Compromised SARS-CoV-2-specific placental antibody transfer.

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

Effects of Maternal HIV Infection and Alcohol Use in Pregnancy on Birth Outcomes in Uganda.

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (ß = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (ß = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.

Risk factors for postpartum maternal mortality and hospital readmission in low- and middle-income countries: a systematic review.

BACKGROUND: In low- and middle-income countries, approximately two thirds of maternal deaths occur in the postpartum period. Yet, care for women beyond 24 h after discharge is limited. The objective of this systematic review is to summarize current evidence on socio-demographic and clinical risk factors for (1) postpartum mortality and (2) postpartum hospital readmission. METHODS: A combination of keywords and subject headings (i.e. MeSH terms) for postpartum maternal mortality or readmission were searched. Articles published up to January 9, 2021 were identified in MEDLINE, EMBASE, and CINAHL databases, without language restrictions. Studies reporting socio-demographic or clinical risk factors for postpartum mortality or readmission within six weeks of delivery among women who delivered a livebirth in a low- or middle-income country were included. Data were extracted independently by two reviewers based on study characteristics, population, and outcomes. Included studies were assessed for quality and risk of bias using the Downs and Black checklist for ratings of randomized and non-randomized studies. RESULTS: Of 8783 abstracts screened, seven studies were included (total N = 387,786). Risk factors for postpartum mortality included Caesarean mode of delivery, nulliparity, low or very low birthweight, and shock upon admission. Risk factors for postpartum readmission included Caesarean mode of delivery, HIV positive serostatus, and abnormal body temperature. CONCLUSIONS: Few studies reported individual socio-demographic or clinical risk factors for mortality or readmission after delivery in low- and middle-income countries; only Caesarean delivery was consistently reported. Further research is needed to identify factors that put women at greatest risk of post-discharge complications and mortality. Understanding post-discharge risk would facilitate targeted postpartum care and reduce adverse outcomes in women after delivery. TRIAL REGISTRATION: PROSPERO registration number: CRD42018103955.

Altered Maternal Antibody Profiles in Women With Human Immunodeficiency Virus Drive Changes in Transplacental Antibody Transfer.

BACKGROUND: Human immunodeficiency virus (HIV)-exposed, uninfected (HEU) children have a higher risk of severe infection, but the causes are poorly understood. Emerging data point to altered antibody transfer in women with HIV (WHIV); however, specific perturbations and the influence of antiretroviral therapy (ART) and HIV viremia remain unclear. METHODS: We evaluated antigen-specific transplacental antibody transfer across 14 antigens in paired maternal and umbilical cord plasma from 352 Ugandan women; 176 were WHIV taking ART. We measured antigen-specific immunoglobulin G (IgG) sub-class (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used partial least squares discrimi-nant analysis to define antigen-specific transplacental antibody transfer features. RESULTS: Global antibody transfer patterns were similar by maternal HIV serostatus, pointing to effective placental function in WHIV. However, HEU umbilical cord antibody profiles were altered, driven by perturbed WHIV seroprofiles, with higher levels of herpesvirus antibodies (P < .01 for Epstein-Barr virus, herpes simplex virus) and lower levels of classic vaccine-induced antibodies (P < .01 for tetanus, polio, Haemophilus influenzae type b), suggesting that umbilical cord antibody profile differences arise from imbalanced WHIV immunity. Abnormal WHIV antibody profiles were associated with HIV viremia, lower CD4 count, and postconception ART initiation (P = .01). CONCLUSIONS: Perturbed immune-dominance profiles in WHIV shift the balance of immunity delivered to neonates. Perturbed HIV-associated maternal antibody profiles are a key determinant of com-promised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.

The interaction between antenatal care and abnormal temperature during delivery and its relationship with postpartum care: a prospective study of 1,538 women in semi-rural Uganda.

