Opportunities and Challenges in Global Perinatal Research.

BACKGROUND: The global plight of stillbirths and neonatal mortality is concentrated in low- and middle-income countries. The ambitious targets introduced by the World Health Organization in the Every Newborn Action Plan demand a commitment to research that promotes equitable perinatal outcomes. OBJECTIVES: The aim of this review was to understand the opportunities for global perinatal research and the accompanying challenges. METHODS: We conducted a literature search to identify research prioritization exercises from 2014 to 2018 pertaining to global perinatal health. The top 50 questions with the highest research prioritization scores were extracted and analyzed. RESULTS: The greatest priorities centered on community-based, implementation research targeting major causes of stillbirth and neonatal mortality in low-resource settings. The priorities are saddled with prerequisite conditions, design obstacles, and ethical considerations that require attention. CONCLUSIONS: While the challenges are undeniable, the need to make the perinatal period healthier for babies worldwide has never been clearer.

Prioritizing research for integrated implementation of early childhood development and maternal, newborn, child and adolescent health and nutrition platforms.

BACKGROUND: Existing health and nutrition services present potential platforms for scaling up delivery of early childhood development (ECD) interventions within sensitive windows across the life course, especially in the first 1000 days from conception to age 2 years. However, there is insufficient knowledge on how to optimize implementation for such strategies in an integrated manner. In light of this knowledge gap, we aimed to systematically identify a set of integrated implementation research priorities for health, nutrition and early child development within the 2015 to 2030 timeframe of the Sustainable Development Goals (SDGs). METHODS: We applied the Child Health and Nutrition Research Initiative method, and consulted a diverse group of global health experts to develop and score 57 research questions against five criteria: answerability, effectiveness, deliverability, impact, and effect on equity. These questions were ranked using a research priority score, and the average expert agreement score was calculated for each question. FINDINGS: The research priority scores ranged from 61.01 to 93.52, with a median of 82.87. The average expert agreement scores ranged from 0.50 to 0.90, with a median of 0.75. The top-ranked research question were: i) "How can interventions and packages to reduce neonatal mortality be expanded to include ECD and stimulation interventions?"; ii) "How does the integration of ECD and MNCAH&N interventions affect human resource requirements and capacity development in resource-poor settings?"; and iii) "How can integrated interventions be tailored to vulnerable refugee and migrant populations to protect against poor ECD and MNCAH&N outcomes?". Most highly-ranked research priorities varied across the life course and highlighted key aspects of scaling up coverage of integrated interventions in resource-limited settings, including: workforce and capacity development, cost-effectiveness and strategies to reduce financial barriers, and quality assessment of programs. CONCLUSIONS: Investing in ECD is critical to achieving several of the SDGs, including SDG 2 on ending all forms of malnutrition, SDG 3 on ensuring health and well-being for all, and SDG 4 on ensuring inclusive and equitable quality education and promotion of life-long learning opportunities for all. The generated research agenda is expected to drive action and investment on priority approaches to integrating ECD interventions within existing health and nutrition services.

Setting an implementation research agenda for Canadian investments in global maternal, newborn, child and adolescent health: a research prioritization exercise.

BACKGROUND: Improving global maternal, newborn, child and adolescent health (MNCAH) is a top development priority in Canada, as shown by the $6.35 billion in pledges toward the Muskoka Initiative since 2010. To guide Canadian research investments, we aimed to systematically identify a set of implementation research priorities for MNCAH in low- and middle-income countries. METHODS: We adapted the Child Health and Nutrition Research Initiative method. We scanned the Child Health and Nutrition Research Initiative literature and extracted research questions pertaining to delivery of interventions, inviting Canadian experts on MNCAH to generate additional questions. The experts scored a combined list of 97 questions against 5 criteria: answerability, feasibility, deliverability, impact and effect on equity. These questions were ranked using a research priority score, and the average expert agreement score was calculated for each question. RESULTS: The overall research priority score ranged from 40.14 to 89.25, with a median of 71.84. The average expert agreement scores ranged from 0.51 to 0.82, with a median of 0.64. Highly-ranked research questions varied across the life course and focused on improving detection and care-seeking for childhood illnesses, overcoming barriers to intervention uptake and delivery, effectively implementing human resources and mobile technology, and increasing coverage among at-risk populations. Children were the most represented target population and most questions pertained to interventions delivered at the household or community level. INTERPRETATION: Investing in implementation research is critical to achieving the Sustainable Development Goal of ensuring health and well-being for all. The proposed research agenda is expected to drive action and Canadian research investments to improve MNCAH.

