Immediate skin-to-skin contact for low birth weight infants is safe in terms of cardiorespiratory stability in limited-resource settings.

Aim: To investigate the safety of skin-to-skin contact initiated immediately after birth on cardiorespiratory parameters in unstable low birth weight infants. Methods: A randomized clinical trial was conducted in tertiary newborn units in Ghana, India, Malawi, Nigeria and Tanzania in 2017-2020, in infants with birth weight 1.0-1.799 kg. The intervention was Kangaroo mother care initiated immediately after birth and continued until discharge compared to conventional care with Kangaroo mother care initiated after meeting stability criteria. The results of the primary study showed that immediate Kangaroo mother care reduced neonatal mortality by 25% and the results have been published previously. The post-hoc outcomes of this study were mean heart rate, respiratory rate, oxygen saturation during the first four days and the need of respiratory support. Results: 1,602 infants were allocated to control and 1,609 to intervention. Mean birth weight was 1.5 kg (SD 0.2) and mean gestational age was 32.6 weeks (SD 2.9). Infants in the control group had a mean heart rate 1.4 beats per minute higher (95% CI -0.3-3.1, p = 0.097), a mean respiratory rate 0.4 breaths per minute higher (-0.7-1.5, p = 0.48) and a mean oxygen saturation 0.3% higher (95% CI -0.1-0.7, p = 0.14) than infants in the intervention group. Conclusion: There were no significant differences in cardiorespiratory parameters during the first four postnatal days. Skin-to-skin contact starting immediately after birth is safe in low birth weight infants in limited-resource settings.

Limited resources restrict the provision of adequate neonatal respiratory care in the countries of Africa.

AIM: Over two thirds of newborn deaths occur in Africa and South Asia, and respiratory failure is a major contributor of these deaths. The exact availability of continuous positive airway pressure (CPAP) and surfactant in Africa is unknown. The aim of this study was to describe the availability of newborn respiratory care treatments in the countries of Africa. METHODS: Surveys, in English, French and Portuguese, were sent to neonatal leaders in all 48 continental countries and the two islands with populations over 1 million. RESULTS: Forty-nine (98%) countries responded. Twenty-one countries reported less than 50 paediatricians, and 12 countries had no neonatologists. Speciality neonatal nursing was recognised in 57% of countries. Most units were able to provide supplemental oxygen. CPAP was available in 63% and 67% of the most well-equipped government and private hospitals. Surfactant was available in 33% and 39% of the most well-equipped public and private hospitals, respectively. Availability of CPAP and surfactant was greatly reduced in smaller cities. Continuous oxygen saturation monitoring was only available in 33% of countries. CONCLUSION: The availability of proven life-saving interventions in Africa is inadequate. There is a need to sustainably improve availability and use of these interventions.

Immediate "Kangaroo Mother Care" and Survival of Infants with Low Birth Weight.

BACKGROUND: "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (<2.0 kg) when initiated after stabilization, but the majority of deaths occur before stabilization. The safety and efficacy of kangaroo mother care initiated soon after birth among infants with low birth weight are uncertain. METHODS: We conducted a randomized, controlled trial in five hospitals in Ghana, India, Malawi, Nigeria, and Tanzania involving infants with a birth weight between 1.0 and 1.799 kg who were assigned to receive immediate kangaroo mother care (intervention) or conventional care in an incubator or a radiant warmer until their condition stabilized and kangaroo mother care thereafter (control). The primary outcomes were death in the neonatal period (the first 28 days of life) and in the first 72 hours of life. RESULTS: A total of 3211 infants and their mothers were randomly assigned to the intervention group (1609 infants with their mothers) or the control group (1602 infants with their mothers). The median daily duration of skin-to-skin contact in the neonatal intensive care unit was 16.9 hours (interquartile range, 13.0 to 19.7) in the intervention group and 1.5 hours (interquartile range, 0.3 to 3.3) in the control group. Neonatal death occurred in the first 28 days in 191 infants in the intervention group (12.0%) and in 249 infants in the control group (15.7%) (relative risk of death, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P = 0.001); neonatal death in the first 72 hours of life occurred in 74 infants in the intervention group (4.6%) and in 92 infants in the control group (5.8%) (relative risk of death, 0.77; 95% CI, 0.58 to 1.04; P = 0.09). The trial was stopped early on the recommendation of the data and safety monitoring board owing to the finding of reduced mortality among infants receiving immediate kangaroo mother care. CONCLUSIONS: Among infants with a birth weight between 1.0 and 1.799 kg, those who received immediate kangaroo mother care had lower mortality at 28 days than those who received conventional care with kangaroo mother care initiated after stabilization; the between-group difference favoring immediate kangaroo mother care at 72 hours was not significant. (Funded by the Bill and Melinda Gates Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12618001880235; Clinical Trials Registry-India number, CTRI/2018/08/015369.).

T cell responses to the RTS,S/AS01(E) and RTS,S/AS02(D) malaria candidate vaccines administered according to different schedules to Ghanaian children.

BACKGROUND: The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01(E) or the oil-in-water based adjuvant AS02(D) induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults. METHODS: This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01(E) and RTS,S/AS02(D) in children aged 5-17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites. RESULTS: Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01(E) induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01(E) induced higher CD4 T cell responses as compared to RTS,S/AS02(D) when given on a 0,1,7-month schedule. CONCLUSIONS: These findings support further Phase III evaluation of RTS,S/AS01(E). The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360230.

Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children.

BACKGROUND: The target delivery channel of RTS,S candidate malaria vaccines in malaria-endemic countries in Africa is the World Health Organisation Expanded Program on Immunization. As an Adjuvant System, age de-escalation and schedule selection step, this study assessed 3 schedules of RTS,S/AS01(E) and RTS,S/AS02(D) in infants and young children 5-17 months of age in Ghana. METHODOLOGY: A Phase II, partially-blind randomized controlled study (blind to vaccine, not to schedule), of 19 months duration was conducted in two (2) centres in Ghana between August 2006 and May 2008. Subjects were allocated randomly (1:1:1:1:1:1) to one of six study groups at each study site, each defining which vaccine should be given and by which schedule (0,1-, 0,1,2- or 0,1,7-months). For the 0,1,2-month schedule participants received RTS,S/AS01(E) or rabies vaccine at one center and RTS,S/AS01(E) or RTS,S/AS02(D) at the other. For the other schedules at both study sites, they received RTS,S/AS01(E) or RTS,S/AS02(D). The primary outcome measure was the occurrence of serious adverse events until 10 months post dose 1. RESULTS: The number of serious adverse events reported across groups was balanced. One child had a simple febrile convulsion, which evolved favourably without sequelae, considered to be related to RTS,S/AS01(E) vaccination. Low grade reactions occurred slightly more frequently in recipients of RTS,S/AS than rabies vaccines; grade 3 reactions were infrequent. Less local reactogenicity occurred with RTS,S/AS01(E) than RTS,S/AS02(D). Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01(E) compared to RTS,S/AS02(D) had higher peak anti-circumsporozoite antibody responses for all 3 schedules. Three dose schedules were more immunogenic than 2 dose schedules. Area under the curve analyses for anti-circumsporozoite antibodies were comparable between the 0,1,2- and 0,1,7-month RTS,S/AS01(E) schedules. CONCLUSIONS: Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01(E) than RTS,S/AS02(D) and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01(E) and a 3 dose schedule for further development in children and infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360230.