Overview of the Global and US Burden of Preterm Birth.

Preterm birth (PTB) is the leading cause of morbidity and mortality in children globally, yet its prevalence has been difficult to accurately estimate due to unreliable methods of gestational age dating, heterogeneity in counting, and insufficient data. The estimated global PTB rate in 2020 was 9.9% (95% confidence interval: 9.1, 11.2), which reflects no significant change from 2010, and 81% of prematurity-related deaths occurred in Africa and Asia. PTB prevalence in the United States in 2021 was 10.5%, yet with concerning racial disparities. Few effective solutions for prematurity prevention have been identified, highlighting the importance of further research.

A biosocial analysis of perinatal and late neonatal mortality among Indigenous Maya Kaqchikel communities in Tecpán, Guatemala: a mixed-methods study.

INTRODUCTION: Neonatal mortality is a global public health challenge. Guatemala has the fifth highest neonatal mortality rate in Latin America, and Indigenous communities are particularly impacted. This study aims to understand factors driving neonatal mortality rates among Maya Kaqchikel communities. METHODS: We used sequential explanatory mixed methods. The quantitative phase was a secondary analysis of 2014-2016 data from the Global Maternal and Newborn Health Registry from Chimaltenango, Guatemala. Multivariate logistic regression models identified factors associated with perinatal and late neonatal mortality. A number of 33 in-depth interviews were conducted with mothers, traditional Maya midwives and local healthcare professionals to explain quantitative findings. RESULTS: Of 33 759 observations, 351 were lost to follow-up. There were 32 559 live births, 670 stillbirths (20/1000 births), 1265 (38/1000 births) perinatal deaths and 409 (12/1000 live births) late neonatal deaths. Factors identified to have statistically significant associations with a higher risk of perinatal or late neonatal mortality include lack of maternal education, maternal height <140 cm, maternal age under 20 or above 35, attending less than four antenatal visits, delivering without a skilled attendant, delivering at a health facility, preterm birth, congenital anomalies and presence of other obstetrical complications. Qualitative participants linked severe mental and emotional distress and inadequate maternal nutrition to heightened neonatal vulnerability. They also highlighted that mistrust in the healthcare system-fueled by language barriers and healthcare workers' use of coercive authority-delayed hospital presentations. They provided examples of cooperative relationships between traditional midwives and healthcare staff that resulted in positive outcomes. CONCLUSION: Structural social forces influence neonatal vulnerability in rural Guatemala. When coupled with healthcare system shortcomings, these forces increase mistrust and mortality. Collaborative relationships among healthcare staff, traditional midwives and families may disrupt this cycle.

Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh.

BACKGROUND: There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. METHODS: Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1ß, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders. RESULTS: 248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants, elevated concentrations (>75%) of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevated IL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1ß with lower expressive communication and motor z-scores. CONCLUSIONS: In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetal growth restriction. IMPACT: Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh. 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants. Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

Facilitators, barriers, and key influencers of breastfeeding among low birthweight infants: a qualitative study in India, Malawi, and Tanzania.

BACKGROUND: Low birthweight (LBW) infants are at increased risk of morbidity and mortality. Exclusive breastfeeding up to six months is recommended to help them thrive through infection prevention, growth improvements, and enhancements in neurodevelopment. However, limited data exist on the feeding experiences of LBW infants, their caregivers and key community influencers. The qualitative component of the Low Birthweight Infant Feeding Exploration (LIFE) study aimed to understand practices, facilitators, and barriers to optimal feeding options in the first six months for LBW infants in low-resource settings. METHODS: This study was conducted in four sites in India, Malawi, and Tanzania from July 2019 to August 2020. We conducted 37 focus group discussions with mothers and family members of LBW infants and community leaders and 142 in-depth interviews with healthcare providers, government officials, and supply chain and donor human milk (DHM) experts. Data were analyzed using a framework approach. RESULTS: All participants believed that mother's own milk was best for LBW infants. Direct breastfeeding was predominant and feeding expressed breast milk and infant formula were rare. DHM was a new concept for most. Adequate maternal nutrition, lactation support, and privacy in the facility aided breastfeeding and expression, but perceived insufficient milk, limited feeding counseling, and infant immaturity were common barriers. Most believed that DHM uptake could be enabled through community awareness by overcoming misconceptions, safety concerns, and perceived family resistance. CONCLUSION: This study fills an evidence gap in LBW infant feeding practices and their facilitators and barriers in resource-limited settings. LBW infants face unique feeding challenges such as poor latching and tiring at the breast. Similarly, their mothers are faced with numerous difficulties, including attainment of adequate milk supply, breast pain and emotional stress. Lactation support and feeding counseling could address obstacles faced by mothers and infants by providing psychosocial, verbal and physical support to empower mothers with skills, knowledge and confidence and facilitate earlier, more and better breast milk feeding. Findings on DHM are critical to the future development of human milk banks and highlight the need to solicit partnership from stakeholders in the community and health system.

