Preterm birth and severe morbidity in hospitalized neonates who are HIV exposed and uninfected compared with HIV unexposed.

OBJECTIVES: Infants who are HIV exposed but uninfected (HEU) compared with HIV unexposed uninfected (HUU) have an increased risk of adverse birth outcomes, morbidity and hospitalization. In the era of universal maternal antiretroviral treatment, there are few insights into patterns of neonatal morbidity specifically. DESIGN: A prospective cohort study. METHODS: We compared neonatal hospitalizations among infants who were HEU (n = 463) vs. HUU (n = 466) born between 2017 and 2019 to a cohort of pregnant women from a large antenatal clinic in South Africa. We examined maternal and infant factors associated with hospitalization using logistic regression. RESULTS: Hospitalization rates were similar between neonates who were HEU and HUU (13 vs. 16%; P = 0.25). Overall, most hospitalizations occurred directly after birth (87%); infection-related causes were identified in 34%. The most common reason for hospitalization unrelated to infection was respiratory distress (25%). Very preterm birth (<32 weeks) (29 vs. 11%; P = 0.01) as well as very low birthweight (<1500 g) (34 vs. 16%; P = 0.02) occurred more frequently among hospitalized neonates who were HEU. Of those hospitalized, risk of intensive care unit (ICU) admission was higher in neonates who were HEU (53%) than HUU (27%) [risk ratio = 2.1; 95% confidence interval (95% CI) 1.3-3.3]. Adjusted for very preterm birth, the risk of ICU admission remained higher among neonates who were HEU (aRR = 1.8; 95% CI 1.1-2.9). CONCLUSION: Neonates who were HEU (vs. HUU) did not have increased all-cause or infection-related hospitalization. However, very preterm birth, very low birthweight and ICU admission were more likely in hospitalized neonates who were HEU, indicating increased severity of neonatal morbidity.

Short-term outcomes of HIV-exposed and HIV-unexposed preterm, very low birthweight neonates: a longitudinal, hospital-based study.

OBJECTIVE: To compare short-term outcomes of very low birthweight (VBLW, <1500 g) neonates by maternal HIV status. DESIGN: Retrospective hospital-based cohort in Cape Town, South Africa. RESULTS: Of 1579 mothers, 316 (20%) were HIV-positive; 183/316 (58%) received ≥8 weeks of antenatal antiretrovirals. HIV-exposed neonates (HIVE, vs HIV-unexposed, HIVU) had increased risk of necrotising enterocolitis (NEC; OR 1.93, 95% CI 1.27-2.92) and invasive ventilation (OR 1.35, 95% CI 1.01-1.79). Extremely low birthweight (ELBW, <1000 g) modified the HIV-exposure-mortality relationship: among ELBW neonates, HIVE vs HIVU mortality OR 1.75 (95% CI 1.13-2.69); among non-ELBW, OR 0.89 (95% CI 0.54-1.49). Antiretrovirals (≥8 vs <8 weeks/none) reduced NEC (OR 0.46, 95% CI 0.22-0.97) and invasive ventilation risks (OR 0.57, 95% CI 0.32-0.99). HIV-PCR results were available for 228/316 (72%) HIVE neonates; 11/228 (5%) tested positive. CONCLUSIONS: Among VLBW neonates, HIV-exposure was associated with increased risk of adverse short-term outcomes; antenatal antiretrovirals were protective.

HIV Transmission to Premature Very Low Birth Weight Infants.

There is sparse literature about HIV transmission in preterm infants. Eighty-two HIV-exposed preterm infants received birth polymerase chain reactions (PCRs). Five (6.1%) were HIV positive with all 5 mothers receiving inadequate antiretrovirals. Of the PCR-negative infants, 9 died and 87% of the survivors received further PCR testing which remained negative. With correct care, intrapartum transmission of HIV can virtually be eliminated.

Impact of an educational intervention and clinical performance dashboard on neonatal bloodstream infections.

BACKGROUND: Blood cultures are the most direct method of detecting bacteraemia. Reducing contamination rates improves the specificity and positive predictive value of the blood culture. Clinical performance dashboards have been shown to be powerful tools in improving patient care and outcomes. OBJECTIVES: To determine whether prospective surveillance of bloodstream infections (BSIs), introduction of an educational intervention and the use of a clinical performance dashboard could reduce BSIs and blood culture contamination rates in a neonatal nursery. METHODS: We compared two time periods, before and after an intervention. Blood culture data were extracted from the local microbiology laboratory database. The educational intervention included the establishment of hand-washing protocols, blood culture techniques and video tools. A clinical performance dashboard was developed to demonstrate the monthly positive blood culture and contamination rates, and this was highlighted and referred to weekly at the unit staff meeting. RESULTS: Before the intervention, 1 460 blood cultures were taken; 206 (14.1%) were positive, of which 104 (7.1% of the total) were contaminants. In the period following the intervention, 1 282 blood cultures were taken; 131 (10.2%) were positive, of which 42 (3.3% of the total) were contaminants. The number of positive blood cultures and contamination rates after the intervention were both statistically significantly reduced (p=0.002 and p<0.001, respectively). CONCLUSION: This study demonstrates that adopting a relatively simple educational tool, making use of a clinical performance dashboard indicator and benchmarking practice can significantly reduce the level of neonatal sepsis while also reducing contaminated blood cultures.

