Search

Background: Non-communicable diseases [NCDs] are leading causes of ill health among women of reproductive age and an increasingly important cause of maternal morbidity and mortality worldwide. Reliable data on NCDs is necessary for accurate measurement and response. However, inconsistent definitions of NCDs make reliable data collection challenging. We aimed to map the current global literature to understand how NCDs are defined, operationalized and discussed during pregnancy, childbirth and the postnatal period.  METHODS: For this scoping review, we conducted a comprehensive global literature search for NCDs and maternal health covering the years 2000 to 2020 in eleven electronic databases, five regional WHO databases and an exhaustive grey literature search without language restrictions. We used a charting approach to synthesize and interpret the data.  RESULTS: Only seven of the 172 included sources defined NCDs. NCDs are often defined as chronic but with varying temporality. There is a broad spectrum of conditions that is included under NCDs including pregnancy-specific conditions and infectious diseases. The most commonly included conditions are hypertension, diabetes, epilepsy, asthma, mental health conditions and malignancy. Most publications are from academic institutions in high-income countries [HICs] and focus on the pre-conception period and pregnancy. Publications from HICs discuss NCDs in the context of pre-conception care, medications, contraception, health disparities and quality of care. In contrast, publications focused on low- and middle-income countries discuss NCDs in the context of NCD prevention. They take a life cycle approach and advocate for integration of NCD and maternal health services., Conclusion: Standardising the definition and improving the articulation of care for NCDs in the maternal health setting would help to improve data collection and facilitate monitoring. It would inform the development of improved care for NCDs at the intersection with maternal health as well as through a woman's life course. Such an approach could lead to significant policy and programmatic changes with the potential corresponding impact on resource allocation., (© 2022. The Author(s).)

Objective: To study the effect of delivery on the pO 2 /FiO 2 ratio (P/F ratio) in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and to compare characteristics between delivered and undelivered pregnant patients with COVID-19., Design: Retrospective cohort., Setting: Four hospitals in Houston, Texas., Population: Pregnant patients admitted to the hospital for COVID-19., Methods: Among patients with ARDS who were delivered during their hospitalisation for COVID-19, linear mixed models were used to investigate time trends before and after delivery of the P/F ratio. Patient characteristics were compared between patients delivered during their hospitalisation for COVID-19 and those discharged undelivered., Main Outcome Measures: The P/F ratio, age, gestational age, length of stay and severity of illness, RESULTS: Between 4 May 2020 and 26 July 2020, a total of 61 pregnant patients were admitted for COVID-19. Baseline characteristics were similar between the study groups. Delivery occurred in 21 (34%) of patients during their hospitalisation for COVID-19. Delivered patients had more severe disease and were admitted at a later gestational age than patients not delivered. Ten of these 21 patients (48%) were delivered preterm; of these, six were delivered due to complications of COVID-19 and four were delivered for obstetric indications. In patients with ARDS who were delivered (n = 17), the P/F ratio had a negative slope that improved after delivery., Conclusions: COVID-19-related ARDS in pregnancy requires multidisciplinary care and individualised decision-making, but delivery slows the deterioration of the P/F ratio in these patients., Tweetable Abstract: Delivery improves the P/F ratio in COVID-19-related ARDS, though individualised delivery management is needed., (© 2021 John Wiley & Sons Ltd.)

