Maternal Infection Research Articles

Brucellosis (Malta Fever) In Pregnancy and Childbirth: A Case Report

Background: Brucellosis is a multi-organ infectious disease that can affect people of all ages. Systemic symptoms of brucellosis include back pain, headache, fatigue, weakness, general body pain, fever and chills, anorexia, muscle pain, sweating, weight loss, joint pain, cough, neurological symptoms, abdominal pain, diarrhea, and constipation. In this report, the case of a pregnant woman suffering from Malta fever with severe signs that she could not walk is reported. Case Presentation: In this paper, the case of a 28-year-old G3P2 female patient (third pregnancy, two normal deliveries) with 37 weeks of pregnancy and a history of brucellosis in the last two months, being under painkiller treatment, and who has been unable to walk (sacroiliitis) for two weeks, has been reported. Previously, treatment with gentamicin 2 times a day for 6 days was started, and in May 2022, the patient was admitted to Imam Reza Hospital in Mashhad by ambulance. After consultation with an infectious disease specialist, the patient received gentamicin IV QID at a dose of 5 mg/kg, ceftriaxone BID at a dose of 1 mg and IV, and rifampin QID at a dose of 600 mg and PO. She was subjected to CBC differential test twice a week, and BUN and CR assessments were performed every other day. She has received acetaminophen 500 mg PO and Q 6 hrs in the hospital during hospitalization. Radiography of the pelvis was done to check the bilateral sacroiliac joint; it has been found to be normal and no evidence of joint effusion has been seen. After a week of hospitalization and observation in the hospital, vaginal delivery was performed without any problems and she gave birth to a baby boy with an Apgar score of 9-10. Conclusion: Clinical manifestations of brucellosis in pregnant women are weakness, arthralgia, fever, fatigue, excessive night sweats, anorexia, muscle pain, chills, depression, weight loss, headache, and back pain. The most common symptoms are fever, hepatomegaly, spleen involvement, joint complications, and obstetric symptoms, including vaginal bleeding, postpartum endometritis, pelvic or groin pain, premature rupture of membranes, and chorioamnionitis. Rifampicin and trimethoprim- sulfamethoxazole for 6 to 8 weeks constitute the most common and recommended treatment.

Risk factors of developmental delay in children from the age group of 6 months to 6 years

Background: Infants at risk for developmental delay (DD) have a history of one or more risk factors that occurred during pregnancy, the perinatal period, or after birth. Despite numerous studies on high-risk pregnancies and child development in advanced countries, there is scanty data from developing nations like India. Objectives: To determine the antenatal, natal and postnatal risk factors of DD in children aged 6 months to 6 years. Method: A case-control study comprising 61 infants with DD and 61 controls was carried out at Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe) in Maharashtra from December 2019 to May 2020. Children with DD were taken as cases and children without DD as controls. A questionnaire delivered to mothers was used to gather data. Data analysis was carried out using STATA, version 10 software. Results: Common risk factors were caesarean sections (55%), infections (58%), and chronic disorders during pregnancy (49%). Maternal infections, chronic diseases during pregnancy, caesarean section, failure to cry after birth and absence of breastfeeding were significantly more in cases compared to controls. Conclusions: In this case-control study, maternal infections, chronic diseases during pregnancy, caesarean section, failure to cry after birth and absence of breastfeeding were risk factors of DD in children aged 6 months to 6 years.

Near-miss and maternal sepsis mortality: A qualitative study of survivors and support persons

