James Ndirangu

National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010

Summary Background National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Methods Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. Findings In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh. Interpretation The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. Funding Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG).

Cohort Profile: Hlabisa HIV Treatment and Care Programme

This article evaluates the Hlabisa HIV treatment and Care Programme in South Africa. The goal of this program is to promote prevention practices as part of HIV services with the ultimate goal of curbing the HIV epidemic. A cohort study monitored the success of this integrated system and the impact on the communities. It includes a tracking system treatment checkpoints and children evaluations. The study concluded that this program is properly placed in a location where the population needs a variety of services and a complex approach to treatment. However more research is needed to determine whether maternal health ART treatment and TB are impacted by this program.

Decline in early life mortality in a high HIV prevalence rural area of South Africa: evidence of HIV prevention or treatment impact?

Objective:We present early life mortality rates in a largely rural population with high antenatal HIV prevalence, and investigate temporal and spatial associations with a prevention of mother-to-child transmission (PMTCT) programme, an HIV treatment programme, and maternal HIV. Design:A retrospective cohort analysis. Methods:All births from January 2000 to January 2007 to women in the Africa Centre demographic surveillance were included. Under-two child mortality rates (U2MR) computed as deaths per 1000 live-births per year; factors associated with mortality risk assessed with Weibull regression. Availability of PMTCT (single-dose nevirapine; sdNVP) and antiretroviral therapy (ART) in a programme included in multivariable analysis. Results:Eight hundred and forty-eight (6.2%) of 13 583 children under 2 years died. Deaths in under twos declined by 49% between 2001 and 2006, from 86.3 to 44.1 deaths per thousand live-births. Mortality was independently associated with birth season (adjusted hazard ratio 1.16, 95% confidence interval 1.02–1.33), maternal education (1.21, 1.02–1.43), maternal HIV (4.34, 3.11–6.04) and ART availability (0.46, 0.33–0.65). Children born at home (unlikely to have received sdNVP) had a 35% higher risk of dying than children born in a facility where sdNVP was available (1.35, 1.04–1.74). For 2005 births the availability of PMTCT and ART in public health programmes would have explained 8 and 31% of the decline in U2MR since 2000. Conclusion:These findings confirm the importance of maternal survival, and highlight the importance of the PMTCT and especially maternal HIV treatment with direct benefits of improved survival of their young children.

Levels of childhood vaccination coverage and the impact of maternal HIV status on child vaccination status in rural KwaZulu-Natal South Africa*.

Objectives  To analyse coverage of childhood vaccinations in a rural South African population and investigate whether maternal HIV status is associated with children’s vaccination status.

Maternal HIV infection associated with small-for-gestational age infants but not preterm births: evidence from rural South Africa

BACKGROUND Human immunodeficiency virus (HIV) is prevalent in many countries where small-for-gestational age (SGA) and premature delivery are also common. However, the associations between maternal HIV, preterm delivery and SGA infants remain unclear. We estimate the prevalence of SGA and preterm (<37 weeks) births, their associations with antenatal maternal HIV infection and their contribution to infant mortality, in a high HIV prevalent, rural area in South Africa. METHODS Data were collected, in a non-randomized intervention cohort study, on all women attending antenatal clinics (2001–2004), before the availability of antiretroviral treatment. Newborns were weighed and gestational age was determined (based on last menstrual period plus midwife assessment antenatally). Poisson regression with robust variance assessed risk factors for preterm and SGA birth, while Cox regression assessed infant mortality and associated factors. RESULTS Of 2368 live born singletons, 16.6% were SGA and 21.4% were preterm. HIV-infected women (n= 1189) more commonly had SGA infants than uninfected women (18.1 versus 15.1%; P = 0.051), but percentages preterm were similar (21.8 versus 20.9%; P = 0.621). After adjustment for water source, delivery place, parity and maternal height, the SGA risk in HIV-infected women was higher [adjusted relative risk (aRR) 1.28, 95% confidence interval (CI): 1.06–1.53], but the association between maternal HIV infection and preterm delivery remained weak and not significant (aRR: 1.07, 95% CI: 0.91–1.26). In multivariable analyses, mortality under 1 year of age was significantly higher in SGA and severely SGA than in appropriate-for-gestational-age infants [adjusted hazard ratio (aHR): 2.12, 95% CI: 1.18–3.81 and 2.77, 95% CI: 1.56–4.91], but no difference in infant mortality was observed between the preterm and term infants (aHR: 1.18 95% CI: 0.79–1.79 for 34–36 weeks and 1.31, 95% CI: 0.58–2.94 for <34 weeks). CONCLUSIONS Maternal HIV infection increases the risk of SGA, but not preterm births, in this cohort.

Exclusive Breastfeeding, Diarrhoeal Morbidity and All-Cause Mortality in Infants of HIV-Infected and HIV Uninfected Mothers: An Intervention Cohort Study in KwaZulu Natal, South Africa

