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The gut microbiota of infants is shaped by both the mode of delivery and the type of feeding. The gut of vaginally and cesarean-delivered infants is colonized at different rates and with different bacterial species, leading to differences in the gut microbial composition, which may persist up to 6 months. In a multicenter, randomized, controlled, double-blind trial conducted in South Africa, we tested the effect of a formula supplemented with a prebiotic (a mixture of bovine milk-derived oligosaccharides [BMOS] generated from whey permeate and containing galactooligosaccharides and milk oligosaccharides such as 3'- and 6'-sialyllactose) and the probiotic Bifidobacterium animalis subsp. lactis ( B. lactis ) strain CNCM I-3446 on the bifidobacteria levels in the gut of infants born vaginally or via cesarean section in early life. Additionally, the safety of the new formulation was evaluated. A total of 430 healthy, full-term infants born to HIV-positive mothers who had elected to feed their child beginning from birth (≤3 days old) exclusively with formula were randomized into this multicenter trial of four parallel groups. A total of 421 infants who had any study formula intake were included in the full analysis set (FAS). The first two groups consisted of cesarean-delivered infants assigned to the Test formula (n = 92) (a starter infant formula [IF] containing BMOS at a total oligosaccharide concentration of 5.8 ± 1.0 g/100 g of powder formula [8 g/L in the reconstituted formula] + B. lactis [1 × 10 7 colony-forming units {cfu}/g]) or a Control IF (n = 101); the second two groups consisted of vaginally delivered infants randomized to the same Test (n = 115) or Control (n = 113) formulas from the time of enrollment to 6 months. The primary efficacy outcome was fecal bifidobacteria count at 10 days, and the primary safety outcome was daily weight gain (g/d) between 10 days and 4 months. At 10 days, fecal bifidobacteria counts were significantly higher in the Test formula than in the Control formula group among infants with cesarean birth (median [range] log: 9.41 [6.30-10.94] cfu/g versus 6.30 [6.30-10.51] cfu/g; P = 0.002) but not among those with vaginal birth (median [range] log: 10.06 [5.93-10.77] cfu/g versus 9.85 [6.15-10.79] cfu/g; P = 0.126). The lower bound of the two-sided 95% confidence interval of the difference in the mean daily weight gain between the Test and Control formula groups was more than -3 g/d in both the vaginally and cesarean-delivered infants, indicating that growth in the Test formula-fed infants was not inferior to that of Control formula-fed infants. At 10 days and 4 weeks, the fecal pH of infants fed the Test formula was significantly lower than in those fed the Control formula, irrespective of mode of delivery: for vaginal delivery: 4.93 versus 5.59; P < 0.001 (10 days) and 5.01 versus 5.71; P < 0.001 (4 weeks); for cesarean delivery: 5.14 versus 5.65, P = 0.009 (10 days) and 5.06 versus 5.75, P < 0.001 (4 weeks). At 3 months, this acidification effect only persisted among cesarean-born infants. IF supplemented with the prebiotic BMOS and probiotic B. lactis induced a strong bifidogenic effect in both delivering modes, but more explicitly correcting the low bifidobacteria level found in cesarean-born infants from birth. The supplemented IF lowered the fecal pH and improved the fecal microbiota in both normal and cesarean-delivered infants. The use of bifidobacteria as a probiotic even in infants who are immunologically at risk is safe and well tolerated.

Objective: To compare the effects of a biologically and chemically acidified formula with or without probiotics with a standard formula on growth of infants negative for human immunodeficiency virus (HIV)., Methods: This was a double-masked, randomized, clinical trial. Infants born to consenting HIV-positive women who had decided not to breast-feed before being approached for participating in the study were randomized to receive one of four milk formulas: a chemically acidified formula with or without probiotics (Bifidobacterium lactis), a biologically acidified formula, or a standard whey formula. Infants who subsequently became HIV-positive according to polymerase chain reaction at 6 wk were excluded. Their growth and biochemical status were monitored for 4-6 mo. The z scores at the last visit of infants in each of the four formula groups were compared using analysis of covariance correcting for the z scores at baseline. Blood gases and pH were analyzed using a two-way analysis of variance corrected for center., Results: One hundred thirty-two HIV-negative infants were monitored for growth and biochemical parameters for 4-6 mo. There was an improvement of z scores for all formulas, and there were no differences in weight for age (P = 0.22), length for age (P = 0.56), head circumference for age (P = 0.66), or weight for length (P = 0.13). There were no differences in blood pH and biochemical parameters among the formula groups., Conclusion: The growth of infants fed one of the three acidified formulas was not inferior to the standard formula. Growth and metabolism in HIV-negative infants fed the acidified formulas were not affected by the method of milk acidification.

