higher peritoneal fluid IL-12 levels were found in women with moderate or severe endometriosis (stages III and IV) than in healthy controls (p<0.01). Conversely, subjects with endometriosis showed remarkably lower peritoneal fluid IL-13 concentrations than controls, independent of the severity of the disease (p<0.05). Considering immune system effectors, patients with endometriosis presented a significantly higher peritoneal fluid CD8+/CD4+ratio when compared with healthy controls. Moreover, the number of peritoneal fluid CD8+and CD4+activated T cells was significantly lower in the former than in the latter group, independent of the endometriosis stage. Connections were observed between peritoneal fluid interleukins and peritoneal fluid T cells: both patients with endometriosis and controls presented an inverse correlation between peritoneal fluid activated T cells and IL-13 levels, and a direct correlation between peritoneal fluid T cells and IL-12 concentrations. These data seem to suggest that a reciprocal modulation exists between peritoneal fluid cytokines and T lymphocyte subsets in patients with endometriosis.

Clinical use of nitric oxide donors and L-arginine in obstetrics.

Nitric oxide (NO) is a free radical that plays a fundamental role in human physiology, being involved in the homeostasis of different functions. In obstetrics this molecule is determinant in the physiology of labor and cervical ripening; it possibly plays a fundamental role in the etiology of preeclampsia and intrauterine growth restriction, and it could also be utilized in view of its ability to induce smooth muscle relaxation. Several clinical trials have ascertained the ability of the topical application of NO donors to promote cervical ripening, and also labor induction. There is much less evidence on the use of NO donors in the vascular complications of pregnancy, either as prophylactics or therapeutic agents. Due to the capacity of NO to promote relaxation of smooth muscle, NO donors have been employed as tocolytics with performance similar to other agents. Moreover, although anecdotal, the experience of sudden uterine relaxation using NO donors in obstetric emergencies remains of great clinical value.

Early trophoblast invasion and placentation in women with different PCOS phenotypes

This study evaluated the impact of different phenotypes of polycystic ovary syndrome (PCOS) on early trophoblast invasion and placentation. Pregnant patients with different PCOS phenotypes and healthy pregnant women, matched for age and body mass index, were enrolled. Histological analysis of trophoblastic and decidual tissue and macroscopic and microscopic assessment of the placentas were performed. Implantation-site vessels with endovascular trophoblast differed significantly among PCOS phenotypes. Placental weight, thickness, density and fetal-placental weight ratio were significantly different in the full-blown and non-polycystic ovary (PCO) phenotypes versus the ovulatory and non-hyperandrogenic phenotypes. The incidence of macroscopic placental lesions was only significantly different between controls and the full-blown and non-PCO phenotypes. The overall incidence of microscopic placental lesions was significantly different among PCOS phenotypes and was significantly higher in the full-blown and non-PCO phenotypes than in the ovulatory and non-hyperandrogenic phenotypes. The rates of chorionic villitis and intervillositis were significantly higher in full-blown and non-PCO phenotypes than in ovulatory and non-hyperandrogenic phenotypes. In conclusion, alterations in early trophoblast invasion and placentation observed in PCOS vary widely according to phenotype.

Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

Alterations in lipid pattern and increased risk for obstetric/neonatal complications have been observed in patients with polycystic ovary syndrome (PCOS). Pregnancy leads to physiologic changes in lipoprotein metabolism, and alterations in lipid profile have been related with adverse pregnancy outcomes. Based on these considerations, the aim of the present prospective controlled clinical study was to test the hypothesis that the changes in the lipid profile in patients with PCOS during pregnancy are characteristic and potentially related to the increased risk of obstetric/neonatal complications. One hundred and fifty nonobese PCOS women and 150 age- and body mass index (BMI)-matched healthy controls were enrolled. Serum lipids, glucose, insulin, and androgens levels were serially assayed in all subjects before and throughout pregnancy. Serum low-density lipoprotein (LDL) and triglyceride (TG) concentrations were significantly (P<0.05) higher in PCOS group than in healthy controls at each assessment. Throughout pregnancy, serum LDL and TG levels increased significantly (P<0.05) in both groups, although the change from pre-pregnancy values was significantly (P<0.05) greater in PCOS patients than in healthy controls. A significant (P<0.05) relationship was observed between serum LDL and TG changes and changes in both insulin sensitivity indexes and androgen levels in PCOS patients alone. After adjusting for maternal age, pre-pregnancy BMI and lipid levels, body weight gain, and insulin-resistance markers, serum TG concentrations during pregnancy were directly and independently associated with obstetric complications in both groups, whereas serum LDL levels only in PCOS patients. We can conclude that nonobese PCOS patients had specific changes in lipid profile during pregnancy, and that the lipid pattern typical of PCOS may account for the more frequent adverse pregnancy outcomes. PCOS-related hormonal and metabolic features, such as insulin resistance and high androgen levels, may mediate this phenomenon.

