SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status - Los Angeles County, California, May 1-July 25, 2021.

COVID-19 vaccines fully approved or currently authorized for use through Emergency Use Authorization from the Food and Drug Administration are critical tools for controlling the COVID-19 pandemic; however, even with highly effective vaccines, a proportion of fully vaccinated persons will become infected with SARS-CoV-2, the virus that causes COVID-19 (1). To characterize postvaccination infections, the Los Angeles County Department of Public Health (LACDPH) used COVID-19 surveillance and California Immunization Registry 2 (CAIR2) data to describe age-adjusted infection and hospitalization rates during May 1-July 25, 2021, by vaccination status. Whole genome sequencing (WGS)-based SARS-CoV-2 lineages and cycle threshold (Ct) values from qualitative reverse transcription-polymerase chain reaction (RT-PCR) for two SARS-CoV-2 gene targets, including the nucleocapsid (N) protein gene region and the open reading frame 1 ab (ORF1ab) polyprotein gene region,* were reported for a convenience sample of specimens. Among 43,127 reported SARS-CoV-2 infections in Los Angeles County residents aged ≥16 years, 10,895 (25.3%) were in fully vaccinated persons, 1,431 (3.3%) were in partially vaccinated persons, and 30,801 (71.4%) were in unvaccinated persons. Much lower percentages of fully vaccinated persons infected with SARS-CoV-2 were hospitalized (3.2%), were admitted to an intensive care unit (0.5%), and required mechanical ventilation (0.2%) compared with partially vaccinated persons (6.2%, 1.0%, and 0.3%, respectively) and unvaccinated persons (7.6%, 1.5%, and 0.5%, respectively) (p<0.001 for all comparisons). On July 25, the SARS-CoV-2 infection rate among unvaccinated persons was 4.9 times and the hospitalization rate was 29.2 times the rates among fully vaccinated persons. During May 1-July 25, the percentages of B.1.617.2 (Delta) variant infections estimated from 6,752 samples with lineage data increased among fully vaccinated persons (from 8.6% to 91.2%), partially vaccinated persons (from 0% to 88.1%), and unvaccinated persons (from 8.2% to 87.1%). In May, there were differences in median Ct values by vaccination status; however, by July, no differences were detected among specimens from fully vaccinated, partially vaccinated, and unvaccinated persons by gene targets. These infection and hospitalization rate data indicate that authorized vaccines were protective against SARS-CoV-2 infection and severe COVID-19 during a period when transmission of the Delta variant was increasing. Efforts to increase COVID-19 vaccination, in coordination with other prevention strategies, are critical to preventing COVID-19-related hospitalizations and deaths.

Interventions to reduce neonatal mortality: a mathematical model to evaluate impact of interventions in sub-Saharan Africa.

AIM: To determine which interventions would have the greatest impact on reducing neonatal mortality in sub-Saharan Africa in 2012. METHODS: We used MANDATE, a mathematical model, to evaluate scenarios for the impact of available interventions on neonatal deaths from primary causes, including: (i) for birth asphyxia - obstetric care preventing intrapartum asphyxia, newborn resuscitation and treatment of asphyxiated infants; (ii) for preterm birth - corticosteroids, oxygen, continuous positive air pressure and surfactant; and, (iii) for serious newborn infection - clean delivery, chlorhexidine cord care and antibiotics. RESULTS: Reductions in infection-related mortality have occurred. Between 80 and 90% of deaths currently occurring from infections and asphyxia can be averted from available interventions, as can 58% of mortality from preterm birth. More than 200 000 neonatal deaths can each be averted from asphyxia, preterm birth and infections. Using available interventions, more than 80% of the neonatal deaths occurring today could be prevented in sub-Saharan Africa. CONCLUSION: Reducing neonatal deaths from asphyxia require improvements in infrastructure and obstetric care to manage maternal conditions such as obstructed labour and preeclampsia. Reducing deaths from preterm birth would also necessitate improved infrastructure and training for preterm infant care. Reducing infection-related mortality requires less infrastructure and lower-level providers.

Diagnosis of placental malaria in poorly fixed and processed placental tissue.

