Junk food use and neurodevelopmental and growth outcomes in infants in low-resource settings.

Introduction: Feeding infants a sub-optimal diet deprives them of critical nutrients for their physical and cognitive development. The objective of this study is to describe the intake of foods of low nutritional value (junk foods) and identify the association with growth and developmental outcomes in infants up to 18 months in low-resource settings. Methods: This is a secondary analysis of data from an iron-rich complementary foods (meat versus fortified cereal) randomized clinical trial on nutrition conducted in low-resource settings in four low- and middle-income countries (Democratic Republic of the Congo, Guatemala, Pakistan, and Zambia). Mothers in both study arms received nutritional messages on the importance of exclusive breastfeeding up to 6 months with continued breastfeeding up to at least 12 months. This study was designed to identify the socio-demographic predictors of feeding infants' complementary foods of low nutritional value (junk foods) and to assess the associations between prevalence of junk food use with neurodevelopment (assessed with the Bayley Scales of Infant Development II) and growth at 18 months. Results: 1,231 infants were enrolled, and 1,062 (86%) completed the study. Junk food feeding was more common in Guatemala, Pakistan, and Zambia than in the Democratic Republic of Congo. 7% of the infants were fed junk foods at 6 months which increased to 70% at 12 months. Non-exclusive breastfeeding at 6 months, higher maternal body mass index, more years of maternal and paternal education, and higher socioeconomic status were associated with feeding junk food. Prevalence of junk foods use was not associated with adverse neurodevelopmental or growth outcomes. Conclusion: The frequency of consumption of junk food was high in these low-resource settings but was not associated with adverse neurodevelopment or growth over the study period.

Impact of enacted stigma on mental health, substance use, and HIV-related behaviors among sexual minority men in Zambia.

Sexual minority men (SMM) in Zambia face significant challenges including stigma, discrimination, and mental health issues, which further impact their HIV-related risk behaviors. This study aimed to investigate the associations between enacted stigma, substance abuse, HIV-related behaviors, and mental health (i.e., depression, anxiety, and post-traumatic stress disorder [PTSD] symptoms) among SMM in Zambia. SMM aged 18-35 years who reported having multiple and/or concurrent sexual partners or low and/or inconsistent condom use in the past three months were recruited from four districts in Zambia between February and November 2021. Participants completed an anonymous interviewer-administered survey. Key variables of interest were compared between participants with higher vs. lower levels of enacted stigma. Independent samples t-tests were used for continuous variables, and chi-squared tests were used for categorical variables. A total of 197 eligible SMM participated in the study (mean age = 24.41 years). Participants with a higher level of enacted stigma showed a higher level of anxiety symptoms (χ2 = 12.91, p ≤ .001), PTSD symptoms (χ2 = 7.13, p < .01), tobacco use (χ2 = 10.47, p < .01), cannabis use (χ2 = 5.90, p < .05), and a higher number of sexual partners (t = 1.99, p < .05) in the past three months. Stigma reduction interventions may help mitigate substance abuse, HIV-related behaviors, and adverse mental health outcomes among SMM in Zambia. Health care providers, especially psychiatric-mental health nurses, can incorporate strategies for recognizing and addressing stigma into their practice through training and integrate multiple resources to create an inclusive and non-judgmental environment for SMM to improve their well-being.

The Impacts of Stigma Against Sexual Minority Men Within and Between Various Socioecological Levels: Breaking the Vicious Cycle in Zambia.

Sexual minority men (SMM) face persistent stigma in Zambia. From a holistic perspective, we aim to explore its impacts within and between multiple socioecological levels, demonstrating how their interactions create a vicious cycle of barriers to the well-being of SMM. In-depth interviews were conducted with 20 purposively recruited SMM from Lusaka, Zambia. All interviews were audio-recorded, after written consent, transcribed verbatim, and iteratively coded employing inductive (i.e., data-driven) approaches for thematic analysis using NVivo. Results suggest three key themes: (1) interpersonal socially perpetuated sexual minority stigma (SMS); (2) multidirectional interactions between psychosocial well-being and risk-taking behaviors; and (3) institutionally perpetuated SMS as a barrier to seeking and receiving health care. SMS permeates across all levels of the socioecological model to negatively impact the psychosocial well-being of SMM while acting also as a barrier to accessing HIV prevention and care. Our study necessitates structural public health intervention to decrease stigma and discrimination against SMM in Zambia, in efforts to increase their psychosocial well-being as well as their access to and utilization of HIV care by breaking the vicious cycle of SMS that pervades through the intrapersonal, interpersonal, and institutional levels of the socioecological model.

