The γ-Protocadherins Regulate the Survival of GABAergic Interneurons during Developmental Cell Death.

Inhibitory interneurons integrate into developing circuits in specific ratios and distributions. In the neocortex, inhibitory network formation occurs concurrently with the apoptotic elimination of a third of GABAergic interneurons. The cell surface molecules that select interneurons to survive or die are unknown. Here, we report that members of the clustered Protocadherins (cPCDHs) control GABAergic interneuron survival during developmentally-regulated cell death. Conditional deletion of the gene cluster encoding the γ-Protocadherins (Pcdhgs) from developing GABAergic neurons in mice of either sex causes a severe loss of inhibitory populations in multiple brain regions and results in neurologic deficits such as seizures. By focusing on the neocortex and the cerebellar cortex, we demonstrate that reductions of inhibitory interneurons result from elevated apoptosis during the critical postnatal period of programmed cell death (PCD). By contrast, cortical interneuron (cIN) populations are not affected by removal of Pcdhgs from pyramidal neurons or glial cells. Interneuron loss correlates with reduced AKT signaling in Pcdhg mutant interneurons, and is rescued by genetic blockade of the pro-apoptotic factor BAX. Together, these findings identify the PCDHGs as pro-survival transmembrane proteins that select inhibitory interneurons for survival and modulate the extent of PCD. We propose that the PCDHGs contribute to the formation of balanced inhibitory networks by controlling the size of GABAergic interneuron populations in the developing brain.SIGNIFICANCE STATEMENT A pivotal step for establishing appropriate excitatory-inhibitory ratios is adjustment of neuronal populations by cell death. In the mouse neocortex, a third of GABAergic interneurons are eliminated by BAX-dependent apoptosis during the first postnatal week. Interneuron cell death is modulated by neural activity and pro-survival pathways but the cell-surface molecules that select interneurons for survival or death are unknown. We demonstrate that members of the cadherin superfamily, the clustered γ-Protocadherins (PCDHGs), regulate the survival of inhibitory interneurons and the balance of cell death. Deletion of the Pcdhgs in mice causes inhibitory interneuron loss in the cortex and cerebellum, and leads to motor deficits and seizures. Our findings provide a molecular basis for controlling inhibitory interneuron population size during circuit formation.

Impact of universal home visits on child health in Bauchi State, Nigeria: a stepped wedge cluster randomised controlled trial.

BACKGROUND: Nigeria is the second biggest contributor to global child mortality. Infectious diseases continue to be major killers. In Bauchi State, Nigeria, a stepped wedge cluster randomised controlled trial tested the health impacts of universal home visits to pregnant women and their spouses. We present here the findings related to early child health. METHODS: The home visits took place in eight wards in Toro Local Government Authority, randomly allocated into four waves with a delay of 1 year between waves. Female and male home visitors visited all pregnant women and their spouses every 2 months during pregnancy, with a follow up visit 12-18 months after the birth. They presented and discussed evidence about household prevention and management of diarrhoea and immunisation. We compared outcomes among children 12-18 months old born to mothers visited during the first year of intervention in each wave (intervention group) with those among children 12-18 months old pre-intervention in subsequent waves (control group). Primary outcomes included prevalence and management of childhood diarrhoea and immunisation status, with intermediate outcomes of household knowledge and actions. Generalised Estimating Equations (GEE), with an exchangeable correlation matrix and ward as cluster, tested the significance of differences in outcomes. RESULTS: The analysis included 1796 intervention and 5109 control children. In GEE models including other characteristics of the children, intervention children were less likely to have suffered diarrhoea in the last 15 days (Odds Ratio (OR) 0.40, 95% confidence interval (CI) 0.30-0.53) and more likely to have received increased fluids and continued feeding in their last episode of diarrhoea (OR 6.06, 95% CI 2.58-14.20). Mothers of intervention children were more likely to identify lack of hygiene as a cause of diarrhoea (OR 2.24, 95% CI 1.27-3.95) and their households had better observed hygiene (OR 3.29, 95% CI 1.45-7.45). Intervention children were only slightly more likely to be fully immunised (OR 1.67, 95% CI 0.78-3.57). CONCLUSIONS: Evidence-based home visits to both parents stimulated household actions that improved prevention and management of childhood diarrhoea. Such visits could help to improve child health even in settings with poor access to quality health services. TRIAL REGISTRATION: ISRCTN82954580 . Date: 11/08/2017. Retrospectively registered.

Added value of video edutainment on android handsets in home visits to improve maternal and child health in Bauchi State, Nigeria: Secondary analysis from a cluster randomised controlled trial.

