Adverse effects of exposure to armed conflict on pregnancy : a systematic review

Exposure to armed conflict has manifold implications for both military and civilian populations. Prenatal stress has detrimental effects on both obstetric outcomes, fetal development and the development of an individual later in life. As well as causing stress to the mother, armed conflicts can decimate local infrastructures making it increasingly difficult to access antenatal and general healthcare. The present review is particularly salient in light of the many ongoing current conflicts. It examines the impacts of exposure to armed conflicts on the pregnancy outcomes.A thorough literature search was carried out on three databases using MeSH and truncation terms. 13 studies were included in the final analysis relating to mothers exposed to armed conflicts since 1990.The studies include data from 1 172 151 patients: mothers from Libya, Bosnia, Herzegovina, Israel, Palestine, Kosovo, Yugoslavia, Nepal, Somalia, Iraq, Kuwait and Afghanistan. There is evidence of an increased risk of mothers giving birth to babies of low birth weight as reported in nine included studies. All have a degree of bias, with four at lower and five at higher risk of bias, either not adjusting for confounders or not employing robust measures of exposure to conflict. Further evidence suggested an increase in the incidence of miscarriage, stillbirth, prematurity, congenital abnormalities, miscarriage and premature rupture of membranes among mothers exposed to armed conflict.Despite the varying degrees of bias which must be considered for the available evidence, the data with the lowest risk of bias suggest a relationship between exposure to armed conflict and low birth weight. In light of the current level of displacement experienced by such populations, the identification of pregnancies at risk could improve the efficacy of antenatal care. Clinicians should consider additional ultrasound scanning where appropriate to monitor for restricted growth in such pregnancies

Gestational hypertension and childhood atopy: a Millennium Cohort Study analysis.

Gestational hypertension may confer risk of atopic disease in offspring through a direct biological mechanism, but another possibility is that risk is mediated through complications of pregnancy. To explore these associations, we conducted an analysis of a nationally representative birth cohort based in the UK involving children born 2000-2002. We included 12,450 mother-child pairs. We used logistic regression to estimate the association between hypertensive disease and asthma, hay fever, or eczema by age 5, and parentally reported early wheeze and severe wheeze. Mediation by gestation at delivery and caesarean delivery was explored using causal mediation analysis. Odds ratios (95% CI) for gestational hypertension and childhood asthma, hay fever, and eczema were 1.32 (1.09, 1.59), 1.22 (0.97, 1.55), and 1.12 (0.96, 1.32) respectively, adjusted for confounding. The population attributable fractions were 2.4% (1.0-3.8%), 0.9% (-0.3% to 2.1%), and 1.8% (0.0-3.7%), respectively. Accounting for mediation by gestational age and caesarean delivery, odds ratios (95% CI) for the potential direct effects of gestational hypertension were 1.21 (0.97, 1.50), 1.17 (0.91, 1.49), and 1.11 (0.94, 1.31) for the same.Conclusion: Gestational hypertension was weakly positively associated with asthma and this was partly mediated by earlier delivery. Only a small proportion of early childhood asthma was attributable to gestational hypertensive disease in this representative UK-based birth cohort. What is known: • Gestational hypertension has been shown to be an inconsistent risk factor for the atopic diseases. • The in utero immune environment may modify the risk of atopy in offspring; alternatively, complications of pregnancy including caesarean delivery and prematurity may explain an association between hypertensive disease and atopy. What is new: • Self-reported gestational hypertension was a weak risk factor for asthma and wheeze in the Millennium Cohort Study. • Part of the association between gestational hypertensive disease and asthma was explained by earlier delivery

Full dilatation caesarean section and the risk of preterm delivery in a subsequent pregnancy : a historical cohort study

