Outcomes associated with planned place of birth among women with low-risk pregnancies

Background:Previous studies have shown that planned home birth is associated with a decreased likelihood of intrapartum intervention with no difference in neonatal outcomes compared with planned hospital birth. The purpose of our study was to evaluate different birth settings by comparing neonatal mortality, morbidity and rates of birth interventions between planned home and planned hospital births in Ontario, Canada.Methods:We used a provincial database of all midwifery-booked pregnancies between 2006 and 2009 to compare women who planned home birth at the onset of labour to a matched cohort of women with low-risk pregnancies who had planned hospital births attended by midwives. We conducted subgroup analyses by parity. Our primary outcome was stillbirth, neonatal death (< 28 d) or serious morbidity (Apgar score < 4 at 5 min or resuscitation with positive pressure ventilation and cardiac compressions).Results:We compared 11 493 planned home births and 11 493 planned hospital births. The risk of our primary outcome did not differ significantly by planned place of birth (relative risk [RR] 1.03, 95% confidence interval [CI] 0.68–1.55). These findings held true for both nulliparous (RR 1.04, 95% CI 0.62–1.73) and multiparous women (RR 1.00, 95% CI 0.49–2.05). All intrapartum interventions were lower among planned home births.Interpretation:Compared with planned hospital birth, planned home birth attended by midwives in a jurisdiction where home birth is well-integrated into the health care system was not associated with a difference in serious adverse neonatal outcomes but was associated with fewer intrapartum interventions.In Ontario, Canada, the College of Midwives of Ontario has regulated midwifery since 1994, and increasing numbers of women with low obstetrical risk and their newborns receive care in a publicly funded, midwifery-led continuity of care model.¹ Midwives have admission and discharge privileges at their local hospitals and are able to consult or transfer care to other health care providers if required. In Ontario, midwives attend a small proportion of all births in the province (10%), and about 20% of the births they attend take place at home.² A comprehensive record is maintained for every woman and infant in a midwife’s care. Until 2009, this record was submitted to the provincial Ministry of Health and Long-term Care (MOHLTC) through the Ontario Midwifery Program to access reimbursement for care provided.In the last century, Western culture has come to view hospital birth as safer than home birth.³ Recently, however, the value of hospital birth for all women with low-risk pregnancies has come into question; it has been suggested that in the absence of benefit, a planned hospital birth for this population may increase the use of intrapartum interventions, including cesarean delivery.^4–7 Even though recent studies comparing planned home and hospital births have had moderate sample sizes, they are individually limited in their ability to report definitively on rare outcomes such as death. Owing to a lack of evidence from randomized controlled trials (RCTs) to show that restricting a woman’s freedom to choose a place of birth prevents harm, the authors of a 2012 Cochrane review of planned hospital versus planned home births concluded that home birth services with collaborative medical backup should be established and offered to women with low-risk pregnancies in all jurisdictions.⁸ This conclusion, along with findings from the large English Birthplace Cohort Study,⁴ may be what prompted the National Institute for Health and Care Excellence (NICE) in England to update its intrapartum care guidelines to recommend that, for women at low risk of birth-associated complications, home birth should be considered a generally safe option.⁹ With the paucity of information derived from RCTs,⁸ observational studies are essential to continue to inform and monitor maternal and infant outcomes for women at low obstetrical risk who plan home or hospital birth, and to continue to provide pregnant women with quality information about choice of birthplace.The primary purpose of this retrospective cohort study was to determine the risk of stillbirth or neonatal death or serious neonatal morbidity among women at low obstetrical risk whose deliveries were attended by midwives and who had planned a home birth at the onset of labour, compared with women at low obstetrical risk who planned a hospital birth at the onset of labour. In addition, we also compared the incidence of maternal death and morbidity, birth interventions and breastfeeding between planned home births and planned hospital births.     

Neuropädiatrische Differenzialdiagnostik der Mikrozephalie im Kindesalter

Microcephaly affects 2–3?% of the population and is often associated with intellectual disability. The underlying reduction in brain volume can result from various exogenous factors or genetic causes. Microcephaly remains a poorly defined condition lacking both uniform diagnostic approaches and classification. A definite etiological diagnosis is the key to predict the prognosis, identify co-morbidities and offer genetic counseling. In addition, the identification of the underlying cause increases our knowledge of brain development and the clinical spectrum of microcephaly. We propose a diagnostic approach for children with microcephaly from a pediatric neurologist point of view.     