Objective: Central nervous system (CNS) derived exosomes can be purified from peripheral blood and have been used widely in adult neurological disease. Application to neonatal neurological disease deserves investigation in the setting of hypoxic-ischaemic encephalopathy (HIE)., Design: Observational cohort., Setting: Level III neonatal intensive care unit., Participants: Term/near-term neonates undergoing therapeutic hypothermia (TH) for HIE., Interventions: Blood samples were collected at 0-6, 12, 24, 48 and 96 hours of life., Main Outcomes and Measures: CNS exosomes were purified from serum using previously described methods. Biomarker protein levels were quantified using standard ELISA methods and normalised to exosome marker CD-81. The slope of change for biomarker levels was calculated for each time interval. Our primary outcome was MRI basal ganglia/watershed score of ≥3., Results: 26 subjects were included (umbilical artery pH range 6.6-7.29; 35% seizures). An increasing MRI injury score was significantly associated with decreasing levels of synaptopodin between 0-6 and 12 hours (p=0.03) and increasing levels of lipocalin-2 (NGAL) between 12 and 48 hours (p<0.0001). Neuronal pentraxin was not significant. The negative predictive values for increasing synaptopodin and decreasing NGAL was 70.0% and 90.9%, respectively., Conclusions and Relevance: Our results indicate that CNS exosome cargo has the potential to act as biomarkers of the severity of brain injury and response to TH as well as quantify pharmacological response to neuroactive therapeutic/adjuvant agents. Rigorous prospective trials are critical to evaluate potential clinical use of exosome biomarkers., Competing Interests: Competing interests: LG has a patent for isolating fetal/neonatal neural exosomes using Contactin-2, but there is no current commercial use., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Genome-Wide Association Studies (GWAS) are used to identify statistically significant genetic variants in case-control studies. The main objective is to find single nucleotide polymorphisms (SNPs) that influence a particular phenotype (i.e., disease trait). GWAS typically use a p-value threshold of 5*10 -8 to identify highly ranked SNPs. While this approach has proven useful for detecting disease-susceptible SNPs, evidence has shown that many of these are, in fact, false positives. Consequently, there is some ambiguity about the most suitable threshold for claiming genome-wide significance. Many believe that using lower p-values will allow us to investigate the joint epistatic interactions between SNPs and provide better insights into phenotype expression. One example that uses this approach is multifactor dimensionality reduction (MDR), which identifies combinations of SNPs that interact to influence a particular outcome. However, computational complexity is increased exponentially as a function of higher-order combinations making approaches like MDR difficult to implement. Even so, understanding epistatic interactions in complex diseases is a fundamental component for robust genotype-phenotype mapping. In this paper, we propose a novel framework that combines GWAS quality control and logistic regression with deep learning stacked autoencoders to abstract higher-order SNP interactions from large, complex genotyped data for case-control classification tasks in GWAS analysis. We focus on the challenging problem of classifying preterm births which has a strong genetic component with unexplained heritability reportedly between 20-40 percent. A GWAS data set, obtained from dbGap is utilised, which contains predominantly urban low-income African-American women who had normal and preterm deliveries. Epistatic interactions from original SNP sequences were extracted through a deep learning stacked autoencoder model and used to fine-tune a classifier for discriminating between term and preterm births observations. All models are evaluated using standard binary classifier performance metrics. The findings show that important information pertaining to SNPs and epistasis can be extracted from 4,666 raw SNPs generated using logistic regression (p-value = 5*10 -3 ) and used to fit a highly accurate classifier model. The following results (Sen = 0.9562, Spec = 0.8780, Gini = 0.9490, Logloss = 0.5901, AUC = 0.9745, and MSE = 0.2010) were obtained using 50 hidden nodes and (Sen = 0.9289, Spec = 0.9591, Gini = 0.9651, Logloss = 0.3080, AUC = 0.9825, and MSE = 0.0942) using 500 hidden nodes. The results were compared with a Support Vector Machine (SVM), a Random Forest (RF), and a Fishers Linear Discriminant Analysis classifier, which all failed to improve on the deep learning approach.