BACKGROUND: Placental histopathology has been considered the gold standard for diagnosis of malaria during pregnancy. However, in under-resourced areas placental tissue is often improperly fixed and processed; the resulting formalin pigment is difficult to distinguish from malaria pigment. This study examines two alternative diagnostic methods: polymerase chain reaction (PCR) and a novel immunohistochemistry (IHC)-based method using an antibody against histidine-rich protein 2 (HRP2). METHODS: Placental histopathology from 151 pregnant women in Kinshasa was assessed by two blinded microscopists and compared with peripheral blood PCR and IHC for HRP2. The Cohen's kappa coefficients were calculated to assess the test agreement. The sensitivity and specificity of individual tests were calculated using PCR or IHC as the reference standard as well as latent class analysis (LCA). RESULTS: PCR and IHC correlated fairly well. The correlation between the two blinded microscopists was poor, as there was widespread formalin pigment. Using LCA, all of the tests had high specificities. The most sensitive test was IHC (67.7 %), with PCR as second-best (56.1 %). CONCLUSIONS: PCR and/or IHC are suitable diagnostics when the presence of formalin pigment substantially compromises placental histopathology.

Maternal Mortality from Obstructed Labor: A MANDATE Analysis of the Ability of Technology to Save Lives in Sub-Saharan Africa.

Objective The aim of the study is to evaluate clinical interventions to significantly reduce maternal mortality from prolonged labor, obstructed labor, and prolonged obstructed labor (PL/OL/POL) in sub-Saharan Africa (SSA). Methods A mathematical model-Maternal and Neonatal Directed Assessment of Technology ("MANDATE")-was created for SSA with estimated prevalence for PL/OL/POL and case fatality rates from hemorrhage, infection, and uterine rupture. Based on a literature review and expert opinion, the model was populated with estimated likelihoods of the current healthcare system ability to diagnose, transfer, and treat women with these conditions. Impact on maternal mortality of improved diagnosis, transfer, and delivery to relieve PL/OL/POL was assessed. Results Without current technologies, the model estimated 8,464 maternal deaths annually in SSA from these conditions. Imputing current diagnosis, transfer, and treatment of PL/OL/POL, an estimated 7,033 maternal deaths occur annually from these complications. With improved PL/OL/POL diagnosis and improved transfer, 1,700 and 740 lives could be saved, respectively. Improved diagnosis, transfer, and treatment for PL/OL/POL reduce the mortality rate to 864 maternal deaths annually, saving 6,169 lives. If improved transfusion and antibiotic use were added, only 507 women per year would die from PL/OL/POL in SSA. Conclusion In SSA, increasing diagnostics, transfer to higher care, and operative delivery could substantially reduce maternal mortality from PL/OL/POL. Synopsis A computerized model of obstructed labor in SSA was created to explore the interventions necessary to reduce maternal mortality from this condition.

Reducing maternal mortality from preeclampsia and eclampsia in low-resource countries--what should work?

OBJECTIVE: Preeclampsia/eclampsia (PE/E) remains a major cause of maternal death in low-income countries. We evaluated interventions to reduce PE/E-related maternal mortality in sub-Saharan Africa. DESIGN: Mathematical model to assess impact of interventions on PE/E-related maternal morbidity and mortality. SETTING: Sub-Saharan Africa countries. POPULATION: Pregnant women in sub-Saharan Africa in 2012. METHODS: A systematic literature review populated a decision-tree mathematical model with interventions to diagnose, prevent, and treat women with PE/E. The impact of increased use of interventions [diagnostics, transfer to a hospital, magnesium sulfate (MgSO4 ) use, cesarean section/labor induction] on PE/E-related maternal mortality was analyzed. MAIN OUTCOME MEASURES: Prevalence of PE/E and PE/E-associated maternal mortality rates in sub-Saharan Africa. RESULTS: Without interventions, an estimated 20 570 PE/E-associated deaths would have occurred in sub-Saharan Africa in 2012. With current low rates of diagnosis, MgSO4 use, transfers and cesarean section/induction rates, about 17 520 maternal deaths were associated with PE/E in 2012. Higher use of MgSO4 would have prevented about 610 deaths. With high diagnostic levels, MgSO4 use, transfer and cesarean section/induction, mortality was reduced to 3750 annual deaths, saving about 13 770 maternal lives. If all MgSO4 use was removed from the model, 4060 maternal deaths would occur, increasing maternal deaths by only 310. CONCLUSIONS: In sub-Saharan Africa, our model suggests that increasing use of PE/E diagnostics, transfer to higher levels of care and increased hospitalization with cesarean section/induction of labor would substantially reduce maternal mortality from PE/E. Increasing use of MgSO4 would have a smaller impact on maternal mortality.

