A ten-year review of neonatal tetanus cases managed at a tertiary health facility in a resource poor setting: The trend, management challenges and outcome.

BACKGROUND: Neonatal Tetanus (NNT) is a vaccine preventable disease of public health importance. It is still being encountered in clinical practice largely in developing countries including Nigeria. NNT results from unhygienic delivery practices and some harmful traditional cord care practices. The easiest, quickest and most cost-effective preventive measure against NNT is vaccination of the pregnant women with the tetanus toxoid (TT) vaccine. The case-fatality rate from tetanus in resource-constrained settings can be close to 100% but can be reduced to 50% if access to basic medical care with adequate number of experienced staff is available. MATERIALS AND METHODS: This retrospective study reviewed the admissions into the Special Care Baby Unit (SCBU) of the Ekiti State University Teaching Hospital, Ado-Ekiti from January 2011 to December 2020. The folders were retrieved from the records department of the hospital; Information obtained from folders were entered into a designed proforma for the study. RESULTS: During the study period, NNT constituted 0.34% of all neonatal admissions with case fatality rate of 52.6%. Seven [36.8%] of the babies were delivered at Mission home/Traditional Birth Attendant's place while 5 [26.3%] were delivered in private hospitals. Cord care was with hot water compress in most of these babies16 [48.5%] while only 9% of the mothers cleaned the cord with methylated spirit. Age at presentation of less than one week was significantly associated with mortality, same with presence of autonomic dysfunction. Low family socio-economic class 5 was significantly associated with poor outcome, so also maternal age above 24 years. CONCLUSION: This study revealed that neonatal tetanus is still being seen in our clinical practice with poor outcome and the risk factors are the same as of old. Increased public health campaign, promotion of clean deliveries, safe cord care practices, affordable and accessible health care provision are recommended to combat NNT scourge.

Dealing with neonatal emergencies in low-resource settings.

We describe the development and delivery of neonatal care including trends and impacts of major interventions on neonatal mortality particularly in low-resource settings. Low- and middle-income countries continue to be major contributors to neonatal mortality. Although there has been progress in reducing neonatal mortality, neonatal deaths are contributing an increasing percentage of childhood mortality. Several interventions targeting neonatal care such as neonatal resuscitation and essential newborn care have contributed to improved outcomes. However, there are still many neonatal deaths that are preventable with known effective interventions. This review addresses interventions proven effective in reducing neonatal mortality, challenges to implement them, and future directions of implementing these interventions in low- and middle-income countries.

The role of immune correlates of protection on the pathway to licensure, policy decision and use of group B Streptococcus vaccines for maternal immunization: considerations from World Health Organization consultations.

The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined.

Conditional cash transfers to prevent mother-to-child transmission in low facility-delivery settings: evidence from a randomised controlled trial in Nigeria.

BACKGROUND: Nigeria suffers from the highest burden of mother-to-child transmission worldwide. To increase retention in care and prevention programmes, we piloted and evaluated a conditional cash transfer (CCT) programme for preventing mother-to-child transmission (PMTCT) in Akwa Ibom, Nigeria. METHODS: In a randomised controlled trial, pregnant women testing positive for HIV during antenatal care registration at three public hospitals were randomised to one of two study arms: (1) offered enrolment into the CCT programme or (2) continue in standard care for (PMTCT). In the CCT programme, women could receive a compensation package totaling 33,300 Naira (~US$114) for enroling, delivering at the facility, and obtaining a newborn early infant diagnosis (EID) test. The intent-to-treat (ITT) and per protocol (PP) effects of the programme on the primary outcomes of facility delivery and EID testing and on the secondary outcome of nevirapine administration were estimated with logistic regressions. RESULTS: From August 1, 2015 to April 19, 2017, 554 pregnant women tested positive for HIV; 273 were randomised to standard care and 281 were offered enrolment into the CCT intervention. Women offered the CCT programme were more likely to give birth at the facility (n = 109/263; 41.4%) compared to women in standard care (n = 80/254; 31.5%), an absolute difference of 9.9% (OR = 1.54, 95% CI: 1.07-2.21, p = 0.019). For EID testing there was an absolute difference of 12.8% between those offered the CCT intervention (n = 69/263; 26.2%) and those in standard care (n = 34/254; 13.4%; OR = 2.30, 95% CI 1.46-3.62, p = 0.000). PP results show larger differences for both facility deliveries (16.7% absolute difference; OR = 2.02, 95% CI 1.38-2.98, p = 0.000) and EID testing (18.9% absolute difference; OR = 3.09, 95% CI 1.93-4.94, p = 0.000) among intervention enrolees. Over 86% of the facility-delivered newborns received nevirapine, and ITT and PP estimates were similar to those for facility deliveries. CONCLUSIONS: Results show that CCTs improved the likelihood of HIV-positive women giving birth at a facility, of nevirapine being administered to their newborn, and of undergoing EID testing in Akwa Ibom, Nigeria. Effects are especially large among those who agreed to participate in the CCT intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02447159 , May 18, 2015.