Accuracy of screening tests for cervical pre-cancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia.

Introduction: To provide evidence to improve cervical screening for women living with HIV (WLHIV), we assessed the accuracy of screening tests that can be used in low-resource settings and give results at the same visit. Methods: We conducted a paired, prospective study among consecutive eligible WLHIV, aged 18-65 years, receiving cervical cancer screening at one hospital in Lusaka, Zambia. The histopathological reference standard was multiple biopsies taken at two time points. The target condition was high-grade cervical intraepithelial neoplasia (CIN2+). The index tests were high-risk human papillomavirus detection (hrHPV, Xpert HPV, Cepheid), portable colposcopy (Gynocular, Gynius), and visual inspection with acetic acid (VIA). Accuracy of stand-alone and test combinations were calculated as the point estimate with 95% confidence intervals. A sensitivity analysis considered disease when only visible lesions were biopsied. Results: Among 371 participants with histopathological results, 27% (101/371) women had CIN2+ and 23% (23/101) was not detected by any index test. Sensitivity and specificity for stand-alone tests were: hrHPV, 67.3% (95% CI: 57.7-75.7) and 65.3% (59.4-70.7); Gynocular 51.5% (41.9-61.0) and 80.0% (74.8-84.3); and VIA 22.8% (15.7-31.9) and 92.6% (88.8-95.2), respectively. The combination of hrHPV testing followed by Gynocular had the best balance of sensitivity (42.6% [33.4-52.3]) and specificity (89.6% [85.3-92.7]). All test accuracies improved in sensitivity analysis. Conclusion: The low accuracy of screening tests assessed might be explained by our reference standard, which reduced verification and misclassification biases. Better screening strategies for WLHIV in low-resource settings are urgently needed. Registration number: The trial was registered prospectively at ClinicalTrials.gov (ref: NCT03931083 ). The study protocol has been previously published, and the statistical analysis plan can be accessed on ClinicalTrials.gov . Key messages: What is already known on this topic: The 2021 World Health Organization guidelines recommend that women living with HIV (WLHIV) receive screening for high risk human papillomavirus high-risk human papillomavirus (hrHPV) genotypes at three- to five-year intervals, followed by a triage test to determine whether treatment is needed but this is based on low and moderate certainty evidence.What this study adds: This study among WLHIV in Lusaka, Zambia evaluated three screening tests that allow same-day treatment; hrHPV test, portable colposcopy (Gynocular), and visual inspection with acetic acid (VIA), using strict methods to reduce verification and misclassification biases. The test accuracy of the different screening was poor, with sensitivities and specificity for stand-alone tests: hrHPV, 67.3% and 65.3%; Gynocular 51.5% and 80.0%; and VIA 22.8% and 92.6%; respectively.How this study might affect research, practice or policy: Our findings have implications for research and cervical cancer screening policies among WLHIV if test-accuracy in this high-risk population has been overestimated from a majority of exsisting studies that are affected by verification and misclassification biases. Methodologically robust studies are crucial to inform cervical cancer screening practices and policies for the successful implementation of a cervical cancer elimination plan in sub-Saharan Africa, where 85% of women with cervical cancer and HIV live.

Diagnostic accuracy of ASQ for screening of neurodevelopmental delays in low resource countries.