Full dilatation caesarean sections (CS) have increased risk of uterine extensions, which leads to cervical trauma that has been associated with an increased risk of spontaneous preterm birth (sPTB) in a subsequent pregnancy. The aim of this study was to determine if CS at full dilatation increased the risk of sPTB in a subsequent pregnancy in our unit. A historical cohort study was performed on women delivered by emergency CS between 2008–2015 (n = 5808) in a university hospital who had a subsequent pregnancy in this time frame (n = 1557). Women were classified into two exposure groups; those who were 6–9 cm and those fully dilated at index CS. The reference group was CS at 0–5 cm dilated. The primary outcome was sPTB < 37 weeks’ gestation. CS at 6–9 cm or fully dilated did not significantly increase the odds of sPTB in a subsequent pregnancy (aOR 1.64, 95% CI: 0.83–3.28, p = 0.158; aOR 1.86, 95% CI: 0.91–3.83; p = 0.090, respectively). However, a short interpregnancy interval of <1 year significantly increased the odds of sPTB in a subsequent pregnancy (aOR 3.10, 95% CI: 1.71–5.61). This study has found a short interpregnancy interval following a CS conferred a higher risk of sPTB than full dilatation CS. This finding highlights postnatal contraception and increased surveillance of women with short interpregnancy interval post CS as possible interventions to reduce sPTB

History repeats itself : the relevance of historical pandemics to the medical school curriculum

Introduction: The dramatic global impact of the coronavirus pandemic has increased consideration on epidemiological progressions of pandemics. Measures implemented to reduce viral transmission have been largely historical, comparable in nature with the 1918 and 2009 influenza pandemics, demonstrating the importance of clinicians’ awareness on historical pandemics. Despite this, literature suggests medical students’ knowledge on previous pandemics is poor. Objectives: This study aims to gather stakeholder information from UK medical students on the importance of including the history of pandemics in the medical school curriculum. Methods: A cross-sectional cohort study conducted via a mixed question type online survey was distributed to all UK medical schools to explore stakeholder views. Grounded theory emergent coding was used to generate themes to free-text answers and SPSS and Excel were used to analyse quantitative data using pivot tables and Fishers exact tests. Results: Two hundred and forty-one students consented to take part from eight medical schools in the UK with 98% of these students completing the questionnaire. 34% of students reported having teaching on pandemics with 78% of students stating it would be beneficial. Knowledge was poor with 5.7% of students achieving 100% on knowledge-based questions. 72% of students believed that learning about the history of medicine would be beneficial with 87% of these students referring to ‘benefiting (the) future’ in their answers. Additionally, 79% of students thought it would be beneficial to learn about historical pandemics with reference to the current COVID-19 pandemic. Conclusion: To date, this is the only UK based study assessing stakeholders’ views on including the history of pandemics in the medical school curriculum. Our findings demonstrate that medical students wish to have more historical content included in their degree to better prepare tomorrow's doctors for situations that may occur when history repeats itself

Volatile organic compound analysis, a new tool in the quest for preterm birth prediction—an observational cohort study

Preterm birth is the leading cause of death worldwide in children under five years. Due to its complex multifactorial nature, prediction is a challenge. Current research is aiming to develop accurate predictive models using patient history, ultrasound and biochemical markers. Volatile organic compound (VOC) analysis is an approach, which has good diagnostic potential to predict many disease states. Analysis of VOCs can reflect both the microbiome and host response to a condition. We aimed to ascertain if VOC analysis of vaginal swabs, taken throughout pregnancy, could predict which women go on to deliver preterm. Our prospective observational cohort study demonstrates that VOC analysis of vaginal swabs, taken in the midtrimester, is a fair test (AUC 0.79) for preterm prediction, with a sensitivity of 0.66 (95%CI 0.56–0.75) and specificity 0.89 (95%CI 0.82–0.94). Using vaginal swabs taken closest to delivery, VOC analysis is a good test (AUC 0.84) for the prediction of preterm birth with a sensitivity of 0.73 (95%CI 0.64–0.81) and specificity of 0.90 (95%CI 0.82–0.95). Consequently, VOC analysis of vaginal swabs has potential to be used as a predictive tool. With further work it could be considered as an additional component in models for predicting preterm birth