Objective: A trial of evidence-based health promotion home visits to pregnant women and their spouses in northern Nigeria found significant improvements in maternal and child health outcomes. This study tested the added value for these outcomes of including video edutainment in the visits. Methods: In total, 19,718 households in three randomly allocated intervention wards (administrative areas) received home visits including short videos on android handsets to spark discussion about local risk factors for maternal and child health; 16,751 households in three control wards received visits with only verbal discussion about risk factors. We compared outcomes between wards with and without videos in the visits, calculating the odds ratio (OR) and 95% confidence interval (95%CI) of differences, in bivariate and then multivariate analysis adjusting for socio-economic differences between the video and non-video wards. Results: Pregnant women from video wards were more likely than those from non-video wards to have discussed pregnancy and childbirth often with their husbands (OR 2.22, 95%CI 1.07-4.59). Male spouses in video wards were more likely to know to give more fluids and continued feeding to a child with diarrhoea (OR 1.61, 95%CI 1.21-2.13). For most outcomes there was no significant difference between video and non-video wards. The home visitors who shared videos considered they helped pregnant women and their spouses to appreciate the information about risk factors. Conclusion: The lack of added value of the videos in the context of a research study may reflect the intensive training of home visitors and the effective evidence-based discussions included in all the visits. Further research could rollout routine home visits with and without videos and test the impact of video edutainment added to home visits carried out in a routine service context.

The Equity Impact of Universal Home Visits to Pregnant Women and Their Spouses in Bauchi State, Nigeria: Secondary Analysis From a Cluster Randomised Controlled Trial.

BACKGROUND: Socio-economically disadvantaged women have poor maternal health outcomes. Maternal health interventions often fail to reach those who need them most and may exacerbate inequalities. In Bauchi State, Nigeria, a recent cluster randomised controlled trial (CRCT) showed an impressive impact on maternal health outcomes of universal home visits to pregnant women and their spouses. The home visitors shared evidence about local risk factors actionable by households themselves and the program included specific efforts to ensure all households in the intervention areas received visits. PURPOSE: To examine equity of the intervention implementation and its pro-equity impact. RESEARCH DESIGN AND STUDY SAMPLE: The overall study was a CRCT in a stepped wedge design, examining outcomes among 15,912 pregnant women. ANALYSIS: We examined coverage of the home visits (three or more visits) and their impact on maternal health outcomes according to equity factors at community, household, and individual levels. RESULTS: Disadvantaged pregnant women (living in rural communities, from the poorest households, and without education) were as likely as those less disadvantaged to receive three or more visits. Improvements in maternal knowledge of danger signs and spousal communication, and reductions in heavy work, pregnancy complications, and post-natal sepsis were significantly greater among disadvantaged women according to the same equity factors. CONCLUSIONS: The universal home visits had equitable coverage, reaching all pregnant women, including those who do not access facility-based services, and had an important pro-equity impact on maternal health.

Universal home visits improve male knowledge and attitudes about maternal and child health in Bauchi State, Nigeria: Secondary outcome analysis of a stepped wedge cluster randomised controlled trial.

BACKGROUND: The World Health Organization recommends increased male involvement to improve maternal and newborn health in low- and middle-income countries, but few studies have measured the impact of male-engagement interventions on targeted men. A trial of universal home visits to pregnant women and their spouses in Nigeria improved maternal and child health outcomes. This analysis examines the impact of the visits on male spouses. METHODS: In Toro Local Government Area in Bauchi State, Nigeria, we randomly allocated eight wards into four waves, beginning the intervention at one-year intervals. The intervention comprised two-monthly evidence-based home visits to discuss local risk factors for maternal and child health with all pregnant women and their male spouses. Measured secondary outcomes of the intervention in the men included knowledge about danger signs in pregnancy and childbirth, beliefs about heavy work in pregnancy, discussion with their wives about pregnancy and childbirth, knowledge about causes and intentions about management of childhood diarrhoea, and views about childhood immunisation. The analysis compared outcomes between men in visited wards (intervention group) and pre-intervention wards (control group), using a cluster t test. Generalised linear mixed modelling accounted for the effect of socio-economic differences on the measured impact. RESULTS: The analysis included 6931 men in the intervention group and 9434 in the control group. More men in the intervention group knew four or more danger signs in pregnancy (risk difference (RD) = 0.186, 95% confidence interval (CI) = 0.044 to 0.327), and three danger signs in childbirth (RD = 0.091, 95%CI = 0.013 to 0.170), thought pregnant women should reduce heavy work before the third trimester (RD = 0.088, 95% CI = 0.015 to 0.162), and had discussed pregnancy and childbirth with their spouse (RD = 0.157, 95% CI = 0.026 to 0.288). More knew correct management of childhood diarrhoea with fluids and feeding (RD = 0.300, 95% CI = 0.203 to 0.397) and less would give a child medicine to stop diarrhoea (RD = 0.206, 95% CI = 0.125 to 0.287). Socio-economic differences did not explain the effect of the intervention on any of the outcomes. CONCLUSION: Universal home visits improved knowledge of male spouses about maternal and child health, which could contribute to improved maternal and child outcomes. TRIAL REGISTRATION: ISRCTN, ISRCTN82954580. 11 August 2017. Retrospectively registered. http://www.isrctn.com/ISRCTN82954580.

