Iron transport across the human placenta is regulated by hepcidin.

BACKGROUND: Transport of iron across the placenta is critical for appropriate development of the fetus. Iron deficiency during pregnancy remains a major public health concern, particularly in low- and middle-income countries, often exacerbated by infectious diseases leading to altered iron trafficking via inflammatory responses. Herein, we investigate the role of hepcidin, a master regulator of iron homeostasis, on regulation of iron transport across trophoblast cells. METHODS: We utilized the Jeg-3 choriocarcinoma cell line for analysis of the expression of transferrin receptor, ferritin, and ferroportin as well as the export of 59Fe in the presence of hepcidin. Placental tissue from human term pregnancies was utilized for immunohistochemistry. RESULTS: Hepcidin treatment of Jeg-3 cells decreased the expression of ferroportin and transferrin receptor (TfR) and reduced the cellular export of iron. Lower expression of TfR on the syncytiotrophoblast was associated with the highest levels of hepcidin in maternal circulation, and ferroportin expression was positively associated with placental TfR. Placentas from small-for-gestational-age newborns had significantly lower levels of ferroportin and ferritin gene expression at delivery. CONCLUSIONS: Our data suggest that hepcidin plays an important role in the regulation of iron transport across the placenta, making it a critical link in movement of iron into fetal circulation. IMPACT: Hepcidin has a direct impact on iron transport across the human placenta. This study provides the first evidence of direct regulation of iron efflux from human trophoblast cells by hepcidin. These data extend our understanding of iron transport across the maternal-fetal interface, a process critical for fetal health and development.

Dyspareunia and childbirth: a prospective cohort study.

OBJECTIVE: To investigate the relationship between mode of delivery, perineal trauma and dyspareunia. DESIGN: Prospective cohort study. SETTING: Six maternity hospitals in Melbourne, Australia. SAMPLE: A total of 1507 nulliparous women recruited in the first and second trimesters of pregnancy. METHOD: Data from baseline and postnatal questionnaires (3, 6, 12 and 18 months) were analysed using univariable and multivariable logistic regression. MAIN OUTCOME MEASURE: Study-designed self-report measure of dyspareunia at 18 months postpartum. RESULTS: In all, 1244/1507 (83%) women completed the baseline and all four postpartum questionnaires; 1211/1237 (98%) had resumed vaginal intercourse by 18 months postpartum, with 289/1211 (24%) women reporting dyspareunia. Compared with women who had a spontaneous vaginal delivery with an intact perineum or unsutured tear, women who had an emergency caesarean section (adjusted odds ratio [aOR] 2.41, 95% confidence interval [95% CI] 1.4-4.0; P = 0.001), vacuum extraction (aOR 2.28, 95% CI 1.3-4.1; P = 0.005) or elective caesarean section (aOR 1.71, 95% CI 0.9-3.2; P = 0.087) had increased odds of reporting dyspareunia at 18 months postpartum, adjusting for maternal age and other potential confounders. CONCLUSIONS: Obstetric intervention is associated with persisting dyspareunia. Greater recognition and increased understanding of the roles of mode of delivery and perineal trauma in contributing to postpartum maternal morbidities, and ways to prevent postpartum dyspareunia where possible, are warranted.

Current management of relapsing-remitting multiple sclerosis.

Multiple sclerosis was without effective disease-modifying therapy for many years. The introduction of the injectable therapies (interferon and glatiramer acetate) some 20 years ago was considered a major advance. Recent years have heralded a revolution in treatment options with the introduction of intravenous natalizumab and, even more recently, three oral agents. We are currently in a period of determining the best use of these therapies to ensure prevention of disease progression while maintaining patient safety. Despite these new treatments, there are still many patients living with disability as a result of multiple sclerosis and significant attention must be given to symptomatic management.

Does method of birth make a difference to when women resume sex after childbirth?