BackgroundPrior studies have shown that maternal deaths due to sepsis occur due to delays in recognition, treatment, and escalation of care through medical chart reviews. This study was conducted to obtain the patient perspective for near-miss and maternal mortality cases due to sepsis. ObjectiveTo identify quality improvement opportunities for improving maternal sepsis through patient and support person experiences. Study designTwenty semi-structured interviews and three follow-up focus groups with patients who experienced critical illness from maternal sepsis in the United States and their support persons (when available) were conducted from May 23, 2022, through October 14, 2022. In this qualitative study, data were analyzed using inductive thematic analysis. ResultsIn this qualitative study of patients with maternal sepsis and their support persons, four main quality improvement themes were identified. The themes were the following: (1) participants reported a lack of awareness of pregnancy-related warning signs and symptoms of when to seek care, (2) many of the presenting symptoms participants experienced were not typical of expected warning signs of maternal sepsis, such as severe pain, overwhelming tiredness, and lack of fever (3) participant concerns were met with dismissal leading to delays in diagnosis, (4) participants experienced long-term sequelae but had difficulty receiving screening and referrals for treatment. ConclusionsThe findings of this study suggest that standardized patient education about the warning signs of maternal sepsis and provider education about the presentation of maternal sepsis, improved listening to patients, and follow-up for sequalae of sepsis are needed.

Hepatitis B virus infection during pregnancy and the risk of postpartum hemorrhage: a protocol for systematic review and meta-analysis

Background: Hepatitis B virus (HBV) infection is a significant public health issue worldwide, with a hepatitis B surface antigen (HBsAg) seroprevalence of 3.5%. Maternal HBV infection during pregnancy, a common comorbidity, is associated with an increase in the risk of adverse obstetric and perinatal outcomes. However, the relationship between maternal HBV infection and postpartum hemorrhage (PPH), a leading contributor to maternal morbidity and mortality, is currently uncertain. The aim of this study is to comprehensively clarify the potential impact of maternal HBV on PPH risk. Methods and Analysis: The authors initially searched five English databases and three Chinese databases from their inception to 26th June 2023. Two reviewers will independently conduct study selection, data extraction, and quality assessment. Cohort and case–control studies investigating the effect of maternal HBV infection on PPH will be included, with study quality assessed using the Newcastle–Ottawa Scale (NOS). Meta-analyses will be performed using a fixed-effects model for I 2≤50% or a random-effects model otherwise. Several categories of subgroup analyses (e.g. sample size more than 1000 vs. less than 1000) and sensitivity analyses (e.g. omit NOS scores less than 7) will be conducted, and publication bias will be assessed through funnel plots, Begg’s and Egger’s tests using STATA 18.0. Ethics and Dissemination: This systematic review and meta-analysis do not require ethics approval and the results will be published in peer-reviewed journals. The findings of this systematic review will provide evidence on the impact of maternal HBV infection on PPH, which will contribute to better prevention and management of PPH in clinical practice and a better understanding of the disease burden of HBV infection. PROSPERO registration number: CRD42023442626

Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus

Pregnant people and their fetuses are vulnerable to adverse health outcomes from coronavirus 2019 disease (COVID-19) due to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been associated with higher rates of maternal mortality, preterm birth, and stillbirth. While SARS-CoV-2 infection of the placenta and vertical transmission is rare, this may be due to the typically longer time interval between maternal infection and testing of the placenta and neonate. Placental injury is evident in cases of SARS-CoV-2-associated stillbirth with massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. Maternal COVID-19 can also polarize fetal immunity, which may have long-term effects on neurodevelopment. Although the COVID-19 pandemic continues to evolve, the impact of emerging SARS-CoV-2 variants on placental and perinatal injury/mortality remains concerning for maternal and perinatal health. Here, we highlight the impact of COVID-19 on the placenta and fetus and remaining knowledge gaps.

HIV-related immune activation attenuates polyfunctional IgG and memory B-cell responses to Tdap immunization during pregnancy

Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown. In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline. One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH. Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants. This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, under Award No. U19AI145825. N.D. is a clinical researcher and A.M. is Research Director at the Fonds de la Recherche Scientifique (F.R.S.-FNRS), Belgium. M.E.A. was partially supported by NIHNIAID1U19AI14825. This article is published with the support of the Fondation Universitaire of Belgium.