Background: Our goal was to examine differences in maternal and neonatal outcomes following the transition from a private practice to an academic model at a community hospital., Methods: This is a retrospective cohort study of a high-volume community hospital labor and delivery unit. A private practice hospitalist group was replaced with academic hospitalists. Maternal and neonatal outcomes for patients cared for by these groups were compared. The primary outcome was a composite of maternal morbidity that included blood transfusion, anal sphincter injuries, dilation and curettage, hysterectomy, chorioamnionitis, endometritis, wound infection, intensive care unit admission, and readmission. The secondary outcomes were cesarean delivery rate and a composite of neonatal morbidity that included Apgar score ≤3 at 5 min, shoulder dystocia, birth trauma, seizure, sepsis, necrotizing enterocolitis, intraventricular hemorrhage, or mechanical ventilation., Results: 245 patients were delivered by private physicians and 447 by academic physicians over the study period. No difference in the composite maternal morbidity between private and academic hospitalist groups was identified (21 vs. 25%; aOR 1.37, 95% CI: 0.36-5.21). The academic hospitalist group had a higher cesarean delivery rate compared to the private group (25 vs. 18%; aOR 2.03, 95% CI: 1.17-3.53). There was no difference in a composite neonatal morbidity (9 vs. 8%; aOR 0.92, 95% CI: 0.052-1.63)., Conclusion: Women cared for by academic hospitalists were more likely to have a cesarean delivery, but there was no difference in maternal or neonatal morbidity in patients delivered by private or academic hospitalists., (© 2020 S. Karger AG, Basel.)

Objective: Our team created a knowledge, attitudes, and practice (KAP) survey in order to assess changes over time in healthcare provider and community member awareness of Zika virus symptoms, transmission, treatment, and current and future concerns., Study Design: The cross-sectional survey was issued at an academic medical center in Washington, DC, and via an online link to healthcare providers and community members between June and August 2016. Survey distribution was then repeated the following year, from March to April 2017. Outcomes were compared by survey year and healthcare provider versus community member status using SAS Program Version 9.4., Results: Significant differences in knowledge, attitudes, and practices existed between 2016 and 2017 survey time points. By 2017, more respondents had knowledge of various Zika virus infection characteristics; however healthcare provider knowledge also waned in certain areas. Attitudes towards Zika virus infection displayed an overall decreased concern by 2017. Practice trends by 2017 demonstrated fewer travel restrictions to Zika-endemic areas and increased mosquito protective measures within the US., Conclusions: Our results provide novel insight into the transformation of knowledge, attitudes, and practice of community members and healthcare providers regarding Zika virus since its declaration as a public health emergency of international concern in 2016.

Objective: MicroRNAs (miRNAs) are noncoding RNAs involved in posttranscriptional regulation of target genes. The objective of this study was to determine the miRNA expression profile of the human uterine cervix after spontaneous term labor (TL)., Study Design: The miRNA expression pattern of cervical tissue was characterized using microarrays. Samples were collected at term from patients with (n = 8) and without (n = 9) TL. Moderated t tests and false discovery rate correction were applied. Results were confirmed using quantitative reverse transcriptase-polymerase chain reaction., Results: A total of 226 miRNAs were expressed in human cervical tissue. miR-223, miR-34b, and miR-34c were overexpressed in cervical tissue of patients with TL compared to those without. Quantitative reverse transcriptase-polymerase chain reaction assays confirmed these findings (miR-223 [fold change {FC} = 5.7], miR-34b [FC = 4.5], miR-34c [FC = 6.2]; P < .001)., Conclusion: This is the first report of miRNA expression in the human uterine cervix in pregnancy. Cervical remodeling after TL and delivery was associated with changes in miR-223, miR-34b, and miR-34c., (2010 Mosby, Inc.)

Problem: Galectin-1 can regulate immune responses upon infection and inflammation. We determined galectin-1 expression in the chorioamniotic membranes and its changes during histological chorioamnionitis., Method of Study: Chorioamniotic membranes were obtained from women with normal pregnancy (n = 5) and from patients with pre-term pre-labor rupture of the membranes (PPROM) with (n = 8) and without histological chorioamnionitis (n = 8). Galectin-1 mRNA and protein were localized by in situ hybridization and immunohistochemistry. Galectin-1 mRNA expression was also determined by quantitative reverse transcriptase polymerase chain reaction., Results: Galectin-1 mRNA and protein were detected in the amniotic epithelium, chorioamniotic fibroblasts/myofibroblasts and macrophages, chorionic trophoblasts, and decidual stromal cells. In patients with PPROM, galectin-1 mRNA expression in the fetal membranes was higher (2.07-fold, P = 0.002) in those with chorioamnionitis than in those without. Moreover, chorioamionitis was associated with a strong galectin-1 immunostaining in amniotic epithelium, chorioamniotic mesodermal cells, and apoptotic bodies., Conclusion: Chorioamnionitis is associated with an increased galectin-1 mRNA expression and strong immunoreactivity of the chorioamniotic membranes; thus, galectin-1 may be involved in the regulation of the inflammatory responses to chorioamniotic infection.