Neonatal vitamin A supplementation for the prevention of mortality and morbidity in term neonates in low and middle income countries.

BACKGROUND: Vitamin A deficiency is a major public health problem in low and middle income countries. Vitamin A supplementation in children six months of age and older has been found to be beneficial, but no effect of supplementation has been noted for children between one and five months of age. Supplementation during the neonatal period has been suggested to have an impact by increasing body stores in early infancy. OBJECTIVES: To evaluate the role of vitamin A supplementation for term neonates in low and middle income countries with respect to prevention of mortality and morbidity. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE via PubMed (1966 to 13 March 2016), Embase (1980 to 13 March 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 13 March 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials. Also trials with a factorial design. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted study data. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: We included 12 trials (168,460 neonates) in this review, with only a few trials reporting disaggregated data for term infants. Therefore, we analysed data and presented estimates for term infants (when specified) and for all infants.Data for term neonates from three studies did not show a statistically significant effect on the risk of infant mortality at six months in the vitamin A group compared with the control group (typical risk ratio (RR) 0.80; 95% confidence interval (CI) 0.54 to 1.18; I2 = 63%). Analysis of data for all infants from 11 studies revealed no evidence of a significant reduction in the risk of infant mortality at six months among neonates supplemented with vitamin A compared with control neonates (typical RR 0.98, 95% CI 0.89 to 1.07; I2 = 47%). We observed similar results for infant mortality at 12 months of age with no significant effect of vitamin A compared with control (typical RR 1.04, 95% CI 0.94 to 1.15; I2 = 47%). Limited data were available for the outcomes of cause-specific mortality and morbidity, vitamin A deficiency, anaemia and adverse events. AUTHORS' CONCLUSIONS: Given the high burden of death among children younger than five years of age in low and middle income countries, and the fact that mortality in infancy is a major contributory cause, it is critical to obtain sound scientific evidence of the effect of vitamin A supplementation during the neonatal period on infant mortality and morbidity. Evidence provided in this review does not indicate a potential beneficial effect of vitamin A supplementation among neonates at birth in reducing mortality during the first six months or 12 months of life. Given this finding and the absence of a clear indication of the biological mechanism through which vitamin A could affect mortality, along with substantial conflicting findings from individual studies conducted in settings with potentially varying levels of maternal vitamin A deficiency and infant mortality, absence of follow-up studies assessing any long-term impact of a bulging fontanelle after supplementation and the finding of a potentially harmful effect among female infants, additional research is warranted before a decision can be reached regarding policy recommendations for this intervention.

Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD).

RATIONALE: Acute administration of serotonergic agonist, meta-chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in an animal model of obsessive-compulsive disorder (OCD). It is not known whether mCPP has a similar effect on development of compulsive checking. OBJECTIVES: The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model. METHODS: Four groups of male rats (N = 14/group) were tested: two experimental groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with quinpirole and saline, the other receiving injections of saline. The time course of development of compulsive checking across injections 1 to 10 in quinpirole-treated rats was compared to rats co-injected with quinpirole and mCPP. RESULTS: Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg) significantly attenuated performance of checking behavior. However, when these rats were retested for expression of compulsive checking (that is, with an injection of quinpirole only), their profile of compulsive checking was no different from the control rats treated throughout with quinpirole only. CONCLUSIONS: Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.