OBJECTIVE: The Bayley Scales of Infant Development (BSID) is the most used diagnostic tool to identify neurodevelopmental disorders in children under age 3 but is challenging to use in low-resource countries. The Ages and Stages Questionnaire (ASQ) is an easy-to-use, low-cost clinical tool completed by parents/caregivers that screens children for developmental delay. The objective was to determine the performance of ASQ as a screening tool for neurodevelopmental impairment when compared with BSID second edition (BSID-II) for the diagnosis of moderate-to-severe neurodevelopmental impairment among infants at 12 and 18 months of age in low-resource countries. METHODS: Study participants were recruited as part of the First Bites Complementary Feeding trial from the Democratic Republic of Congo, Zambia, Guatemala and Pakistan between October 2008 and January 2011. Study participants underwent neurodevelopmental assessment by trained personnel using the ASQ and BSID-II at 12 and 18 months of age. RESULTS: Data on both ASQ and BSID-II assessments of 1034 infants were analysed. Four of five ASQ domains had specificities greater than 90% for severe neurodevelopmental delay at 18 months of age. Sensitivities ranged from 23% to 62%. The correlations between ASQ communications subscale and BSID-II Mental Development Index (MDI) (r=0.38) and between ASQ gross motor subscale and BSID-II Psychomotor Development Index (PDI) (r=0.33) were the strongest correlations found. CONCLUSION: At 18 months, ASQ had high specificity but moderate-to-low sensitivity for BSID-II MDI and/or PDI <70. ASQ, when administered by trained healthcare workers, may be a useful screening tool to detect severe disability in infants from rural low-income to middle-income settings. TRIAL REGISTRATION NUMBER: NCT01084109.

"Testing Can Be Done Anywhere": A Qualitative Assessment of Targeted Community-Based Point-of-Care Early Infant Diagnosis of HIV in Lusaka, Zambia.

INTRODUCTION: Delayed HIV diagnosis in HIV-exposed infants (HEIs) results in missed opportunities for early antiretroviral therapy (ART), causing significant morbidity and mortality. Early infant diagnosis (EID) depends on the availability of accessible and reliable testing services. We explored the acceptability, appropriateness, and feasibility of deploying a targeted community-based point-of-care (POC) EID testing model (i.e., "community POC model") to reach high-risk mother-infant pairs (MIPs) in Lusaka, Zambia. METHODS: We conducted in-depth interviews with a purposive sample of health care workers, study staff, and caregivers in high-risk MIPs at 6 health facilities included in a larger implementation research study evaluating the community POC model. We defined "high-risk MIPs" as mothers who did not receive antenatal testing or an attended delivery or infants who missed EID testing milestones. Interviews were audio-recorded, translated, and transcribed verbatim in English. Content and thematic analysis were done using NVivo 10 software. RESULTS: Health care workers (n=20) and study staff (n=12) who implemented the community POC model noted that the portability and on-screen prompts of the POC platform made it mobile and easy to use, but maintenance and supply chain management were key to field operations. Respondents also felt that the community POC model reached more infants who had never had EID testing, allowing them to find infants with HIV infection and immediately initiate them on ART. Caregivers (n=22) found the community POC model acceptable, provided that privacy could be ensured because the service was convenient and delivered close to home. CONCLUSION: We demonstrate the acceptability, appropriateness, and feasibility of implementing the community POC model in Zambia, while identifying potential challenges related to client privacy and platform field operations. The community POC model may represent a promising strategy to further facilitate active HIV case finding and linkage to ART for children with undiagnosed HIV infection in the community.

Strengthening Kangaroo Mother Care at a tertiary level hospital in Zambia: A prospective descriptive study.