Objective: Pyelonephritis has a more severe course during pregnancy than in the non-pregnant state. This has been attributed to the increased susceptibility of pregnant women to microbial products. An acquired protein Z deficiency has been reported when there is excessive thrombin activity. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma protein Z concentrations., Study Design: A cross-sectional study was conducted to compare plasma protein Z concentrations between normal pregnant women (N = 71) and pregnant women with pyelonephritis (N = 42). Protein Z concentrations were measured by enzyme-linked immunosorbent assay. Parametric and non-parametric statistics were used for analysis., Results: Patients with pyelonephritis had a significantly lower median plasma concentration of protein Z than did patients with normal pregnancies (median 2.14 microg/mL (0.4-3.4) vs. median 2.36 microg/mL (1.09-3.36); p = 0.03). There was no difference in the median plasma concentration of anti-protein Z antibodies between patients with pyelonephritis and those with normal pregnancies., Conclusion: The median maternal plasma protein Z concentration was significantly lower in patients with pyelonephritis during pregnancy than in patients with normal pregnancies.

Objective: The objective of the study was to determine whether first-trimester maternal serum placental protein 13 (PP13) concentrations can be used in the risk assessment for preeclampsia., Study Design: This case-control study included 50 patients with preeclampsia and 250 patients with normal pregnancies. Samples were collected between 8 and 13 weeks of gestation. Serum PP13 concentrations were measured by immunoassay and expressed as medians and multiples of the median (MoM) for gestational age. Sensitivity and specificity were derived from receiver-operating characteristic curve analysis., Results: (1) Serum PP13 concentration in the first trimester was significantly lower in patients who developed preterm and early-onset preeclampsia than in those with normal pregnancies; and (2) at 80% specificity, a cutoff of 0.39 MoM had a sensitivity of 100% for early-onset preeclampsia and 85% for preterm preeclampsia., Conclusion: Maternal serum first-trimester PP13 appears to be a reasonable marker for risk assessment for preterm preeclampsia but a weak marker for severe preeclampsia at term, and ineffective for identifying mild preeclampsia at term.

Objective: Preeclampsia (PE) is characterized by excessive thrombin generation, which has been implicated in the multiple organ damage associated with the disease. The biological effects of thrombin on coagulation and inflammation are mediated by protease-activated receptor-1 (PAR-1), a G protein-coupled receptor. The aim of this study was to determine whether preterm PE is associated with changes in placental expression of PAR-1., Study Design: This cross-sectional study included two groups matched for gestational age at delivery: (1) patients with preterm PE (<37 weeks of gestation; n = 26) and (2) a control group of patients with preterm labor without intra-amniotic infection (n = 26). Placental tissue microarrays were immunostained for PAR-1. Immunoreactivity of PAR-1 in the villous trophoblasts was graded as negative, weak-positive, or strong-positive., Results: (1) The proportion of cases with strong PAR-1 immunoreactivity was significantly higher in placentas of patients with PE than in placentas from the control group (37.5% (9/24) vs. 8.7% (2/23); p = 0.036, respectively). (2) PAR-1 immunoreactivity was found in the cellular compartments of the placental villous tree, mainly in villous trophoblasts and stromal endothelial cells. (3) PAR-1 was detected in 92.3% (24/26) of the placentas of women with PE and in 88.5% (23/26) of the placentas from the control group., Conclusion: Placentas from pregnancies complicated by preterm PE had a significantly higher frequency of strong PAR-1 expression than placentas from women with spontaneous preterm labor. This observation is consistent with a role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in PE. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of PAR-1, the major receptor for this enzyme.