BACKGROUND: Postnatal care (PNC) is an important tool for reducing maternal and neonatal morbidity and mortality. However, what predicts receipt and maintenance in PNC, particularly events during pregnancy and the peripartum period, is not well understood. We hypothesized that fever or hypothermia during delivery would engender greater health consciousness among those attending antenatal care, leading to greater PNC engagement after hospital discharge and our objective was to evaluate this relationship. METHODS: Women were prospectively enrolled immediately postpartum at Mbarara Regional Referral Hospital (MRRH). We collected postpartum vital signs and surveyed women by telephone about PNC receipt, fever, and infection at two and six weeks postpartum. Our outcome of interest was receipt of PNC post-discharge, defined as whether a participant visited a health facility and/or was hospitalized in the postpartum period. Our explanatory variables were whether a participant was ever febrile (> 38.0˚C) or hypothermic (< 36.0˚C) during delivery stay and whether a participant attended at least 4 antenatal care (ANC) visits. We used logistic regressions to estimate the association between ANC and fever/hypothermia with PNC, including an interaction term between ANC and fever/hypothermia to determine whether there was a modifying relationship between variables on PNC. Regression models were adjusted for age, marital status, parity, HIV serostatus, Mbarara residency, and whether the participant was referred to MRRH, RESULTS: Of the 1,541 women, 86 (5.6%) reported visiting a health facility and/or hospitalization and 186 (12.0%) had an abnormal temperature recorded during delivery stay. Of those who reported at least one visit, 59/86 (68.6%) delivered by cesarean, 37/86 (43.0%) reported post-discharge fever, and 44/86 (51.2%) reported post-discharge infection. Neither ANC attendance, abnormal temperature after delivery, nor their interaction term, were significantly associated with post-discharge PNC. The included covariates were not significantly associated with the outcome. CONCLUSIONS: While the overall proportion of women reporting post-discharge PNC was low, those who reported visiting a health facility and/or hospitalization had high proportions of post-discharge fever, post-discharge infection, and cesarean delivery, which suggests that these visits may have been related to problem-focused care. No significant associations between ANC and PNC were observed in this cohort. Further research assessing ANC quality and PNC visit focus is needed to ensure ANC and PNC are optimized to reduce morbidity and mortality.

Severe Acute Respiratory Syndrome Coronavirus 2 ACE2 and TMPRSS2 Receptor Protein Expression Patterns Throughout Gestation.

We previously demonstrated that the late gestation placental expression pattern of ACE2 (the primary severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) is localized to the villous syncytiotrophoblast (ST), usually in a polarized membranous pattern at the ST base sparing the apical surface (that directly exposed to maternal blood). We found that the late gestation placental expression pattern of TMPRSS2 (the spike proteinase required for SARS-CoV-2 cellular infection), is usually absent in the trophoblast but is rarely, weakly expressed in the placental endothelium. We now show the developmental protein expression patterns of ACE2 and TMPRSS2 by immunohistochemistry throughout gestation, from the first through third trimester. We found that TMPRSS2 expression was rarely detectable in villous endothelium and very rarely detectable in the ST across gestation. We found that ACE2 expression varied during gestation with circumferential ST expression more common in early gestations and polarized expression more common in later gestation. Although this study is small, these preliminary results suggest that earlier gestation pregnancies may be more vulnerable to infection than later gestation pregnancies.

Placental Decidual Arteriopathy and Vascular Endothelial Growth Factor A Expression Among Women With or Without Human Immunodeficiency Virus.

BACKGROUND: Women with human immunodeficiency virus (HIV) (WHIV) are at higher risk of adverse birth outcomes. Proposed mechanisms for the increased risk include placental arteriopathy (vasculopathy) and maternal vascular malperfusion (MVM) due to antiretroviral therapy and medical comorbid conditions. However, these features and their underlying pathophysiologic mechanisms have not been well characterized in WHIV. METHODS: We performed gross and histologic examination and immunohistochemistry staining for vascular endothelial growth factor A (VEGF-A), a key angiogenic factor, on placentas from women with ≥1 MVM risk factors including: weight below the fifth percentile, histologic infarct or distal villous hypoplasia, nevirapine-based antiretroviral therapy, hypertension, and preeclampsia/eclampsia during pregnancy. We compared pathologic characteristics by maternal HIV serostatus. RESULTS: Twenty-seven of 41 (placentas 66%) assessed for VEGF-A were from WHIV. Mean maternal age was 27 years. Among WHIV, median CD4 T-cell count was 440/µL, and the HIV viral load was undetectable in 74%. Of VEGF-A-stained placentas, both decidua and villous endothelium tissue layers were present in 36 (88%). VEGF-A was detected in 31 of 36 (86%) with decidua present, and 39 of 40 (98%) with villous endothelium present. There were no differences in VEGF-A presence in any tissue type by maternal HIV serostatus (P = .28 to >.99). MVM was more common in placentas selected for VEGF-A staining (51 vs 8%; P < .001). CONCLUSIONS: VEGF-A immunostaining was highly prevalent, and staining patterns did not differ by maternal HIV serostatus among those with MVM risk factors, indicating that the role of VEGF-A in placental vasculopathy may not differ by maternal HIV serostatus.

Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?

BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.

Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study.

BACKGROUND: Pregnant and lactating women were excluded from initial coronavirus disease 2019 vaccine trials; thus, data to guide vaccine decision making are lacking. OBJECTIVE: This study aimed to evaluate the immunogenicity and reactogenicity of coronavirus disease 2019 messenger RNA vaccination in pregnant and lactating women compared with: (1) nonpregnant controls and (2) natural coronavirus disease 2019 infection in pregnancy. STUDY DESIGN: A total of 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 nonpregnant women) were enrolled in a prospective cohort study at 2 academic medical centers. Titers of severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin G, immunoglobulin A, and immunoglobulin M were quantified in participant sera (n=131) and breastmilk (n=31) at baseline, at the second vaccine dose, at 2 to 6 weeks after the second vaccine, and at delivery by Luminex. Umbilical cord sera (n=10) titers were assessed at delivery. Titers were compared with those of pregnant women 4 to 12 weeks from the natural infection (n=37) by enzyme-linked immunosorbent assay. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Postvaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed-effects model, with correction for multiple comparisons, were used to assess differences among groups. RESULTS: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared with nonpregnant women (pregnant, median, 5.59; interquartile range, 4.68-5.89; lactating, median, 5.74; interquartile range, 5.06-6.22; nonpregnant, median, 5.62; interquartile range, 4.77-5.98, P=.24). All titers were significantly higher than those induced by severe acute respiratory syndrome coronavirus 2 infection during pregnancy (P<.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord than maternal sera, although this finding did not achieve statistical significance (maternal sera, median, 104.7; interquartile range, 61.2-188.2; cord sera, median, 52.3; interquartile range, 11.7-69.6; P=.05). The second vaccine dose (boost dose) increased severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G, but not immunoglobulin A, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups. CONCLUSION: Coronavirus disease 2019 messenger RNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in nonpregnant women. Vaccine-induced immune responses were statistically significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

Wireless versus routine physiologic monitoring after cesarean delivery to reduce maternal morbidity and mortality in a resource-limited setting: protocol of type 2 hybrid effectiveness-implementation study.

BACKGROUND: Women in sub-Saharan Africa have the highest rates of morbidity and mortality during childbirth globally. Despite increases in facility-based childbirth, gaps in quality of care at facilities have limited reductions in maternal deaths. Infrequent physiologic monitoring of women around childbirth is a major gap in care that leads to delays in life-saving interventions for women experiencing complications. METHODS: We will conduct a type-2 hybrid effectiveness-implementation study over 12 months to evaluate using a wireless physiologic monitoring system to detect and alert clinicians of abnormal vital signs in women for 24 h after undergoing emergency cesarean delivery at a tertiary care facility in Uganda. We will provide physiologic data (heart rate, respiratory rate, temperature and blood pressure) to clinicians via a smartphone-based application with alert notifications if monitored women develop predefined abnormalities in monitored physiologic signs. We will alternate two-week intervention and control time periods where women and clinicians use the wireless monitoring system during intervention periods and current standard of care (i.e., manual vital sign measurement when clinically indicated) during control periods. Our primary outcome for effectiveness is a composite of severe maternal outcomes per World Health Organization criteria (e.g. death, cardiac arrest, jaundice, shock, prolonged unconsciousness, paralysis, hysterectomy). Secondary outcomes include maternal mortality rate, and case fatality rates for postpartum hemorrhage, hypertensive disorders, and sepsis. We will use the RE-AIM implementation framework to measure implementation metrics of the wireless physiologic system including Reach (proportion of eligible women monitored, length of time women monitored), Efficacy (proportion of women with monitoring according to Uganda Ministry of Health guidelines, number of appropriate alerts sent), Adoption (proportion of clinicians utilizing physiologic data per shift, clinical actions in response to alerts), Implementation (fidelity to monitoring protocol), Maintenance (sustainability of implementation over time). We will also perform in-depth qualitative interviews with up to 30 women and 30 clinicians participating in the study. DISCUSSION: This is the first hybrid-effectiveness study of wireless physiologic monitoring in an obstetric population. This study offers insights into use of wireless monitoring systems in low resource-settings, as well as normal and abnormal physiologic parameters among women delivering by cesarean. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04060667 . Registered on 08/01/2019.