Resuscitation and Obstetrical Care to Reduce Intrapartum-Related Neonatal Deaths: A MANDATE Study.

To evaluate the impact of neonatal resuscitation and basic obstetric care on intrapartum-related neonatal mortality in low and middle-income countries, using the mathematical model, Maternal and Neonatal Directed Assessment of Technology (MANDATE). Using MANDATE, we evaluated the impact of interventions for intrapartum-related events causing birth asphyxia (basic neonatal resuscitation, advanced neonatal care, increasing facility birth, and emergency obstetric care) when implemented in home, clinic, and hospital settings of sub-Saharan African and India for 2008. Total intrapartum-related neonatal mortality (IRNM) was acute neonatal deaths from intrapartum-related events plus late neonatal deaths from ongoing intrapartum-related injury. Introducing basic neonatal resuscitation in all settings had a large impact on decreasing IRNM. Increasing facility births and scaling up emergency obstetric care in clinics and hospitals also had a large impact on decreasing IRNM. Increasing prevalence and utilization of advanced neonatal care in hospital settings had limited impact on IRNM. The greatest improvement in IRNM was seen with widespread advanced neonatal care and basic neonatal resuscitation, scaled-up emergency obstetric care in clinics and hospitals, and increased facility deliveries, resulting in an estimated decrease in IRNM to 2.0 per 1,000 live births in India and 2.5 per 1,000 live births in sub-Saharan Africa. With more deliveries occurring in clinics and hospitals, the scale-up of obstetric care can have a greater effect than if modeled individually. Use of MANDATE enables health leaders to direct resources towards interventions that could prevent intrapartum-related deaths. A lack of widespread implementation of basic neonatal resuscitation, increased facility births, and emergency obstetric care are missed opportunities to save newborn lives.

Tranexamic acid to reduce postpartum hemorrhage: A MANDATE systematic review and analyses of impact on maternal mortality.

OBJECTIVE: Postpartum hemorrhage (PPH) is a major cause of maternal mortality, with almost 300,000 cases and ~72,000 PPH deaths annually in sub-Saharan Africa. Novel prevention methods practical in community settings are required. Tranexamic acid, a drug to reduce bleeding during surgical cases including postpartum bleeding, is potentially suitable for community settings. Thus, we sought to determine the impact of tranexamic acid on PPH-related maternal mortality in sub-Saharan Africa. STUDY DESIGN: We created a mathematical model to determine the impact of interventions on PPH-related maternal mortality. The model was populated with baseline birth rates and mortality estimates based on a review of current interventions for PPH in sub-Saharan Africa. Based on a systematic review of literature on tranexamic acid, we assumed 30% efficacy of tranexamic acid to reduce PPH; the model assessed prophylactic and treatment tranexamic acid use, for deliveries at homes, clinics, and hospitals. RESULTS: With tranexamic acid only in the hospitals, less than 2% of the PPH mortality would be reduced. However, if tranexamic acid were available in the home and clinic settings for PPH prophylaxis and treatment, a nearly 30% reduction (nearly 22,000 deaths per year) in PPH mortality is possible. CONCLUSION: These analyses point to the importance of preventive and treatment interventions compatible with home and clinic use, especially for sub-Saharan Africa, where the majority of births occur at home or community health clinics. Given its feasibility to be given in the home, tranexamic acid has potential to save many lives.

Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study.

BACKGROUND: During early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks' gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction. METHODS: Data were analysed from 548 antenatal visits after 20 weeks' gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction. RESULTS: There were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia. CONCLUSIONS: Early pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk of intrauterine growth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy.

Vaginal ring acceptability: A systematic review and meta-analysis of vaginal ring experiences from around the world.