Is adding maternal vaccination to prevent whooping cough cost-effective in Australia?

Pertussis or whooping cough, a highly infectious respiratory infection, causes significant morbidity and mortality in infants. In adolescents and adults, pertussis presents with atypical symptoms often resulting in under-diagnosis and under-reporting, increasing the risk of transmission to more vulnerable groups. Maternal vaccination against pertussis protects mothers and newborns. This evaluation assessed the cost-effectiveness of adding maternal dTpa (reduced antigen diphtheria, Tetanus, acellular pertussis) vaccination to the 2016 nationally-funded pertussis program (DTPa [Diphtheria, Tetanus, acellular Pertussis] at 2, 4, 6, 18 months, 4 years and dTpa at 12-13 years) in Australia. A static cross-sectional population model was developed using a one-year period at steady-state. The model considered the total Australian population, stratified by age. Vaccine effectiveness against pertussis infection was assumed to be 92% in mothers and 91% in newborns, based on observational and case-control studies. The model included conservative assumptions around unreported cases. With 70% coverage, adding maternal vaccination to the existing pertussis program would prevent 8,847 pertussis cases, 422 outpatient cases, 146 hospitalizations and 0.54 deaths per year at the population level. With a 5% discount rate, 138.5 quality-adjusted life-years (QALYs) would be gained at an extra cost of AUS$ 4.44 million and an incremental cost-effectiveness ratio of AUS$ 32,065 per QALY gained. Sensitivity and scenario analyses demonstrated that outcomes were most sensitive to assumptions around vaccine effectiveness, duration of protection in mothers, and disutility of unreported cases. In conclusion, dTpa vaccination in the third trimester of pregnancy is likely to be cost-effective from a healthcare payer perspective in Australia.

Glucose Gel in Infants at Risk for Transitional Neonatal Hypoglycemia.

OBJECTIVE: To evaluate whether glucose gel as a supplement to feedings in infants admitted to the newborn nursery at risk for neonatal hypoglycemia (NH) reduces the frequency of transfer to a higher level of care for intravenous dextrose treatment. STUDY DESIGN: We revised our newborn nursery protocol for management of infants at risk for NH to include use of 40% glucose gel (200 mg/kg). Study population included late preterm, small and large for gestational age infants, and infants of diabetic mothers. We compared outcomes before (4/1/14-3/31/15: Year 1) and after (4/1/15-3/31/16: Year 2) initiation of the revised protocol. Our prospective primary outcome was transfer to the neonatal intensive care unit (NICU) for treatment with a continuous infusion of dextrose. RESULTS: NICU transfer for management of NH fell from 8.1% in Year 1 (34 of 421 at-risk infants screened) to 3.7% in Year 2 (14 of 383 at-risk infants screened). Rate of exclusive breastfeeding increased from 6% in Year 1 to 19% in Year 2. Hospital charges for the study population decreased from 801,276 USD to 387,688 USD in Year 1 and Year 2, respectively. CONCLUSION: Our study supports the adjunctive use of glucose gel to reduce NICU admissions and total hospitalization expense.

The impact of prenatal group B streptococcus screening as a national health policy in Taiwan.

OBJECTIVE: There was no national data on group B streptococcus (GBS) infections in Taiwan. Until 2012, when prenatal GBS screening was introduced to obstetric practices as a national health policy aimed at reducing neonatal GBS infections. The purpose of this study was to examine the impact of this national health policy on the incidence of maternal GBS colonization and neonatal GBS infection rate. Relatedly, the clinical characteristics of neonatal GBS infection were investigated to determine the correlations between the incidence of maternal GBS colonization and the neonatal GBS infection rate. MATERIALS AND METHODS: This population-based nationwide study used data for 2012-2013 from the National Health Insurance Research Database of Taiwan. A total of 789 newly diagnosed pregnant women with genital GBS infection were recruited. RESULTS: The maternal GBS screening rate was 93.2%. The maternal colonization rate of GBS was around 8.2%, and the incidence of neonatal GBS infection was 22.6%. The data indicate that no sepsis was developed in any of the cases, while fever was found in 3 cases (3/179, 1.7%) and UTI was found in 1 case (1/179, 0.6%). CONCLUSIONS: We conclude that a policy calling for universal maternal rectovaginal cultures for GBS with intrapartum antibiotic prophylaxis is a good national policy for reducing morbidity due to GBS infections in neonates in Taiwan.

