[Show abstract][Hide abstract] ABSTRACT: Background:
Vaccinating pregnant women may prevent invasive Group B Streptococcus (GBS) disease in their young infants. In a low-middle income setting, we sought to determine an association between natural maternal antibody responses and the development of invasive GBS disease.
We undertook a matched case-control study in Johannesburg, South Africa. Maternal and infant antibody concentrations were compared between serotype-specific Ia and III GBS cases and well-baby controls in which the mother was colonized with the same serotype.
The median maternal serotype Ia and III antibody concentrations (in μg/mL) were 0.05 (IQR: 0.02-0.24; n=27) and 0.14 (IQR: 0.08-0.33; n=29) in cases, and 0.29 (IQR: 0.06-1.60; n=43) and 0.29 (IQR: 0.13-0.58; n=31) in homotypic controls, respectively. A smaller proportion of cases as compared to homotypic controls had higher serotype Ia and III maternal antibody concentrations. Using Bayesian modeling, we demonstrated that the risk of invasive GBS disease was less than 10% with maternal antibody concentrations ≥6μg/mL and ≥3μg/mL for serotypes Ia and III, respectively.
Maternal capsular antibody concentrations are associated with the risk of invasive GBS disease in infants. In a low-middle income setting with a high burden of invasive disease, we have demonstrated a sero-correlate of protection for GBS serotypes Ia and III which could facilitate vaccine licensure.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Group B Streptococcus (GBS) surface-proteins have been shown to be immunogenic and potential vaccine candidates. We aim to determine the association between maternal IgG antibodies to select GBS surface-proteins and invasive GBS disease in their infants.
Using a matched case-control study, maternal antibody levels for GBS-immunogenic bacterial adhesin, fibrinogen-binding protein A and pilus-island (PI) PI-1, PI-2a, PI-2b were compared between infants with invasive GBS disease and well-baby controls.
The absolute risk of disease did not differ between cases and colonized controls with increasing antibody concentrations for these surface-proteins. There was, however, a relative risk reduction in invasive disease associated with fibrinogen-binding protein A, with an adjusted odds ratio of 0.04 (95% CI: 0.01-0.69) at antibody levels ≥10,000 AU/ml.
We have not demonstrated an association between naturally occurring fibrinogen-binding protein A, GBS-immunogenic bacterial adhesin, and PI surface-protein antibodies and the risk of invasive disease in young infants. These surface-proteins may not be suitable GBS vaccine candidates.
[Show abstract][Hide abstract] ABSTRACT: Although group B Streptococcus (GBS) is a leading cause of severe invasive disease in young infants worldwide, epidemiologic data and knowledge about risk factors for the disease are lacking from low- to middle-income countries. To determine the epidemiology of invasive GBS disease among young infants in a setting with high maternal HIV infection, we conducted hospital-based surveillance during 2004-2008 in Soweto, South Africa. Overall GBS incidence was 2.72 cases/1,000 live births (1.50 and 1.22, respectively, among infants with early-onset disease [EOD] and late-onset [LOD] disease). Risk for EOD and LOD was higher for HIV-exposed than HIV-unexposed infants. GBS serotypes Ia and III accounted for 84.0% of cases, and 16.9% of infected infants died. We estimate that use of trivalent GBS vaccine (serotypes Ia, Ib, and III) could prevent 2,105 invasive GBS cases and 278 deaths annually among infants in South Africa; therefore, vaccination of all pregnant women in this country should be explored.
[Show abstract][Hide abstract] ABSTRACT: Objective:
To determine the incidence of asphyxia and hypoxic ischaemic encephalopathy (HIE) and predictors of poor outcome in a hospital in a developing country.
Neonates of birth weight ≥ 2,000 g who required bag-and-mask ventilation and were admitted with a primary diagnosis of asphyxia from January to December 2011 were included. Medical records were retrieved and maternal and infant data collected and analysed. Infants who had severe HIE and/or died were compared with those who survived to hospital discharge with no or mild to moderate HIE.