Impact of an educational intervention on WHO surgical safety checklist and pre-operative antibiotic use at a referral hospital in southwestern Uganda.

INTRODUCTION: The World Health Organization (WHO) recommends adherence to its surgical safety checklist (SSC) to optimize patient safety and reduce cesarean surgical site infection (SSI). Educational interventions combined with audit and feedback mechanisms on the checklist use by clinicians have the potential to improve adherence and clinical outcomes. Despite the increase in cesarean delivery rates, there is a paucity of data on how such interventions can improve adherence in resource-limited settings. OBJECTIVE: We performed a quality improvement project to measure the impact of an educational intervention with daily audit and feedback procedures on rates of WHO SSC adherence, including pre-operative antibiotic administration and SSI at Mbarara Regional Referral Hospital maternity ward in Uganda. METHODS: The study involved chart abstraction of WHO SSC and pre-operative antibiotic use during cesarean deliveries and signs of subsequent SSI in three phases. First, we conducted a retrospective review of all charts from May to June 2018 (pre-intervention phase). Second, we instituted an educational intervention on the WHO SSC and pre-operative antibiotics use, followed by a daily audit of charts and feedback to clinicians from July to August 2018 (the intervention phase). Third, we reviewed charts from September to October 2018 (the post-intervention phase). The WHO SSC adherence, pre-operative antibiotic administration and SSI rates were measured as the proportion of the total cesarean deliveries per study phase and then compared across the three phases. RESULTS: We reviewed 678 patients' charts (200 in the pre-intervention phase, 230 in the intervention phase and 248 in the post-intervention phase). The mean patient age was 25 years. The use of the WHO SSC was 7% in the pre-intervention phase compared to 92% in the intervention phase (P < 0.001), and 77% in the post-intervention phase (P < 0.001). Pre-intervention antibiotic receipt was 18% compared to 90% in the intervention phase (P < 0.001) and 84% in the post-intervention phase (P < 0.001). The documented SSI rate in the pre-intervention phase was 15% compared to 7% in the intervention phase (P = 0.02) and 11% in the post-intervention phase (P = 0.20). CONCLUSIONS: An educational intervention, daily audit and feedback to clinicians increased the use of the WHO SSC and prophylactic antibiotics for cesarean delivery-although the rates waned with time. Research to understand factors influencing the checklist use and antibiotic prophylaxis including prescriber knowledge, motivation and clinical process is required. Implementation interventions to sustain usage and impact on clinical outcomes need to be explored.

Antenatal Care Visit Attendance Frequency and Birth Outcomes in Rural Uganda: A Prospective Cohort Study.

OBJECTIVES: Antenatal care (ANC) is designed to improve pregnancy outcomes by providing screening and treatment for preventable and treatable diseases. However, data are lacking on whether ANC affects stillbirth risk. We hypothesized stillbirth risk in Uganda is lower in women attending the recommended ≥ 4 ANC visits compared to those attending ≤ 3. METHODS: We performed a secondary analysis of subset of 1,785 women enrolled in a prospective cohort of postpartum infection who presented to a regional referral hospital for delivery. Our primary outcome was documented stillbirth; a secondary composite poor birth outcome included stillbirth, early neonatal death, low birth weight (< 2500 g), and 5-min APGAR score < 7. We performed multivariable logistic regression analyses to identify independent correlates of stillbirth and poor birth outcome. RESULTS: Of 1,785 participants, 58 (3%) pregnancies resulted in stillbirth and 198 (11%) had a poor birth outcome. Of 1,236 women attending ≥ 4 ANC visits, 31 (2.5%) had a stillbirth, compared to 27/510 (5.2%) attending ≤ 3. In multivariable analyses controlling for age, parity, distance traveled, referral status to hospital, malaria prophylaxis, and syphilis infection; attending ≥ 4 ANC visits was associated with significantly reduced odds of stillbirth (aOR 0.5, 95% CI 0.3-0.9, P = 0.02) and poor birth outcome (aOR 0.66, 95% CI 0.4-0.96, P = 0.03). Malaria prophylaxis was also independently associated with reduced odds of stillbirth (aOR 0.05, 95% CI 0.2-1.0, P = 0.04). CONCLUSIONS: Attending ≥ 4 ANC visits was associated with reduced odds of stillbirth and poor birth outcomes in this Ugandan cohort, which may be related to more comprehensive infection screening, treatment, and prevention services.