Background: During pregnancy, mechanisms that allow for regulation of continuous fetal and placental vasculogenesis with prevention of maternal neo-vascularization remain elusive. The vascular endothelial growth factor (VEGF) biological system has a key role during vasculogenesis. The aims of this study were to validate a bioassay for soluble vascular endothelial growth factor receptors 1 and 2 (sVEGFR-1 and sVEGFR-2) in baboon plasma and to determine the maternal and fetal plasma concentration of these receptors at the end of the baboon pregnancy., Methods: Maternal peripheral blood samples were obtained from eight baboons (Papio anubis) prior to elective cesarean section and from the umbilical cord after the fetuses were delivered. Spike and recovery experiments at various concentrations in pooled baboon maternal plasma were used to validate a human quantitative sandwich immunoassay for sVEGFR-1 and -2. Concentrations of sVEGFR-1 and -2 were then determined in maternal and fetal plasma samples., Results: No significant correlations were observed between sVEGFR-1 or -2 concentrations in maternal and fetal circulations. The concentration of sVEGFR-1 was at least 30 times greater and that of sVEGFR-2 approximately two times greater, in maternal than in cord plasma (both P < 0.01)., Conclusion: These findings suggest that baboons can be used to study the regulation of vasculogenesis during pregnancy.

Objective: This study aimed to discover "signature pathways" that characterize biologic processes, based on genes differentially expressed in the uterine cervix before and after spontaneous labor., Study Design: The cervical transcriptome was characterized previously from biopsy specimens taken before and after term labor. Pathway analysis was used to study the differentially expressed genes, based on 2 gene-to-pathway annotation databases (Kyoto Encyclopedia of Genes and Genomes [Kanehisa Laboratories, Kyoto University, Kyoto, Japan] and Metacore software [GeneGo, Inc, St. Joseph, MI]). Overrepresented and highly impacted pathways and connectivity nodes were identified., Results: Fifty-two pathways in the Metacore database were enriched significantly in differentially expressed genes. Three of the top 5 pathways were known to be involved in cervical remodeling. Two novel pathways were plasmin signaling and plasminogen activator urokinase signaling. The same analysis with the Kyoto Encyclopedia of Genes and Genomes database identified 4 significant pathways that the impact analysis confirmed. Multiple nodes that provide connectivity within the plasmin and plasminogen activator urokinase signaling pathways were identified., Conclusion: Three strategies for pathway analysis were consistent in their identification of novel, unexpected, and expected pathways, which suggests that this approach is both valid and effective for the elucidation of biologic mechanisms that are involved in cervical dilation and remodeling.

Objective: Protein Z, a vitamin K-dependent plasma protein, has an important role in the regulation of the coagulation cascade. Protein Z deficiency has been associated with unexplained pregnancy loss and adverse pregnancy outcome in patients with thrombophilia. This study was conducted to determine if preeclampsia (PE), small for gestational age (SGA), and fetal demise are associated with changes in maternal plasma concentrations of protein Z., Study Design: This cross-sectional study included normal pregnant women (N = 71), patients with PE (N = 130), patients who delivered an SGA neonate (N = 58), and patients with fetal demise (N = 58). Maternal plasma protein Z concentrations were measured by a sensitive and specific immunoassay. Protein Z deficiency was defined as maternal plasma concentrations 0.05); and (3) women in the PE and fetal demise groups had significantly higher rates of protein Z deficiency than those with normal pregnancy outcome., Conclusions: (1) PE, but not SGA or fetal demise, is associated with a significantly lower maternal median plasma concentration of protein Z than normal pregnancy, and (2) a high rate of protein Z deficiency is observed in patients with PE and fetal demise.