There were 21 086 liveborn infants with a birth weight of 2 000 g over the study period. The incidence of asphyxia ranged from 8.7 to 15.2/1 000 live births and that of HIE from 8.5 to 13.3/1 000, based on the definition of asphyxia used. In 60% of patients with HIE it was moderate to severe. The overall mortality rate was 7.8%. The mortality rate in infants with moderate and severe HIE was 7.1% and 62.5%, respectively. The odds of severe HIE and/or death were high if the Apgar score was <5 at 10 minutes (odds ratio (OR) 19.1; 95% confidence interval (CI) 5.7-66.9) and if there was no spontaneous respiration at 20 minutes (OR 27.2; 95% CI 6.9-117.4), a need for adrenaline (OR 81.2; 95% CI 13.2-647.7) and a pH of < 7 (OR 5.33; 95% CI 1.31-25.16). Predictors of poor outcome were Apgar score at 10 minutes (p = 0.004), need for adrenaline (p = 0.034) and low serum bicarbonate (p = 0.028).
The incidence of asphyxia in term and near-term infants is higher than that reported in developed countries. Apgar score at 10 minutes and need for adrenaline remain important factors in predicting poor outcome in infants with asphyxia.
[Show abstract][Hide abstract] ABSTRACT: Background:
Human immunodeficiency virus (HIV)-exposed infants are at increased risk of invasive Group B Streptococcus (GBS) disease; however, the reason for this increased susceptibility has not been characterized.
We compared GBS capsular and surface-protein maternal immunoglobin G antibody concentrations and cord-maternal ratios between HIV-infected and HIV-uninfected mother-newborn dyads.
Median capsular antibody concentrations (µg/mL) were lower in HIV-infected than HIV-uninfected women for serotypes Ib (P = .033) and V (P = .040); and for pilus island (PI)-1 (P = .016), PI-2a (P = .015), PI-2b (P = .015), and fibrinogen-binding protein A (P < .001). For serotypes Ia and III, cord-maternal ratios were 37.4% (P < .001) and 32.5% (P = .027) lower in HIV-infected compared to HIV-uninfected mother-newborn dyads. The adjusted odds of having capsular antibody concentration ≥2 µg/mL when comparing HIV-infected to -uninfected women were 0.33 (95% confidence interval [CI], .15-.75) and 0.34 (95% CI, .12-1.00) for serotypes Ia and III, respectively. Antibody levels and cord-maternal ratios were independent of CD4(+) lymphocyte counts or HIV-1 viral load.
The lower GBS antibody concentrations and reduced transplacental antibody transfer in HIV-infected women, which likely contribute to their infants being at heightened susceptibility for invasive GBS disease, could possibly be mitigated by vaccination with a GBS conjugate vaccine currently under clinical development.
The Journal of Infectious Diseases 02/2015; 212(3). DOI:10.1093/infdis/jiv064 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Cytomegalovirus (CMV) infection is a common congenital infection in neonates. Clinical presentation and laboratory findings in CMV-infected infants in a setting where HIV is prevalent are not well characterised.
South African journal of child health 12/2014; 8(4):133. DOI:10.7196/sajch.752
[Show abstract][Hide abstract] ABSTRACT: Background:
Despite high herpes simplex virus type 2 (HSV-2) incidence and prevalence among women in Africa, we are unaware of published neonatal herpes reports. To assess neonatal HSV transmission potential in South Africa, we investigated the frequency of the strongest risk factors: HSV acquisition in late pregnancy and HSV shedding during labor.
Women admitted in early labor to a hospital in Soweto underwent HSV serologic testing and genital swab collection for HSV PCR. HSV-2 seronegative women were assessed for seroconversion 4-6 weeks after delivery.
Of 390 women enrolled, 229 (58.7%) were HSV-2 seropositive. Genital HSV-2 was detected in 17.2% of HSV-2 seropositive women, including 26 of 115 HIV-positive and 13 of 110 HIV-negative women (22.6% versus 11.8%; RR, 1.91; 95% CI, 1.04-3.53; P = 0.038), but in none of 161 HSV-2 seronegative women. Among the 91 HSV-2 seronegative women followed after delivery, none seroconverted.
