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Global response to COVID-19 pandemic has inadvertently undermined the achievement of existing public health priorities and laregely overlooked local context. Recent evidence suggests that this will cause additional maternal and childhood mortality and morbidity especially in low- and middle-income countries (LMICs). Here we have explored the contextual factors influencing maternal, neonatal and children health (MNCH) care in Bangladesh, Nigeria and South Africa amidst the pandemic. Our findings suggest that between March and May 2020, there was a reduction in utilisation of basic essential MNCH services such as antenatal care, family planning and immunization due to: a) the implementation of lockdown which triggered fear of contracting the COVID-19 and deterred people from accessing basic MNCH care, and b) a shift of focus towards pandemic, causing the detriment to other health services, and c) resource constraints. Taken together these issues have resulted in compromised provision of basic general healthcare. Given the likelihood of recurrent waves of the pandemic globally, COVID-19 mitigation plans therefore should be integrated with standard care provision to enhance system resilience to cope with all health needs. This commentary suggests a four-point contextualised mitigation plan to safeguard MNCH care during the pandemic using the observed countries as exemplars for LMIC health system adaptations to maintain the trajectory of progress regarding sustainable development goals (SDGs).

The gut and genital tract microbiota of females represent very complex biological ecosystems that are in continuous communication with each other. The crosstalk between these two ecosystems impacts host physiological, immunological and metabolic homeostasis and vice versa. The vaginal microbiota evolved through a continuous translocation of species from the gut to the vagina or through a mother-to-child transfer during delivery. Though the organisms retain their physio-biochemical characteristics while in the vagina, the immune responses elicited by their metabolic by-products appear to be at variance with those in the gut. This has critical implications for the gynecological, reproductive as well as overall wellbeing of the host and by extension her offspring. The homeostatic and immunomodulatory effects of the bacterial fermentation products (short chain fatty acids, SCFAs) in the gut are better understood compared to the genital tract. While gut SCFAs prevent a leakage of bacteria and bacterial products from the gut in to circulation (leaky gut) and consequent systemic inflammation (anti-inflammatory/protective role); they have been shown to exhibit dysbiotic and proinflammatory effects in the genital tract that can lead to unfavorable gynecological and reproductive outcomes. Therefore, this review was conceived to critically examine the correlation between the female gut and genital tract microbiota. Secondly, we explored the metabolic patterns of the respective microbiota niches; and thirdly, we described the diverse effects of products of bacterial fermentation on immunological responses in the vaginal and rectal ecosystems.

Multi-marker tests hold promise for identifying symptomatic women at risk of imminent preterm delivery (PTD, <37 week's gestation). This study sought to determine the relationship of inflammatory mediators and metabolites in cervicovaginal fluid (CVF) with spontaneous PTD (sPTD) and delivery within 14 days of presentation with symptoms of preterm labour (PTL). CVF samples from 94 (preterm = 19, term = 75) singleton women with symptoms of PTL studied between 19+0-36+6 weeks' gestation were analysed for cytokines/chemokines by multiplexed bead-based immunoassay, while metabolites were quantified by enzyme-based spectrophotometry in a subset of 61 women (preterm = 16, term = 45). Prevalence of targeted vaginal bacterial species was determined for 70 women (preterm = 14, term = 66) by PCR. Overall, 10 women delivered within 14 days of sampling. Predictive capacities of individual biomarkers and cytokine-metabolite combinations for sPTD and delivery within 14 days of sampling were analysed by logistic regression models and area under the receiver operating characteristic curve. Fusobacterium sp., Mubiluncus mulieris and Mycoplasma hominis were detected in more preterm-delivered than term women (P<0.0001), while, M. curtisii was found in more term-delivered than preterm women (P<0.0001). RANTES (0.91, 0.65-1.0), IL-6 (0.79, 0.67-0.88), and Acetate/Glutamate ratio (0.74, 0.61-0.85) were associated with delivery within 14 days of sampling (AUC, 95% CI). There were significant correlations between cytokines and metabolites, and several cytokine-metabolite combinations were associated with sPTD or delivery within 14 days of sampling (e.g. L/D-lactate ratio+Acetate/Glutamate ratio+IL-6: 0.84, 0.67-0.94). Symptomatic women destined to deliver preterm and within 14 days of sampling express significantly higher pro-inflammatory mediators at mid to late gestation. In this cohort, IL-6, Acetate/Glutamate ratio and RANTES were associated with delivery within 14 days of sampling, consistent with their roles in modulating infection-inflammation-associated preterm labour in women presenting with symptoms of preterm birth. Replication of these observations in larger cohorts of women could show potential clinical utility.