HIV Infection and risk of postpartum infection, complications and mortality in rural Uganda.

HIV infection may increase risk of postpartum infection and infection-related mortality. We hypothesized that postpartum infection incidence and attributable mortality in Mbarara, Uganda would be higher in HIV-infected than HIV-uninfected women. We performed a prospective cohort study of 4231 women presenting to a regional referral hospital in 2015 for delivery or postpartum care. All febrile or hypothermic women, and a subset of randomly selected normothermic women were followed during hospitalization and with 6-week postpartum phone interviews. The primary outcome was in-hospital postpartum infection. Secondary outcomes included in-hospital complications (mortality, re-operation, intensive care unit transfer, need for imaging or blood transfusion) and 6-week mortality. We performed multivariable regression analyses to estimate adjusted differences in each outcome by HIV serostatus. Mean age was 25.2 years and 481 participants (11%) were HIV-infected. Median CD4+ count was 487 (IQR 325, 696) cells/mm3, and 90% of HIV-infected women (193/215 selected for in-depth survey) were on antiretroviral therapy. Overall, 5% (205/4231) of women developed fever or hypothermia. Cumulative in-hospital postpartum infection incidence was 2.0% and did not differ by HIV status (aOR 1.4, 95% CI 0.6-3.3, P = 0.49). However, more HIV-infected women developed postpartum complications (4.4% vs. 1.2%, P = 0.001). In-hospital mortality was rare (2/1768, 0.1%), and remained so at 6 weeks (4/1526, 0.3%), without differences by HIV serostatus (P = 1.0 and 0.31, respectively). For women in rural Uganda with high rates of antiretroviral therapy coverage, HIV infection did not predict postpartum infection or mortality, but was associated with increased risk of postpartum complications.

Incidence of postpartum infection, outcomes and associated risk factors at Mbarara regional referral hospital in Uganda.

BACKGROUND: There is a paucity of recent prospective data on the incidence of postpartum infections and associated risk factors in sub-Saharan Africa. Retrospective studies estimate that puerperal sepsis causes approximately 10% of maternal deaths in Africa. METHODS: We enrolled 4231 women presenting to a Ugandan regional referral hospital for delivery or postpartum care into a prospective cohort and measured vital signs postpartum. Women developing fever (> 38.0 °C) or hypothermia (< 36.0 °C) underwent symptom questionnaire, structured physical exam, malaria testing, blood, and urine cultures. Demographic, treatment, and post-discharge outcomes data were collected from febrile/hypothermic women and a random sample of 1708 normothermic women. The primary outcome was in-hospital postpartum infection. Multivariable logistic regression was used to determine factors independently associated with postpartum fever/hypothermia and with confirmed infection. RESULTS: Overall, 4176/4231 (99%) had ≥1 temperature measured and 205/4231 (5%) were febrile or hypothermic. An additional 1708 normothermic women were randomly selected for additional data collection, for a total sample size of 1913 participants, 1730 (90%) of whom had complete data. The mean age was 25 years, 214 (12%) were HIV-infected, 874 (51%) delivered by cesarean and 662 (38%) were primigravidae. Among febrile/hypothermic participants, 174/205 (85%) underwent full clinical and microbiological evaluation for infection, and an additional 24 (12%) had a partial evaluation. Overall, 84/4231 (2%) of participants met criteria for one or more in-hospital postpartum infections. Endometritis was the most common, identified in 76/193 (39%) of women evaluated clinically. Twenty-five of 175 (14%) participants with urinalysis and urine culture results met criteria for urinary tract infection. Bloodstream infection was diagnosed in 5/185 (3%) participants with blood culture results. Another 5/186 (3%) tested positive for malaria. Cesarean delivery was independently associated with incident, in-hospital postpartum infection (aOR 3.9, 95% CI 1.5-10.3, P = 0.006), while antenatal clinic attendance was associated with reduced odds (aOR 0.4, 95% CI 0.2-0.9, P = 0.02). There was no difference in in-hospital maternal deaths between the febrile/hypothermic (1, 0.5%) and normothermic groups (0, P = 0.11). CONCLUSIONS: Among rural Ugandan women, postpartum infection incidence was low overall, and cesarean delivery was independently associated with postpartum infection while antenatal clinic attendance was protective.

