Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and ...middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting.
This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization's International Classification of Diseases, Tenth Revision application to perinatal deaths.
A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%).
In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause.
About 2·6 million third-trimester stillbirths occur annually worldwide, mostly in low-income and middle-income countries, where the causes of these deaths are rarely investigated.
We did a ...prospective, hospital-based, observational study in Soweto, South Africa, to investigate the causes of stillbirths in fetuses of at least 22 weeks' gestational age or with a birthweight of at least 500 g. Maternal clinical information was abstracted from medical records. Investigations included placental macroscopic and histopathological examination and fetal blood culture (including screening for pathogenic bacteria associated with stillbirth). Cases missing one or more of these investigations were considered to have incomplete samples and were excluded from the analysis of cause of stillbirth. Causes of stillbirths were assessed by individual case reviews by at least two obstetricians, and classified with a modified Stillbirth Collaborative Research Network classification system.
Between Oct 9, 2014, and Nov 8, 2015, we enrolled 354 stillbirths (born to 350 women). Among the women with available data, 133 (38%) of 350 had hypertension, median age was 27 years (IQR 23–33), 51 (18%) of 291 were obese, six (2%) of 344 had syphilis, and 94 (27%) of 350 had HIV. 63 (18%) of 341 fetuses showed intrauterine growth restriction. Of 298 cases (born to 294 mothers) with complete samples, the most common causes of stillbirth were maternal medical conditions (64 21% cases; among them 56 19% with hypertensive disorders and six 2% with diabetes), placental or fetal infections (58 19%; 47 16% with fetal invasive bacterial infection), pathological placental conditions (57 19%; among them 27 9% with fetal membrane and placental inflammation and 26 9% with circulatory abnormalities), and clinical obstetric complications (54 18%; 45 15% with placental abruption). Six (2%) stillbirths were attributed to fetal, genetic, or structural abnormalities. In 55 (18%) cases, no cause of death was identified. The most common bacteria to which stillbirths due to fetal invasive infections were attributed were group B streptococcus (15 5% cases), E coli (12 4%), E faecalis (six 2%), and S aureus (five 2%).
Targeted investigation of stillbirths (even without fetal autopsy) can ascertain a cause of stillbirth in most cases. Further studies using such investigations are needed to inform the prioritisation of interventions to reduce stillbirths globally.
Novartis and GlaxoSmithKline.
Objective
The primary objective was to describe the incidence of post‐partum hemorrhage at cesarean delivery before and after implementation of a new high dose oxytocin protocol at Chris Hani ...Baragwanath Academic Hospital.
Methods
This was a cross sectional retrospective record review 3 months before and 3 months after the implementation of a high dose oxytocin protocol. The study included all women that underwent cesarean delivery between 1 November 2016 and 30 April 2017 with a gestation of >24 weeks.
Results
A total of 4604 Cesarean deliveries were performed during the study period, 2162 before the implementation of the new protocol and 2442 after. The incidence of post‐partum hemorrhage was 4.8% (n = 91) in the Before group and 3.9% (n = 89) in the After group (P = 0.17). There was a 17.9% change in incidence of postpartum hemorrhage between the groups (P = 0.17). There was no significant difference in uterine atony between the Before and After groups (21.8% and 30.1%, P = 0.30).
Conclusion
There was no difference in the incidence of postpartum hemorrhage at cesarean delivery after the implementation of a high dose oxytocin protocol.
This is a clinical article describing the incidence of post‐partum hemorrhage before and after implementation of a new high dose oxytocin protocol. No difference in the incidence of postpartum hemorrhage at cesarean section was found after the implementation of this protocol.
In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN), the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent ...cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ).
Women with high grade squamous intraepithelial lesions or worse (HSIL), less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap) smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression
The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear.
We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.
Abstract
Background
Licensure of a group B Streptococcus (GBS) polysaccharide-protein conjugate vaccine for protecting infants against invasive GBS disease (IGbsD) will likely need to be based on ...demonstrating vaccine safety in pregnant women, and benchmarking immunogenicity against a serological threshold associated with risk reduction of IGbsD. We investigated the association between naturally derived GBS serotype Ia and III IgG and risk reduction of IGbsD in infants ≤90 days of age.
Methods
In a matched case-control study, IGbsD cases were identified from a cohort of 38 233 mother-newborn dyads. Mothers colonized vaginally with serotype Ia or III at birth and their healthy infants were eligible as matched controls. GBS serotype-specific anticapsular immunoglobulin G (IgG) was measured on maternal and cord blood/infant sera by multiplex Luminex assay, and the IgG threshold associated with 90% risk reduction of IGbsD was derived by estimating absolute disease risk.
Results
In infants born at ≥34 weeks’ gestational age, cord-blood IgG geometric mean concentrations (GMCs) were lower in cases than controls for serotypes Ia (0.05 vs 0.50 µg/mL; P = .004) and III (0.20 vs 0.38 µg/mL; P = .078). Cord-blood IgG concentrations ≥1.04 and ≥1.53 µg/mL were associated with 90% risk reduction of serotype Ia and III IGbsD, respectively. The maternal sera IgG threshold associated with 90% risk reduction was ≥2.31 µg/mL and ≥3.41 µg/mL for serotypes Ia and III, respectively.