Epidural analgesia during labour, routinely or on request: a cost-effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of routine labour epidural analgesia (EA), from a societal perspective, as compared with labour analgesia on request. STUDY DESIGN: Women delivering of a singleton in cephalic presentation beyond 36+0 weeks' gestation were randomly allocated to routine labour EA or analgesia on request in one university and one non-university teaching hospital in the Netherlands. Costs included all medical, non-medical and indirect costs from randomisation to 6 weeks postpartum. Effectiveness was defined as a non-operative, spontaneous vaginal delivery without EA-related maternal adverse effects. Incremental cost-effectiveness ratio (ICER) was defined as the ratio of the difference in costs and the difference in effectiveness between both groups. Data were analysed according to intention to treat and divided into a base case analysis and a sensitivity analysis. RESULTS: Total delivery costs in the routine EA group (n=233) were higher than in the labour on request group (n=255) (difference -€ 322, 95% CI -€ 60 to € 355) due to more medication costs (including EA), a longer stay in the labour ward, and more operations including caesarean sections. Total postpartum hospital costs in the routine EA group were lower (difference -€ 344, 95% CI -€ 1338 to € 621) mainly due to less neonatal admissions (difference -€ 472, 95% CI -€ 1297 to € 331), whereas total postpartum home and others costs were comparable (difference -€ 20, 95% CI -€ 267 to € 248, and -€ 1, 95% CI -€ 67 to € 284, respectively). As a result, the overall mean costs per woman were comparable between the routine EA group and the analgesia on request group (€ 8.708 and € 8.710, respectively, mean difference -€ 2, 95% CI -€ 1.012 to € 916). Routine labour EA resulted in more deliveries with maternal adverse effects, nevertheless the ICER remained low (€ 8; bootstrap 95% CI -€ 6.120 to € 8.659). The cost-effectiveness acceptability curve indicated a low probability that routine EA is cost-effective. CONCLUSION: Routine labour EA generates comparable costs as analgesia on request, but results in more operative deliveries and more EA-related maternal adverse effects. Based on cost-effectiveness, no preference can be given to routine labour EA as compared with analgesia on request.

Reducing the global burden of Preterm Birth through knowledge transfer and exchange: a research agenda for engaging effectively with policymakers.

Preterm birth (PTB) is the world's leading cause of death in children under 5 years. In 2013, over one million out of six million child deaths were due to complications of PTB. The rate of decline in child death overall has far outpaced the rate of decline attributable to PTB. Three key reasons for this slow progress in reducing PTB mortality are: (a) the underlying etiology and biological mechanisms remain unknown, presenting a challenge to discovering ways to prevent and treat the condition; (ii) while there are several evidence-based interventions that can reduce the risk of PTB and associated infant mortality, the coverage rates of these interventions in low- and middle-income countries remain very low; and (c) the gap between knowledge and action on PTB--the "know-do gap"--has been a major obstacle to progress in scaling up the use of existing evidence-based child health interventions, including those to prevent and treat PTB.In this review, we focus on the know-do gap in PTB as it applies to policymakers. The evidence-based approaches to narrowing this gap have become known as knowledge transfer and exchange (KTE). In our paper, we propose a research agenda for promoting KTE with policymakers, with an ambitious but realistic goal of reducing the global burden of PTB. We hope that our proposed research agenda stimulates further debate and discussion on research priorities to soon bend the curve of PTB mortality.

Reaching the poor with health interventions: programme-incidence analysis of seven randomised trials of women's groups to reduce newborn mortality in Asia and Africa.