BACKGROUND: Globally, complications due to preterm birth are the leading contributor to neonatal mortality, resulting in an estimated one million deaths annually. Kangaroo Mother Care (KMC) has been endorsed by the World Health Organisation as a low cost, safe, and effective intervention in reducing morbidity and mortality among preterm infants. The objective of this study was to describe the implementation of a KMC model among preterm infants and its impact on neonatal outcomes at a tertiary level hospital in Lusaka, Zambia. METHODS: We conducted a prospective descriptive study using data collected from the KMC room at the University Teaching Hospital between January 2016 and September 2017. Mothers and government nurses were trained in KMC. We monitored skin-to-skin and breastfeeding practices, weight at admission, discharge, and length of admission. RESULTS: We enrolled 573 neonates into the study. Thirteen extremely low weight infants admitted to the KMC room had graduated to Group A (1,000g-1,499g) at discharge, with a median weight gain of 500g. Of the 419 very low weight neonates at admission, 290 remained in Group A while 129 improved to Group B (1,500g-2,499g), with a median weight gain of 280g. Among the 89 low weight neonates, 1 regressed to Group A, 77 remained in Group B, and 11 improved to Group C (≥2,500g), individually gaining a median of 100g. Of the seven normal weight neonates, 6 remained in Group C individually gaining a median of 100g, and 1 regressed to Group B. Among all infants enrolled, two (0.35%) died in the KMC room. CONCLUSIONS: Based on the RE-AIM metrics, our results show that KMC is a feasible intervention that can improve neonatal outcomes among preterm infants in Zambia. The study findings show a promising, practical approach to scaling up KMC in Zambia. TRIAL REGISTRATION: The trial is registered under ClinicalTrials.gov under the following ID number: NCT03923023.

Cervical cancer screening outcomes in Zambia, 2010-19: a cohort study.

BACKGROUND: Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort. METHODS: We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a screening result. Follow-up was accomplished per national guidelines. We did descriptive analyses and mixed-effects logistic regression for cervical cancer screening results allowing random effects at the individual and clinic level. FINDINGS: Between Jan 1, 2010, and July 31, 2019, we included 183 165 women with 204 225 results for visual inspection with acetic acid and digital cervicography (VIAC) in the analysis. Of all those screened, 21 326 (10·4%) were VIAC-positive, of whom 16 244 (76·2%) received treatment. Of 204 225 screenings, 92 838 (45·5%) were in women who were HIV-negative, 76 607 (37·5%) were in women who were HIV-positive, and 34 780 (17·0%) had an unknown HIV status. Screening frequency increased 65·7% between 2010 and 2019 with most appointments being first-time screenings (n=158 940 [77·8%]). Women with HIV were more likely to test VIAC-positive than women who were HIV-negative (adjusted odds ratio 3·60, 95% CI 2·14-6·08). Younger women (≤29 years) with HIV had the highest predictive probability (18·6%, 95% CI 14·2-22·9) of screening positive. INTERPRETATION: CCPPZ has effectively increased women's engagement in screening since its inception in 2006. Customised sensitisation strategies relevant to different age groups could increase uptake and adherence to screening. The high proportion of screen positivity in women younger than 20 years with HIV requires further consideration. Our data are not able to discern if women with HIV have earlier disease onset or whether this difference reflects misclassification of disease in an age group with a higher sexually transmitted infection prevalence. These data inform scale-up efforts required to achieve WHO elimination targets. FUNDING: US President's Emergency Plan for AIDS Relief.

Early Skin-to-Skin Care with a Polyethylene Bag for Neonatal Hypothermia: A Randomized Clinical Trial.

OBJECTIVE: To determine whether early polyethylene bag use with skin-to-skin care compared with skin-to skin care alone reduce hypothermia among infants born at term in resource-limited settings. STUDY DESIGN: Infants born at term in the tertiary referral center in Lusaka, Zambia, were randomized using sequentially numbered sealed opaque envelopes in 2 phases: after birth (phase 1) and at 1 hour after birth (phase 2) to either skin-to-skin care with polyethylene bags or skin-to-skin care alone. Infant and maternal temperatures were recorded at birth, 1 hour, and every 4 hours until discharge or 24 hours. RESULTS: We enrolled 423 infants from May 2017 to August 2017. The rate of moderate-severe hypothermia (temperature <36.0°C) at 1 hour was 72 of 208 (34.6%) in the skin-to-skin care with a polyethylene bag group compared with 101 of 213 (47.4%) in the skin-to-skin care alone group (relative risk, 0.71; 95% CI 0.56-0.90; P < .01; number needed to treat = 8). phase 1 treatment assignment significantly modified the effect of phase 2 treatment (P = .02 for interaction effect). Among infants randomized to skin-to-skin care with a polyethylene bag in phase 1, the risk of moderate-severe hypothermia was decreased in infants randomized to continue this intervention until discharge compared with infants randomized to skin-to-skin care alone. The rates of severe hypothermia, hyperthermia, and other adverse events did not differ significantly between groups. CONCLUSIONS: Low-cost polyethylene bags started after birth in combination with skin-to-skin care reduced moderate or severe hypothermia at 1 hour and at discharge among infants born at term in a resource-limited setting compared with skin-to-skin care alone. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03141723.