Health care seeking behaviors of pregnant women in rural Amhara, Ethiopia: a qualitative study of perceptions of pregnant women, community members, and health care providers.

Introduction: in Ethiopia, increasing access to basic antenatal and neonatal health services may improve maternal and newborn survival. This study examined perceptions regarding antenatal health seeking behaviors from pregnant women, their families, community members, and health care providers in rural Amhara, Ethiopia. Methods: the study was conducted in four rural districts of the Amhara region of Ethiopia. A total of forty participants who were living and working within the catchment areas of the selected health centres were interviewed from October 3rd through October 14th, 2018. A phenomenological qualitative study design was used to understand participants' perceptions and experiences about pregnant women's health care seeking behaviors. Results: early disclosure of pregnancy status was not common in the study area. However, the data from the present study further provided new information, suggesting that some women did disclose their pregnancy status early but preferentially only to their partners and close relatives. Most women did not seek care unless sick or experienced new discomfort or pain. Some reasons for the low utilization of available antenatal services include long distance to health facilities, lack of transportation, difficult topography, and discomfort with male providers. Conclusion: despite the rapid expansion of health posts and deployment of health extension workers since 2003, there are still critical barriers to accessing facility-based care that limit women's health care seeking practices.

Dietary Perspectives and Practices during Pregnancy in Rural Amhara Region of Ethiopia: An Exploratory Qualitative Study.

Background: Nutrition during pregnancy has lifelong impacts on the mother and fetus. In Ethiopia, nearly a third of pregnant women experience undernutrition. When designing nutrition interventions during pregnancy, it is important to understand existing dietary perspectives and practices in local communities. Objectives: To explore the processes that shape dietary perspectives and practices during pregnancy in rural West Gojjam and South Gondar Zones of the Amhara region in Ethiopia. Methods: From October to November 2018, we conducted 40 in-depth interviews with pregnant women (n = 16), family members (n = 12), and healthcare providers (n = 12) using a semistructured interview guide. Interviews were conducted in Amharic, transcribed in Amharic, and translated into English. We used a thematic analysis approach to organize data per the predefined topic areas and identify emerging themes, as well as barriers and enablers to healthy nutrition during pregnancy. Results: Pregnant women and their family members recognized the benefits of a diversified diet to promote the health of the mother and the fetus. However, participants reported low dietary diversity because of limited access to nutritious foods and particular perspectives on food restrictions during pregnancy. The common practice of religious fasting also limited pregnant women's dietary intake. Women reported restricting their food intake in later pregnancy because of loss of appetite, as well as concerns about having a large infant, which might complicate delivery. Intake of locally made alcoholic drinks (Tella) was reported among pregnant women because participants thought it had low levels of alcohol that would not harm the fetus. Conclusions: Although participants understood the importance of a healthy and diverse diet in pregnancy, we identified several barriers and perspectives regarding nutrition during pregnancy. Low income and lack of access to diverse foods, particularly in certain seasons, religious fasting, intentional food restrictions to limit the size of the infant, and alcohol use were commonly reported. Locally appropriate counseling and interventions should be developed, with an emphasis on increasing access to and consumption of diverse foods. Curr Dev Nutr 2023;x:xx.

Harmonization of maternal balanced energy-protein supplementation studies for individual participant data (IPD) meta-analyses - finding and creating similarities in variables and data collection.

BACKGROUND: Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. METHODS: We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. DISCUSSION: We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study: protocol of a pragmatic clinical effectiveness study to improve birth outcomes in Ethiopia.

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.

A systematic review on estimating population attributable fraction for risk factors for small-for-gestational-age births in 81 low- and middle-income countries.

