Genetic effects on the timing of parturition and links to fetal birth weight.

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.

Surgical Treatment of Single-Level Lumbar Stenosis Is Associated with Lower 2-Year Mortality and Total Cost Compared with Nonsurgical Treatment: A Risk-Adjusted, Paired Analysis.

BACKGROUND: Spine surgery has demonstrated cost-effectiveness in reducing pain and restoring function, but the impact of spine surgery relative to nonsurgical care on longer-term outcomes has been less well described. Our objective was to compare single-level surgical treatment for lumbar stenosis, with or without spondylolisthesis, and nonsurgical treatment with respect to patient mortality, resource utilization, and health-care payments over the first 2 years following initial treatment. METHODS: A retrospective review of the Medicare National Database Fee for Service Files from 2011 to 2017 was performed. A 2-year prediction of mortality risk (risk stratification index, RSI) was used as a measure of patient baseline health. Patients (88%) were matched by RSI and demographics. Mortality, spine-related health-care utilization, and 2-year total Medicare payments for patients undergoing surgical treatment were compared with matched patients undergoing nonsurgical treatment. RESULTS: We identified 61,534 patients with stenosis alone and 83,813 with stenosis and spondylolisthesis. Surgical treatment was associated with 28% lower 2-year mortality compared with matched patients undergoing nonsurgical treatment. Total Medicare payments were significantly lower for patients with stenosis alone undergoing laminectomy alone and for patients with stenosis and spondylolisthesis undergoing laminectomy with or without fusion compared with patients undergoing nonsurgical treatment. There was no significant difference in mortality when fusion or laminectomy was compared with combined fusion and laminectomy. However, laminectomy alone was associated with significantly lower 2-year payments when treating stenosis with or without spondylolisthesis. CONCLUSIONS: Surgical treatment for stenosis with or without spondylolisthesis within the Medicare population was associated with significantly lower mortality and total medical payments at 2 years compared with nonsurgical treatment, although residual confounding could have contributed to these findings. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus.

Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic traits in pregnancy and gestational diabetes mellitus (GDM). Participants in two cohorts (Genetics of Glucose regulation in Gestation and Growth [Gen3G] and Hyperglycemia and Adverse Pregnancy Outcome [HAPO]) underwent oral glucose tolerance testing at 24-32 weeks' gestation. We built genetic risk scores (GRSs) for elevated fasting glucose and insulin, reduced insulin secretion and sensitivity, and T2D, using variants discovered in studies of nonpregnant individuals. We tested for associations between these GRSs, glycemic traits in pregnancy, and GDM. In both cohorts, the fasting glucose GRS was strongly associated with fasting glucose. The insulin secretion and sensitivity GRSs were also significantly associated with these traits in Gen3G, where insulin measurements were available. The fasting insulin GRS was weakly associated with fasting insulin (Gen3G) or C-peptide (HAPO). In HAPO (207 GDM case subjects), all five GRSs (T2D, fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity) were significantly associated with GDM. In Gen3G (43 GDM case subjects), both the T2D and insulin secretion GRSs were associated with GDM; effect sizes for the other GRSs were similar to those in HAPO. Thus, despite the profound changes in glycemic physiology during pregnancy, genetic determinants of fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity discovered outside of pregnancy influence GDM risk.

Microbial communities in placentas from term normal pregnancy exhibit spatially variable profiles.

The placenta is the principal organ nurturing the fetus during pregnancy and was traditionally considered to be sterile. Recent work has suggested that the placenta harbours microbial communities, however the location and possible function of these microbes remain to be confirmed and elucidated. Here, we employed genomic DNA sequencing of multiple variable (V) regions of the bacterial 16S ribosomal gene, to interrogate microbial profiles in term pregnancies, from the basal plate, which is in direct contact with maternal uterine, endothelial, and immune cells; placental villi, which are bathed in maternal blood, and fetal membranes, which encapsulate the amniotic cavity. QIIME, R package "Phyloseq" analysis was used to assess alpha and beta diversity and absolute abundance of the 16S rRNA gene per location. We demonstrate that (1) microbiota exhibit spatially distinct profiles depending on the location within the placenta and (2) "semi-composite" 16S profiles using multiple V regions validated by quantitative PCR analysis confirmed that distinct bacterial taxa dominate in different placental niches. Finally, profiles are not altered by mode of delivery. Together these findings suggest that there is niche-specificity to the placental microbiota and placental microbiome studies should consider regional differences, which may affect maternal, fetal, and/or neonatal health and physiology.