Correlation between differentiation plasticity and mRNA expression profiling of CD34+-derived CD14- and CD14+ human normal myeloid precursors

In spite of their apparently restricted differentiation potentiality, hematopoietic precursors are plastic cells able to trans-differentiate from a maturation lineage to another. To better characterize this differentiation plasticity, we purified CD14− and CD14+ myeloid precursors generated by ‘in vitro’ culture of human CD34+ hematopoietic progenitors. Morphological analysis of the investigated cell populations indicated that, as expected, they consisted of granulocyte and monocyte precursors, respectively. Treatment with differentiation inducers revealed that CD14− cells were bipotent granulo-monocyte precursors, while CD14+ cells appeared univocally committed to a terminal macrophage maturation. Flow cytometry analysis demonstrated that the conversion of granulocyte precursors to the mono-macrophage maturation lineage occurs through a differentiation transition in which the granulocyte-related myeloperoxidase enzyme and the monocyte-specific CD14 antigen are co-expressed. Expression profiling evidenced that the observed trans-differentiation process was accompanied by a remarkable upregulation of the monocyte-related MafB transcription factor.

Effect of age and gender on the progression of adult vascular dysfunction in a mouse model of fetal programming lacking endothelial nitric oxide synthase

The objective of this study was to investigate vascular function at different ages in a transgenic murine model of fetal vascular programming using a model of uteroplacental insufficiency induced by lack of endothelial nitric oxide synthase. Homozygous NOS3 knockout (KO) and wild-type (WT) mice were cross bred to produce WT, KO, and heterozygous that developed in WT (KOP) or KO (KOM) mothers. Male/female offspring from the four groups were killed at 7, 14, and 21 wk of age (n = 5-10/group), and carotid arteries were used for in vitro vascular studies. Responses to phenylephrine (PE), with/without N(G)-nitro-L-arginine methyl ester (L-NAME), angiotensin (ANG), acetylcholine (ACh), sodium nitroprusside, and isoproterenol (ISO) were studied. At 7 wk, only KO offspring showed higher contractile response to PE, whereas, at 14 and 21 wk, both KO and KOM had a higher response. Incubation with L-NAME abolished these differences. ANG contraction was higher in male KO in all age groups and in 21-wk-old females. Relaxation to ACh and ISO was absent in KO, and significantly decreased in KOM offspring in all age groups compared with KOP and WT, independent of gender. Sodium nitroprusside was not different between groups. The effect of the altered intrauterine environment on the development of abnormal vascular function was limited at 7 wk of age and most evident at 14 wk; further deterioration was limited to ANG-mediated vascular contractility in KO offspring. Our findings provide some hope that at least the first seven postnatal weeks may be an appropriate therapeutic window to prevent cardiovascular disease later in life.

Customized vs population-based growth charts to identify neonates at risk of adverse outcome: systematic review and Bayesian meta-analysis of observational studies

To compare the effectiveness of customized vs population‐based growth charts for the prediction of adverse pregnancy outcomes.

The Effects of Prostaglandin E1 and Prostaglandin E2 on in vitro Myometrial Contractility and Uterine Structure

OBJECTIVE To estimate the effects of prostaglandin E1 (PGE1) and E2 (PGE2) on myometrial contractility and structure in vitro. STUDY DESIGN Myometrial strips from 18 women were incubated with PGE1 (10-5 mol/L), PGE2 (10-5 mol/L), or solvent (CTR) for up to 360 minutes in organ chambers for isometric tension recording. The area under the contraction curve, total collagen content, and percentage of the area covered by connective tissue were calculated at various time periods. RESULTS PGE1 significantly increased in vitro myometrial contractility up to 90 minutes when compared with PGE2 and CTR (p < 0.01) and up to 180 minutes as compared with PGE2 (p < 0.05). After 360 minutes, CTR and PGE1 samples had lower total collagen content and area covered by connective tissue than PGE2 (p < 0.01). CONCLUSION The effects of prostaglandins on the uterus cannot be solely explained by contractility. Treatment with PGE1 significantly increased myometrial contractions and decreased both total collagen content and the area covered by connective tissue. Such findings may explain the higher rates of vaginal delivery, tachysystole, and uterine rupture associated with PGE1 use.