Screening test accuracy to improve detection of precancerous lesions of the cervix in women living with HIV: a study protocol.

INTRODUCTION: The simplest and cheapest method for cervical cancer screening is visual inspection after application of acetic acid (VIA). However, this method has limitations for correctly identifying precancerous cervical lesions (sensitivity) and women free from these lesions (specificity). We will assess alternative screening methods that could improve sensitivity and specificity in women living with humanimmunodeficiency virus (WLHIV) in Southern Africa. METHODS AND ANALYSIS: We will conduct a paired, prospective, screening test accuracy study among consecutive, eligible women aged 18-65 years receiving treatment for HIV/AIDS at Kanyama Hospital, Lusaka, Zambia. We will assess a portable magnification device (Gynocular, Gynius Plus AB, Sweden) based on the Swede score assessment of the cervix, test for high-risk subtypes of human papillomavirus (HR-HPV, GeneXpert, Cepheid, USA) and VIA. All study participants will receive all three tests and the reference standard at baseline and at six-month follow-up. The reference standard is histological assessment of two to four biopsies of the transformation zone. The primary histological endpoint is cervical intraepithelial neoplasia grade two and above (CIN2+). Women who are VIA-positive or have histologically confirmed CIN2+ lesions will be treated as per national guidelines. We plan to enrol 450 women. Primary outcome measures for test accuracy include sensitivity and specificity of each stand-alone test. In the secondary analyses, we will evaluate the combination of tests. Pre-planned additional studies include use of cervigrams to test an automated visual assessment tool using image pattern recognition, cost-analysis and associations with trichomoniasis. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Zambia Biomedical Research Ethics Committee, Zambian National Health Regulatory Authority, Zambia Medicines Regulatory Authority, Swissethics and the International Agency for Research on Cancer Ethics Committee. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03931083; Pre-results.

The association of maternal age with adverse neonatal outcomes in Lusaka, Zambia: a prospective cohort study.

BACKGROUND: Pregnancy among adolescents, whether intended or not, is a public health concern as it is generally considered high risk for both mothers and their newborns. In Zambia, where many women engage in early sexual behaviour or marry at a young age, 28.5% of girls aged 15-19 years were pregnant with their first child in the year 2013-2014. This study sought to explore associations between maternal age and neonatal outcomes among pregnant women in Lusaka, Zambia. METHODS: This was a secondary analysis of data nested within a larger population-based prospective cohort study which was implemented in three government health facilities-two first level hospitals and one clinic in Lusaka, Zambia. Women presenting to the study sites for antenatal care were enrolled into the study and followed up for collection of maternal and neonatal outcomes at 7, 28 and 42 days postpartum. The study's primary outcomes were the incidence of maternal and newborn complications and factors associated with adverse neonatal outcomes. Statistical significance was evaluated at a significance level of P < 0.05. RESULTS: The study included 11,501 women, 15.6% of whom were adolescents aged 10-19 years. Generally, adolescence did not have statistically significant associations with poor maternal health outcomes. However, the risk of experiencing obstructed labour, premature rupture of membranes and postpartum hemorrhage was higher among adolescents than women aged 20-24 years while the risk of severe infection was lower and non-significant. Adolescents also had 1.36 times the odds of having a low birthweight baby (95% CI 1.12, 1.66) and were at risk of preterm birth (aOR = 1.40, 95% CI 1.06, 1.84). Their newborns were in need of bag and mask resuscitation at birth (aOR = 0.62, 95% CI 0.41, 0.93). Advanced maternal age was significantly associated with increased odds of hypertension/ pre-eclampsia (95% CI 1.54, 5.89) and preterm labour (aOR = 2.78, 95% CI 1.24, 6.21). CONCLUSIONS: Adolescence is a risk factor for selected pregnancy outcomes in urban health facilities in Lusaka, Zambia. Health care workers should intensify the provision of targeted services to improve neonatal health outcomes. TRIAL REGISTRATION: Clinical trial number and URL:  NCT03923023 (Retrospectively registered). Clinical trial registration date: April 22, 2019.