Maternal microbiomes in preterm birth: Recent progress and analytical pipelines.

Worldwide, 10% of babies are born preterm, defined as birth before 37 weeks' gestation. We have had little success in developing strategies to prevent preterm births, the majority of which are due to infection or are idiopathic. An emerging hypothesis is that the maternal microbiome-the bacteria that inhabit the mother's body and play vital functions in normal health-contributes to the etiology of preterm birth. Here, we highlight the latest data revealing correlations between preterm birth and maternal intestinal, vaginal, cervical, and placental microbiomes. Additionally, we describe the most commonly used comparative microbiome analysis methods and highlight important issues to consider when conducting such studies.

Findings from a needs assessment of public sector emergency obstetric and neonatal care in four governorates in Yemen: a human resources crisis.

Recent reviews suggest that it is unlikely Yemen will reach Millennium Development Goal 5 on maternal health by 2015. We conducted a needs assessment in 2010 to identify the human resources constraints in delivery of emergency obstetric and neonatal care (EmONC), in one urban and three under-served rural governorates. The assessment tools were adapted from the UN Guidelines for Monitoring Availability and Use of EmONC. Findings showed that while the urban governorate (total population 666,210 with 26,648 expectant mothers yearly) had 54 obstetricians, 10 anaesthetists and 72 paediatricians, the three rural governorates (total population 1,885,371 with 75,414 expectant mothers yearly) together had only three obstetricians, three anaesthetists, and eight paediatricians. Furthermore, in the rural governorates, with an 0.5% caesarean section rate, which is far below the 5% minimum for this UN indicator, no district hospital had an operating surgeon or an anaesthetist. There was also a marked scarcity of female general physicians and a large disparity in the proportion of births with a skilled attendant between the rural (12%) and urban (34%) governorates. Findings emphasize the need for increasing the coverage of EmONC nationally, but especially in rural areas, through more equitable staff distribution and promotion of task shifting. Developing a national human resources plan and ensuring an enabling policy are prerequisites.

Untreated peristomal skin complications among long-term colorectal cancer survivors with ostomies.

This ethnography of family caregiving explored why peristomal skin complications are common and undertreated among colorectal cancer survivors with intestinal ostomies. Data were collected through in-depth interviews with 31 cancer survivors and their family caregivers, fieldwork, structured assessments, and medical records review, and analyzed with qualitative theme and matrix analyses. Survivors who received help changing the skin barrier around their stoma had fewer obstacles to detection and treatment of peristomal skin complications. Half of the survivors received unpaid help with ostomy care, and all such help came from spouses. Married couples who collaborated in ostomy care reported that having assistance in placing the ostomy appliance helped with preventing leaks, detecting skin changes, and modifying ostomy care routines. In addition, survivors who struggled to manage ostomy care independently reported more obstacles to alleviating and seeking treatment for skin problems. Oncology nurses can improve treatment of peristomal skin problems by asking patients and caregivers about ostomy care and skin problems, examining the peristomal area, and facilitating routine checkups with a wound, ostomy, and continence nurse.

An attempt to determine the benefits of a 'home-for-life' principle in residential care for people with dementia and behavioural problems: a comparative cohort study.

It is not clear whether moving individuals with dementia and behavioural problems as part of a rehabilitation and relocation ('intermediate care', IC) nursing home model worsens behaviour, compared with a 'home for life' philosophy. We studied this in contiguous services with the same formal admission criteria but different models of subsequent care. 37 patients admitted to 'homes for life' and 24 to IC homes were followed up for 1 year using the BEHAVE-AD. Scores were lower at baseline in the IC group. Both groups deteriorated over the year, although more in IC patients (trend), and those actually moving home were worse after the move. Use of neuroleptic medication increased significantly in the IC group. Our results confirm previous studies of the disruptive effects of re-location for patients with severe dementia but do not suggest major differences between the two models of care.