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Background Air pollution and several prenatal factors, such as socio-demographic, behavioural, physical activity and clinical factors influence adverse birth outcomes. The study aimed to investigate the impact of ambient air pollution exposure during pregnancy adjusting prenatal risk factors on adverse birth outcomes among pregnant women in MACE birth cohort. Methods Data for the study was obtained from the Mother and Child in the Environment (MACE) birth cohort study in Durban, South Africa from 2013 to 2017. Land use regression models were used to determine household level prenatal exposure to PM2.5, SO2 and NOx. Six hundred and fifty-six births of pregnant females were selected from public sector antenatal clinics in low socio-economic neighbourhoods. We employed a Generalised Structural Equation Model with a complementary log–log-link specification. Results After adjustment for potential prenatal factors, the results indicated that exposure to PM2.5 was found to have both significant direct and indirect effects on the risk of all adverse birth outcomes. Similarly, an increased level of maternal exposure to SO2 during pregnancy was associated with an increased probability of being small for gestational age. Moreover, preterm birth act a mediating role in the relationship of exposure to PM2.5, and SO2 with low birthweight and SGA. Conclusions Prenatal exposure to PM2.5 and SO2 pollution adversely affected birth outcomes after controlling for other prenatal risk factors. This suggests that local government officials have a responsibility for better control of air pollution and health care providers need to advise pregnant females about the risks of air pollution during pregnancy.

The association between in utero exposure to indoor PM2.5 and birth outcomes is not conclusive. We assessed the association between in utero exposure to indoor PM2.5 , birth weight, gestational age, low birth weight, and/or preterm delivery. Homes of 800 pregnant women were assessed using a structured walkthrough questionnaire. PM2.5 measurements were undertaken in 300 of the 800 homes for a period of 24 h. Repeated sampling was conducted in 30 of these homes to determine PM2.5 predictors that can reduce within-and/or between-home variability. A predictive model was used to estimate PM2.5 levels in unmeasured homes (n = 500). The mean (SD) for PM2.5 was 37 µg/m3 (29) with a median of 28µg/m3 . The relationship between PM2.5 exposure, birth weight, gestational age, low birth weight, and preterm delivery was assessed using multivariate linear and logistic regression models. We explored infant sex as a potential effect modifier, by creating an interaction term between PM2.5 and infant sex. The odds ratio of low birth weight and preterm delivery was 1.75 (95%CI: 1.47, 2.09) and 1.21 (95%CI: 1.06, 1.39), respectively, per interquartile increase (18 µg/m3 ) in PM2.5 exposure. The reduction in birth weight and gestational age was 75 g (95%CI: 107.89, 53.15) and 0.29 weeks (95%CI: 0.40, 0.19) per interquartile increase in PM2.5 exposure. Infant sex was an effect modifier for PM2.5 on birth weight and gestational age, and the reduction in birth weight and gestational age was 103 g (95%CI: 142.98, 64.40) and 0.38 weeks (95% CI: 0.53, 0.23), respectively, for boys, and 54 g (95%CI: 91.78,15.62) and 0.23 weeks (95%CI:0.37, 0.08), respectively, for girls. Exposure to PM2.5 is associated with adverse pregnancy outcomes. To protect the population during their reproductive period, public health policy should focus on indoor PM2.5 levels.

The association between in utero exposure to indoor PM

In epidemiological studies, levels of PM2.5 need to be estimated over time and space. Because of logistical constraints, very few studies have been conducted to assess the variability within and across homes and the predictors of this variability. This study evaluated within- and between-home variability of indoor PM2.5 and identified predictors for PM2.5 in homes of mothers participating in the urban Mother and Child in the Environment birth cohort study in Durban, South Africa. Thirty homes were selected from 300 homes that were previously sampled for PM2.5. Two measurements of PM2.5 levels were conducted in each home within a 1 week interval in both warm and cold seasons (four samplings per home) using Airmetrics MiniVol samplers. A linear mixed-effect model was used to evaluate within- and between-home variability and to identify fixed effects (predictors) that result in reduced variability. The PM2.5 levels in the 30 homes ranged from 2 to 303 μg m-3. The within-home variability accounted for 94% of the total variability in the log-transformed PM2.5 levels for the 30 homes. The fixed effects extracted from the repeated samplings in the present study were used to improve a previously developed multivariable linear regression model for 300 homes, and thereby increased the R2 from 0.50 to 0.54. Inclusion of fixed-effects in multivariable linear regression models resulted in a reasonably robust model that can be used to predict PM2.5 levels in unmeasured homes of the cohort.

In epidemiological studies, levels of PM2.5 need to be estimated over time and space. Because of logistical constraints, very few studies have been conducted to assess the variability within and across homes and the predictors of this variability. This study evaluated within- and between-home variability of indoor PM2.5 and identified predictors for PM2.5 in homes of mothers participating in the urban Mother and Child in the Environment birth cohort study in Durban, South Africa. Thirty homes were selected from 300 homes that were previously sampled for PM2.5. Two measurements of PM2.5 levels were conducted in each home within a 1 week interval in both warm and cold seasons (four samplings per home) using Airmetrics MiniVol samplers. A linear mixed-effect model was used to evaluate within- and between-home variability and to identify fixed effects (predictors) that result in reduced variability. The PM2.5 levels in the 30 homes ranged from 2 to 303 μg m-3. The within-home variability accounted for 94% of the total variability in the log-transformed PM2.5 levels for the 30 homes. The fixed effects extracted from the repeated samplings in the present study were used to improve a previously developed multivariable linear regression model for 300 homes, and thereby increased the R2 from 0.50 to 0.54. Inclusion of fixed-effects in multivariable linear regression models resulted in a reasonably robust model that can be used to predict PM2.5 levels in unmeasured homes of the cohort.

HIV has been implicated in adverse birth outcomes, due to increased oxidative stress and inflammation. In addition, HIV has been reported to increase nitric oxide levels. Therefore the combined exposures to HIV and traffic-related air pollution, within South Durban, South Africa (SA), may lead to adverse birth outcomes. However, the exact mechanism is still unknown; this study aimed to identify a potential mechanism. First, the influence of HIV on oxidative and nitrosative stress markers in pregnant women was assessed. Secondly, the effect of these stress makers and exposure to oxides of nitrogen (NOx) on neonatal birthweight (BW) was evaluated. Finally, the effect HIV and traffic-related pollution exposure has on the oxidative and endoplasmic profile and epigenetic regulation of Nrf2-Keap1 pathway by miR-144 and miR-28 in pregnant women was determined. Women, in their third trimester with singleton pregnancies, who were HIV+ and HIV−, were recruited from Durban, SA. Biomarker levels of serum nitrites/nitrates (NO) and malondialdehyde (MDA) were analysed and mRNA expression levels of oxidative and endoplasmic stress response genes were assessed. Land regression modelling was performed to determine NOx exposure levels. HIV exposure during pregnancy was associated with increased NO levels. NO was shown to reduce neonatal BW. NO and MDA was found to reciprocally increase each other, with HIV differentially influencing MDA's effect on BW. HIV down-regulated miR-144 which was negatively associated with Nrf2, suggesting a potential mechanism for HIV associated chronic oxidative stress. This study proposes that NO plays a key role in neonatal BW reduction in response to HIV and traffic-related air pollution. Keywords: HIV, Oxidative stress, NO, Adverse birth outcomes, Traffic-pollution, Nrf2-Keap1 pathway

Introduction In South Africa (SA), steroid-resistant nephrotic syndrome (SRNS) is more frequent in black than in Indian children. Methods Seeking a genetic basis for this disparity, we enrolled 33 Indian and 31 black children with steroid-sensitive nephrotic syndrome (SSNS) and SRNS from KwaZulu-Natal, SA; SRNS children underwent kidney biopsy. We sequenced NPHS2 and genotyped APOL1 in 15 SSNS and 64 SRNS unrelated patients and 104 controls and replicated results in 18 black patients with steroid-resistant focal segmental glomerulosclerosis (SR-FSGS). Known FSGS genes (n = 21) were sequenced in a subset of patients. Results Homozygosity for NPHS2 V260E was found in 8 of 30 black children with SRNS (27%); all 260E/E carriers had SR-FSGS. Combining SR-FSGS patients from the 2 groups, 14 of 42 (33%) were homozygous for V260E. One black control was heterozygous for V260E; no Indian patients or controls were carriers. Haplotype analysis indicated that homozygosity for V260E was not explained by cryptic consanguinity. Children with NPHS2 260E/E developed SRNS at earlier age than noncarriers (34 vs. 78 months, P = 0.01), and none achieved partial or complete remission (0% vs. 47%, P = 0.002). APOL1 variants did not associate with NS. Sequencing FSGS genes identified a CD2AP predicted pathogenic variant in the heterozygous state in 1 Indian case with SR-FSGS. Conclusion NPHS2 260E/E was present in one-third of black FSGS patients, was absent in black controls and Indian patients, and affected patients were unresponsive to therapy. Genotyping V260E in black children from South Africa with NS will identify a substantial group with SR-FSGS, potentially sparing these children biopsy and ineffective steroid treatment.

Interleukin (IL-)17A, plays a role in pathogenic defence, but is implicated in chronic inflammatory diseases, and has recently been associated with variable pregnancy outcomes. We investigated the role of maternal IL-17-[G197A]-specific effects of third-trimester IL-17 mRNA expression, NOx exposure levels and other variables on gestational age, in the Mother and Child in the Environment (MACE) birth cohort in South Africa. A total of 327 participants were genotyped for IL-17-[G197A] by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to quantitate IL-17-mRNA expression in whole blood. Multivariate linear regression analysis, stratified by IL-17-[G197A] genotype, was used to test for effects of NOx , IL17A/GAPDH, haemoglobin, body mass index, HIV-1 positivity, maternal education and income level on gestational age. Lower expression was associated with the IL-17-GG versus GA in the cohort and HIV-1-negative group (p = .0007, p = .0058), while no difference was observed in the HIV-1 positives. Elevated IL-17A expression was observed in the high NOx exposure groups, within IL-17[G197G] (p = .0004). IL-17[G197G] was associated with PTB (p < .0001), and the PTB group had lower IL-17A expression compared to the full-term group (p = .0002). IL-17 expression was associated with an increase in gestational age (p = .038), and NOx was associated with a decrease in gestational age in the IL-17[G197G] model (p = .046).

The purpose of the study was to evaluate the effect nitric oxide (NO x ) pollution had on maternal serum 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OHdG) levels and neonatal outcomes in pregnant women living in Durban, South Africa (SA). Women, in their third trimester with singleton pregnancies, were recruited from the heavily industrialised south (n = 225) and less industrialised north (n = 152). Biomarker levels of serum 8-OHdG concentrations were analysed, and the women were genotyped for glutathione-S-transferases pi 1 (GSTP1) and glutathione-S-transferases mu 1 (GSTM1) polymorphisms. The level of NO x pollution in the two regions was determined by using land use regression modelling. The serum 8-OHdG was shown to correlate significantly with NO x levels; this relationship was strengthened in the south (p

Objective: Cytokines, molecules within the immune system that affect either a pro- or anti-inflammatory response, have previously been shown to influence birth outcomes. The maternal cytokine gene–environment interactions are thought to alter their expression, potentially influencing susceptibility to adverse birth outcomes. The aim of this study was to determine the association between the maternal interleukin-1β (IL-1β) haplotype and expression variation with oxides of nitrogen (NOx) levels, and thereafter investigate the IL-1β haplotype-specific effects of NOx exposure levels, IL-1β mRNA expression and other variables on gestational age. Material and methods: Using the prospective Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa, 335 participants were genotyped for the IL-1β haplotype. Previous studies showed that three single nucleotide polymorphisms (SNPs), IL-1β-1464G/C, -511C/T and -31C/T, constitute the IL-1β functional haplotype. These SNPs were genotyped using a restriction fragment length polymorphism assay, while IL-1β mRNA expression was measured using a quantitative real-time polymerase chain reaction assay. Individual estimates of NOx exposure were obtained by land use regression modelling. A multivariate linear regression analysis was employed to test for significant effects on gestational age. Results: IL-1β mRNA expression was found to possess a haplotype-dependent effect ( p = 0.0001) and its expression levels positively correlated with NOx levels ( r = 0.34; p = 0.006). In the high haplotype model, a unit increase in NOx exposure level was associated with a decrease in gestational age by 1 week ( p = 0.02). Furthermore, gestational age decreased by 0.9 weeks for every unit increase of IL-1β mRNA expression level ( p = 0.025). HIV-1 positivity was associated with a 0.2-week decrease in gestational age ( p = 0.035) in the intermediate haplotype model and a 0.4-week decrease in the high haplotype model ( p = 0.044). Conclusion: These data have implications for better understanding the effect of prenatal NOx exposure on gestational age and demonstrate the role of the IL-1β haplotype in modulating the effects of NOx exposure.

Additional file 1.

Birthweight is strongly associated with infant mortality and is a major determinant of infant survival. Several factors such as maternal, environmental, clinical, and social factors influence birthweight, and these vary geographically, including across low, middle, and economically advanced countries. The aim of the study was to investigate the geographical modification of the effect of oxides of nitrogen exposure on birthweight adjusted for clinical and socio-demographic factors. Data for the study was obtained from the Mother and Child in the Environment birth cohort study in Durban, South Africa. Pregnant females were selected from public sector antenatal clinics in low socioeconomic neighborhoods. Land use regression models were used to determine household level antenatal exposure to oxides of nitrogen (NOx). Six hundred and seventy-seven births were analysed, using the geoadditive model with Gaussian distribution and identity link function. The newborns in the cohort had a mean birthweight of 3106.5 g (standard deviation (SD): 538.2 g and the maternal mean age was 26.1 years (SD: 5.7). A spatially modified NOx exposure-related effect on birthweight was found across two geographic regions in Durban. Prenatal exposure to NOx was also found to have a non-linear effect on the birthweight of infants. The study suggested that incorporating spatial variability is important to understand and design appropriate policies to reduce air pollution in order to prevent risks associated with birthweight.

Background Low birthweight (LBW) and preterm birth (PB) remain the leading cause of morbidity and mortality in neonates worldwide. The aim of this study was to identify maternal demographic and antenatal factors associated with PB and LBW among low socio-economic communities. Methods Pregnant women (n = 1099) were recruited in the first trimester into the Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa. Maternal factors such as demographic information, health status, residential area, occupational, personal and environmental smoking and biomass fuel use were obtained through standardised interviews, while clinical status was obtained in each trimester and antenatal information on HIV status and treatment, syphilis and conditions such as pregnancy induced hypertension, diabetes etc. was extracted from the antenatal assessments. Key outcomes of interest were preterm birth and low birthweight. The latter data was obtained from the clinical assessments performed by midwives at delivery. Logistic regression models identified factors associated with PB and LBW. Results Of the 760 live births, 16.4 and 13.5% were preterm and LBW, respectively. Mothers who delivered by caesarean section had an increased odds of having LBW babies (Adjusted odds ratio (AOR): 1.7; 95% CI: 1.1–2.7) and PB (AOR: 1.7, 95% CI: 1.1–2.7) versus normal vaginal deliveries. Mothers > 30 years (AOR: 1.8, 95% CI: 1.1–2.9) and current smokers (AOR: 2.7, 95% CI: 1.3–5.8) had an increased odds of having PB babies. Compared to younger mothers and non-smokers respectively. An effect of PB and LBW was seen among mothers with high BMI (25.0–29.9 kg/m2) (PB: AOR: 0.5, 95% CI: 0.3–0.9 and LBW: AOR: 0.5, 0.5, CI: 0.3–0.8), and obese BMI (> 30 kg/m2) (PB: AOR: 0.5, 95% CI: 0.3–0.9 and LBW: AOR: 0.4, CI: 0.2–0.7). Maternal HIV (PB AOR: 1.4 and LBW AOR: 1.2) and history of sexually transmitted infections (PB AOR: 2.7 and LBW AOR: 4.2) were not statistically significant. Conclusion Maternal age, cigarette smoking and caesarean delivery were associated with LBW and PB. Findings highlight the need of maternal health interventions to improve new-born health outcomes.

Objective: Nitrogen oxide (NOx) pollution and human immunodeficiency virus (HIV)/AIDS intensify inflammation during pregnancy and linked with adverse birth outcomes (ABOs). MicroRNA (miRNA)-146a plays a crucial role in regulating inflammation in the NF-κB pathway. The G/C rs2910164 dampens miRNA-146a activity and linked with inflammatory diseases. The present study investigated whether HIV/AIDS and NOx exposure throughout pregnancy further intensifies ABO in Black South African women genotyped for the rs2910164. Methods: Pregnant women ( n = 300) were subdivided into low, medium and high NOx exposure groups, genotyped for the miRNA-146a G/C rs2910164 using polymerase chain reaction-restriction fragment length polymorphism, and further stratified based on HIV status. Results: Unstratified data (HIV+ and HIV− mothers combined): Mothers from the high NOx group with the variant C-allele had low blood iron levels ( p = 0.0238), and had babies with reduced birthweights ( p = 0.0283). As NOx increased, the prevalence of preterm birth and low birth weight also increased in mothers with the variant C-allele versus wildtype G-allele. HIV-infected mothers: In all NOx exposure groups, mothers with the variant C-allele had higher systolic blood pressure (low: p = 0.0386, medium: p = 0.0367 and high: p = 0.0109) and had babies with lower Appearance, Pulse, Grimace, Activity and Respiration scores at 1 min (low: p = 0.0190, medium: p = 0.0301 and high: p = 0.0361). Conclusion: Maternal rs2910164 variant C-allele, NOx pollution and HIV/AIDS might collectively play a role in intensifying gestational hypertension and ABO.

The in utero environment has the potential to influence epigenetic programming and subsequently the health of offspring. Even though pregnant women living in urban Africa are exposed to multiple chemicals and infectious agents that may impact their developing children, the neonatal epigenome has not been studied in these regions. We assessed whether prenatal exposures to air pollution and maternal human immunodeficiency virus (HIV) are associated with changes to DNA methylation throughout the epigenome using a pilot sample from the Mother and Child Environmental (MACE) birth cohort, of which 36% of the mothers are HIV positive. Families living in a high air pollution region (south Durban, n = 11) and a low air pollution region (north Durban, n = 11) with comparable socioeconomic characteristics were selected for analysis. DNA methylation was quantified in cord blood plasma DNA at >430 000 CpG sites using the Infinium HumanMethylation450 BeadChip. Sites associated with living in south Durban or maternal HIV infection (p < 0.001) were more likely to be hypomethylated and located in CpG islands. Top differentially methylated sites by region of Durban were enriched in pathways related to xenobiotic metabolism, oxygen and gas transport, and sensory perception of chemical stimuli when performing gene set enrichment testing with LRpath. Differentially methylated sites by maternal HIV status were enriched in cytochrome P450s, pathways involved in detection of chemical stimuli, metabolic processes, and viral regulation and processing. Given the small sample size of the study, future work examining the impact of prenatal exposures to air pollution, maternal infection, and antiviral treatment on the epigenome and downstream health implications is merited in Sub-Saharan African populations.

The global HIV and obesity epidemics are major public health concerns; particularly as both are associated with increased risk of adverse birth outcomes. Despite extensive research, their combined effect, in terms of birth outcomes, has not been investigated. A single-nucleotide polymorphism (SNP) within 8-oxoguanine glycosylase 1 (OGG1) (Ser326Cys) has been suggested to affect body mass indices and therefore could predispose South African (SA) women to adverse effects of obesity. This study investigated the associations of OGG1 Ser326Cys SNP in relation to HIV and obesity on the susceptibility of low-birthweight (LBW) and pre-term birth (PTB) in SA women exposed to ambient air-pollution living in Durban. In our study population, the OGG1 SNP was associated with HIV and obesity. Wild-type (CC)-carrying patients had increased susceptibility for HIV-associated LBW and PTB. Co-morbid HIV and obese patients delivered neonates with decreased birthweights. Living within the heavily-polluted south-Durban and carrying the CC-genotype increased the risk for PTB within our study population.

Environmental insults and microsomal epoxide hydrolase 1 (EPHX1) single nucleotide polymorphisms (SNPs), Tyr113His T/C rs1051740 and His139Arg A/G rs2234922, aberrantly alters microRNA (miR) expression and are linked to low birthweights (LBW).To investigate the interplay between pollution, EPHX1 SNPs and miRs during pregnancy and associated LBW outcomes.South African pregnant women (n=241) were recruited in the MACE birth cohort study in Durban, a city with high levels of industry and traffic related pollutants. EPHX1 SNPs were genotyped using PCR-RFLP and grouped into their respective phenotypes, i.e. normal (N), slow (S), very slow (VS) and fast (F). EPHX1, miR-26b-5p, miR-193b-3p and miR-1207-5p expression were determined using quantitative PCR.Mothers with the Tyr113His SNP had low iron levels [TT vs. TC+CC: mean difference (MD)=0.67g/dl; p=0.0167], LBW [TT vs. TC+CC: MD=189.30g; p=0.0067], and low EPHX1 expression; p0.0001. miR-26b-5p and miR-1207-5p expression were significantly higher in the CC genotypes compared to TT+TC groups; p0.0001. The opposite trend occurred for miR-193b-3p; p=0.0045. Mothers with the VS phenotype had low iron levels [N vs. VS and VS vs. F: MD=2.03 and -1.96g/dl; p=0.0021, respectively], decreased gestational age [VS vs. F: MD=-2.14weeks; p=0.0051, respectively], and LBW [N vs. VS, VS vs. F and S vs. VS: MD=1000, -940.30 and 968.80g; p0.0001, respectively]; F phenotype had the highest EPHX1 expression [N vs. F, VS vs. F and S vs. F: MD=-1.067, -1.854 and -1.379; p=0.0002, respectively]; and N phenotype had low miR-26b-5p [N vs. VS: MD=-0.6100; p=0.0159] and miR-1207-5p [N vs. VS and VS vs. F: MD=-0.834 and 1.103; p=0.0007, respectively] expression. miR-193b-3p expression between phenotypes remained unchanged.The Tyr113His T/C variant of rs1051740 and VS phenotype alters EPHX1, miR-26b-5p and miR-1207-5p expression, and contributes towards low blood iron levels and LBW.

The Mother and Child Environmental Cohort (MACE) study piloted in South Africa in 2010 to 2011, collected genetic, biochemical and clinical data from pregnant females residing in south and north Durban. We evaluated birth outcomes and the influence of GSTM1pos→GSTM1null and theGSTP1 (Ile105Val; AA→AG/GG) polymorphisms on the extent of DNA damage and with biomarkers [glutathione (GSH) and malondialdehyde (MDA)] related to oxidative stress in mothers with different levels of pollutant exposure. There was no significant difference in adverse birth outcomes or genotype distribution between mothers from the exposed and lower exposed areas. Mean GSH and comet tail length did not differ significantly between GSTM1pos and GSTM1null genotypes. When stratified by genotype, mean MDA levels was higher among GSTM1 null mothers compared to the GSTM1pos mothers (p = 0.01). When each of the genotypes was stratified by exposure, mean GSH concentration was significantly higher in north Durban for theGSTM1pos, GSTM1null and GSTP1AG+GG genotypes (p < 0.05), and mean comet tail length was significantly increased in south Durban among participants with the GSTM1pos, GSTM1null, and the GSTP1AG+GG genotypes. The expression of GSTM1 and GSTP1 polymorphic genotypes may lead to varying susceptibility to the adverse effects of pollutants by modifying the response to oxidative stress. Key words: Glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase pi gene(GSTP1), oxidative stress, birth cohort, glutathione, gene polymorphism, DNA damage.

Introduction: The in utero environment has the potential to influence epigenetic programming and subsequently the health of the offspring. Even though African pregnant women are exposed to multiple...

The burden of chronic kidney disease (CKD) in children in developing countries remains unknown, due to the lack of a national data-reporting system. We undertook a retrospective study of all children16 years old in our hospital, which is the tertiary referral centre for children with complex kidney disorders, to analyse the spectrum of CKD (stages 2-5) from 1994-2006. Six hundred and fifty-three children with kidney disorders were screened for CKD; 286 (44.0%) were5 years old. Of these, 177 (62%) were male, 202 (70.6%) were black, 77 (26.9%) were Indian, five (1.8%) were mixed race and two (0.7%) were white. One hundred and twenty-six children had CKD (stages 2-5); 55 (43.7%) were5 years olds; 41 (74.5%) were male. There were 71 (56.3%) that were5 years old, 42 (59.2%) were male. The commonest cause of CKD (stages 2-5) in all children was nephrotic syndrome, comprising 30.9% in children5 years old and 40.8% in children5 years old. Within the observation period of 11 years, end-stage kidney disease was diagnosed in 20 children; only nine had been on long-term dialysis, and seven qualified for transplantation. Five (25%) children had died, four from sepsis during dialysis and one from tuberculosis after receiving a transplant. We concluded that lack of resources, late referrals, and high cost of renal replacement therapy in developing countries leads to poor outcome in CKD.

This was a retrospective study of HIV-infected children aged 0-12 years attending the King Edward VIII Hospital in Durban, South Africa over a 5-year period (January 1996 to December 2001) with culture-proven urinary tract infection (UTI). UTI was defined as the presence of a single bacterial growth of10(5) colony-forming units/ml in a clean-catch, mid-stream urine sample or10(3) organisms/ml in a catheter or suprapubic aspirate of urine. HIV/AIDS was diagnosed in accordance with World Health Organization and/or Centers for Disease Control criteria. Comparison between HIV-positive and HIV-negative children with UTI was done using the chi2 and Wilcoxon rank sum tests. Of the 55 children recruited into the study, 29 (52.1%) were HIV-positive and 26 (47.3%) HIV-negative. Escherichia coli was isolated in 50 (87.2%) children. Clinical presentation, aetiological agents, response to therapy and renal function were similar in both groups. This study showed no significant impact of HIV/AIDS on the presentation of UTI in children.

Background: The use of tacrolimus in steroid-resistant (SR) focal segmental glomerulosclerosis (FSGS) has been reported in single and small series case reports. Aim: To determine the efficacy of tacrolimus in the management of SR FSGS in children. Study Design: This was a prospective study of 20 children with SR FSGS treated with tacrolimus (0.2–0.4 mg/kg/day in two divided doses over 12 h adjusted to a trough level between 7 and 15 ng/ml) for 12 months in combination with low-dose steroids. Other therapies included angiotensin-converting enzyme inhibitors, folic acid, multivitamins and lipid-lowering agents. Results: The mean age at study entry was 11.1 years (range 5.6–16.8). The mean duration of nephrotic syndrome before initiation of tacrolimus therapy was 4.7 years (range 2.1–7.6). At the end of the treatment period, 8 (40%) children were in complete remission, 9 (45%) were in partial remission, and 3 (15%) failed to respond. The average follow-up period following cessation of tacrolimus treatment was 27.5 months (range 13.7–43.7). At last hospital follow-up, 5 (25%) children were in complete remission, 10 (50%) in partial remission, and 2 (10%) in relapse. Three children died from dialysis-related complications following cessation of tacrolimus treatment. Adverse events included sepsis (2), nausea (2), diarrhea (2), anemia (4) and worsening of hypertension (4). Conclusion: Tacrolimus is a safe and effective treatment for SR FSGS. However, like cyclosporine, some children tend to relapse following cessation of treatment.

Steroid-resistant (SR) forms of nephrotic syndrome (NS) have a poorer outcome in blacks compared to other racial groups. In this study, 223 children with SRNS, aged 1-16 years old, were analysed retrospectively for the period 1976-2004. Treatment schedules included oral cyclophosphamide (2-3 mg/kg) with prednisone 0.5-1 mg/kg (maximum 60 mg) only (n=90); prednisone on alternate days with methylprednisolone (30 mg/kg, maximum 1 g) and oral cyclophosphamide (n=117); oral prednisone on alternate days, three doses of intravenous methylprednisolone on alternate days and monthly doses of intravenous cyclophosphamide (500-750 mg m(-2) dose(-1)x7 doses monthly) (n=10); or cyclosporine 5 mg kg(-1) day(-1) adjusted to a trough level of 150-200 mg/ml (n=6). We compared the clinical and biochemical characteristics and outcome using different forms of therapies. A total of 183 (82.1%) underwent biopsy; 84 (45.9%) were Indian and 99 (54.1%) were black. Sixty-six (36.1%) had minimal change NS, 66 (36.1%) had focal segmental glomerulosclerosis (FSGS), 15 (8.2%) had a proliferative form of NS, and 36 (19.7%) had other forms of NS. Of the 84 Indian children biopsied, 58 (69.0%) were in complete remission, including 29 of 40 (72.5%) treated with oral cyclophosphamide and prednisone only. Of the 99 black children who were biopsied, 20 (20.2%) achieved complete remission; none of those treated with oral cyclophosphamide and prednisone only achieved complete remission. Of the 40 Indian children who were not biopsied who received only oral prednisone and cyclophosphamide, 32 (80%) achieved complete remission. This study shows Indian children with SRNS respond better to treatment than black children (69.0 vs. 20.2%). Since 80% of Indian children with SRNS responded to a trial of oral cyclophosphamide and prednisone, we propose the use of oral cyclophosphamide therapy in non-black children before embarking on renal biopsy.