Association between birth attendant type and delivery site and perinatal outcomes.

OBJECTIVE: To test the hypothesis that modified perinatal mortality, early neonatal mortality, and other measures of perinatal mortality are lower with facility births than with home births among deliveries conducted by traditional birth attendants (TBAs) or nurse-midwives. METHOD: This population-based observational study used data collected prospectively for home and facility deliveries conducted by TBAs and nurse-midwives in 13 rural communities in Zambia between September 1, 2009, and December 31, 2015. RESULTS: We enrolled 48 956 pregnant women. In adjusted analysis, modified perinatal mortality (adjusted odds ratio [aOR] 0.63, 95% confidence interval [CI] 0.45-0.88), early neonatal mortality (0.48, 0.33-0.69), and fresh stillbirth/day-1 neonatal mortality (0.55, 0.38-0.80) were lower among home deliveries than among facility deliveries conducted by TBAs, but did not differ among deliveries conducted by nurse-midwives. Rates of fresh stillbirth did not differ between home and facility delivery by either TBAs (aOR 1.03, 95% CI 0.64-1.66) or nurse-midwives (1.19, 0.67-2.10). CONCLUSION: Our findings show significant reductions in modified perinatal mortality, early neonatal mortality, and fresh stillbirth/day-1 neonatal mortality among home deliveries done by TBAs. This may be explained by robust community structures built by our program and referral bias of complicated cases.

Home deliveries in the capital: a qualitative exploration of barriers to institutional deliveries in peri-urban areas of Lusaka, Zambia.

BACKGROUND: A shortage of skilled birth attendants and low quality of care in health facilities along with unattended home deliveries contribute to the high maternal and neonatal mortality in sub Saharan Africa. Identifying and addressing context-specific reasons for not delivering at health care facilities could increase births assisted by skilled attendants who, if required, can provide life-saving interventions. METHODS: We conducted 22 in-depth interviews (IDIs) with midwives at three health facilities in peri-urban communities and 24 semi-structured surveys with mothers in two areas served by health facilities with the highest number of reported home deliveries in Lusaka, Zambia. Both IDIs and surveys were audio-recorded, transcribed and coded to identify themes around delivery and birthing experience. RESULTS: We found that most women preferred institutional deliveries to home deliveries, but were unable to utilize these services due to inability to recognize labour symptoms or lack of resources. Midwives speculated that women used herbal concoctions to reduce the duration of delivery with the result that women either did not present in time or endangered themselves and the baby with powerful contractions and precipitous labour. Respondents suggested that disrespectful and abusive maternity care dissuaded some women from delivering at health facilities. However, some midwives viewed such tactics as necessary to ensure women followed instructions and successfully delivered live babies. CONCLUSION: Difference in beliefs and birthing practices between midwives and mothers suggest the need for open dialogue to co-design appropriate interventions to increase facility usage. Further examination of the pharmaceutical properties and safety of herbal concoctions being used to shorten labour are required. Measures to reduce the economic burden of care seeking within this environment, increase respectful and patient-centred care, and improve the quality of midwifery could increase institutional deliveries.

Risk factors for maternal death and trends in maternal mortality in low- and middle-income countries: a prospective longitudinal cohort analysis.

