Maureen O'Leary

Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial

BACKGROUND Results of randomised controlled trials of newborn (age 1-3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana. METHODS This study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50,000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055. FINDINGS We assessed 26,414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22,955 newborn infants, with 11,474 randomly assigned to receive vitamin A and 11,481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22,698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95-1·33; p=0·183) and risk difference (RD) 2·66 (95% CI -1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94-1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88-2·62, p=0·130). INTERPRETATION The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana. FUNDING Bill & Melinda Gates Foundation grant to the WHO.

Efficacy of Early Neonatal Vitamin A Supplementation in Reducing Mortality During Infancy in Ghana, India and Tanzania: Study Protocol for a Randomized Controlled Trial

BackgroundVitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo.Methods/DesignThe trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrolment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation.DiscussionThe three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.Trial RegistrationGhana: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000582055; India: CLINICALTRIALS.GOV - NCT01138449; Tanzania: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055.

A continuous common-source outbreak of campylobacteriosis associated with changes to the preparation of chicken liver pâté

In December 2006 an outbreak of Campylobacter infection occurred in Forth Valley, Scotland, affecting 48 people over a 3-week period. All cases dined at restaurant A. We conducted a cohort study in a party of 30 who ate lunch at restaurant A on 21 December to identify the vehicle of infection. Of 29 respondents, the attack rate in those who ate chicken liver pâté was 86% (6/7) compared to 0% (0/22) for those who did not. Between 1 December and 1.30 p.m. on 21 December the restaurant had used a different method of cooking the pâté. No cases reported dining at the restaurant after this time. The outbreaks duration suggested a continuous source. This is the first continuous source outbreak of Campylobacter documented in Scotland. Chicken liver pâté was the most likely vehicle of infection. This outbreak illustrates the hazards associated with undercooking Campylobacter-contaminated food.

Socio-economic determinants and inequities in coverage and timeliness of early childhood immunisation in rural Ghana

To assess the extent of socio‐economic inequity in coverage and timeliness of key childhood immunisations in Ghana.

The path to longer and healthier lives for all Africans by 2030: the Lancet Commission on the future of health in sub-Saharan Africa.

Sub-Saharan Africa’s health challenges are numerous and wide-ranging. Most sub-Saharan African countries face a double burden of traditional, persisting health challenges, such as infectious diseases, malnutrition, and child and maternal mortality, and emerging challenges from an increasing prevalence of chronic conditions, mental health disorders, injuries, and health problems related to climate change and environmental degradation. Although there has been real progress on many health indicators, life expectancy and most population health indicators remain behind most low-income and middle-income countries in other parts of the world. Our Commission was prompted by sub-Saharan Africa’s potential to improve health on its own terms, and largely with its own resources. The spirit of this Commission is one of evidence-based optimism, with caution. We recognise that major health inequities exist and that health outcomes are worst in fragile countries, rural areas, urban slums, and conflict zones, and among the poor, disabled, and marginalised. Moreover, sub- Saharan Africa is facing the challenges and opportunities of the largest cohort of young people in history, with the youth population aged under 25 years predicted to almost double from 230 million to 450 million by 2050. The future of health in Africa is bright, but only if no one is left behind.

Vaccination timing of low-birth-weight infants in rural Ghana: a population-based prospective cohort study.

Abstract Objective To investigate delays in first and third dose diphtheria–tetanus–pertussis (DTP1 and DTP3) vaccination in low-birth-weight infants in Ghana, and the associated determinants. Methods We used data from a large, population-based vitamin A trial in 2010–2013, with 22 955 enrolled infants. We measured vaccination rate and maternal and infant characteristics and compared three categories of low-birth-weight infants (2.0–2.4 kg; 1.5–1.9 kg; and < 1.5 kg) with infants weighing ≥ 2.5 kg. Poisson regression was used to calculate vaccination rate ratios for DTP1 at 10, 14 and 18 weeks after birth, and for DTP3 at 18, 22 and 24 weeks (equivalent to 1, 2 and 3 months after the respective vaccination due dates of 6 and 14 weeks). Findings Compared with non-low-birth-weight infants (n = 18 979), those with low birth weight (n = 3382) had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio, aRR: 0.58; 95% confidence interval, CI: 0.43–0.77) and at age 18 weeks (aRR: 0.63; 95% CI: 0.50–0.80). Infants weighing 1.5–1.9 kg (n = 386) had vaccination rates approximately 25% lower than infants weighing ≥ 2.5 kg at these time points. Similar results were observed for DTP3. Lower maternal age, educational attainment and longer distance to the nearest health facility were associated with lower DTP1 and DTP3 vaccination rates. Conclusion Low-birth-weight infants are a high-risk group for delayed vaccination in Ghana. Efforts to improve the vaccination of these infants are warranted, alongside further research to understand the reasons for the delays.