Background: Small for gestational age (SGA) is a public health concern since it is associated with mortality in neonatal and post-neonatal period. Despite the large magnitude of the problem, little is known about the population-attributable risk (PAR) of various risk factors for SGA. This study estimated the relative contribution of risk factors for SGA, as a basis for identifying priority areas for developing and/or implementing interventions to reduce the incidence of SGA births and related mortality and morbidity. Methods: We conducted a literature review on 63 potential risk factors for SGA to quantify the risk relationship and estimate the prevalence of risk factors (RFs). We calculated the population-attributable fraction for each of the identified RF for 81 Countdown countries and calculated regional estimates. Twenty-five RFs were included in the final model while extended model included all the 25 RFs from the final model and two additional RFs. Results: In the final and extended models, the RFs included in each model have a total PAF equal to 63.97% and 69.66%, respectively of SGA across the 81 LMICs. In the extended model, maternal nutritional status has the greatest PAF (28.15%), followed by environmental and other exposures during pregnancy (15.82%), pregnancy history (11.01%), and general health issues or morbidity (10.34%). The RFs included in the final and extended model for Sub-Saharan African (SSA) region have a total PAF of 63.28% and 65.72% of SGA, respectively. In SSA, the top three RF categories in the extended model are nutrition (25.05%), environment and other exposure (13.01%), and general health issues or morbidity (10.72%), while in South-Asia's it was nutrition (30.56%), environment and other exposure (15.27%) and pregnancy history (11.68%). Conclusions: The various types of RFs that play a role in SGA births highlight the importance of a multifaceted approach to tackle SGA. Depending on the types of RFs, intervention should be strategically targeted at either individual or household and/or community or policy level. There is also a need to research the mechanisms by which some of the RFs might hinder fetal growth.

Population attributable fractions for risk factors for spontaneous preterm births in 81 low- and middle-income countries: A systematic analysis.

Background: Complications associated with preterm birth (PTB) are the largest contributor to under-five mortality globally. Success in reaching the Sustainable Development Goal target requires identifying potentially modifiable risk factors for PTB, estimating the relative importance of these risk factors, and identifying/implementing effective prevention strategies to address them. Methods: We conducted a literature review to define risk relationships and estimate prevalence for established risk factors for spontaneous PTB (sPTB). We then estimated population attributable fractions (PAF) for the sPTB risk factors identified in the review as statistically significant for the 81 low- and middle-income (LMIC) countries included in the Countdown 2030 initiative. We summed country-level findings to produce PAFs for each risk factor and regional estimates for sub-Saharan Africa and South Asia. Results: Forty-four potential sPTB risk factors were identified. and the final analysis included twenty-four risk factors with evidence of significant associations with sPTB. A second model with three additional risk factors with borderline insignificant associations was also run. Taken together, the twenty-four risk factors had a total PAF of 73% for all 81 countries and 77% and 72% of sPTB in sub-Saharan Africa and South Asia, respectively. For all countries, maternal undernutrition had the highest PAF (17.5%), followed by maternal infections (16.6%), environmental exposures (16%) and pregnancy history (8.7%). Conclusions: While multiple risk factors contribute to sPTB, no single risk factor addresses a predominant fraction, and 27% of spontaneous preterm births are not associated with risk factors that we identified. Despite the significant role of preterm birth in child survival, there are major data gaps in LMIC settings. Furthermore, there is a paucity of evidence for effective interventions to prevent preterm birth. Preventing sPTB requires understanding underlying mechanisms leading to sPTB in different populations, and the identification/implementation of effective interventions.

Breastfeeding in a Global Context: Epidemiology, Impact, and Future Directions.

