The association between adverse pregnancy outcomes and non-viral genital pathogens among women living in sub-Saharan Africa: a systematic review

Adverse pregnancy outcomes are the main causes of maternal and neonatal morbidity and mortality, including long-term physical and psychological sequelae. These events are common in low- and middle-income countries, particularly in Sub Saharan Africa, despite national efforts. Maternal infections can cause complications at any stage of pregnancy and contribute to adverse outcomes. Among infections, those of the genital tract are a major public health concern worldwide, due to limited availability of prevention, diagnosis and treatment approaches. This applies even to treatable infections and holds true especially in Sub-Saharan Africa. As late as 2017, the region accounted for 40% of all reported treatable non-viral genital pathogens worldwide, many of which have been independently associated with various adverse pregnancy outcomes, and that include Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum. Two databases (PubMed and Embase) were examined to identify eligible studies published up to October 2022. This study reviewed findings on the association between infections by treatable non-viral genital pathogens during pregnancy and adverse pregnancy outcomes among women living in Sub-Saharan Africa. Articles' title and abstract were screened at first using keywords as “sexually transmitted infections”, “non-viral”, “adverse pregnancy outcome”, “Africa”, “sub-Saharan Africa”, “pregnant women”, “pregnancy”, and “pregnancy outcome”. Subsequently, according to the eligibility criteria, potential articles were read in full. Results showed that higher risk of preterm birth is associated with Treponema pallidum, Chlamydia trachomatis and Candida albicans infections. Additionally, rates of stillbirth, neonatal death, low birth weight and intrauterine growth restriction are also associated with Treponema pallidum infection. A better insight on the burden of non-viral genital pathogens and their effect on pregnancy is needed to inform antenatal care guidelines and screening programs, to guide the development of innovative diagnostic tools and other strategies to minimize transmission, and to prevent short- and long-term complications for mothers and children

Screening of chorioamnionitis using volatile organic compound detection in exhaled breath: a pre-clinical proof of concept study

Chorioamnionitis is a major risk factor for preterm birth and an independent risk factor for postnatal morbidity for which currently successful therapies are lacking. Emerging evidence indicates that the timing and duration of intra-amniotic infections are crucial determinants for the stage of developmental injury at birth. Insight into the dynamical changes of organ injury after the onset of chorioamnionitis revealed novel therapeutic windows of opportunity. Importantly, successful development and implementation of therapies in clinical care is currently impeded by a lack of diagnostic tools for early (prenatal) detection and surveillance of intra-amniotic infections. In the current study we questioned whether an intra-amniotic infection could be accurately diagnosed by a specific volatile organic compound (VOC) profile in exhaled breath of pregnant sheep. For this purpose pregnant Texel ewes were inoculated intra-amniotically with Ureaplasma parvum and serial collections of exhaled breath were performed for 6 days. Ureaplasma parvum infection induced a distinct VOC-signature in expired breath of pregnant sheep that was significantly different between day 0 and 1 vs. day 5 and 6. Based on a profile of only 15 discriminatory volatiles, animals could correctly be classified as either infected (day 5 and 6) or not (day 0 and 1) with a sensitivity of 83% and a specificity of 71% and an area under the curve of 0.93. Chemical identification of these distinct VOCs revealed the presence of a lipid peroxidation marker nonanal and various hydrocarbons including n-undecane and n-dodecane. These data indicate that intra-amniotic infections can be detected by VOC analyses of exhaled breath and might provide insight into temporal dynamics of intra-amniotic infection and its underlying pathways. In particular, several of these volatiles are associated with enhanced oxidative stress and undecane and dodecane have been reported as predictive biomarker of spontaneous preterm birth in humans. Applying VOC analysis for the early detection of intra-amniotic infections will lead to appropriate surveillance of these high-risk pregnancies, thereby facilitating appropriate clinical course of action including early treatment of preventative measures for pre-maturity-associated morbidities

Midtrimester preterm prelabour rupture of membranes (PPROM):expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL - III trial)

BACKGROUND: Babies born after midtrimester preterm prelabour rupture of membranes (PPROM) are at risk to develop neonatal pulmonary hypoplasia. Perinatal mortality and morbidity after this complication is high. Oligohydramnios in the midtrimester following PPROM is considered to cause a delay in lung development. Repeated transabdominal amnioinfusion with the objective to alleviate oligohydramnios might prevent this complication and might improve neonatal outcome. METHODS/DESIGN: Women with PPROM and persisting oligohydramnios between 16 and 24 weeks gestational age will be asked to participate in a multi-centre randomised controlled trial. Intervention: random allocation to (repeated) abdominal amnioinfusion (intervention) or expectant management (control). The primary outcome is perinatal mortality. Secondary outcomes are lethal pulmonary hypoplasia, non-lethal pulmonary hypoplasia, survival till discharge from NICU, neonatal mortality, chronic lung disease (CLD), number of days ventilatory support, necrotizing enterocolitis (NEC), periventricular leucomalacia (PVL) more than grade I, severe intraventricular hemorrhage (IVH) more than grade II, proven neonatal sepsis, gestational age at delivery, time to delivery, indication for delivery, successful amnioinfusion, placental abruption, cord prolapse, chorioamnionitis, fetal trauma due to puncture. The study will be evaluated according to intention to treat. To show a decrease in perinatal mortality from 70% to 35%, we need to randomise two groups of 28 women (two sided test, β-error 0.2 and α-error 0.05). DISCUSSION: This study will answer the question if (repeated) abdominal amnioinfusion after midtrimester PPROM with associated oligohydramnios improves perinatal survival and prevents pulmonary hypoplasia and other neonatal morbidities. Moreover, it will assess the risks associated with this procedure. TRIAL REGISTRATION: NTR3492 Dutch Trial Register (http://www.trialregister.nl)