Participatory health research under COVID-19 restrictions in Bauchi State, Nigeria: Feasibility of cellular teleconferencing for virtual discussions with community groups in a low-resource setting.

INTRODUCTION: During the COVID-19 pandemic, researchers have used Internet-based applications to conduct virtual group meetings, but this is not feasible in low-resource settings. In a community health research project in Bauchi State, Nigeria, COVID-19 restrictions precluded planned face-to-face meetings with community groups. We tested the feasibility of using cellular teleconferencing for these meetings. METHODS: In an initial exercise, we used cellular teleconferencing to conduct six male and six female community focus group discussions. Informed by this experience, we conducted cellular teleconferences with 10 male and 10 female groups of community leaders, in different communities, to discuss progress with previously formulated action plans. Ahead of each teleconference call, a call coordinator contacted individual participants to seek consent and confirm availability. The coordinator connected the facilitator, the reporter, and the participants on each conference call, and audio-recorded the call. Each call lasted less than 1 h. Field notes and debriefing meetings with field teams supported the assessment of feasibility of the teleconference meetings. RESULTS: Cellular teleconferencing was feasible and inexpensive. Using multiple handsets at the base allowed more participants in a call. Guidelines for facilitators and participants developed after the initial meetings were helpful, as were reminder calls ahead of the meeting. Connecting women participants was challenging. Facilitators needed extra practice to support group interactions without eye contact and body language signals. CONCLUSIONS: With careful preparation and training, cellular teleconferencing can be a feasible and inexpensive method of conducting group discussions in a low-resource setting.

The impact of universal home visits with pregnant women and their spouses on maternal outcomes: a cluster randomised controlled trial in Bauchi State, Nigeria.

INTRODUCTION: Maternal mortality in Nigeria is extremely high. Access to quality antenatal and obstetric care is limited. In Bauchi State, we found maternal morbidity was associated with domestic violence, heavy work in pregnancy, ignorance of danger signs, and lack of spousal communication. This cluster randomized controlled trial tested the impact of universal home visits that discussed these upstream risk factors with pregnant women and their spouses, to precipitate household actions protecting pregnant women. METHODS: We randomly allocated four wards in Toro Local Government Authority to immediate or delayed intervention. Female and male home visitors visited all pregnant women and their spouses in the two intervention wards every 2 months. We compared completed pregnancies between intervention and pre-intervention wards after 1 year. Primary outcomes were pregnancy, delivery, and postnatal complications, analysed with intention to treat using a cluster t-test. Ancillary analysis examined the influence of baseline and health service use differences. RESULTS: Among 1837 women in intervention wards and 1853 women in pre-intervention wards, the intervention reduced problems in pregnancy and post partum: raised blood pressure (relative risk reduction (RRR) 0.120, cluster-adjusted 95% CI (CIca) 0.045 to 0.194; risk difference (RD) 0.116, 95% CIca 0.042 to 0.190) and swelling of face or hands (RRR 0.271, 95% CIca 0.201 to 0.340; RD 0.264, 95% CIca 0.194 to 0.333) and postpartum sepsis (RRR 0.399, 95% CIca 0.220 to 0.577; RD 0.324, 95% CIca 0.155 to 0.493). The intervention reduced the targeted upstream risk factors such as heavy work during pregnancy (RRR 0.234, 95% CIca 0.085 to 0.383; RD 0.222, 95% CIca 0.073 to 0.370). It did not increase use of antenatal care, institutional delivery or skilled birth attendance. CONCLUSION: Home visits reduced upstream maternal risks, improving maternal outcomes without increased use of health services. This could have implications in other settings with poor access to quality antenatal and delivery care services. TRIAL REGISTRATION: ISRCTN82954580.