Effect of Individualized Care for Pregnant Women with Diabetes Mellitus

Gestational diabetes mellitus (GDM) is the first occurrence of diabetes mellitus after pregnancy due to abnormal maternal glucose metabolism pregnant women with obvious clinical symptoms, but they are prone to maternal infection, polyhydramnios, macrosomia, etc. A series of adverse pregnancy outcomes cause physical and mental harm to pregnant women and their families. Individualized care refers to the development of a care plan tailored to the needs of the individual in order to improve the effectiveness and adherence of treatment. The effect of individualized care on maternal blood glucose levels in GDM is significant. Individualized care can help pregnant women effectively control blood sugar levels and reduce adverse pregnancy outcomes. Through personalized care pairs 100 pregnant women were selected as study subjects and randomly divided into two groups. By comparing fasting blood glucose, individualized care can be effective in controlling blood glucose levels in pregnant women with GDM and reducing the incidence of adverse pregnancy outcomes.

A randomised trial comparing preoperative administration of single-dose kefazolin to kefazolin plus metronidazole as prophylactic antibiotics at caesarean section.

Caesarean section is a life-saving procedure which is associated with high rates of maternal and neonatal complications. It has been estimated that globally, 29.7 million births occur by caesarean section annually. The risk of postpartum infection is estimated to be five to ten times higher compared with normal vaginal delivery. Pregnancy-related sepsis was listed as a top-six cause of maternal mortality in the South African Saving Mothers report between 2017 and 2019. Multiple trials have been conducted in an attempt to optimise administration of prophylactic antibiotics in an effort to reduce postpartum infection and maternal sepsis, and current practice guidelines suggest that there is sufficient evidence that extended-spectrum antibiotics, in combination with kefazolin, result in reduction of postpartum infections. To investigate the effect of perioperative administration of kefazolin alone compared with kefazolin plus metronidazole on postpartum infection in women undergoing caesarean section at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa. All patients undergoing emergency or elective caesarean section were randomised and then sequentially numbered in opaque sealed envelopes, which were placed in the caesarean section operating theatre. The intervention group received kefazolin and a sealed envelope with metronidazole. The control group received kefazolin and a sealed envelope with normal saline. A total of 57/1 010 patients (5.64%) had surgical site infections, of which 27 (5.33%) were in the control group, and 30 (5.96%) were in the intervention group (p=0.66). Two patients in each arm (0.40% in the intervention arm and 0.39% in the control arm) underwent laparotomy procedures, while three women (0.60%) in the intervention arm and four women (0.79%) in the control arm underwent hysterectomy procedures. There were no statistically significant differences in all the measured secondary outcomes between the two groups. The overall sepsis rate in this study was 5.64%. Postpartum infection is multifactorial and there are multiple factors that can be addressed in strengthening the sepsis care bundle. We do not recommend the addition of metronidazole to kefazolin as prophylaxis at caesarean section.

Gastrointestinal nematode infection during pregnancy and lactation enhances spatial reference memory and reduces indicators of anxiety-like behaviour in uninfected adult female mouse offspring.

Maternal bacterial and viral infections that induce neuroinflammation in the developing brain are associated with impaired cognitive function and increased anxiety in the offspring. In contrast, maternal infection with the immunoregulatory murine gastrointestinal (GI) nematode, Heligmosomoides bakeri, appears to benefit neurodevelopment as juvenile 2- and 3-week-old male and female offspring had enhanced spatial memory, which may be due to a Th2/Treg biased neuroimmune environment. Here, the impact of maternal H. bakeri infection during pregnancy and lactation on the spatial and anxiety-like behaviours of adult, 3-month-old uninfected male and female offspring was explored for the first time. It was observed that adult female offspring of H. bakeri-infected dams had enhanced spatial reference memory and reduced anxiety-like behaviour compared to females of uninfected dams. These effects were not observed in adult male offspring. Thus, the positive influence of a maternal GI nematode infection on spatial memory of juvenile offspring persists in adult female offspring.

Correlative analysis of different treatments of persistent occipitotransverse position on the outcome for mother and infant.