Conclusions
The threshold associated with a reduced risk for serotype Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on an immunogenicity evaluation benchmarked against the defined thresholds.
Clinical Trials Registration
NCT02215226.
Infant serotype-specific anticapsular IgG concentrations ≥1.04 and ≥1.53 µg/mL were associated with 90% risk reduction of serotype Ia and III invasive group B Streptococcus (GBS) disease, respectively. These findings could assist in the licensure of a GBS polysaccharide-protein conjugate vaccine based on immunogenicity and safety.
In pregnant women, antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein cross the placenta and can be detected in cord-blood at the time of delivery. We ...measured SARS-CoV-2 full-length antispike IgG in blood samples collected from women living with HIV (WLWHIV) and without HIV when presenting for labour, and from paired cord-blood samples. Antispike IgG was measured in maternal blood at delivery on the Luminex platform. Cord-blood samples from newborns of women in with detectable antispike IgG were analysed. The IgG geometric mean concentrations (GMCs) and the percentage of cord-blood samples with detectable antispike IgG were compared between WLWHIV and without HIV. A total of 184 maternal and cord-blood pairs were analysed, including 47 WLWHIV and 137 without HIV. There was no difference in antispike GMCs between WLWHIV and without HIV 157 binding antibody units (BAU)/ml vs. 187 BAU/ml; P = 0.17). Cord-blood samples from newborns of WLWHIV had lower GMCs compared with those without HIV (143 vs. 205 BAU/ml; P = 0.033). Cord-to-maternal blood antibody ratio was 1.0 and similar between the two HIV groups. In WLWHIV, those who were 30 years old or less had lower cord-to-maternal blood antibody ratio (0.75 vs. 1.10; P = 0.037) and their newborns had lower cord-blood GMCs (94 vs. 194 BAU/ml; P = 0.04) compared with the older women. Independently of maternal HIV infection status, there was efficient transplacental transfer of antispike antibodies. The GMCs in cord-blood from newborns of WLWHIV were lower than those in HIV-unexposed newborns.
Sub-Saharan Africa and south Asia contributed 81% of 5·9 million under-5 deaths and 77% of 2·6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the ...estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts.
The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhiça, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths.
Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 72% of 180 stillbirths) and congenital infection or sepsis (27 15%). The most common underlying causes of neonatal death were preterm birth complications (187 42% of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 22%), and neonatal sepsis (50 11%). The most common underlying causes of child deaths were congenital birth defects (39 13% of 304 deaths), lower respiratory infection (37 12%), and HIV (35 12%). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 31%), Streptococcus pneumoniae (54 20%), HIV (40 15%), and cytomegalovirus (34 12%), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths.
Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths.
Bill & Melinda Gates Foundation.
Background. Human immunodeficiency virus (HIV)-exposed infants are at increased risk of invasive Group B Methods, Streptococcus (GBS) disease; however, the reason for this increased susceptibillity ...has not been characterized. Methods. We compared GBS capsular and surface-protein maternal immunoglobin G antibody concentrations and cord-maternal ratios between HIV-infected and HIV-uninfected mother-newborn dyads. Results. Median capsular antibody concentrations (µg/mL) were lower in HIV-infected than HIV-uninfected women for serotypes Ib (P= .033) and V (P= .040); and for pilus island (PI)-1 (P = .016), P1-2a (P = .015), P1-2b (P = .015), and fibrinogen-binding protein A (P< .001). For serotypes la and III, cord-maternal ratios were 37.4% (P< .001) and 32.5% (P= .027) lower in HIV-infected compared to HIV-uninfected mother-newborn dyads. The adjusted odds of having capsular antibody concentration ≥2 µg/mL when comparing HIV-infected to -uninfected women were 0.33 (95% confidence interval CI, .15-. 75) and 0.34 (95% CI, .12-1.00) for serotypes la and III, respectively. Antibody levels and cord-maternal ratios were independent of CD4⁺ lymphocyte counts or HIV-1 viral load. Conclusions. The lower GBS antibody concentrations and reduced transplacental antibody transfer in HIVinfected women, which likely contribute to their infants being at heightened susceptibility for invasive GBS disease, could possibly be mitigated by vaccination with a GBS conjugate vaccine currently under clinical development.
Abstract
Background
Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The ...Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high–mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV).
Methods
We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies.
Results
We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12–59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1–5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions.
Conclusions
RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high–mortality rate settings.
Abstract
From April to September 2020, we investigated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a cohort of 396 healthcare workers (HCWs) from 5 departments at Chris ...Hani Baragwanath Hospital, South Africa. Overall, 34.6% of HCWs had polymerase chain reaction–confirmed SARS-CoV-2 infection (132.1 95% confidence interval, 111.8–156.2 infections per 1000 person-months); an additional 27 infections were identified by serology. HCWs in the internal medicine department had the highest rate of infection (61.7%). Among polymerase chain reaction–confirmed cases, 10.4% remained asymptomatic, 30.4% were presymptomatic, and 59.3% were symptomatic.
PDF