Detection of Group B Streptococcus in pregnancy by vaginal volatile organic compound analysis : a prospective exploratory study

Our objective was to assess whether volatile organic compound (VOC) analysis of vaginal swabs can detect maternal Group B Streptococcus (GBS) during pregnancy in a prospective exploratory study. Around 243 women attending a high-risk antenatal clinic at one university teaching hospital in the UK consented to take part and provide vaginal swabs throughout pregnancy. VOC analysis of vaginal swabs was undertaken and compared with the reference standard of GBS detected using enrichment culture method. The chemical components that emanated from the vaginal swabs were measured by gas chromatograph ion mobility spectrometry. This platform has both high sensitivity and good specificity to a range of chemical compounds. Our main outcome was to determine the sensitivity and specificity of VOC analysis for the detection of maternal GBS in vaginal swabs during pregnancy. Our study has demonstrated that the sensitivity and specificity of the VOC analysis by GC–IMS for the detection of GBS from vaginal swabs was 0.81 (95% confidence interval [CI], 0.71–0.89) and 0.97 (95% CI, 0.91–1) respectively. We conclude that the use of VOCs as biomarkers for the detection of maternal GBS in the vagina is a novel tool. As this test produces results within minutes and is of low unit test cost it has the potential to be used in clinical settings, where fast diagnosis is important, for example, a patient in early labour

Assessing the association between oral hygiene and preterm birth by quantitative light-induced fluorescence

The aim of this study was to investigate the purported link between oral hygiene and preterm birth by using image analysis tools to quantify dental plaque biofilm. Volunteers (η = 91) attending an antenatal clinic were identified as those considered to be “at high risk” of preterm delivery (i.e., a previous history of idiopathic preterm delivery, case group) or those who were not considered to be at risk (control group). The women had images of their anterior teeth captured using quantitative light-induced fluorescence (QLF). These images were analysed to calculate the amount of red fluorescent plaque (ΔR%) and percentage of plaque coverage. QLF showed little difference in ΔR% between the two groups, 65.00% case versus 68.70% control, whereas there was 19.29% difference with regard to the mean plaque coverage, 25.50% case versus 20.58% control. A logistic regression model showed a significant association between plaque coverage and case/control status (Ρ = 0.031), controlling for other potential predictor variables, namely, smoking status, maternal age, and body mass index (BMI)

Deficiency in clonogenic endometrial mesenchymal stem cells in obese women with reproductive failure – a pilot study

The mechanisms of obesity associated reproductive complications remain poorly understood. Endometrial mesenchymal stem-cells are critical for cyclic renewal and uterine function. Recently, W5C5+ cells, with high clonogenicity, capable of producing endometrial stroma in vivo, have been described. We sought to investigate the abundance and cloning efficiency of W5C5+ and W5C5− endometrial cells in relation to Body Mass Index, age and reproductive outcome. Design W5C5+ and W5C5− cells were purified from mid-luteal endometrial biopsies (n = 54) by magnetic bead separation and subjected to in vitro colony-forming assays. Results First trimester pregnancy losses were significantly higher in obese subjects (n = 12) compared to overweight (n = 20) and subjects with normal Body Mass Index (n = 22) (P0.05). Conclusions Our observations suggest that the regenerative capacity and plasticity of the endometrium of obese women is suboptimal, which in turn may account for the increased risk of reproductive complications associated with obesity

Heparin for assisted reproduction (Review)