A cohort study of low birth weight and health outcomes in the first year of life, Ghana.

Abstract Objective To investigate the effect of birth weight on infant mortality, illness and care seeking in rural Ghana. Methods Using randomized controlled trial data, we compared infants weighing 2.00–2.49, 1.50–1.99 and < 1.50 kg with non-low-birth-weight infants. We generated adjusted mortality hazard ratios (aHR), adjusted illness rate ratios (aRR) and adjusted odds ratios (aOR) for health-facility admissions and absence of care seeking for four time periods: infancy, the neonatal period, early infancy and late infancy – represented by ages of 0–364, 0–27, 28–182 and 183–364 days, respectively. Findings Among 22 906 infants, compared with non-low-birth-weight infants: (i) infants weighing 2.00–2.49, 1.50–1.99 and < 1.50 kg were about two (aHR: 2.13; 95% confidence interval, CI: 1.76–2.59), eight (aHR: 8.21; 95% CI: 6.26–10.76) and 25 (aHR: 25.38; 95% CI: 18.36–35.10) times more likely to die in infancy, respectively; (ii) those born weighing < 1.50 kg were about 48 (aHR: 48.45; 95% CI: 32.81–71.55) and eight (aHR: 8.42; 95% CI: 3.09–22.92) times more likely to die in the neonatal period and late infancy, respectively; (iii) those born weighing 1.50–1.99 kg (aRR: 1.57; 95% CI: 1.27–1.95) or < 1.50 kg (aRR: 1.58; 95% CI: 1.13–2.21) had higher neonatal illness rates; and (iv) for those born weighing 1.50–1.99 kg, care was less likely to be sought in the neonatal period (aOR: 3.30; 95% CI: 1.98–5.48) and early infancy (aOR : 1.74; 95% CI: 1.26–2.39). Conclusion For low-birth-weight infants in Ghana, strategies to minimize mortality and improve care seeking are needed.

Neonatal vaccination of low birthweight infants in Ghana

Objectives Global vaccination policy advocates for identifying and targeting groups who are underserved by vaccination to increase equity and uptake. We investigated whether birth weight and other factors are determinants of neonatal BCG vaccination in order to identify infants underserved by vaccination. Methods We used logistic regression to calculate adjusted ORs (AORs) for the association between birth weight (categorised as non-low birth weight (NLBW) (≥2.50 kg) and low birth weight (LBW) (2–2.49 kg, 1.50–1.99 kg and <1.50 kg)) and non-vaccination with BCG at the end of the neonatal period (0–27 days). We assessed whether this association varied by place of delivery and infant illness. We calculated how BCG timing and uptake would improve by ensuring the vaccination of all facility-born infants prior to discharge. Results There was a strong dose–response relationship between LBW and not receiving BCG in the neonatal period (p-trend<0.0001). Infants weighing 1.50–1.99 kg had odds of non-vaccination 1.6 times (AOR 1.64; 95% CI 1.30 to 2.08), and those weighing <1.50 kg 2.4 times (AOR 2.42; 95% CI 1.50 to 3.88) those of NLBW infants. Other determinants included place of delivery, distance to the health facility and socioeconomic status. Neither place of delivery nor infant illness modified the association between birth weight and vaccination (p-interaction all >0.19). Facility-born infants were vaccinated at a mean of 6 days, suggesting that they were not vaccinated in the facility at birth but were referred for vaccination. Conclusions LBW is a risk factor for neonatal under-vaccination, even for facility-born infants. Ensuring vaccination at facility births would substantively improve timing and equitable BCG vaccination.