In addition to being a passage for sperm, menstruum, and the baby, the human vagina and its microbiota can influence conception, pregnancy, the mode and timing of delivery, and the risk of acquiring sexually transmitted infections. The physiological status of the vaginal milieu is important for the wellbeing of the host as well as for successful reproduction. High estrogen states, as seen during puberty and pregnancy, promote the preservation of a homeostatic (eubiotic) vaginal microenvironment by stimulating the maturation and proliferation of vaginal epithelial cells and the accumulation of glycogen. A glycogen-rich vaginal milieu is a haven for the proliferation of facilitated by the production of lactic acid and decreased pH. and their antimicrobial and anti-inflammatory products along with components of the epithelial mucosal barrier provide an effective first line defense against invading pathogens including bacterial vaginosis, aerobic vaginitis-associated bacteria, viruses, fungi and protozoa. An optimal host-microbial interaction is required for the maintenance of eubiosis and vaginal health. This review explores the composition, function and adaptive mechanisms of the vaginal microbiome in health and those disease states in which there is a breach in the host-microbial relationship. The potential impact of vaginal dysbiosis on reproduction is also outlined.

Malaria in pregnancy (MiP) remains a key cause of poor maternal and neonatal health outcomes, particularly in the African region. Two strategies globally promoted to address MiP require pregnant women in malaria-endemic regions to sleep under insecticide-treated bed nets (ITNs) and take at least three doses of intermittent preventive treatment (IPTp) during pregnancy. Yet, several multilevel factors influence the effective uptake of these strategies. This study explored the factors for the poor uptake of IPTp and use of ITNs in lower socio-economic communities in Nigeria. We conducted semi-structured interviews (SSI) and focus group discussions (FGD) with a total of 201 key stakeholders in six communities in Ogun State, South-Western Nigeria. Twelve SSIs were conducted with traditional birth attendants (TBAs), faith-based birth attendants and healthcare providers operating in public health facilities. Community leaders (7), pregnant women (30) and 20 caregivers were individually interviewed. Sixteen FGDs were conducted with multi- and first-time pregnant women grouped by location and pregnancy experiences. A thematic approach was used for data analysis. At the individual and social levels, there is a high general awareness of MiP, its consequences and ITNs but low awareness of IPTp, with type of antenatal care (ANC) provider being a key factor influencing access to IPTp. The choice of ANC provider, which facilitates access to IPTp and ITNs, is influenced by the experiences of women, relatives and friends, as well as the attitudes of ANC providers and community perceptions of the type of ANC providers. Concurrent use of multiple ANC providers and ANC providers’ relationships further influence acceptability and coverage for IPTp and ITN use. At the health sector level, there is low awareness about preventive malarial strategies including IPTp among TBAs and faith-based birth attendants, in contrast to high IPTp awareness among public healthcare providers. The findings highlight several factors that influence the utilisation of IPTp services and call for greater synergy and collaboration between the three groups of healthcare providers towards enhancing access to and acceptability of IPTp for improving maternal and child outcomes.

Addressing the problem of maternal mortality in Nigeria requires proper identification of maternal deaths and their underlying causes in order to focus evidence-based interventions to decrease mortality and avert morbidity. The objective of the study was to classify maternal deaths that occurred at a Nigerian teaching hospital using the WHO International Classification of Diseases Maternal mortality (ICD-MM) tool. This was a retrospective observational study of all maternal deaths that occurred in a tertiary Nigerian hospital from 1st January 2014 to 31st December,2018. The WHO ICD-MM classification system for maternal deaths was used to classify the type, group, and specific underlying cause of identified maternal deaths. Descriptive analysis was performed using Statistical Package for Social Sciences (SPSS). Categorical and continuous variables were summarized respectively as proportions and means (standard deviations). The institutional maternal mortality ratio was 831/100,000 live births. Maternal deaths occurred mainly amongst women aged 25-34 years;30(57.7%), without formal education; 22(42.3%), married;47(90.4%), unbooked;24(46.2%) and have delivered at least twice;34(65.4%). The leading causes of maternal death were hypertensive disorders in pregnancy, childbirth, and the puerperium (36.5%), obstetric haemorrhage (30.8%), and pregnancy related infections (17.3%). Application of the WHO ICD-MM resulted in reclassification of underlying cause for 3.8% of maternal deaths. Postpartum renal failure (25.0%), postpartum coagulation defects (17.3%) and puerperal sepsis (15.4%) were the leading final causes of death. Among maternal deaths, type 1, 2, and 3 delays were seen in 30(66.7%), 22(48.9%), and 6(13.3%), respectively. Our institutional maternal mortality ratio remains high. Hypertensive disorders during pregnancy, childbirth, and the puerperium and obstetric haemorrhage are the leading causes of maternal deaths. Implementation of evidence-based interventions both at the hospital and community levels may help in tackling the identified underlying causes of maternal mortality in Nigeria.