BACKGROUND: Because large, prospective, population-based data sets describing maternal outcomes are typically not available in low- and middle-income countries, it is difficult to monitor maternal mortality rates over time and to identify factors associated with maternal mortality. Early identification of risk factors is essential to develop comprehensive intervention strategies preventing pregnancy-related complications. Our objective was to describe maternal mortality rates in a large, multi-country dataset and to determine maternal, pregnancy-related, delivery and postpartum characteristics that are associated with maternal mortality. METHODS: We collected data describing all pregnancies from 2010 to 2013 among women enrolled in the multi-national Global Network for Women's and Children's Health Research Maternal and Neonatal Health Registry (MNHR). We reported the proportion of mothers who died per pregnancy and the maternal mortality ratio (MMR). Generalized linear models were used to evaluate the relationship of potential medical and social factors and maternal mortality and to develop point and interval estimates of relative risk associated with these factors. Generalized estimating equations were used to account for the correlation of outcomes within cluster to develop appropriate confidence intervals. RESULTS: We recorded 277,736 pregnancies and 402 maternal deaths for an MMR of 153/100,000 live births. We observed an improvement in the total MMR from 166 in 2010 to 126 in 2013. The MMR in Latin American sites (91) was lower than the MMR in Asian (178) and African sites (125). When adjusted for study site and the other variables, no formal education (RR 3.2 [1.5, 6.9]), primary education only (RR 3.4 [1.6, 7.5]), secondary education only (RR 2.5 [1.1, 5.7]), lack of antenatal care (RR 1.8 [1.2, 2.5]), caesarean section delivery (RR 1.9 [1.3, 2.8]), hemorrhage (RR 3.3 [2.2, 5.1]), and hypertensive disorders (RR 7.4 [5.2, 10.4]) were associated with higher risks of death. CONCLUSIONS: The MNHR identified preventable causes of maternal mortality in diverse settings in low- and middle-income countries. The MNHR can be used to monitor public health strategies and determine their association with reducing maternal mortality. TRIAL REGISTRATION: clinicaltrials.gov NCT01073475.

Neonatal mortality and coverage of essential newborn interventions 2010 - 2013: a prospective, population-based study from low-middle income countries.

BACKGROUND: Approximately 3 million neonatal deaths occur each year worldwide. Simple interventions have been tested and found to be effective in reducing the neonatal mortality. In order to effectively implement public health interventions, it is important to know the rates of neonatal mortality and understand the contributing risk factors. Hence, this prospective, population-based, observational study was carried out to inform these needs. METHODS: The Global Network's Maternal Newborn Health Registry was initiated in the seven sites in 2008. Registry administrators (RAs) attempt to identify and enroll all eligible women by 20 weeks gestation and collect basic health data, and outcomes after delivery and at 6 weeks post-partum. All study data were collected, reviewed, and edited by staff at each study site. The study was reviewed and approved by each sites' ethics review committee. RESULTS: Overall, the 7-day neonatal mortality rate (NMR) was 20.6 per 1000 live births and the 28-day NMR was 25.7 per 1000 live births. Higher neonatal mortality was associated with maternal age > 35 and <20 years relative to women 20-35 years of age. Preterm births were at increased risk of both early and 28-day neonatal mortality (RR 8.1, 95% CI 7.5-8.8 and 7.5, 95% CI 6.9-8.1) compared to term as were those with low birth weight (<2500g). Neonatal resuscitation rates were 4.8% for hospital deliveries compared to 0.9% for home births. In the hospital, 26.5% of deliveries were by cesarean section with an overall cesarean section rate of 12.5%. Neonatal mortality rates were highest in the Pakistan site and lowest in Argentina. CONCLUSIONS: Using prospectively collected data with high follow up rates (99%), we documented characteristics associated with neonatal mortality. Low birth weight and prematurity are among the strongest predictors of neonatal mortality. Other risk factors for neonatal deaths included male gender, multiple gestation and major congenital anomalies. Breech presentation/transverse lie, and no antenatal care were also significant risk factors for neonatal death. Coverage of interventions varied by setting of delivery, with the overall population rate of most evidence-based interventions low. This study informs about risk factors for neonatal mortality which can serve to design strategies/interventions to reduce risk of neonatal mortality. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov. ClinicalTrial.gov TRIAL REGISTRATION: NCT01073475.

Stillbirth rates in low-middle income countries 2010 - 2013: a population-based, multi-country study from the Global Network.