To explore the clinical feasibility of different treatment methods for persistent occipitotransverse position and the influence on maternal and infant complications. During the trial of vaginal delivery from April 2020 to March 2023 in our hospital, the cervix was fully dilated and the presentation was located at +2 station. Ninety-six pregnant women with fetal presentation at +4 station, occipitotransverse fetal position, maternal complications, abnormalities in the second stage of labor, and or fetal distress were divided into two groups: 65 patients with Kielland forceps vaginal delivery and 31 patients underwent emergency cesarean section. The delivery time, vaginal laceration rate, postpartum blood loss volume, puerperal infection rate, neonatal birth injury rate, and neonatal 1 min Apgar scores were analyzed. The delivery outcomes and maternal and neonatal complications of 96 pregnant women were analyzed: the application of Kielland forceps delivery time was shorter, while the vaginal laceration rate, postpartum hemorrhage, puerperal infection rate were significantly lower than that of patients undergoing emergency cesarean section and the neonatal 1 min Apgar score was higher than that of emergency cesarean section group (p < 0.05). It was clinically appropriate to use Kielland forceps in vaginal delivery when the persistent occipitotransverse position was present and delivery needed to be expediated. Use of Kielland forceps can shorten the delivery time, improve the success rate of vaginal delivery and reduce the complications of mothers and infants.

Characteristics, risk factors, and outcomes related to Zika virus infection during pregnancy in Northeastern Thailand: A prospective pregnancy cohort study, 2018-2020.

In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

Early online.

Caesarean section is a life-saving procedure which is associated with high rates of maternal and neonatal complications. It has been estimated that globally, 29.7 million births occur by caesarean section annually. The risk of postpartum infection is estimated to be five to ten times higher compared to normal vaginal delivery. Pregnancy-related sepsis was listed as a top six cause of maternal mortality in the South African Saving Mothers report between 2017 and 2019. Multiple trials have been conducted in an attempt to optimise administration of prophylactic antibiotics in an effort to reduce postpartum infection and maternal sepsis, and current practice guidelines suggest that there is sufficient evidence that extended spectrum antibiotics, in combination with kefazolin, result in reduction of postpartum infections Objectives. To investigate the effect of perioperative administration of kefazolin alone compared to kefazolin plus metronidazole on postpartum infection in women undergoing caesarean section at Kalafong Provincial Tertiary Hospital. All patients undergoing emergency or elective caesarean section were randomised and then sequentially numbered in opaque sealed envelopes, which were placed in the caesarean section operating theatre. The intervention group received kefazolin and a sealed envelope with metronidazole. The control group received kefazolin and a sealed envelope with normal saline. A total of 57/1 010 patients (5.64%) had surgical site infections, of which 27 (5.33%) were in the control group, and 30 (5.96%) were in the intervention group (p=0.66). Two patients in each arm (0.40% in the intervention arm and 0.39% in the control arm) underwent laparotomy procedures, while three women (0.60%) in the intervention arm and four women (0.79%) in the control arm underwent hysterectomy procedures. There were no statistically significant differences in all the measured secondary outcomes between the two groups. The overall sepsis rate in this study was 5.64%. Postpartum infection is multifactorial and there are multiple factors that can be addressed in strengthening the sepsis care bundle. We do not recommend the addition of metronidazole to kefazolin as prophylaxis at caesarean section.

Effects of the timing of maternal SARS-CoV-2 infection and vaccination status on placental transfer of antibodies to neonates: A cross-sectional study

ObjectivesTo assess the effects of timing of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status on placental transfer of antibodies to neonates. MethodsIn this cross-sectional study, chemiluminescence was employed to measure SARS-CoV-2 IgG antibody titers in paired maternal-infant samples from women infected during pregnancy who were vaccinated or unvaccinated. Generalized linear regression assessed factors affecting antibody transfer in infected pregnant women and neonatal titers. ResultsThe group with ≥90 days between infection and delivery showed a higher antibody transfer rate than the <90 days group (β= 0.33, 95%CI: 0.01-0.65). Neonatal IgG titers correlated significantly with maternal titers and with maternal infections more than 90 days before delivery. Among infected pregnant women, those who had received 2 or 3 doses of vaccine before pregnancy had higher neonatal antibody titers than those who were not vaccinated (β = 57.70, 95%CI: 31.33-84.07). ConclusionNeonates born to pregnant women who were vaccinated before infection showed higher antibody titers than neonates of pregnant women who were not vaccinated before infection. The transfer rate is higher in pregnant women with ≥90 days from infection to delivery than in those with <90 days. These findings highlight the importance of timely maternal vaccination to optimize maternal and infant immunity.