INTRODUCTION: More than 98% of infant deaths occur in low- and middle-income countries (LMICs). Breastfeeding improves infant survival and protects against certain illnesses, such as diarrhea and pneumonia, which are leading causes of deaths in those <5 years of age in LMICs. The World Health Organization (WHO) recommends early initiation of breastfeeding within 1 hour of birth, exclusive breastfeeding up to 6 months of age, and continued breastfeeding up to 2 years of age. However, fewer than half of infants in LMICs are breastfed optimally to these standards. The objectives of this article are to describe the global epidemiology and health benefits of breastfeeding with particular focus on LMICs. METHODS: We searched PubMed to identify original research articles on breastfeeding in LMICs and reviews related to the benefits of breastfeeding, with particular focus on articles published in the past 5 years. We used reports and data published by the WHO and the United Nations Children's Fund (UNICEF) related to global breastfeeding rates, targets, and programmatic initiatives. We used the Lives Saved Tool to estimate mortality related to breastfeeding practices. FINDINGS: Less than half of infants globally receive early, exclusive, or continued breastfeeding. Certain high-risk groups, such as premature or HIV-exposed infants, face particular challenges and benefits related to breastfeeding. The WHO, UNICEF, and other global partners have developed a multipronged strategy to promote global breastfeeding, ranging from government-level advocacy to grassroots community support groups. Using the Lives Saved Tool, we estimate that nearly 200,000 lives of those <5 years of age could be saved in LMICs from 2020 to 2030 if early, exclusive, and continued breastfeeding rates were linearly increased from current rates to meet the WHO 2030 goals of 60% to 80% coverage. If this goal were exceeded and near-universal coverage were achieved, the number of lives would increase even further such that >820,000 lives per year could potentially be saved by universal breastfeeding. In this review, we delineate the health and economic benefit of breastfeeding in LMICs, discuss breastfeeding epidemiology in the global context, and describe targeted strategies to improve breastfeeding uptake.

Mixed-methods, descriptive and observational cohort study examining feeding and growth patterns among low birthweight infants in India, Malawi and Tanzania: the LIFE study protocol.

INTRODUCTION: Ending preventable deaths of newborns and children under 5 will not be possible without evidence-based strategies addressing the health and care of low birthweight (LBW, <2.5 kg) infants. The majority of LBW infants are born in low- and middle-income countries (LMICs) and account for more than 60%-80% of newborn deaths. Feeding promotion tailored to meet the nutritional needs of LBW infants in LMICs may serve a crucial role in curbing newborn mortality rates and promoting growth. The Low Birthweight Infant Feeding Exploration (LIFE) study aims to establish foundational knowledge regarding optimal feeding options for LBW infants in low-resource settings throughout infancy. METHODS AND ANALYSIS: LIFE is a formative, multisite, observational cohort study involving 12 study facilities in India, Malawi and Tanzania, and using a convergent parallel, mixed-methods design. We assess feeding patterns, growth indicators, morbidity, mortality, child development and health system inputs that facilitate or hinder care and survival of LBW infants. ETHICS AND DISSEMINATION: This study was approved by 11 ethics committees in India, Malawi, Tanzania and the USA. The results will be disseminated through peer-reviewed publications and presentations targeting the global and local research, clinical, programme implementation and policy communities. TRIAL REGISTRATION NUMBERS: NCT04002908 and CTRI/2019/02/017475.

Maternal Diet, Infection, and Risk of Cord Blood Inflammation in the Bangladesh Projahnmo Pregnancy Cohort.

Inflammation may adversely affect early human brain development. We aimed to assess the role of maternal nutrition and infections on cord blood inflammation. In a pregnancy cohort in Sylhet, Bangladesh, we enrolled 251 consecutive pregnancies resulting in a term livebirth from July 2016-March 2017. Stillbirths, preterm births, and cases of neonatal encephalopathy were excluded. We prospectively collected data on maternal diet (food frequency questionnaire) and morbidity, and analyzed umbilical cord blood for interleukin (IL)-1α, IL-1ß, IL-6, IL-8 and C-reactive protein. We determined associations between nutrition and infection exposures and cord cytokine elevation (≥75% vs. <75%) using logistic regression, adjusting for confounders. One-third of mothers were underweight (BMI < 18.5 kg/m2) at enrollment. Antenatal and intrapartum infections were observed among 4.8% and 15.9% of the sample, respectively. Low pregnancy intakes of B vitamins (B1, B2, B3, B6, B9 (folate)), fat-soluble vitamins (D, E), iron, zinc, and linoleic acid (lowest vs. middle tertile) were associated with higher risk of inflammation, particularly IL-8. There was a non-significant trend of increased risk of IL-8 and IL-6 elevation with history of ante-and intrapartum infections, respectively. In Bangladesh, improving micronutrient intake and preventing pregnancy infections are targets to reduce fetal systemic inflammation and associated adverse neurodevelopmental outcomes.