BACKGROUND: Stillbirth rates remain nearly ten times higher in low-middle income countries (LMIC) than high income countries. In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented characteristics or care for mothers with stillbirths. Non-macerated stillbirths, those occurring around delivery, are generally considered preventable with appropriate obstetric care. METHODS: We undertook a prospective, population-based observational study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). Staff collected demographic and health care characteristics with outcomes obtained at delivery. RESULTS: From 2010 through 2013, 269,614 enrolled women had 272,089 births, including 7,865 stillbirths. The overall stillbirth rate was 28.9/1000 births, ranging from 13.6/1000 births in Argentina to 56.5/1000 births in Pakistan. Stillbirth rates were stable or declined in 6 of the 7 sites from 2010-2013, only increasing in Pakistan. Less educated, older and women with less access to antenatal care were at increased risk of stillbirth. Furthermore, women not delivered by a skilled attendant were more likely to have a stillbirth (RR 2.8, 95% CI 2.2, 3.5). Compared to live births, stillbirths were more likely to be preterm (RR 12.4, 95% CI 11.2, 13.6). Infants with major congenital anomalies were at increased risk of stillbirth (RR 9.1, 95% CI 7.3, 11.4), as were multiple gestations (RR 2.8, 95% CI 2.4, 3.2) and breech (RR 3.0, 95% CI 2.6, 3.5). Altogether, 67.4% of the stillbirths were non-macerated. 7.6% of women with stillbirths had cesarean sections, with obstructed labor the primary indication (36.9%). CONCLUSIONS: Stillbirth rates were high, but with reductions in most sites during the study period. Disadvantaged women, those with less antenatal care and those delivered without a skilled birth attendant were at increased risk of delivering a stillbirth. More than two-thirds of all stillbirths were non-macerated, suggesting potentially preventable stillbirth. Additionally, 8% of women with stillbirths were delivered by cesarean section. The relatively high rate of cesarean section among those with stillbirths suggested that this care was too late or not of quality to prevent the stillbirth; however, further research is needed to evaluate the quality of obstetric care, including cesarean section, on stillbirth in these low resource settings. STUDY REGISTRATION: Clinicaltrials.gov (ID# NCT01073475).

A color-coded tape for uterine height measurement: a tool to identify preterm pregnancies in low resource settings.

INTRODUCTION: Neonatal mortality associated with preterm birth can be reduced with antenatal corticosteroids (ACS), yet <10% of eligible pregnant women in low-middle income countries. The inability to accurately determine gestational age (GA) leads to under-identification of high-risk women who could receive ACS or other interventions. To facilitate better identification in low-resource settings, we developed a color-coded tape for uterine height (UH) measurement and estimated its accuracy identifying preterm pregnancies. METHODS: We designed a series of colored-coded tapes with segments corresponding to UH measurements for 20-23.6 weeks, 24.0-35.6 weeks, and >36.0 weeks GA. In phase 1, UH measurements were collected prospectively in the Democratic Republic of Congo, India and Pakistan, using distinct tapes to address variation across regions and ethnicities. In phase 2, we tested accuracy in 250 pregnant women with known GA from early ultrasound enrolled at prenatal clinics in Argentina, India, Pakistan and Zambia. Providers masked to the ultrasound GA measured UH. Receiver operating characteristics (ROC) analysis was conducted. RESULTS: 1,029 pregnant women were enrolled. In all countries the tapes were most effective identifying pregnancies between 20.0-35.6 weeks, compared to the other GAs. The ROC areas under the curves and 95% confidence intervals were: Argentina 0.69 (0.63, 0.74); Zambia 0.72 (0.66, 0.78), India 0.84 (0.80, 0.89), and Pakistan 0.83 (0.78, 0.87). The sensitivity and specificity (and 95% confidence intervals) for identifying pregnancies between 20.0-35.6 weeks, respectively, were: Argentina 87% (82%-92%) and 51% (42%-61%); Zambia 91% (86%-95%) and 50% (40%-60%); India 78% (71%-85%) and 89% (83%-94%); Pakistan 63% (55%-70%) and 94% (89%-99%). CONCLUSIONS: We observed moderate-good accuracy identifying pregnancies ≤ 35.6 weeks gestation, with potential usefulness at the community level in low-middle income countries to facilitate the preterm identification and interventions to reduce preterm neonatal mortality. Further research is needed to validate these findings on a population basis.

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial.

BACKGROUND: Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS: In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS: The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION: Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.