Low birth weight as a risk factor for undervaccination in Ghana : evidence from a population-based cohort

In this thesis I analysed population-based data on 22955 infants enrolled in a neonatal vitamin A supplementation trial in rural Ghana to investigate whether low birth weight (LBW: born weighing <2.50kg) was a risk factor for under-vaccination. I also investigated whether under-vaccination among LBW infants was occurring within a broader context of poorer health outcomes such as increased mortality, illness and health facility admissions and lower care-seeking. I additionally investigated how using routine contacts with health services (opportunities for vaccination) could be used to improve their vaccination. Compared to non-LBW (NLBW) infants, LBW infants were less likely to be vaccinated in both the neonatal and postneonatal period. The smaller the baby at delivery the less likely they were to be vaccinated (p-trend <0.0001). By the end of the neonatal period, moderately LBW (MLBW) infants (1.50-1.99kg) were 1.6 times (adjusted odds ratio (aOR)=1.64; 95%CI:1.30-2.08), and very LBW (VLBW) infants (<1.50kg) were 2.4 times (aOR=2.42; 95%CI:1.50-3.88) more likely to be BCG unvaccinated. In the postneonatal period, VLBW infants had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio (aRR)=0.58; 95%CI:0.43-0.77) and 18 weeks (aRR=0.63; 95%CI:0.50- 0.80). MLBW infants had vaccination rates approximately 25% lower at these time points. Similar results were observed for DTP3. LBW infants had much higher mortality rates in infancy compared to NLBW infants. Infants weighing 2.00-2.50kg were >2 times (adjusted hazard ratio (aHR)=2.13; 95%CI:1.76-2.59); MLBW infants were >8 times (aHR=8.21; 95%CI:6.26-10.76), and VLBW infants were >25 times (aHR=25.38; 95%CI:18.36-35.10) more likely to die. The trend of higher mortality with lower birth weight was seen in each of the neonatal, early and late infant periods, but the magnitude of the association declined over time. There was also some evidence that LBW infants had increased illness rates in the neonatal period, and in each of the neonatal and early infant periods. An absence of care seeking was found for MLBW infants in the first year of life (aOR=1.46; 95%CI:1.18-1.81), and in each of the neonatal (aOR=3.30; 95%CI:1.98-5.48) and early infant periods (aOR=1.74; 95%CI:1.26-2.39) respectively. No association was found in the late infant period (p-interaction=0.0002). Among all infants (NLBW and LBW) with opportunities for vaccination, most opportunities were missed. There was no association between birth weight and uptake of opportunities. In conclusion LBW infants are under-served by vaccination in Ghana. Given their poorer health outcomes, efforts to improve their access to care services, including vaccination are warranted. Further research into the barriers and facilitators of vaccination of LBW infants is warranted, including qualitative research targeting care givers and vaccine providers.

The seroprevalence of hepatitis C virus infection among children and their mothers attending for dental care in Glasgow, Scotland, United Kingdom

This paper describes a voluntary anonymous survey to investigate the seroprevalence of Hepatitis C (HCV) in children in Glasgow, UK attending a Dental Hospital and the proportion of HCV positive mothers who have a child who is HCV seropositive. The study was undertaken among children and accompanying parents and household contacts attending a general anaesthetic assessment clinic at Glasgow Dental Hospital and School. Children were asked to provide an oral fluid specimen for HCV testing. Accompanying adults were asked to provide demographic data on the child and information on familial risk factors for HCV infection using a standardised questionnaire. Birth mothers were also asked to provide an oral fluid specimen. Specimens and questionnaires were linked by a unique anonymous study number. Between June 2009 and December 2011, samples were collected from 2141 children and 1698 mothers. None of the samples from the children were HCV seropositive but 16 (0.9%, 95% CI 0.6-1.5%) of the specimens from mothers were HCV antibody positive. In summary, the prevalence of HCV seropositivity in the birth mothers of the children was similar to that estimated in the general population served by the hospital and showed no evidence of mother-to-child transmission of HCV.