Candidiasis in Pregnancy: Relevant Aspects of the Pathology for the Mother and the Fetus and Therapeutic Strategies.

Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives. During pregnancy, the prevalence of VVC is estimated to be around 20%, peaking at about 30% in the third trimester, with a number of specific risk factors predisposing to yeast infection being identified and needing elucidation. This review aims to provide updated knowledge on candidiasis during pregnancy, addressing risk factors and maternal and neonatal outcomes, as well as discussing optimal therapeutic strategies to safeguard mothers and newborns. The bibliographic search involved two biomedical databases, PubMed and Embase, without imposing time limits. Among all Candida spp., Candida albicans remains the most frequent causative species. The hyperestrogenic environment of the vaginal mucosa and reduced immune defenses, physiological effects of pregnancy, create conditions favorable for Candida spp. vaginal colonization and hence VVC. Recent evidence shows an association between VVC and adverse obstetric outcomes, including premature membrane rupture (PROM), chorioamnionitis, preterm birth, and puerperal infections. Prompt and effective management of this condition is therefore crucial to prevent adverse obstetric outcomes, maternal-fetal transmission, and neonatal disease. Additional studies are required to confirm the benefits of systemic treatment for maternal candida infection or colonization in preventing premature birth or neonatal systemic candidiasis.

The association between attention deficit hyperactivity disorder and pregnancy, delivery and neonatal outcomes—an evaluation of a population database

BackgroundAttention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without.MethodsA retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without.ResultsOverall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28–1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13–1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17–1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19–1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17–1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36–3.26, p < 0.001).ConclusionWomen with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates.

Interaction between maternal immune activation and postpartum immune stress in neuropsychiatric phenotypes

Epidemiological evidence has shown that maternal infection is a notable risk factor for developmental psychiatric disorders. Animal models have corroborated this link and demonstrated that maternal immune activation (MIA) induces long-term behavioural deficits and neuroimmunological responses to subsequent immune stress in offspring. However, it is unclear whether MIA offspring are more sensitive or more tolerant to immunological challenges from postnatal infections. Pregnant mice were weighed and injected with a single dose of polyinosinic-polycytidylic acid (poly I:C) or saline at gestational day 9.5, and their male offspring were exposed to poly I:C or saline again during adolescence, adulthood, and middle life. After a two-week recovery from the last exposure to poly I:C, the mice underwent behavioural and neuroendophenotypic evaluations. Finally, the mice were sacrificed, and the expression levels of inflammatory factors and the activation levels of glial cells in the cerebral cortex and hippocampus were evaluated. We found MIA mice have lifelong behavioural deficits and glial activation abnormalities. Postpartum infection exposure at different ages has different consequences. Adolescent and middle life exposure prevents sensorimotor gating deficiency, but adult exposure leads to increased sensitivity to MK-801. Moreover, MIA imposed a lasting impact on the neuroimmune profile, resulting in an enhanced cytokine-associated response and diminished microglial reactivity to postnatal infection. Our results reveal an intricate interplay between prenatal and postpartum infection in neuropsychiatric phenotypes, which identify potential windows where preventive or mitigating measures could be applied.

Distinct cytokine profiles in late pregnancy in Ugandan people with HIV

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathrm{\\alpha }$$\\end{document}-KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Examining longitudinal associations between prenatal exposure to infections and child brain morphology