HSV-2 reactivation is common among South African women during labor, especially those with HIV coinfection. To determine the epidemiology of neonatal herpes in South Africa and to investigate whether the lack of reported cases is due to alterations in immune control or HSV-2 virulence, studies evaluating acutely ill neonates for HSV and studies of maternal HSV-2 shedding patterns are needed.
Infectious Diseases in Obstetrics and Gynecology 05/2014; 2014:258291. DOI:10.1155/2014/258291
[Show abstract][Hide abstract] ABSTRACT: Background: Several risk factors have been implicated in the development of necrotising enterocolitis (NEC). However, little has been reported on the risk factors for NEC in infants born in a setting where exposure to maternal human immunodeficiency virus (HIV) is prevalent. Objectives: To determine maternal and infant characteristics associated with NEC in a setting with a high prevalence of HIV infection and to compare clinical presentation and mortality of NEC in HIV-exposed and unexposed infants. Methods: This was a retrospective, case-control study. Infants with a confirmed diagnosis of NEC, admitted between January 2005 and December 2008 were identified as cases. Two controls for each case were selected by matching them for birthweight, gestational age and date of birth. Hospital records were reviewed for maternal and infant characteristics. Results: One hundred and ten infants with confirmed NEC were identified and 220 were selected as controls. Median birthweight and gestational age were similar between cases and controls, (1370 and 1380 g, P = 0·96, and 31 weeks each, P = 0·62, respectively). Lack of use of antenatal corticosteroids (ANS) (OR 2·77, 95% CI 1·42-5·38, P = 0·003), presence of chorio-amnionitis (OR 7·28, 95% CI 2·16-24·51, P = 0·001) and not mechanically ventilated at birth (OR 3·54, 95% CI 1·29-9·69, P = 0·01) were independently associated with NEC. Maternal HIV status was not associated with NEC. Clinical presentation and mortality from NEC were similar between HIV-exposed and unexposed infants. Conclusions: Infants who develop NEC were less likely to have received mechanical ventilation at birth, suggesting that they were less critically ill when born. Use of ANS should be encouraged as it is protective against NEC. Infants born to HIV-infected mothers were not at increased risk of NEC.
Paediatrics and international child health 05/2014; 34(3):2046905514Y0000000126. DOI:10.1179/2046905514Y.0000000126 · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Delayed clamping of the umbilical cord is recommended for term and preterm infants who do not require resuscitation. However, the approach to the newly born infant with signs of fetal compromise, prematurity and extremely low birthweight, or prolonged apnea is less clear. Human and experimental animal data show that delaying the clamping of the umbilical cord until after the onset of respirations promotes cardiovascular stability in the minutes immediately after birth. Rather than regarding delayed cord clamping as a fixed time period before resuscitation begins, a more physiologic concept of transition at birth should encompass the relative timing of onset of respirations and cord occlusion. Further research to explore the potential benefits of resuscitation with the cord intact is needed.
Seminars in Fetal and Neonatal Medicine 09/2013; 18(6). DOI:10.1016/j.siny.2013.08.008 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. Methods For this pooled analysis, we searched all available studies and identifi ed 20 cohorts (providing data for 2 015 019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk diff erences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. Findings Pooled overall RRs for preterm were 6·82 (95% CI 3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34–2·50) for neonatal mortality and 1·90 (1·32–2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11–26·12). Interpretation Many babies in low-income and middle-income countries are SGA. Preterm birth aff ects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Diff erentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4—the reduction of child mortality.
The Lancet 06/2013; 382(9890):417–25. DOI:10.1016/S0140-6736(13)60993-9 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Seizures after an asphyxial insult may result in brain damage in neonates. Prophylactic phenobarbital may reduce seizures. Objective. To determine the effect of prophylactic phenobarbital on seizures, death and neurological outcome at hospital discharge. Methods. Neonates with base deficit >16 mmol/l and Apgar score at 5 minutes <7 or requiring resuscitation for >5 minutes at the time of birth were randomised to prophylactic phenobarbital 40 mg/kg (n=50) or placebo (controls) (n=44) within the first 6 hours of life. They were monitored for clinical seizures, hypoxic ischaemic encephalopathy (HIE) and mortality. Results. Seizures developed in 30.0% of the phenobarbital group as opposed to 47.7% of the control group (relative risk 0.63; 95% confidence interval-0.37-1.06; p=0.083). The proportions of patients who had died and/or had HIE II or III at time of discharge from hospital were similar in the two groups (42.0% v. 45.5%). There were no differences in mortality between the two groups (14.0% v. 15.9%). Conclusion. In infants with asphyxia, prophylactic phenobarbital does not reduce the incidence of seizures, HIE and mortality.