OBJECTIVE: The vaginal ring (ring) is a female-initiated, long-acting drug delivery system for different indications, including HIV prevention. Our aim was to provide evidence for acceptability of the vaginal ring across indications to support dapivirine and multipurpose prevention technology ring introduction and roll out. STUDY DESIGN: This systematic review and meta-analysis followed PRISMA guidelines. We searched PubMed, Web of Science, Embase, and grey literature for publications reporting favorable ring acceptability and secondary outcomes involving actual ring use (comfort, ease of ring use, ring comfort during sex, expulsions, and vaginal symptoms) or hypothetical acceptability for any indication published January 1, 1970-June 15, 2021. We estimated random-effects pooled prevalence, assessing between-study variation using meta-regression. RESULTS: Of 2,234 records, we included 123 studies with 40,434 actual and hypothetical ring users. The primary outcome assessment included 50 studies with 60 ring subgroups totaling 19,271 ring users. The favorable acceptability pooled prevalence was 85.6% (95%CI 81.3, 89.0), while hypothetical acceptability among non-ring users was 27.6% (95%CI 17.5, 40.5). In meta-regression, acceptability was higher in menopause (95.4%; 95%CI 88.4, 98.2) compared to contraceptive rings (83.7%; 95%CI 75.6, 89.5). Acceptability was lower in pharmacokinetic studies (50%; 95%CI 22.1, 77.9) compared to RCTs (89.5%; 95%CI 85.8.92.4) and in studies assessing acceptability at ≥12 months (78.5%; 95%CI 66.5, 87.1) versus studies assessing acceptability at <3 months (91.9%; 95%CI 83.7, 96.1). European (90.6%; 95%CI 83.9, 94.7), Asian (97.1%; 95%CI 92.0, 99.0), and multi-region studies (93.5%; 95%CI 84.6, 97.4) reported more favorable acceptability compared to African studies (59.4%; 95%CI 38.3, 77.5). Secondary outcomes were similarly favorable, including ring comfort (92.9%; 95%CI 89.2, 95.4), ease of use (90.9%; 95%CI 86.5, 94.0), and comfort during sex (82.7%; 95%CI 76.4, 87.6). Limitations include inconsistent outcome definitions and unmeasured factors affecting acceptability. CONCLUSIONS: Women who used vaginal rings reported they were acceptable across indications geographic regions and indications. Policy makers should consider the ring as an important option for pregnancy and HIV prevention drug development. IMPLICATIONS: This review found favorable acceptability among vaginal ring users across indications and geographic areas, in contrast to low hypothetical acceptability among non-users. Vaginal rings are an important drug delivery system for pregnancy and HIV preventions, and scale-up should plan to address initial hesitancy among new users.

High-throughput pooling and real-time PCR-based strategy for malaria detection.

Molecular assays can provide critical information for malaria diagnosis, speciation, and drug resistance, but their cost and resource requirements limit their application to clinical malaria studies. This study describes the application of a resource-conserving testing algorithm employing sample pooling for real-time PCR assays for malaria in a cohort of 182 pregnant women in Kinshasa. A total of 1,268 peripheral blood samples were collected during the study. Using a real-time PCR assay that detects all Plasmodium species, microscopy-positive samples were amplified individually; the microscopy-negative samples were amplified after pooling the genomic DNA (gDNA) of four samples prior to testing. Of 176 microscopy-positive samples, 74 were positive by the real-time PCR assay; the 1,092 microscopy-negative samples were initially amplified in 293 pools, and subsequently, 35 samples were real-time PCR positive (3%). With the real-time PCR result as the referent standard, microscopy was 67.9% sensitive (95% confidence interval [CI], 58.3% to 76.5%) and 91.2% specific (95% CI, 89.4% to 92.8%) for malaria. In total, we detected 109 parasitemias by real-time PCR and, by pooling samples, obviated over 50% of reactions and halved the cost of testing. Our study highlights both substantial discordance between malaria diagnostics and the utility and parsimony of employing a sample pooling strategy for molecular diagnostics in clinical and epidemiologic malaria studies.

Vaginal ring acceptability and related preferences among women in low- and middle-income countries: A systematic review and narrative synthesis.