Ebola Virus Disease and Pregnancy: A Retrospective Cohort Study of Patients Managed at 5 Ebola Treatment Units in West Africa.

BACKGROUND: Reliable data are lacking on pregnancy outcomes during Ebola virus disease (EVD) epidemics. We aimed to characterize symptoms and outcomes among pregnant women admitted to Ebola treatment units (ETUs) with suspected and confirmed EVD to better inform obstetric management. METHODS: We analyzed a retrospective cohort of reproductive-aged women presenting to 5 West African ETUs from September 2014 to September 2015. We compared clinical symptoms, risk of EVD diagnosis, and mortality between pregnant and nonpregnant women. RESULTS: Of 729 reproductive-aged women admitted to study ETUs, 44 (6%) reported pregnancy. Thirteen of 44 pregnant women (30%) tested EVD positive; 6 of 13 (46%) died. Pregnant women were less likely than nonpregnant women to report anorexia, asthenia, diarrhea, fever, myalgias/arthralgias, nausea, or vomiting (P < .05) at admission. Pregnant women with suspected EVD had the same risk, however, of laboratory-confirmed EVD (30% vs 24%, P = .38). While pregnant women with confirmed EVD had similar Ebola viral loads on presentation to nonpregnant women, as measured by initial cycle threshold (26.4 vs 23.2, P = .16), they were less likely to have myalgias/arthralgias (P< .001) and vomiting (P = .02). Both all-cause mortality (14% vs 19%, P = .39) and EVD-specific mortality (46% vs 54%, P = .60) were not significantly different between pregnant and nonpregnant women. Two neonates born live in the ETU died within 8 days. CONCLUSIONS: We find no evidence to support a difference in the risk of death between pregnant women with suspected or confirmed EVD compared to nonpregnant women. Limited data suggest poor fetal and neonatal outcomes in EVD-affected pregnancies.

Prevalence and correlates of MRSA and MSSA nasal carriage at a Ugandan regional referral hospital.

Background: Despite increasing antimicrobial resistance globally, data are lacking on prevalence and factors associated with Staphylococcus aureus (SA) and MRSA carriage in resource-limited settings. Objectives: To determine the prevalence of SA and MRSA nasal carriage and factors associated with carriage among Ugandan regional referral hospital patients. Methods: We enrolled a cross-section of 500 adults, sampling anterior nares for SA and MRSA carriage using Cepheid Xpert SA Nasal Complete. Results: Mean age was 37 years; 321 (64%) were female and 166 (33%) were HIV infected. Overall, 316 (63%) reported risk factors for invasive SA infection; 368 (74%) reported current antibiotic use. SA was detected in 29% and MRSA in 2.8%. MRSA and MSSA carriers were less likely than SA non-carriers to be female (50% and 56% versus 68%, P = 0.03) or to have recently used ß-lactam antibiotics (43% and 65% versus 73%, P = 0.01). MRSA carriers were more likely to have open wounds than MSSA carriers and SA non-carriers (71% versus 27% and 40%, P = 0.001) and contact with pigs (21% versus 2% and 6%, P = 0.008). MRSA carriage ranged from 0% of HIV clinic participants to 8% of inpatient surgical ward participants ( P = 0.01). In multivariable logistic regression analysis, male sex was independently associated with SA carriage (OR 1.68, 95% CI 1.12-2.53, P = 0.01) and recent ß-lactam antibiotic use was associated with reduced odds of SA carriage (OR 0.61, 95% CI 0.38-0.97, P = 0.04). Conclusions: MRSA nasal carriage prevalence was low and associated with pig contact, open wounds and surgical ward admission, but not with HIV infection.