South African journal of child health 02/2013; 7(1). DOI:10.7196/sajch.494
[Show abstract][Hide abstract] ABSTRACT: HIV-exposed newborns may be at higher risk of sepsis because of immune system aberrations, impaired maternal antibody transfer and altered exposure to pathogenic bacteria.
We performed a secondary analysis of a study (clinicaltrials.gov, number NCT00136370) conducted between April 2004 and October 2007 in South Africa. We used propensity score matching to evaluate the association between maternal HIV infection and (1) vaginal colonization with bacterial pathogens; (2) vertical transmission of pathogens to the newborn; and (3) sepsis within 3 days of birth (EOS) or between 4-28 days of life (LOS).
Colonization with group B Streptococcus (17% vs 23%, P = .0002), Escherichia coli (47% vs 45%, P = .374), and Klebsiella pneumoniae (7% vs 10%, P = .008) differed modestly between HIV-infected and uninfected women, as did vertical transmission rates. Maternal HIV infection was not associated with increased risk of neonatal EOS or LOS, although culture-confirmed EOS was >3 times higher among HIV-exposed infants (P = .05). When compared with HIV-unexposed, neonates, HIV-exposed, uninfected neonates (HEU) had a lower risk of EOS (20.6 vs 33.7 per 1000 births; P = .046) and similar rate of LOS (5.8 vs 4.1; P = .563). HIV-infected newborns had a higher risk than HEU of EOS (134 vs 21.5; P < .0001) and LOS (26.8 vs 5.6; P = .042).
Maternal HIV infection was not associated with increased risk of maternal bacterial colonization, vertical transmission, EOS, or LOS. HIV-infected neonates, however, were at increased risk of EOS and LOS.
[Show abstract][Hide abstract] ABSTRACT: Factors associated with neonatal sepsis, an important cause of child mortality, are poorly described in Africa. We characterized factors associated with early-onset (days 0-2 of life) and late-onset (days 3-28) -sepsis and perinatal death among infants enrolled in the Prevention of Perinatal Sepsis Trial (NCT00136370 at ClinicalTrials.gov), Soweto, South Africa.
Secondary analysis of 8011 enrolled mothers and their neonates. Prenatal and labor records were abstracted and neonatal wards were monitored for hospitalized Prevention of Perinatal Sepsis-enrolled neonates. Endpoint definitions required clinical and laboratory signs. All univariate factors associated with endpoints at P < 0.15 were evaluated using multivariable logistic regression.
About 10.5% (837/8011) of women received intrapartum antibiotic prophylaxis; 3.8% of enrolled versus 15% of hospital births were preterm. Among 8129 infants, 289 had early-onset sepsis, 34 had late-onset sepsis, 49 had culture-confirmed neonatal sepsis and 71 died in the perinatal period. Factors associated with early-onset sepsis included preterm delivery [adjusted relative risk (aRR) = 2.6; 95% confidence interval (CI): 1.4-4.8]; low birth weight (<1500 g: aRR = 6.5, 95% CI: 2.4-17.3); meconium-stained amniotic fluid (MSAF) (aRR = 2.8, 95% CI: 2.2-3.7) and first birth (aRR = 1.8; 95% CI: 1.4-2.3). Preterm, low birth weight, MSAF and first birth were similarly associated with perinatal death and culture-confirmed sepsis. MSAF (aRR = 2.4, 95% CI: 1.1-5.0) was associated with late-onset sepsis.
Preterm and low birth weight were important sepsis risk factors. MSAF and first birth were also associated with sepsis and death, warranting further exploration. Intrapartum antibiotic prophylaxis did not protect against all-cause sepsis or death, underscoring the need for alternate prevention strategies.