BackgroundMaternal infection during pregnancy has been identified as a prenatal risk factor for the later development of psychopathology in exposed offspring. Neuroimaging data collected during childhood has suggested a link between prenatal exposure to maternal infection and child brain structure and function, potentially offering a neurobiological explanation for the emergence of psychopathology. Additionally, preclinical studies utilizing repeated measures of neuroimaging data suggest that effects of prenatal maternal infection on the offspring’s brain may normalize over time (i.e., catch-up growth). However, it remains unclear whether exposure to prenatal maternal infection in humans is related to long-term differential neurodevelopmental trajectories. Hence, this study aimed to investigate the association between prenatal exposure to infections on child brain development over time using repeated measures MRI data. MethodsWe leveraged data from a population-based cohort, Generation R, in which we examined prospectively assessed self-reported infections at each trimester of pregnancy (N = 2,155). We further used three neuroimaging assessments (at mean ages 8, 10 and 14) to obtain cortical and subcortical measures of the offspring’s brain morphology with MRI. Hereafter, we applied linear mixed-effects models, adjusting for several confounding factors, to estimate the association of prenatal maternal infection with child brain development over time. ResultsWe found that prenatal exposure to infection in the third trimester was associated with a slower decrease in volumes of the pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and a faster increase in the middle temporal gyrus. In the temporal pole we observed a divergent pattern, specifically showing an increase in volume in offspring exposed to more infections compared to a decrease in volume in offspring exposed to fewer infections. We further observed associations in other frontal and temporal lobe structures after exposure to infections in any trimester, though these did not survive multiple testing correction. ConclusionsOur results suggest that prenatal exposure to infections in the third trimester may be associated with slower age-related growth in the regions: pars orbitalis, rostral anterior cingulate and superior frontal gyrus, and faster age-related growth in the middle temporal gyrus across childhood, suggesting a potential sensitive period. Our results might be interpreted as an extension of longitudinal findings from preclinical studies, indicating that children exposed to prenatal infections could exhibit catch-up growth. However, given the lack of differences in brain volume between various infection groups at baseline, there may instead be either a longitudinal deviation or a subtle temporal deviation. Subsequent well-powered studies that extend into the period of full brain development (∼25 years) are needed to confirm whether the observed phenomenon is indeed catch-up growth, a longitudinal deviation, or a subtle temporal deviation.

Simulation training on respectful emergency obstetric and neonatal care in north-western Madagascar: a mixed-methods evaluation of an innovative training program

BackgroundThe rates of maternal and neonatal deaths in Madagascar are among the highest in the world. In response to a request for additional training from obstetrical care providers at the Ambanja district hospital in north-eastern Madagascar, a partnership of institutions in Switzerland and Madagascar conducted innovative training on respectful emergency obstetric and newborn care using e-learning and simulation methodologies. The training focused on six topics: pre-eclampsia, physiological childbirth, obstetric maneuvers, postpartum hemorrhage, maternal sepsis, and newborn resuscitation. Cross-cutting themes were interprofessional communication and respectful patient care. Ten experienced trainers participated in an e-training-of-trainers course conducted by the Swiss partners. The newly-trained trainers and Swiss partners then jointly conducted the hybrid remote/in-person training for 11 obstetrical care providers in Ambanja.MethodsA mixed methods evaluation was conducted of the impact of the training on participants’ knowledge and practices. Trainees’ knowledge was tested before, immediately after, and 6 months after the training. Focus group discussions were conducted to elicit participants’ opinions about the training, including the content and pedagogical methods.ResultsTrainees’ knowledge of the six topics was higher at 6 months (with an average of 71% correct answers) compared to before the training (62%), although it was even higher (83%) immediately after the training. During the focus group discussions, participants highlighted their positive impressions of the training, including its impact on their sense of professional effectiveness. They reported that their interprofessional relationships and focus on respectful care had improved. Simulation, which was a new methodology for the participants native to Madagascar, was appreciated for its engaging and active format, and they enjoyed the hybrid delivery of the training. Participants (including the trainers) expressed a desire for follow-up engagement, including additional training, and improved access to more equipment.ConclusionThe evaluation showed improvements in trainees’ knowledge and capacity to provide respectful emergency care to pregnant women and newborns across all training topics. The hybrid simulation-based training method elicited strong enthusiasm. Significant opportunity exists to expand the use of hybrid onsite/remote simulation-based training to improve obstetrical care and health outcomes for women and newborns in Madagascar and elsewhere.

Association of common maternal infections with birth outcomes: a multinational cohort study.

It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis.