Background HIV infection is known to cause developmental delay, but the effects of HIV exposure without infection during pregnancy on child development are unclear. We compared the neurodevelopmental outcomes of HIV-exposed uninfected and HIV-unexposed children during their first 2 years of life. Methods Pregnant women (>18 years of age) at 20-28 weeks' gestation were enrolled into the Drakenstein Child Health cohort study while attending routine antenatal appointments at one of two peri-urban community-based clinics in Paarl, South Africa. Livebirths born to enrolled women during follow-up were included in the birth cohort. Mothers and infants received antenatal and postnatal HIV testing and antiretroviral therapy per local guidelines. Developmental assessments on the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), were done in a subgroup of infants at 6 months of age, and in the full cohort at 24 months of age, with assessors masked to HIV exposure status. Mean raw scores and the proportions of children categorised as having a delay (scores <-2 SDs from the reference mean) on BSID-III were compared between HIV-exposed uninfected and HIV-unexposed children. Findings 1225 women were enrolled between March 5, 2012, and March 31, 2015. Of 1143 livebirths, 1065 (93%) children were in follow-up at 6 months and 1000 (87%) at 24 months. Two children were diagnosed with HIV infection between birth and 24-month follow-up and were excluded from the analysis. BSID-III assessments were done in 260 (24%) randomly selected children (61 HIV-exposed uninfected, 199 HIV-unexposed) at 6 months and in 732 (73%) children (168 HIV-exposed uninfected, 564 HIV-unexposed) at 24 months. All HIV-exposed uninfected children were exposed to antiretrovirals (88% to maternal triple antiretroviral therapy). BSID-III outcomes did not significantly differ between HIV-exposed uninfected and HIV-unexposed children at 6 months. At 24 months, HIV-exposed uninfected children scored lower than HIV-unexposed for receptive language (adjusted mean difference-1•03 [95% CI-1•69 to-0•37]) and expressive language (-1•17 [-2•09 to-0•24]), whereas adjusted differences in cognitive (-0•45 [-1•32 to 0•43]), fine motor (0•09 [-0•49 to 0•66]), and gross motor (-0•41 [-1•09 to 0•27]) domain scores between groups were not significant. Correspondingly, the proportions of HIV-exposed uninfected children with developmental delay were higher than those of HIV-unexposed children for receptive language (adjusted odds ratio 1•96 [95% CI 1•09 to 3•52]) and expressive language (2•14 [1•11 to 4•15]). Interpretation Uninfected children exposed to maternal HIV infection and antiretroviral therapy have increased odds of receptive and expressive language delays at 2 years of age. Further long-term work is needed to understand developmental outcomes of HIV-exposed uninfected children, especially in regions such as sub-Saharan Africa that have a high prevalence of HIV exposure among children.

BackgroundApproximately 250 million (43%) children under the age of 5 years in low- and middle-income countries (LMICs) are failing to meet their developmental potential. Risk factors are recognised to contribute to this loss of human potential. Expanding understanding of the risks that lead to poor outcomes and which protective factors contribute to resilience in children may be critical to improving disparities.Methods and findingsThe Drakenstein Child Health Study is a population-based birth cohort in the Western Cape, South Africa. Pregnant women were enrolled between 20 and 28 weeks’ gestation from two community clinics from 2012 to 2015; sociodemographic and psychosocial data were collected antenatally. Mothers and children were followed through birth until 2 years of age. Developmental assessments were conducted by trained assessors blinded to background, using the Bayley-III Scales of Infant and Toddler Development (BSID-III), validated for use in South Africa, at 24 months of age. The study assessed all available children at 24 months; however, some children were not able to attend, because of loss to follow-up or unavailability of a caregiver or child at the correct age. Of 1,143 live births, 1,002 were in follow-up at 24 months, and a total of 734 children (73%) had developmental assessments, of which 354 (48.2%) were girls. This sample was characterised by low household employment (n = 183; 24.9%) and household income (n = 287; 39.1% earning 1 domain affected, and 75 (10.2%) had delay in all domains. Bivariate and multivariable analyses revealed several factors that were associated with developmental outcomes. These included protective factors (maternal education, higher birth weight, and socioeconomic status) and risk factors (maternal anaemia in pregnancy, depression or lifetime intimate partner violence, and maternal HIV infection). Boys consistently performed worse than girls (in cognition [β = −0.74; 95% CI −1.46 to −0.03, p = 0.042], receptive language [β = −1.10; 95% CI −1.70 to −0.49, p < 0.001], expressive language [β = −1.65; 95% CI −2.46 to −0.84, p < 0.001], and fine motor [β = −0.70; 95% CI −1.20 to −0.20, p = 0.006] scales). There was evidence that child sex interacted with risk and protective factors including birth weight, maternal anaemia in pregnancy, and socioeconomic factors. Important limitation...

Ultrasound (US) has been proposed as an alternative first-line imaging modality to diagnose community-acquired pneumonia in children. Lung US has the potential benefits over chest radiography of being radiation free, subject to fewer regulatory requirements, relatively lower cost and with immediate bedside availability of results. However, the uptake of lung US into clinical practice has been slow and it is not yet included in clinical guidelines for community-acquired pneumonia in children. The aim of this review is to give an overview of the equipment and techniques used to perform lung US in children with suspected pneumonia and the interpretation of relevant sonographic findings. We also summarise the current evidence of diagnostic accuracy and reliability of lung US compared to alternative imaging modalities in children and critically consider the strengths and limitations of lung US for use in children presenting with suspected community-acquired pneumonia.

Summary Background Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in children. Early-life RSV LRTI might affect long-term health but there are few data from low-income and middle-income countries. We investigated the epidemiology and effect of early-life RSV LRTI on lung health in a South African birth cohort. Methods We conducted the Drakenstein Child Health Study (DCHS), an ongoing birth cohort longitudinal study in the Western Cape province, South Africa. We enrolled pregnant women aged 18 years or older during their second trimester of pregnancy at two public health clinics. We followed up study children from birth to 2 years. The primary outcome of the study was LRTI and RSV LRTI. LRTI and wheezing episodes were identified through active surveillance; respiratory samples were tested for RSV and other pathogens. Wheezing was longitudinally identified by caregiver report and ascertainment at health facilities. Lung function was measured from 6 weeks to 2 years. We analysed the associations between RSV LRTI and subsequent LRTI, wheezing, and lung function using generalised estimating equations and mixed-effects linear regression. Findings We enrolled 1137 mothers between March 5, 2012, and March 31, 2015. Among their 1143 infants, accruing 2093 child-years of follow-up, there were 851 cases of LRTI (incidence 0·41 episodes per child-year, 95% CI 0·38–0·43). Admission to hospital owing to LRTI occurred in 169 (20%) cases (incidence 0·08 episodes per child-year, 0·07–0·09), with a case-fatality ratio of 0·5%. RSV was detected in 164 (21%) of 785 LRTI events with a specimen available for qPCR, an incidence of 0·08 episodes per child-year (0·07–0·09); highest at age 0–6 months (0·15 episodes per child-year, 0·12–0·19). Children with a first RSV LRTI were three times as likely to develop recurrent LRTI compared with those with non-RSV LRTI (0·32 [0·22–0·48] vs 0·10 [0·07– 0·16] episodes per child-year; p<0·0001), particularly following hospitalised RSV LRTI. RSV LRTI and hospitalisation for all-cause LRTI were independently associated with recurrent wheezing (adjusted incident rate ratio 1·41, 95% CI 1·25–1·59, for RSV LRTI and 1·48, 1·30–1·68, for hospitalisation). LRTI or recurrent LRTI was associated with impaired lung function, but a similar outcome was observed following RSV LRTI or non-RSV LRTI. All-cause LRTI was associated with an average 3% higher respiratory rate (95% CI 0·01–0·06; p=0·013) and lower compliance (–0·1, −0·18 to 0·02) at 2 years compared with no LRTI. Recurrent LRTI was associated with further increased respiratory rate (0·01, 0·001–0·02), resistance (0·77 hPa s L −1 , 0·07–1·47), and lower compliance (–0·6 mL hPa −1 , −0·09 to −0·02) with each additional event. Interpretation RSV LRTI was common in young infants and associated with recurrent LRTI, pa...

Background Childhood lower respiratory tract infections (LRTIs) cause substantial morbidity and under-5 child mortality. The epidemiology of LRTI is changing in low- and middle-income countries with expanding access to conjugate vaccines, yet there are few data on the incidence and risk factors for LRTI in these settings. Methods A prospective birth cohort enrolled mother–infant pairs in 2 communities near Cape Town, South Africa. Active surveillance for LRTI was performed for the first 2 years of life over 4 respiratory seasons. Comprehensive data collection of risk factors was done through 2 years of life. World Health Organization definitions were used to classify clinical LRTI and chest radiographs. Results From March 2012 to February 2017, 1143 children were enrolled and followed until 2 years of age. Thirty-two percent of children were exposed to antenatal maternal smoking; 15% were born at low birth weights. Seven hundred ninety-five LRTI events occurred in 429 children by February 2017; incidence of LRTI was 0.51 and 0.25 episodes per child-year in the first and second years of life, respectively. Human immunodeficiency virus (HIV)–exposed, uninfected infants (vs HIV-unexposed infants) were at increased risk of hospitalized LRTI in the first 6 months of life. In regression models, male sex, low birth weight, and maternal smoking were independent risk factors for both ambulatory and hospitalized LRTI; delayed or incomplete vaccination was associated with hospitalized LRTI. Conclusions LRTI incidence was high in the first year of life, with substantial morbidity. Strategies to ameliorate harmful exposures are needed to reduce LRTI burden in vulnerable populations.

Lower respiratory tract illness (LRTI) is a leading cause of mortality and morbidity in children. Sensitive and noninvasive infant lung function techniques are needed to measure risk for and impact of LRTI on lung health. The objective of this study was to investigate whether lung function derived from the intra-breath forced oscillation technique (FOT) was able to identify healthy infants at risk of LRTI in the first year of life.Lung function was measured with the novel intra-breath FOT, in 6-week-old infants in a South African birth cohort (Drakenstein Child Health Study). LRTI during the first year was confirmed by study staff. The association between baseline lung function and LRTI was assessed with logistic regression and odds ratios determined using optimal cut-off values.Of the 627 healthy infants with successful lung function testing, 161 (24%) had 238 LRTI episodes subsequently during the first year. Volume dependence of respiratory resistance (ΔR) and reactance (ΔX) was associated with LRTI. The predictive value was stronger if LRTI was recurrent (n=50 (31%): OR 2.5, ΔX), required hospitalisation (n=38 (16%): OR 5.4, ΔR) or was associated with wheeze (n=87 (37%): OR 3.9, ΔX).Intra-breath FOT can identify healthy infants at risk of developing LRTI, wheezing or severe illness in the first year of life.

ObjectivesThe coverage of prevention of mother-to-child transmission (PMTCT) services in South Africa is variable. Identifying gaps in the implementation of these services is necessary to isolate steps needed to further reduce paediatric infections and eliminate transmission.SettingTwo primary care clinics in Paarl, South Africa.Participants1225 pregnant women; inclusion criteria were 18 years or older, clinic attendance and remaining in area for at least 1 year.MethodsData were collected through the Drakenstein Child Health Study, a population-based birth cohort in a periurban area of the Western Cape, South Africa. A combination of clinic records, hospital records, national database searches and maternal self-report were collected during the study.ResultsOf the 1225 mothers enrolled in the cohort between 2012 and 2015, 260 (21%) were confirmed HIV infected antenatally and 1 mother tested positive in the postnatal period. Of those with documentation (n=250/260, 96%), the majority (99%) received antiretroviral prophylaxis or therapy (ART) before labour; however, there was a high rate of defaulting from ART noted during pregnancy (20%). All HIV-exposed infants with data received antiretroviral prophylaxis, 35% were exclusively breast fed until 6 weeks and 16% for 6 months. There were two cases of infant HIV infection (0.8%) who were initiated on ART but had complicated histories.ConclusionDespite the low transmission rate in this cohort, reaching elimination will require further work, and this study illustrates several areas to improve implementation of PMTCT services and reduce paediatric infections including retesting at-risk HIV-negative mothers through the duration of breast feeding, infant HIV testing at any admission in addition to routine testing and improved counselling to prevent defaulting from treatment. Better data surveillance systems are essential for determining the implementation of PMTCT guidelines.

Objective: To assess the impact of HIV and antiretroviral exposure without infection on lung growth and function over the first 2 years of life. Design: Prospective observational study of an African birth cohort, Drakenstein Child Health Study. Method: Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received antiretroviral therapy (ART) as per local guidelines. The association between HIV and antiretroviral exposure with lung function was assessed using mixed effects modelling. Results: Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume compared with HIV-unexposed infants (1.13 ml, confidence interval: 0.02-2.23, P ¼ 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, confidence interval 0.00-0.34, P ¼ 0.046). First-line ART initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (À2.7 ml, À5.31 to À0.10, P ¼ 0.042), and low maternal CD4 þ cell counts associated with lower infant tidal over 2 years (À11.1 ml, À18.58-3.58, P ¼ 0.004). Conclusion: HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. These data highlight the importance of ongoing surveillance of respiratory health in HEU children.