Abstract BACKGROUND: Heparin as an adjunct in assisted reproduction (peri-implantation heparin) is given at or after egg collection or at embryo transfer during assisted reproduction. Heparin has been advocated to improve embryo implantation and clinical outcomes. It has been proposed that heparin enhances the intra-uterine environment by improving decidualisation with an associated activation of growth factors and a cytokine expression profile in the endometrium that is favourable to pregnancy. OBJECTIVES: To investigate whether the administration of heparin around the time of implantation (peri-implantation heparin) improves clinical outcomes in subfertile women undergoing assisted reproduction. SEARCH METHODS: A comprehensive and exhaustive search strategy was developed in consultation with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group (MDSG). The strategy was used in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress). Relevant trials were identified from both electronic databases and other resources (last search 6 May 2013). SELECTION CRITERIA: All randomised controlled trials (RCTs) were included where peri-implantation heparin was given during assisted reproduction. Peri-implantation low molecular weight heparin (LMWH) during IVF/ICSI was given at or after egg collection or at embryo transfer in the included studies. Live birth rate was the primary outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and quality of trials and extracted relevant data. The quality of the evidence was evaluated using GRADE methods. MAIN RESULTS: Three RCTs (involving 386 women) were included in the review.Peri-implantation LMWH administration during assisted reproduction was associated with a significant improvement in live birth rate compared with placebo or no LMWH (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.07 to 2.90, three studies, 386 women, I(2) = 51%, very low quality evidence with high heterogeneity). There was also a significant improvement in the clinical pregnancy rate with use of LMWH (OR 1.61, 95% CI 1.03 to 2.53, three studies, 386 women, I(2) = 29%, very low quality evidence with low heterogeneity).However these findings should be interpreted with extreme caution as they were dependent upon the choice of statistical method: they were no longer statistically significant when a random-effects model was used.Adverse events were poorly reported in all included studies, with no comparative data available. However, LMWH did cause adverse effects including bruising, ecchymosis, bleeding, thrombocytopenia and allergic reactions. It appeared that these adverse effects were increased if heparin therapy was used over a longer duration. AUTHORS' CONCLUSIONS: The results of this Cochrane review of three randomised controlled trials with a total of 386 women suggested that peri-implantation LMWH in assisted reproduction treatment (ART) cycles may improve the live birth rate in women undergoing assisted reproduction. However, these results were dependent on small low quality studies with substantial heterogeneity, and were sensitive to the choice of statistical model. There were side effects reported with use of heparin, including bruising and bleeding, and no reliable data on long-term effects. The results do not justify this use of heparin outside well-conducted research trials.These findings need to be further investigated with well-designed, adequately powered, double-blind, randomised, placebo-controlled, multicentre trials. Further investigations could also focus on the effects of the local (uterine) and not systemic application of heparin during ART

Routine use of cell salvage during cesarean section : a practice evaluation

Introduction: Intraoperative cell salvage is a well‐documented alternative to donor blood transfusion given the scarcity of donor blood pools and the incumbent risk of allogenic blood transfusion. Its use in obstetrics has been limited by concern over fetal alloimmunization due to the risk of fetomaternal hemorrhage. However, there are a paucity of studies reporting on outcome. The aim of this study was to report on a four‐year experience of routine use of intraoperative cell salvage and the impact on subsequent pregnancy outcomes. Material and methods: This was a tertiary center retrospective service evaluation cohort study and included all women undergoing cesarean section between December 2014 and November 2018 in a tertiary obstetric unit, identifying women who had reinfusion of intraoperative cell salvage. Data regarding index pregnancy as well as subsequent pregnancies at the hospital were extracted from hospital electronic records. Subsequent pregnancy outcome and maternal antibody status in that pregnancy were collected up until November 2022. Results: During the study period, 6656 cesarean sections were performed, with 436 (6.6%) receiving reinfusion of salvaged blood. The mean volume of reinfused blood was 396 mL. A total of 49 (0.7%) women received donor blood transfusion. Of those who received reinfusion of salvaged blood, 79 (18.1%) women had subsequent pregnancies over the eight‐year follow‐up period. There was one case (0.23%) of fetal cell alloimmunization demonstrated by the presence of anti‐D antibodies on the subsequent pregnancy booking bloods. Conclusions: Routine intraoperative cell salvage may be used to reduce the need for blood transfusion during cesarean section. The risk of fetal cell alloimmunization in a future pregnancy following reinfusion of intraoperative cell salvage is one in 436. Given an apparent small risk of fetal cell alloimmunization, further work is required to establish the safety profile of intraoperative cell salvage in pregnancy