Background: Diagnosis of human immunodeficiency virus (HIV) is essential for accessing treatment. Current HIV diagnostic protocols for infants require adaptation and validation before they can be implemented in the developing world. The timing and type of HIV assays will be dictated by country-specific circumstances and experience from similar settings. The performance of an HIV-1 DNA polymerase chain reaction (PCR) test, and in particular a single test at 6 weeks of age, in diagnosing HIV subtype C infection acquired in utero or peripartum was assessed., Methods: A retrospective review of 1825 Amplicor HIV-1 DNA PCR version 1.5 tests performed between 2000 and 2004 in 2 laboratories in Johannesburg, South Africa on 769 effectively non-breast-fed infants from 3 clinically well characterized cohorts was undertaken. The HIV status of each infant was used as the standard against which the HIV PCR results were compared., Results: The overall sensitivity and specificity of the HIV PCR test were 99.3 and 99.5% respectively. A single test was 98.8% sensitive and 99.4% specific in the 627 infants tested at 6 weeks of age (58 HIV-infected and 569 HIV-uninfected). Repeat testing of all positive HIV PCR tests minimized false positive results., Conclusions: In resource-poor settings where HIV PCR testing in an environment of good laboratory practice is feasible, a single 6-week HIV DNA PCR test can increase identification of HIV-infected children substantially from current levels. Further operational research on how best to implement and monitor such a diagnostic protocol in specific local settings, especially in breast-fed infants, is necessary.

Objectives: Assessment of the efficacy of a prevention of mother-to-child transmission (PMTCT) programme in a routine service setting in comparison to a research environment., Design: Descriptive study over a 13-month period utilising retrospective data obtained from hospital records complemented by prospective data on a sample of patients enrolled in a study to determine an affordable HIV diagnostic protocol for infants., Setting: Routine PMTCT service at Coronation Women and Children's Hospital (CWCH) situated in Johannesburg and affiliated to the University of the Witwatersrand., Subjects: Pregnant women known to be HIV infected who delivered at CWCH from 1 October 2001 to 31 October 2002., Outcome Measures: The HIV transmission rate to infants, which reflects nevirapine (NVP) delivery and infant feeding practices, and follow-up rates of perinatally exposed children., Results: Of the 8,221 deliveries, 1,234 (15%) occurred in women known to be HIV infected. HIV transmission rates of 8.7% at 6 weeks and 8.9% at 3 months of age in the study population verifies the high rate of NVP administration and the ability of women to formula-feed their babies and abstain from breast-feeding. More than one-third of infants never return for follow-up and more than 70% are lost to follow-up by 4 months of age., Conclusions: The low HIV transmission rate confirms the efficacy of this routine service PMTCT programme. HIV-infected children are not being identified for medical management as part of PMTCT follow-up. It is imperative that record keeping is improved to facilitate ongoing monitoring.

Objective: To determine if the use of the whistle watch (WW), a simple device to monitor peak flow rate, affects the use of bronchodilators at home., Study Design: Prospective, randomised, crossover design., Setting: The asthma outpatients' clinic at Coronation Hospital, a tertiary care centre in Johannesburg., Patients and Methods: Children between 6 and 18 years of age with moderate or severe asthma for more than a year were enrolled. They were randomised into two groups, with bronchodilator use determined either by the WW or solely by the patient's perceived symptomatology. The patients acted as their own controls, switching over to the other group after 30 days. Eighty patients were enrolled into the study., Results: Forty-three patients completed the study (54%). There were no significant differences between these patients and those who did not complete the study in terms of sex, age and treatment characteristics. There was a significant reduction in the mean monthly number of bronchodilator doses used by the WW group (5.5 doses v. 16.81 doses, paired t-test, t = 3.64, P < 0.001, 95% confidence interval (CI) 6.1-16.55). The change in individual participants varied between 13 extra bronchodilator doses and 71 fewer doses per month with the use of the WW device., Conclusion: The WW device is a cheap, easy-to-use and effective tool that reduces the number of bronchodilator doses used by asthmatic children at home.

Objectives: To examine changes in survival rates among low-birth-weight (LBW) infants between the years 1950 and 1996., Methods: Survival figures were analysed for LBW infants managed at Baragwanath Hospital, a tertiary care centre in Soweto, Johannesburg, over four periods spanning five decades., Results: The overall mortality rates of LBW infants decreased markedly between the early 1950s and the period 1995/96. By the mid-1990's approximately four times the number of infants with birth weight less than 1,500 g were surviving compared with the early 1950s. The reduction in mortality rates occurred in all LBW groups during the first three decades. However, since 1981 infants who weighed less than 1,500 g at birth were the major contributors to the overall reduction in mortality. Between the years 1981/82 and 1995/96, survival increased significantly from 64% to 79% for infants with birth weight 1,000-1,499 g, and from 14% to 32% for those with birth weight less than 1,000 g. Since infants in the latter group were seldom offered mechanical ventilation or artificial surfactant, a large part of these increases in survival can be attributed to improvement in the general level of care., Conclusion: There have been dramatic improvements in the survival of LBW infants over this time period at Baragwanath Hospital. Although newer interventions such as mechanical ventilation and artificial surfactant have played a significant role, improvement in care at primary and secondary levels has been of major importance.