Optimizing initial neonatal resuscitation to reduce neonatal encephalopathy around the world.

One million two hundred thousand neonatal lives are lost each year due to intrapartum-related events; 99% of these deaths occur in low- and lower middle-income countries. Neonates exposed to intrapartum-related events present with failure to breathe at birth. Quick and effective delivery room management of these neonates is critical in the prevention of brain injury. Given the prominent role of lung aeration in the cardiopulmonary transition at birth, the mainstay of neonatal resuscitation is effective ventilation. Basic neonatal resuscitation focuses on simple stimulation, airway positioning and clearing, and bag-mask ventilation. Although principles for basic neonatal resuscitation remain the same for high- and low-resource settings, guidelines may differ based on available human and material resources. Formal training in basic resuscitation reduces intrapartum-related neonatal mortality in low-resource settings. However, there remain opportunities to improve provider performance for increased impact with other strategies such as regular practice and continuous quality improvement.

Associations between malaria in pregnancy and neonatal neurological outcomes.

OBJECTIVE: To compare neurological functioning of neonates born to mothers with and without malaria in pregnancy. METHODS: Pregnant women presenting at Korle Bu Teaching Hospital, Ghana were recruited into this prospective observational study. Malaria exposure was determined by clinically documented antenatal malaria infection; parasitemia in maternal, placental, or umbilical cord blood; or placental histology. Neurological functioning was assessed using the Hammersmith Neonatal Neurological Examination within 48 hours of birth. Performance was classified as "optimal" or "suboptimal" by subdomain and overall. RESULTS: Between November 21, 2018 and February 10, 2019, a total of 211 term-born neonates, of whom 27 (13%) were exposed to malaria in pregnancy, were included. In the reflexes subdomain, exposed neonates tended to score lower (adjusted mean difference -0.34, 95% confidence interval -0.70 to 0.03), with an increased risk (adjusted risk ratio 1.63, 95% confidence interval 1.09 to 2.44) of suboptimal performance compared with unexposed neonates. There were no significant between-group differences in scores or optimality classification for the remaining subdomains and overall. CONCLUSIONS: Malaria-exposed neonates had similar neurological functioning relative to unexposed neonates, with differences confined to the reflexes subdomain, suggesting potential underlying neurological immaturity or injury. Further studies are needed to confirm these findings and determine the significance of malaria in pregnancy on long-term neurological outcomes.

Gestational Age-Specific Distribution of the Hammersmith Neonatal Neurological Examination Scores Among Low-Risk Neonates in Ghana.

OBJECTIVE: To describe gestational age-specific distribution of scores for the Hammersmith Neonatal Neurological Examination (HNNE) up to 48 h after birth in a low-risk, term-born, single-center sample in Ghana. STUDY DESIGN: This is a nested substudy of a larger prospective study (IMPRINT: Impact of Malaria in Pregnancy on Infant Neurodevelopment) comprising 140 low-risk, term-born neonates at Korle Bu Teaching Hospital in Accra, Ghana, between November 2018 and February 2019. The sample was stratified into three gestational age groups: early-term (37 + 0-38 + 6, weeks + days; n = 61), full-term (39 + 0-40 + 6, weeks + days; n = 52), and late/post-term (41 + 0-42 + 6, weeks + days; n = 27). Neonates were administered the 34-item HNNE by trained physicians. As per the original British scoring system, raw scores for the Ghanaian sample were plotted and scores > 10th centile were assigned a score of 1, 5th-10th centile 0.5, and < 5th centile 0. RESULTS: The range of raw scores for 16/34 HNNE items varied with gestational age. Specifically, 100% (7/7), 50% (5/10), 33% (1/3), 33% (1/3), 20% (1/5), and 14% (1/7) of items within the orientation and behavior, tone, abnormal signs/patterns, movements, tone patterns, and reflexes subdomain, respectively showed a different distribution of scores above the 10th centile across the three gestational age groups. CONCLUSION: Differences in gestational age-specific results within our sample in comparison to the original British sample could be, albeit unlikely, due to misclassification of gestational age, unmeasured maternal or fetal morbidity, or perhaps more likely, variation in testing or test conditions, or some combination of these. Genetic variation in neurological development is also a possibility. Further research is warranted to determine the reasons for differences. Our findings highlight the need to determine the accuracy and reliability of standardized neurologic assessments in predicting neurodevelopmental risk for infants in low- and middle-income countries.