The glucose metabolite methylglyoxal inhibits expression of the glucose transporter genes by inactivating the cell surface glucose sensors Rgt2 and Snf3 in yeast

Methylglyoxal (MG) is a cytotoxic by-product of glycolysis. MG has inhibitory effect on the growth of cells ranging from microorganisms to higher eukaryotes, but its molecular targets are largely unknown. The yeast cell-surface glucose sensors Rgt2 and Snf3 function as glucose receptors that sense extracellular glucose and generate a signal for induction of expression of genes encoding glucose transporters (HXTs). Here we provide evidence that these glucose sensors are primary targets of MG in yeast. MG inhibits the growth of glucose-fermenting yeast cells by inducing endocytosis and degradation of the glucose sensors. However, the glucose sensors with mutations at their putative ubiquitin-acceptor lysine residues are resistant to MG-induced degradation. These results suggest that the glucose sensors are inactivated through ubiquitin-mediated endocytosis and degraded in the presence of MG. In addition, the inhibitory effect of MG on the glucose sensors is greatly enhanced in cells lacking Glo1, a key component of the MG detoxification system. Thus the stability of these glucose sensors seems to be critically regulated by intracellular MG levels. Taken together, these findings suggest that MG attenuates glycolysis by promoting degradation of the cell-surface glucose sensors and thus identify MG as a potential glycolytic inhibitor.     

Circulating miRNA‐375 as a potential novel biomarker for active Kaposi’s sarcoma in AIDS patients

The aim of this study was to identify circulating microRNAs (miRNAs) that could be used as biomarkers in patients at risk for or affected by AIDS‐Kaposi's sarcoma (KS). Screening of 377 miRNAs was performed using low‐density arrays in pooled plasma samples of 10 HIV/human herpesvirus 8 (HHV8)‐infected asymptomatic and 10 AIDS‐KS patients before and after successful combined antiretroviral therapy (cART). MiR‐375 was identified as a potential marker of active KS, being the most down‐regulated in AIDS‐KS patients after cART and the most up‐regulated in naïve AIDS‐KS patients compared to naïve asymptomatic subjects. Validation on individual plasma samples confirmed that miR‐375 levels were higher in AIDS‐KS compared to asymptomatic patients, decreased after cART‐induced remission in most AIDS‐KS patients and increased in patients with active KS. In asymptomatic patients miR‐375 was up‐regulated after cART in both screening and validation. Statistical analyses revealed an association between miR‐375 changes and CD4 cell counts, which could explain the discordant cases and the opposite trend between asymptomatic and AIDS‐KS patients. These data suggest that circulating miR‐375 might be a good indicator of active AIDS‐KS. Moreover, changes in miR‐375 levels may have a prognostic value in HIV/HHV8‐infected patients undergoing treatment. Further large‐scale validation is needed.     

Increased level of fibrinogen chains in the proteome of blood platelets in secondary progressive multiple sclerosis patients

Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.     

Effects of nutrient limitation on sperm and seminal fluid: a systematic review and meta‐analysis

Theory predicts that costly sexual traits should be reduced when individuals are in poor condition (i.e. traits should exhibit condition‐dependent expression). It is therefore widely expected that male ejaculate traits, such as sperm and seminal fluid, will exhibit reduced quantity and quality when dietary nutrients are limited. However, reported patterns of ejaculate condition dependence are highly variable, and there has been no comprehensive synthesis of underlying sources of such variation in condition‐dependent responses. In particular, it remains unclear whether all ejaculate traits are equally sensitive to nutrient intake, and whether such traits are particularly sensitive to certain dietary nutrients, respond more strongly to nutrients during specific life stages, or respond more strongly in some taxonomic groups. We systematically reviewed these potential sources of variation through a meta‐analysis across 50 species of arthropods and vertebrates (from 71 papers and 348 effect sizes). We found that overall, ejaculate traits are moderately reduced when dietary nutrients are limited, but we also detected substantial variation in responses. Seminal fluid quantity was strongly and consistently condition dependent, while sperm quantity was moderately condition dependent. By contrast, aspects of sperm quality (particularly sperm viability and morphology) were less consistently reduced under nutrient limitation. Ejaculate traits tended to respond in a condition‐dependent manner to a wide range of dietary manipulations, especially to caloric and protein restriction. Finally, while all major taxa for which sufficient data exist (i.e. arthropods, mammals, fish) showed condition dependence of ejaculate traits, we detected some taxonomic differences in the life stage that is most sensitive to nutrient limitation, and in the degree of condition dependence of specific ejaculate traits. Together, these biologically relevant factors accounted for nearly 20% of the total variance in ejaculate responses to nutrient limitation. Interestingly, body size showed considerably stronger condition‐dependent responses compared to ejaculate traits, suggesting that ejaculate trait expression may be strongly canalised to protect important reproductive functions, or that the cost of producing an ejaculate is relatively low. Taken together, our findings show that condition‐dependence of ejaculate traits is taxonomically widespread, but there are also many interesting, biologically relevant sources of variation that require further investigation. In particular, further research is needed to understand the differences in selective pressures that result in differential patterns of ejaculate condition dependence across taxa and ejaculate traits.