OBJECTIVE: To investigate the timing of resumption of vaginal sex and assess associations with method of birth, perineal trauma and other obstetric and social factors. DESIGN: Prospective pregnancy cohort study of nulliparous women. SETTING: Melbourne, Australia. SAMPLE: A total of 1507 nulliparous women recruited in early pregnancy (≤24 weeks). METHOD: Women were recruited from six public hospitals. Data from hospital records and self-administered questionnaires at recruitment and 3, 6 and 12 months postpartum were analysed using univariable and multivariable logistic regression. MAIN OUTCOME MEASURE: Resumption of vaginal sex. RESULTS: Sexual activity was resumed earlier than vaginal sex, with 53% resuming sexual activity by 6 weeks postpartum, and 41% attempting vaginal sex. By 8 weeks a majority of women had attempted vaginal sex (65%), increasing to 78% by 12 weeks, and 94% by 6 months. Compared with women who had a spontaneous vaginal birth with an intact perineum, women who had a spontaneous vaginal birth with an episiotomy (adjusted odds ratio 3.43, 95% confidence interval 1.9-6.2) or sutured perineal tear (adjusted odds ratio 3.18, 95% confidence interval 2.1-4.9) were more likely not to have resumed vaginal sex by 6 weeks postpartum. Similarly, women who had an assisted vaginal birth or caesarean section had raised odds of delaying resumption of sex. CONCLUSIONS: Most women having a first birth do not resume vaginal sex until later than 6 weeks postpartum. Women who have an operative vaginal birth, caesarean section or perineal tear or episiotomy appear to delay longer.

Adiponectin attenuation of endocrine function within human term trophoblast cells.

The hormone adiponectin has been shown to be important in maintaining insulin sensitivity throughout the body, whereas potential effects on the placenta have not been assessed. Pregnancy constitutes a unique physiological environment in which metabolism has a profound effect on the health of both the mother and the developing fetus. It is imperative that a delicate balance in glucose delivery be maintained between maternal tissues and the fetal/placental unit. Adiponectin's role in regulating peripheral insulin responsiveness suggests it may be a factor in maintaining this balance during gestation as well. Examination of human cytotrophoblast cells revealed that mRNA for both adiponectin receptors, adipoR1 and adipoR2, are abundantly expressed at term. We were, however, unable to reliably detect mRNA for adiponectin in primary cytotrophoblasts. Expression of both receptors was maintained after induction of syncytium formation by exogenous epidermal growth factor treatment. Treatment of cytotrophoblasts with adiponectin resulted in a significant drop, as assessed by quantitative RT-PCR, in expression for a number of genes involved in the endocrine function of the placenta, including the chorionic gonadotropin subunits, placental lactogen, and some steroidogenic enzymes. Immunofluorescent staining for connexin 43 and desmoplakin in primary trophoblasts revealed that adiponectin does not inhibit syncytialization of trophoblast cells in culture. Taken together, these data describe a novel role for maternal adiponectin in regulating the placental environment. Determination of the effects of such adipokines on the maternal-fetal interface is increasingly important, because the incidence of pregnancies complicated by gestational diabetes remains a significant health problem in developed countries.

Lung perfusion scintigraphy in patients with congenital heart disease: sensitivity and important pitfalls.

The lung perfusion scans requested over a 5-year period for children with known congenital heart disease were reviewed retrospectively. Altogether, 102 lung perfusion scans were performed and comparable pulmonary arteriograms were available in 63 cases. There was agreement between scintigraphy and angiography in 50 (79%) cases and discrepancy in 13 (21%) cases. Scintigraphy was more sensitive in detecting small perfusion defects, particularly those seen only on oblique views. Pulmonary arteriography was more specific in identifying the cause of the perfusion abnormalities. The two techniques yield complementary information about lung perfusion. Perfusion scintigraphy is safe in children with congenital heart disease even with known pulmonary to systemic shunting. Many pitfalls could be avoided by careful choice of injection site, by knowledge of previous surgery and comparison with relevant angiograms.

Single catheter approach for occlusion of a patent arterial duct with a Rashkind double umbrella.

OBJECTIVES: To determine the benefits of using a single venous catheter and a single angiogram during catheter occlusion of a patient arterial duct with the Rashkind double umbrella compared with those of venous and arterial catheters and multiple angiograms. DESIGN: Retrospective review of case notes. PATIENTS: 103 consecutive patients. The long sheath could not be advanced adequately in two patients. 101 patients had 104 implantations. Median (range) age was 35 (7-549) months and median (range) weight 13 (7-62) kg. Fifty four implantations were performed using the venous and arterial method and 50 using the venous only method. RESULTS: Median procedure times (70 v 90 min), number of angiograms (one v four), and angiographic dye volume used (2 v 7 ml/kg) were significantly reduced using the venous only method compared with those of the venous and arterial method. There was no significant difference in fluoroscopy time (venous only 9 v venous and arterial 10 min). CONCLUSIONS: Considerable improvements can be made in the technique of catheter closure of patent arterial ducts using the Rashkind double umbrella without compromising outcome using venous cannulation alone and a single angiogram, rather than venous and arterial cannulation and multiple angiograms. reduced risk to arteries from cannulation, The benefits are reduced radiation exposure, reduced risk to arteries from cannulation, shorter procedures, and lower equipment costs.