The prevalence of periventricular-intraventricular haemorrhage (PV-IVH) among very-low-birth-weight infants at Baragwanath Hospital has not been well documented. In this prospective study, a total of 282 live-born infants with birth weights of 1,000-1,749 g were studied over a 4 1/2-month period. Every infant had at least one cranial ultrasound examination at 7-10 days of age, while one-third of non-ventilated and all ventilated infants had ultrasound examinations on days 3, 7 and 14. Where possible, all infants had a follow-up ultrasound scan at 40 weeks' post-conceptional age. The overall prevalence of PV-IVH was 53% for infants weighing less than 1,500 g at birth and 52% for infants born at less than 35 weeks' gestation, but only 12% had either grade III or grade IV haemorrhages. The prevalence and severity of PV-IVH increased with both decreasing birth weight and decreasing gestational age and was also predicted by the need for active resuscitation at birth, mechanical ventilation and the development of pneumothorax. A total of 93% of infants without PV-IVH survived, but survival decreased with increasing grade of PV-IVH. Germinal matrix cysts were noted on follow-up in 55% of surviving infants with grade I PV-IVH. Very-low-birth-weight infants at Baragwanath Hospital therefore seem to have a higher prevalence of PV-IVH when compared with reported figures, but this is due mainly to an increase in smaller haemorrhages.

This study compared growth of a group of very low birth weight infants fed a formula specifically developed for such infants (Formula) with another group fed expressed breast milk (EBM). The Formula contained 2.4 g/dl of protein (lactalbumin:casein ratio, 60:40); 4.1 g/dl of fat (40% medium-chain triglycerides); 8.8 g/dl of carbohydrates; and 81 kcal/dl, with more calcium, phosphorus, and electrolytes than are in human milk. Premature babies with birth weights between 1,200 and 1,500 g and gestational age less than 36 weeks were eligible for the study and were fed either pooled EBM or Formula until they reached a weight of 1,800 g. Twenty infants fed EBM and 19 infants fed Formula completed the trial. Weight gain was faster in the Formula-fed infants after a caloric intake of 100 kcal/kg/day was achieved (Formula 27.7 g/day vs. EBM 17.2 g/day; p less than 0.001). Time to reach 1,800 g was 27 days for the Formula group and 39 days for those on EBM (p less than 0.001). Increments in head circumference and skinfold thickness were also greater in the Formula-fed group. Laboratory studies in the two groups of infants showed higher alkaline phosphatase levels, which were not due to vitamin D deficiency, in the EBM-fed infants.

A congenital pericardial effusion without a clinically obvious cause is rare. The presentation, diagnostic studies, and anatomic findings in three such cases are described. It is postulated that the fluid within the pericardial sac, was a transudate produced by a partially strangulated portion of the liver, trapped in an intrapericardial hernia with sac, which was present in each case. Encroachment with compression by the enlarged pericardium on the developing lung bud structures is the reason given for the pulmonary hypoplasia, associated with this form of diaphragmatic hernia. Severe pulmonary insufficiency was the presenting feature, while cardiac tamponade is noted for its absence, in these cases.

A combined clinic for pregnant diabetic women was established at Baragwanath Hospital to assess the effects of intensive monitoring of mother and fetus and of good glycaemic control on perinatal outcome. Home blood glucose monitoring was introduced as a method for assessing glycaemic control. Standard methods of maternal and fetal monitoring were used. Sixty-two diabetic pregnancies were evaluated prospectively. Twenty women had diabetes diagnosed for the first time in the current pregnancy and the remaining 42 had established diabetes. All patients followed a diabetic diet, and 95% were treated with insulin. The technique and accurate recording of blood glucose were managed by all patients, and a mean capillary blood glucose of 6.5 mmol/l for the group was achieved. Caesarean section was performed in 52% of cases with a mean period of gestation at the time of delivery for the total study population of 37 weeks. The mean neonatal weight was 3,130 g. The perinatal mortality rate of 64/1,000 was accounted for by 3 stillbirths and 1 early neonatal death. No major congenital anomalies occurred.

The timing of umbilical cord clamping in 38 women with preterm labour was randomly assigned. Ultrasonographic evidence of periventricular/intraventricular haemorrhage (PVH/IVH), assessed blindly, was found in 77% of the group clamped early compared with 35% of those in whom clamping of the cord was delayed for 1 minute. A hypothesis to explain the possible contribution of the haemodynamic events which accompany cord clamping to the development of PVH/IVH is presented.