BACKGROUND: Efforts to end preventable newborn deaths will fail if the poor are not reached with effective interventions. To understand what works to reach vulnerable groups, we describe and explain the uptake of a highly effective community-based newborn health intervention across social strata in Asia and Africa. METHODS: We conducted a secondary analysis of seven randomised trials of participatory women's groups to reduce newborn mortality in India, Bangladesh, Nepal and Malawi. We analysed data on 70,574 pregnancies. Socioeconomic and sociodemographic differences in group attendance were tested using logistic regression. Qualitative data were collected at each trial site (225 focus groups, 20 interviews) to understand our results. RESULTS: Socioeconomic differences in women's group attendance were small, except for occasional lower attendance by elites. Sociodemographic differences were large, with lower attendance by young primigravid women in African as well as in South Asian sites. The intervention was considered relevant and interesting to all socioeconomic groups. Local facilitators ensured inclusion of poorer women. Embarrassment and family constraints on movement outside the home restricted attendance among primigravid women. Reproductive health discussions were perceived as inappropriate for them. CONCLUSIONS: Community-based women's groups can help to reach every newborn with effective interventions. Equitable intervention uptake is enhanced when facilitators actively encourage all women to attend, organise meetings at the participants' convenience and use approaches that are easily understandable for the less educated. Focused efforts to include primigravid women are necessary, working with families and communities to decrease social taboos.

Analysis of hospital cost outcome of DHA-rich fish-oil supplementation in pregnancy: Evidence from a randomized controlled trial.

OBJECTIVE: Recent research emphasized the nutritional benefits of omega-3 long chain polyunsaturated fatty acids (LCPUFAs) during pregnancy. Based on a double-blind randomised controlled trial named "DHA to Optimize Mother and Infant Outcome" (DOMInO), we examined how omega 3 DHA supplementation during pregnancy may affect pregnancy related in-patient hospital costs. METHOD: We conducted an econometric analysis based on ordinary least square and quantile regressions with bootstrapped standard errors. Using these approaches, we also examined whether smoking, drinking, maternal age and BMI could influence the effect of DHA supplementation during pregnancy on hospital costs. RESULTS: Our regressions showed that in-patient hospital costs could decrease by AUD92 (P<0.05) on average per singleton pregnancy when DHA supplements were consumed during pregnancy. Our regression results also showed that the cost savings to the Australian public hospital system could be between AUD15 - AUD51 million / year. CONCLUSION: Given that a simple intervention like DHA-rich fish-oil supplementation could generate savings to the public, it may be worthwhile from a policy perspective to encourage DHA supplementation among pregnant women.

New technologies for essential newborn care in under-resourced areas: what is needed and how to deliver it.

Globally, the largest contributors to neonatal mortality are preterm birth, intrapartum complications and infection. Many of these deaths could be prevented by providing temperature stability, respiratory support, hydration and nutrition; preventing and treating infections; and diagnosing and treating neonatal jaundice and hypoglycaemia. Most neonatal health-care technologies which help to accomplish these tasks are designed for high-income countries and are either unavailable or unsuitable in low-resource settings, preventing many neonates from receiving the gold standard of care. There is an urgent need for neonatal health-care technologies which are low-cost, robust, simple to use and maintain, affordable and able to operate from various power supplies. Several technologies have been designed to meet these requirements or are currently under development; however, unmet technology needs remain. The distribution of an integrated set of technologies, rather than separate components, is essential for effective implementation and a substantial impact on neonatal health. Close collaboration between stakeholders at all stages of the development process and an increased focus on implementation research are necessary for effective and sustainable implementation.

Neonatal care in Brazil: hospital structure and adequacy according to newborn obstetric risk.

BACKGROUND: In Brazil, hospital birth care is available to all, but there are important differences between hospitals in the public and private sectors, geographical regions and capitals/inland cities, resulting in inequalities of infant health. AIMS: To assess the hospital structure for birth care in Brazil and analyze hospital adequacy to care for newborns according to levels of risk. METHODS: Data were collected as part of a nationwide hospital-based cohort study, 'Birth in Brazil'. The hospitals were classified according to whether they had a neonatal intensive care unit and divided into two models of governance: public and private financing. Three structure domains were assessed: human resources, medications and equipment for post-natal women and newborn emergency care. Newborns were classified according to the obstetric risk. RESULTS: There are more NICUs in private hospitals and they cater mostly for low obstetric risk newborns; the public sector serves 50% of at-risk patients in hospitals without an NICU. The differences between hospital service structures according to geographic region and capital/inland cities were evident. Hospitals in less developed regions and inland cities had poorer adequacy in the three domains. CONCLUSION: The distribution of neonatal care to Brazilian infants varied between the public and private sectors. The public sector offered less complex services for newborns at risk, and infants without obstetric risk were born in facilities with an NICU, creating the possibility of unnecessary intervention, especially in the private sector.

Improving neonatal care in district and community health facilities in South Africa.