Introduction Antiretroviral drug interventions significantly reduce the risk of HIV transmission to infants through breastfeeding. We report diarrhoea prevalence and all-cause mortality at 12 months of age according to infant feeding practices, among infants born to HIV-infected and uninfected mothers in South Africa. Methods A non-randomised intervention cohort study that followed both HIV-infected and HIV-uninfected mothers and their infants until 18 months of age. Mothers were supported in their infant feeding choice. Detailed morbidity and vital status data were collected over the first year. At the time, only single dose nevirapine was available to prevent mother-to-child transmission of HIV. Results Among 2,589 infants, detailed feeding data and vital status were available for 1,082 HIV-exposed infants and 1,155 HIV non-exposed infants. Among exclusively breastfed (EBF) infants there were 9.4 diarrhoeal days per 1,000 child days (95%CI. 9.12-9.82) while among infants who were never breastfed there were 15.6 diarrhoeal days per 1,000 child days (95%CI. 14.62-16.59). Exclusive breastfeeding was associated with fewer acute, persistent and total diarrhoeal events than mixed or no breastfeeding in both HIV-exposed infants and also infants of HIV uninfected mothers. In an adjusted cox regression analysis, the risk of death among all infants by 12 months of age was significantly greater in those who were never breastfed (aHR 3.5, p<0.001) or mixed fed (aHR 2.65, p<0.001) compared with those who were EBF. In separate multivariable analyses, infants who were EBF for shorter durations had an increased risk of death compared to those EBF for 5-6 months [aHR 2.18 (95% CI, 1.56-3.01); p<0.001]. Discussion In the context of antiretroviral drugs being scaled-up to eliminate new HIV infections among children, there is strong justification for financial and human resource investment to promote and support exclusive breastfeeding to improve HIV-free survival of HIV-exposed and non-exposed infants.

Treating HIV-infected mothers reduces under 5 years of age mortality rates to levels seen in children of HIV-uninfected mothers in rural South Africa.

BACKGROUND Maternal and child survival are highly correlated, but the contribution of HIV infection on this relationship, and in particular the effect of HIV treatment, has not been quantified. We estimate the association between maternal HIV and treatment, and under 5 years of age (under-5) child mortality in a rural population in South Africa. METHODS All children born between January 2000 and January 2007 in the Africa Centre Demographic Surveillance Area were included. Maternal HIV status information was available from HIV surveillance; maternal antiretroviral treatment (ART) information from the HIV Treatment Programme database was linked to surveillance data. Mortality rates were computed as deaths per 1,000 person-years observed. Time-varying maternal HIV effect (positive, negative, ART) on under-5 mortality was assessed in Cox regression, adjusting for other factors associated with under-5 mortality. RESULTS In total, 9,068 mothers delivered 12,052 children, of whom 947 (7.9%) died before age 5. Infant mortality rate declined by 49% from 69.0 in 2000 to 35.5 in 2006 deaths per 1,000 person-years observed; a significant decline was observed post-ART (2004-2006). The estimated proportion of deaths across all age groups were higher among the children born to the HIV-positive and HIV-not-reported status women than among children of HIV-negative women. Multivariably, mortality in children of mothers on ART was not significantly different from children of HIV-negative mothers (adjusted hazard ratio 1.29, 0.53-3.17; P=0.572). CONCLUSIONS These findings highlight the importance of maternal HIV treatment with direct benefits of improved survival among all children under-5. Timely HIV treatment for eligible women is required to benefit both mothers and children.

Cell-Free (RNA) and Cell-Associated (DNA) HIV-1 and Postnatal Transmission through Breastfeeding

Introduction Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum. Materials and Methods Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission. Results There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively]. Conclusions The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.

Variability of Growth in Children Starting Antiretroviral Treatment in Southern Africa

BACKGROUND: Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa. METHODS: Treatment naïve children aged <10 years were included. We calculated weight for age z scores (WAZs), height for age z scores (HAZs), and weight for height z scores (WHZs) up to 3 years after starting ART, by using the World Health Organization standards. Multilevel regression models were used. RESULTS: A total of 17 990 children (range, 238–8975) were followed for 36 181 person-years. At ART initiation, most children were underweight (50%) and stunted (66%). Lower baseline WAZ, HAZ, and WHZ were the most important determinants of faster catch-up growth on ART. WAZ and WHZ increased rapidly in the first year and stagnated or reversed thereafter, whereas HAZ increased continuously over time. Three years after starting ART, WAZ ranged from −2.80 (95% confidence interval [CI]: −3.66 to −2.02) to −1.98 (95% CI: −2.41 to −1.48) in children with a baseline z score < −3 and from −0.79 (95% CI: −1.62 to 0.02) to 0.05 (95% CI: −0.42 to 0.51) in children with a baseline WAZ ≥ −1. For HAZ, the corresponding range was −2.33 (95% CI: −2.62 to −2.02) to −1.27 (95% CI: −1.58 to −1.00) for baseline HAZ < −3 and −0.24 (95% CI: −0.56 to 0.15) to 0.84 (95% CI: 0.53 to 1.16) for HAZ ≥ −1. CONCLUSIONS: Despite a sustained growth response and catch-up growth in children with advanced HIV disease treated with ART, normal weights and heights are not achieved over 3 years of ART.

Use of mid-upper arm circumference for determining overweight and overfatness in children and adolescents

Objective To assess the use of mid-upper arm circumference (MUAC) for identification of overweight and overfatness in rural South African children and adolescents. Methods Anthropometric data (weight, height, MUAC and % body fat) from a cross-sectional sample of 978 black South African 5–14-year-olds were analysed. Receiver operating characteristic (ROC) curve analysis determined the validity of MUAC as a proxy for determining overweight and overfatness. Findings Area under the curve (AUC) results were generally high. Boys and girls aged 10–14 years had ROC-AUC for overfatness classed as ‘excellent’, 0.97 and 0.98 respectively. Cut-points in the MUAC distribution which optimised the ROC-AUC for identification of overfatness and obesity were determined for boys and girls aged 5–9 and 10–14 years, and had high sensitivity and specificity. Conclusions MUAC may have potential for clinical and surveillance applications as an accurate yet simple and widely available indicator of overweight and overfatness in children and adolescents in resource-poor settings.