Antibiotic Use in Pregnancy:A Global Survey on Antibiotic Prescription Practices in Antenatal Care

Antibiotic prescription and use practices in the antenatal care setting varies across countries and populations and has the potential to significantly contribute to the global spread of antibiotic resistance. This study aims to explore how healthcare practitioners make decisions about antibiotic prescriptions for pregnant women and what factors play a role in this process. A cross-sectional exploratory survey consisting of 23 questions, including 4 free-text and 19 multiple-choice questions, was distributed online. Quantitative data were collected through multiple-choice questions and was used to identify the most common infections diagnosed and the type of antibiotics prescribed. Qualitative data were gathered through free-text answers to identify gaps, challenges, and suggestions, and the data were analyzed using thematic analysis. A total of 137 complete surveys mostly from gynecologists/obstetricians from 22 different countries were included in the analysis. Overall, national and international clinical guidelines and hospital guidelines/protocols were the most frequently used sources of information. This study highlights the crucial role of laboratory results and guidelines at different levels and emphasizes region-specific challenges and recommendations. These findings underscore the pressing need for tailored interventions to support antibiotic prescribers in their decision-making practice and to address emerging resistance.</p

Understanding Host-Pathogen Interactions in Acute Chorioamnionitis Through the Use of Animal Models.

Inflammation of the chorion and/or amnion during pregnancy is called chorioamnionitis. Acute chorioamnionitis is implicated in approximately 40% of preterm births and has wide-ranging implications for the mother, fetus, and newborn. Large disease burden and lack of therapeutic approaches drive the discovery programs to define and test targets to tackle chorioamnionitis. Central to the advancement of these studies is the use of animal models. These models are necessary to deepen our understanding of basic mechanisms of host-pathogen interactions central to chorioamnionitis disease pathogenesis. Models of chorioamnionitis have been developed in numerous species, including mice, rabbits, sheep, and non-human primates. The various models present an array of strategies for initiating an inflammatory response and unique opportunities for studying its downstream consequences for mother, fetus, or newborn. In this review, we present a discussion of the key features of human chorioamnionitis followed by evaluation of currently available animal models in light of these features and consideration of how these models can be best applied to tackle outstanding questions in the field

Spiral artery blood flow during pregnancy: a systematic review and meta-analysis

BackgroundDownstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta under all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed.MethodsA systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English written articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model.ResultsIn healthy pregnancies, PI and RI decreased from 0.80 (95% CI: 0.70-0.89) and 0.50 (95% CI: 0.47-0.54) in the first trimester to 0.50 (95% CI: 0.45-0.55,

Spiral artery blood flow during pregnancy:a systematic review and meta-analysis

BackgroundDownstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta under all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed.MethodsA systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English written articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model.ResultsIn healthy pregnancies, PI and RI decreased from 0.80 (95% CI: 0.70-0.89) and 0.50 (95% CI: 0.47-0.54) in the first trimester to 0.50 (95% CI: 0.45-0.55,

Maternal metabolic syndrome, preeclampsia, and small for gestational age infancy

OBJECTIVE: We sought to explore to what extent the presence of cardiometabolic and cardiovascular risk constitutions differ between pregnancies complicated by small-for-gestational-age (SGA) infancy, preeclampsia (PE), or a combination of both. STUDY DESIGN: We conducted a cohort study in women after pregnancies complicated by placental syndrome with fetal manifestations (SGA infancy [n - 113]), maternal manifestations (PE [n = 729]), or both (n = 461). Independent sample t test was used to compare cardiometabolic and cardiovascular risk factors between groups. Logistic regression was used to calculate odds ratios and adjusted odds ratios of the prevalence of the metabolic syndrome and its constituents between groups. Adjustments were made for maternal age, parity, smoking, interval between delivery and measurements, and intrauterine fetal demise. RESULTS: The metabolic syndrome was present in 7.5% of women who delivered SGA infants, 15.6% of former PE women, and 19.8% of women after pregnancy complicated by both SGA and PE. Hypertension was observed in 25% of former PE women and 15% of women with solely SGA. Women who delivered a SGA infant had lower global vascular compliance compared to former PE women without SGA. CONCLUSION: Cardiometabolic risk factors consistent with metabolic syndrome relate to the maternal rather than to the fetal presentation of placental syndrome. Nonetheless, highest incidence of metabolic syndrome was observed in women with both PE and SGA. PE relates to chronic hypertension, whereas increased arterial stiffness seems to be associated with women who deliver a SGA infant