Diagnostic accuracy of neonatal foot length to identify preterm and low birthweight infants: a systematic review and meta-analysis.

INTRODUCTION: Eighty percent of neonatal deaths occur among babies born preterm and/or small for gestational age (SGA). In sub-Saharan Africa and South Asia, approximately 40% of births occur outside of health facilities, and gestational age (GA) and birth weight are commonly unknown. Foot length (FL) has been proposed as a simple, surrogate measurement to identify and triage small babies born in the community. We conducted a systematic review and meta-analysis of the diagnostic accuracy of newborn FL to classify preterm and low birthweight infants. METHODS: PubMed, EMBASE, Cochrane, Web of Science, POPLINE and WHO Global Health Library databases were searched. Studies of live-born infants that compared FL with GA and/or birth weight were included. Data on diagnostic accuracy were summarised, described, and pooled, as appropriate. RESULTS: Six hundred and two studies were identified and 41 included. Techniques for measuring FL included use of a firm plastic ruler, callipers, footprint or a measuring board. Twelve studies assessed the diagnostic accuracy of FL to identify preterm births; however, data were not pooled given heterogeneity and low quality of GA. 19 studies used FL to identify low birthweight infants (<2500 g, <2000 g). Among studies in Asia (n=3), FL <7.7 cm had pooled sensitivity and specificity of 87.6% (95% CI 61.1% to 99.0%) and 70.9% (95% CI 23.5% to 95.1%), respectively, to identify <2500 g infants. FL <7.3 cm had 82.1% (95% CI 63.7% to 92.2%) sensitivity and 82.1% (95% CI 59.2% to 90.8%) specificity for identifying <2000 g infants (n=3). In the African studies (n=3), FL <7.9 cm had pooled sensitivity and specificity of 92.0% (95% CI 85.6% to 95.7%) and 71.9% (95% CI 44.5% to 89.1%), respectively, to identify <2500 g neonates. CONCLUSIONS: FL is a simple proxy measure that can identify babies of low birthweight with high sensitivity, though somewhat lower specificity. Additional research is needed to determine the validity of FL to identify preterm infants, and understand the programmatic impact of screening on healthcare seeking and outcomes. PROSPERO REGISTRATION NUMBER: CRD42015020499.

Neonatal neurological examination in a resource-limited setting: What defines normal?

OBJECTIVE: To describe the results of the Hammersmith Neonatal Neurological Examination (HNNE) in a low-risk, term-born, contemporary sample in Ghana. Of particular interest was to compare these findings with the original British study that validated the HNNE, and published data from other low- and middle-income countries. STUDY DESIGN: In a nested substudy of a larger prospective study (IMPRINT: Impact of Malaria in Pregnancy on Infant Neurodevelopment), 140 low-risk, term-born neonates (39.3 ± 1.4 weeks gestation) at Korle Bu Teaching Hospital in Accra, Ghana were administered the 34-item HNNE from birth to 48 h of age by trained physicians. Neonates' performance was compared with previously published normative data from the United Kingdom (1998), and published data from Thailand, Myanmar, Vietnam, and Uganda. RESULTS: Ghanaian neonates demonstrated lower scores on 29/34 HNNE items relative to normative data from the United Kingdom (P < .05), with only 5% of Ghanaian neonates in our sample classified as neurologically optimal. There were significant differences in the proportion of neonates scoring optimally per HNNE item between our Ghanaian sample, compared with published data from other settings (Thai [13/16 items], Burmese [14/16 items], Vietnamese [7/9 items], and Ugandan [22/34 items] neonates). Raw scores were markedly different between Ghanaian and British neonates, with Ghanaian neonates demonstrating lower median and wider range of scores. These differences were less prominent between Ghanaian and Ugandan neonates. CONCLUSION: Our findings raise questions as to whether or not the thresholds for optimality for the HNNE based on data from the United Kingdom are applicable to Ghanaian newborns. Our study could not fully resolve whether the differences in scores were due to genetic differences in developmental pathways, the implementation of the assessment, or the characteristics of our sample. Low proportions of neonates scoring optimally from other low- and middle-income countries suggest the need for further research to determine the clinical utility of the HNNE in resource-limited settings, including the predictive value for neurodevelopment later in infancy.