The mucosa of the female reproductive tract plays a pivotal role in host defence. Pregnancy must alter immunological mechanisms at this interface to protect the conceptus. We sought to determine how estradiol (E2) alters the immune-responsiveness of cervical epithelial cells to ligand stimulation of Toll-like receptor (TLR)-2 and -4. Human ectocervical epithelial cells (HECECs) were cultured and co-incubated with two concentrations of E2 and peptidoglycan (PGN) or lipopolysaccharide (LPS) over durations that ranged between 10 minutes and 18 hours. Cytometric Bead Array was performed to quantify eight cytokines in the supernatant fluid. In response to PGN, HECECs co-incubated with E2 released lesser quantities of IL-1ß and IFNγ, higher levels of RANTES, and variable levels of IL-6 and IL-8 than those not exposed to E2. In contrast, HECECs co-incubated with LPS and E2 secreted increased levels of IL-1ß, IL-6, IL-8, and IFNγ at 2 and 18 hours than HECECs not exposed to E2, and reduced levels of RANTES at same study time-points. Estradiol alters the immune-responsiveness of cultured HECECs to TLR2 and TLR4 ligands in a complex fashion that appears to vary with bacterial ligand, TLR subtype, and duration of exposure. Our observations are consistent with the functional complexity that this mucosal interface requires for its immunological roles.

Background National guidance (Saving Babies Lives Care Bundle Version 2 (SBLCBv2) Element 5) was published in 2019, with the aim to standardise preterm care in England. We plan to identify how many preterm birth surveillance clinics there are in England, and to define current national management in caring for women who are both asymptomatic and high-risk of preterm birth, and who arrive symptomatically in threatened preterm labour, to assist preterm management both nationally and internationally. Methods An online survey comprising of 27 questions was sent to all maternity units in England between February 2021 to July 2021. Results Data was obtained from 96 units. Quantitative analysis and free text analysis was then undertaken. We identified 78 preterm birth surveillance clinics in England, an increase from 30 preterm clinics in 2017. This is a staggering 160% increase in 4 years. SBLCBv2 has had a considerable impact in increasing preterm birth surveillance clinic services, with the majority (61%) of sites reporting that the NHS England publication influenced their unit in setting up their clinic. Variations exist at every step of the preterm pathway, such as deciding which risk factors warrant referral, distinguishing within particular risk factors, and offering screening tests and treatment options. Conclusions While variations in care still do persist, hospitals have done well to increase preterm surveillance clinics, under the difficult circumstances of the COVID pandemic and many without specific additional funding.

Preterm birth (PTB) refers to a labor before 37 gestational weeks. This is a major global contributor to neonatal morbidity and mortality. Although fetal sex is frequently treated as a confounding variable in PTB research, relatively few studies have conducted sex-stratified analyses to investigate how male and female fetuses may respond differently to various intrauterine exposures. This represents an underexplored area with important implications for understanding fetal sexual dimorphism-specific vulnerability to adverse pregnancy outcomes. Understanding the role of fetal sex differences in the pathophysiology of preterm birth (PTB) regarding processes such as inflammation, placental dysfunction, and oxidative stress is crucial. These delicate processes are tightly interrelated, but also independently contribute to pregnancy complications. Recognizing fetal sex as a biological variable for such processes is essential for improving mechanistic insight, providing refined predictive models.

Demographic studies have revealed a strong association between exposure to high ambient temperatures during pregnancy and increased risks of preterm birth (PTB). The mechanism underlying this association is unclear, but it is plausible that altered placental function may contribute to it. In this study, we conducted differential gene expression analysis, gene set enrichment analysis (GSEA), and gene ontology (GO) analysis on bulk RNA-seq data from human placentas delivered at term and preterm during the warmer months compared to placentas delivered at term and preterm during the colder months in the UK. We detected 48 differentially expressed genes in preterm placentas delivered during the warmer months compared to preterm placentas delivered during the colder months, the majority of which were inflammatory cytokines and chemokines, including SERPINA1, IL1B, CCL3, CCL3L3, CCL4, CCL4L2, CCL20, and CXCL8. The GSEA positively enriched 17 signalling pathways, including the NF-κB, IL17, Toll-like receptor, and chemokine signalling pathways in preterm placentas delivered during warmer months. These results were not observed in the placentas delivered at term during the same times of the year. The GO analysis revealed several enhanced biological processes, including neutrophil, granulocyte, monocyte, and lymphocyte chemotaxis, as well as inflammatory and humoral immune responses in preterm placentas, but not in placentas delivered at term in the summer. We conclude that maternal exposure to warm environmental temperatures during pregnancy likely alters the placental transcriptomes towards inflammation and immune regulation, potentially leading to PTB.