A high standard of newborn care, especially at a primary level, is needed to address the neonatal mortality rate in South Africa. The current approach to continuing training of health-care workers uses traditional methods of centralised teaching by formal tutors away from the place of work. This is no longer affordable, achievable or desirable, particularly in rural areas. An innovative system of self-directed learning by groups of nurses caring for mothers and their newborn infants uses specially prepared course books without the need for trainers. Using self-study supported by peer discussion groups, nurses can take responsibility for their own professional growth. This builds competence, confidence and a sense of pride. Since 1993, the Perinatal Education Programme has provided continuing learning opportunities for thousands of nurses in Southern Africa. A number of prospective trials have demonstrated that study groups can significantly improve knowledge and understanding, attitudes, clinical skills and quality of care provided to mothers and infants. A recent review of 10,000 successful participants across a wide range of provinces, ages and home languages documented the success of the project. Using a question-and-answer format to promote problem-solving, case studies, simple skills workshops and multiple choice tests, each module addresses common conditions with appropriate care practices such as thorough drying at birth, delayed cord-clamping, skin-to-skin care, breast feeding, basic resuscitation, correct use of oxygen therapy, hand-washing, blood glucose monitoring and promotion of parental bonding. The training material is now also available free of charge on an on-line website as well as being presented as e-books which can be downloaded onto personal computers, tablet readers and smart phones. This is supplemented by regular SMS text messages providing nurses with relevant 'knowledge bites'. All nurses caring for newborn infants now have easy, affordable access to continuing education which promises nationwide improvements in newborn care.

Prevention of functional gastrointestinal disorders in neonates: clinical and socioeconomic impact.

Infantile colic, gastro-oesophageal reflux and constipation are the most common functional gastrointestinal disorders (FGIDs) affecting infants during the first months of life. Despite infantile colic, functional constipation and regurgitation had a self-limited pattern, they are considered a risk factor for developing different disorders later in life. The pathophysiology of these functional diseases is still controversial but there is growing evidence that an abnormal gut microbiota colonisation may play a crucial role. An early probiotic supplementation could determine a change in colonisation and may represent a new strategy for preventing FGIDs.

Research on vaccines during pregnancy: protocol design and assessment of safety.

The Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health organized a series of conferences, entitled "Enrolling Pregnant Women in Clinical Trials of Vaccines and Therapeutics", to discuss study design and the assessment of safety in clinical trials conducted in pregnant women. A panel of experts was charged with developing guiding principles for the design of clinical trials and the assessment of safety of vaccines during pregnancy. Definitions and a grading system to evaluate local and systemic reactogenicity, adverse events, and other events associated with pregnancy and delivery were developed. The purpose of this report is to provide investigators interested in vaccine research in pregnancy with a basic set of tools to design and implement maternal immunization studies which may be conducted more efficiently using consistent definitions and grading of adverse events to allow the comparison of safety reports from different trials. These guidelines and safety assessment tools may be modified to meet the needs of each particular protocol based on evidence collected as investigators use them in clinical trials in different settings and share their findings and expertise.

Interventions to reduce neonatal mortality from neonatal tetanus in low and middle income countries--a systematic review.

BACKGROUND: In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting. METHODS: We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total of 26 out of 30 studies were shortlisted for preliminary screening after removing overlapping information. Key words used were "neonatal tetanus, neonatal mortality, tetanus toxoid women". Of these twenty-six studies, 20 were excluded. The pre-defined exclusion criteria was (i) strategies and interventions to reduce mortality among neonates not described (ii) no abstract/author (4 studies) (iii) not freely accessible online (1 study) (iv) conducted in high income countries (2 studies) and (v) not directly related to neonatal tetanus mortality and tetanus toxoid immunization (5). Finally six studies which met the eligibility criteria were entered in the pre-designed data extraction form and five were selected for commentary as they were directly linked with neonatal tetanus reduction. RESULTS: Interventions that were identified to reduce neonatal mortality in LMICs were: a) vaccination of women of child bearing age (married and unmarried both) with tetanus toxoid b) community based interventions i.e. tetanus toxoid immunization for all mothers; clean and skilled care at delivery; newborn resuscitation; exclusive breastfeeding; umbilical cord care and management of infections in newborns c) supplementary immunization (in addition to regular EPI program) d) safer delivery practices. CONCLUSION: The key intervention to reduce neonatal mortality from neonatal tetanus was found to be vaccination of pregnant women with tetanus toxoid. In the resource poor countries like Pakistan, this single intervention coupled with regular effective antenatal checkups, clean delivery practices and compliance with the "high- risk" approach can be effective in reducing neonatal tetanus.