The vaginal ring (VR) is a female-initiated drug-delivery platform used for different indications, including HIV pre-exposure prophylaxis (PrEP). We conducted a systematic review of VR acceptability, values and preferences among women in low- and middle-income countries (LMIC) to inform further investment and/or guidance on VR use for HIV prevention. Following PRISMA guidelines, we used structured methods to search, screen, and extract data from randomized controlled trials (RCTs) and observational studies reporting quantitative outcomes of acceptability of the VR for any indication published 1/1970-2/2019 (PROSPERO: CRD42019122220). Of 1,110 records identified, 68 met inclusion criteria. Studies included women 15-50+ years from 25 LMIC for indications including HIV prevention, contraception, abnormal bleeding, and menopause. Overall VR acceptability was high (71-98% across RCTs; 62-100% across observational studies), with 80-100% continuation rates in RCTs and favorable ease of insertion (greater than 85%) and removal 89-99%). Users reported concerns about the VR getting lost in the body (8-43%), although actual expulsions and adverse events were generally infrequent. Most women disclosed use to partners, with some worrying about partner anger/violence. The VR was not felt during intercourse by 70-92% of users and 48-97% of partners. Acceptability improved over time both within studies (as women gained VR experience and worries diminished), and over chronological time (as the device was popularized). Women expressed preferences for accessible, long-acting, partner-approved methods that prevent both HIV and pregnancy, can be used without partner knowledge, and have no impact on sex and few side effects. This review was limited by a lack of standardization of acceptability measures and study heterogeneity. This systematic review suggests that most LMIC women users have a positive view of the VR that increases with familiarity of use; and, that many would consider the VR an acceptable future delivery device for HIV prevention or other indications.

A Retrospective Cohort Study of Safety Outcomes in New Zealand Infants Exposed to Tdap Vaccine in Utero.

We aimed to evaluate the safety of maternal Tdap; thus, we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 g at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8299 infants were born to 8178 mothers exposed to Tdap (12%), primarily between 28 and 38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap, infant Apgar score at 5 min after birth, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight (not clinically significant) and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and stillbirth, infant death, or microcephaly. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy. NZ Health and Disability Ethics Committee Approval #14/N.T.A/169/AM05.

Estimation of Gestational Age via Image Analysis of Anterior Lens Capsule Vascularity in Preterm Infants: A Pilot Study.

Introduction: Anterior lens capsule vascularity (ALCV) is resorbed in the developing fetus from 27 to 35 weeks gestation. In this pilot study, we evaluated the feasibility and validity of combining smartphone ophthalmoscope videos of ALCV and image analysis for gestational age estimation. Methods: ALCV videos were captured longitudinally in preterm neonates from delivery using a PanOptic® Ophthalmoscope with an iExaminer® adapter (Welch-Allyn). ALCV video frames were manually selected and quantified using semi-automatic image analysis. A predictive model based on ALCV features was compared to gold-standard ultrasound gestational age estimates. Results: A total of 64 image-capture sessions were carried out in 24 neonates. Ultrasound-estimated gestational age and ALCV-predicted gestational age estimates indicate that the two methods are similar (r = 0.78, p < 0.0001). ALCV estimates of gestational age were within 0.11 ± 1.3 weeks of ultrasound estimates. In the final model, gestational age was predicted within ± 1 week for 54% and within ± 2 weeks for 86% of the measures. Conclusions: This novel application of smartphone ophthalmoscopy and ALCV image analysis may provide a safe, accurate and non-invasive technology to estimate postnatal gestational age, especially in low income countries where gestational age may not be known at birth.

Evaluating WHO-Recommended Interventions for Preterm Birth: A Mathematical Model of the Potential Reduction of Preterm Mortality in Sub-Saharan Africa.

BACKGROUND: Preterm birth, a leading cause of neonatal mortality, has the highest burden in low-income countries. In 2015, the World Health Organization (WHO) published recommendations for interventions to improve preterm outcomes. Our analysis uses the Maternal and Neonatal Directed Assessment of Technology (MANDATE) model to evaluate the potential effects that WHO-recommended interventions could have had on preterm mortality in sub-Saharan Africa in 2015. METHODS: We modeled preterm birth subconditions causing mortality (respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, sepsis, birth asphyxia, and low birth weight). For each subcondition, models were populated with estimates of WHO-recommended intervention prevalence, case fatality, coverage, and efficacy. Various scenarios modeled improved coverage of single and combined interventions compared with baseline. RESULTS: In 2015, approximately 500,000 neonatal deaths due to preterm birth occurred in sub-Saharan Africa. Single interventions with the greatest impact on preterm mortality included oxygen/continuous positive airway pressure (44,000 lives saved), cord care (38,500 lives saved), and breastfeeding (30,200 lives saved). Combined with improved diagnosis/transfer to a hospital, the impact of interventions showed greater reductions in mortality (oxygen/continuous positive airway pressure, 134,100 lives saved; antibiotics, 28,600 lives saved). Combined interventions had the greatest impact. Together, hospital delivery with comprehensive care for respiratory distress syndrome saved 190,600 lives, and comprehensive thermal care, breastfeeding, and prevention/treatment for sepsis saved 94,400 lives. CONCLUSION: In 2015, WHO-recommended interventions could have saved the lives of nearly 300,000 infants born preterm in sub-Saharan Africa. Combined interventions are necessary to maximize impact. Mathematical models such as MANDATE can estimate effects on health outcomes to allow health officials to prioritize implementation strategies.