Sexually Transmitted Infections in Pregnancy: A Narrative Review of the Global Research Gaps, Challenges, and Opportunities.

BACKGROUND: Sexually transmitted infections (STI), such as chlamydial, gonorrheal, and trichomonal infections, are prevalent in pregnant women in many countries and are widely reported to be associated with increased risk of poor maternal and neonatal outcomes. Syndromic STI management is frequently used in pregnant women in low- and middle-income countries, yet its low specificity and sensitivity lead to both overtreatment and undertreatment. Etiologic screening for chlamydial, gonorrheal, and/or trichomonal infection in all pregnant women combined with targeted treatment might be an effective intervention. However, the evidence base is insufficient to support the development of global recommendations. We aimed to describe key considerations and knowledge gaps regarding chlamydial, gonorrheal, and trichomonal screening during pregnancy to inform future research needed for developing guidelines for low- and middle-income countries. METHODS: We conducted a narrative review based on PubMed and clinical trials registry searches through January 20, 2020, guidelines review, and expert opinion. We summarized our findings using the frameworks adopted by the World Health Organization for guideline development. RESULTS: Adverse maternal-child health outcomes of potential interest are wide-ranging and variably defined. No completed randomized controlled trials on etiologic screening and targeted treatment were identified. Evidence from observational studies was limited, and trials of presumptive STI treatment have shown mixed results. Subgroups that might benefit from specific recommendations were identified. Evidence on harms was limited. Cost-effectiveness was influenced by STI prevalence and availability of testing infrastructure and high-accuracy/low-cost tests. Preliminary data suggested high patient acceptability. DISCUSSION: Preliminary data on harms, acceptability, and feasibility and the availability of emerging test technologies suggest that etiologic STI screening deserves further evaluation as a potential tool to improve maternal and neonatal health outcomes worldwide.

Development and evaluation of a mobile application for case management of small and sick newborns in Bangladesh.

BACKGROUND: In low-income settings, community health workers (CHWs) are frequently the first point of contact for newborns. Mobile technology may aid health workers in classifying illness and providing referral and management guidance for newborn care. This study evaluates the potential for mobile health technology to improve diagnosis and case management of newborns in Bangladesh. METHODS: A mobile application based on Bangladesh's Comprehensive Newborn Care Package national guidelines (mCNCP) was developed to aid CHWs in identifying and managing small and sick infants. After a 2-day training, CHWs assessed newborns at Sylhet Osmani Medical College Hospital and in the Projahnmo research site (Sylhet, Bangladesh) using either mCNCP or a comparable paper form (pCNCP), similar to standard IMCI-formatted paper forms. CHWs were randomized to conduct a block of ~ 6 newborn assessments starting with either mCNCP or pCNCP, then switched to the alternate method. Physicians using mCNCP served as gold standard assessors. CHW performance with mCNCP and pCNCP were compared using chi-squared tests of independence for equality of proportions, and logistic regressions clustered by CHW. RESULTS: Two hundred seven total CHW assessments were completed on 101 enrolled infants. mCNCP assessments were more often fully completed and completed faster than pCNCP assessments (100% vs 23.8%, p < 0.001; 17.5 vs 23.6 min; p < 0.001). mCNCP facilitated calculations of respiratory rate, temperature, and gestational age. CHWs using mCNCP were more likely to identify small newborns (Odds Ratio (OR): 20.8, Confidence Interval (CI): (7.1, 60.8), p < 0.001), and to correctly classify 7 out of 16 newborn conditions evaluated, including severe weight loss (OR: 13.1, CI: (4.6, 37.5), p < 0.001), poor movement (OR: 6.6, CI: (2.3, 19.3), p = 0.001), hypothermia (OR: 14.9, CI: (2.7, 82.2), p = 0.002), and feeding intolerance (OR: 2.1, CI: (1.3, 3.3), p = 0.003). CHWs with mCNCP were more likely to provide counseling as needed on 4 out of 7 case management recommendations evaluated, including kangaroo mother care. CONCLUSIONS: CHWs in rural Bangladesh with limited experience using tablets successfully used a mobile application for neonatal assessment after a two-day training. mCNCP may aid frontline health workers in Bangladesh to improve completion of neonatal assessment, classification of illnesses, and adherence to neonatal management guidelines.