Open-source, machine and deep learning-based automated algorithm for gestational age estimation through smartphone lens imaging.

Gestational age estimation at time of birth is critical for determining the degree of prematurity of the infant and for administering appropriate postnatal treatment. We present a fully automated algorithm for estimating gestational age of premature infants through smartphone lens imaging of the anterior lens capsule vasculature (ALCV). Our algorithm uses a fully convolutional network and blind image quality analyzers to segment usable anterior capsule regions. Then, it extracts ALCV features using a residual neural network architecture and trains on these features using a support vector machine-based classifier. The classification algorithm is validated using leave-one-out cross-validation on videos captured from 124 neonates. The algorithm is expected to be an influential tool for remote and point-of-care gestational age estimation of premature neonates in low-income countries. To this end, we have made the software open source.

Pertussis Immunisation in Pregnancy Safety (PIPS) Study: A retrospective cohort study of safety outcomes in pregnant women vaccinated with Tdap vaccine.

BACKGROUND: New Zealand has funded the administration of tetanus, diphtheria and acellular pertussis (Tdap) vaccine during pregnancy to prevent infant pertussis since 2013. The aim of this study was to assess the safety of Tdap vaccine administered to pregnant women as part of a national maternal immunisation programme. METHODS: We conducted a national retrospective observational study using linked administrative New Zealand datasets. The study population consisted of pregnant women eligible to receive funded Tdap vaccination from 28 to 38 weeks gestation in 2013. Primary study outcomes were based on prioritised adverse events for the assessment of vaccine safety in pregnant women, as defined by WHO and Brighton Collaboration taskforces. We examined the effect of Tdap vaccination on prioritised maternal outcomes using Cox proportional hazard models. Adjusted hazard ratios controlled for key confounding variables. RESULTS: In the cohort of 68,550 women eligible to receive funded antenatal Tdap vaccination during 2013, 8178 (11.9%) were vaccinated and 60,372 (88.1%) were unvaccinated. The use of Tdap in pregnancy was not associated with an increase in the rate of primary outcomes, including preterm labour; pre-eclampsia; pre-eclampsia with severe features; eclampsia; gestational hypertension; fetal growth restriction; or post-partum haemorrhage. Tdap also did not increase secondary outcomes, including gestational diabetes mellitus; antenatal bleeding; placental abruption; premature rupture of membranes; preterm delivery; fetal distress; chorioamnionitis; or, maternal fever during or after labour. Lactation disorders was the only secondary maternal outcome with a significantly increased hazard ratio. Tdap vaccine had a protective effect on pre-eclampsia with severe features, preterm labour, preterm delivery, and antenatal bleeding. CONCLUSION: We did not detect any biologically plausible adverse maternal outcomes following Tdap vaccination during pregnancy. This study provides further assurance that Tdap administration during pregnancy is not associated with unexpected safety risks.

The MANDATE model for evaluating interventions to reduce postpartum hemorrhage.

OBJECTIVE: To create a comprehensive model of the comparative impact of various interventions on maternal, fetal, and neonatal (MFN) mortality. METHODS: The major conditions and sub-conditions contributing to MFN mortality in low-resource areas were identified, and the prevalence and case fatality rates documented. Available interventions were mapped to these conditions, and intervention coverage and efficacy were identified. Finally, a computer model developed by the Maternal and Neonatal Directed Assessment of Technology (MANDATE) initiative estimated the potential of current and new interventions to reduce mortality. RESULTS: For PPH, the sub-causes, prevalence, and MFN case fatality rates were calculated. Available interventions were mapped to these sub-causes. Most available interventions did not prevent or treat the overall condition of PPH, but rather sub-conditions associated with hemorrhage and thus prevented only a fraction of the associated deaths. CONCLUSION: The majority of current interventions address sub-conditions that cause death, rather than the overall condition; thus, the potential number of lives saved is likely to be overestimated. Additionally, the location at which mother and infant receive care affects intervention effectiveness and, therefore, the potential to save lives. A comprehensive view of MFN conditions is needed to understand the impact of any potential intervention.