Fresh Frozen Plasma Use in a Neonatal Unit in South Africa.

BACKGROUND: Despite limited evidence, fresh frozen plasma (FFP) transfusions are a relatively common neonatal procedure. OBJECTIVES: Quantify FFP usage in our unit; determine indications for transfusions and compliance with published guidelines. METHODS: Data were retrospectively collected on infants who received FFP from January 2009 to December 2013. RESULTS: Admissions totalled 10 912 infants during the study period. In total, 113 case notes were reviewed and 142 FFP transfusions were administered. Infants receiving FFP had a high mortality rate (54.87%) and an increased odds ratio for mortality 17.9 (95% confidence interval 12.0-26.6). In total, 75% FFP transfusions were compliant with guidelines. The difference between pre- and post-transfusion coagulation profile in 36.3% of infants was not statistically significant. CONCLUSIONS: FFP was often used in accordance with published guidelines in our neonatal unit. However, the appropriate use and effectiveness of FFP in improving neonatal outcomes undermines the rationale for FFP usage in current guidelines.

Apnoea of Prematurity : Discontinuation of Methylxanthines in a Resource-Limited Setting

Background. Methylxanthines such as caffeine have been proven to reduce apnoea of prematurity and are often discontinued at 35 weeks' corrected gestational age (GA).Objective. To ascertain whether a caffeine protocol based on international guidelines is applicable in our setting; where GA is often uncertain.Methods. A prospective folder review was undertaken of all premature infants discharged home over a 2-month period.Results. Fifty-five babies were included. All babies born at less than 35 weeks' GA were correctly started on caffeine as per protocol. GA was assigned in 85.5 of cases by Ballard scoring and in 14.5 from antenatal ultrasound findings. Caffeine was discontinued before 35 weeks in 54.5 Discussion. The main reason for discontinuing caffeine early was the baby's ability to feed satisfactorily; a demonstration of physiological maturity. As feeding behaviours mature significantly between 33 and 36 weeks; the ability to feed may be a good indication that caffeine therapy can be stopped

Early clinical signs in neonates with hypoxic ischemic encephalopathy predict an abnormal amplitude-integrated electroencephalogram at age 6 hours.

BACKGROUND: An early clinical score predicting an abnormal amplitude-integrated electroencephalogram (aEEG) or moderate-severe hypoxic ischemic encephalopathy (HIE) may allow rapid triage of infants for therapeutic hypothermia. We aimed to determine if early clinical examination could predict either an abnormal aEEG at age 6 hours or moderate-severe HIE presenting within 72 hours of birth. METHODS: Sixty infants ≥ 36 weeks gestational age were prospectively enrolled following suspected intrapartum hypoxia and signs of encephalopathy. Infants who were moribund, had congenital conditions that could contribute to the encephalopathy or had severe cardio-respiratory instability were excluded. Predictive values of the Thompson HIE score, modified Sarnat encephalopathy grade (MSEG) and specific individual signs at age 3-5 hours were calculated. RESULTS: All of the 60 infants recruited had at least one abnormal primitive reflex. Visible seizures and hypotonia at 3-5 hours were strongly associated with an abnormal 6-hour aEEG (specificity 88% and 92%, respectively), but both had a low sensitivity (47% and 33%, respectively). Overall, 52% of the infants without hypotonia at 3-5 hours had an abnormal 6-hour aEEG. Twelve of the 29 infants (41%) without decreased level of consciousness at 3-5 hours had an abnormal 6-hour aEEG (sensitivity 67%; specificity 71%). A Thompson score ≥ 7 and moderate-severe MSEG at 3-5 hours, both predicted an abnormal 6-hour aEEG (sensitivity 100 vs. 97% and specificity 67 vs. 71% respectively). Both assessments predicted moderate-severe encephalopathy within 72 hours after birth (sensitivity 90%, vs. 88%, specificity 92% vs. 100%). The 6-hour aEEG predicted moderate-severe encephalopathy within 72 hours (sensitivity 75%, specificity 100%) but with lower sensitivity (p = 0.0156) than the Thompson score (sensitivity 90%, specificity 92%). However, all infants with a normal 3- and 6-hour aEEG with moderate-severe encephalopathy within 72 hours who were not cooled had a normal 24-hour aEEG. CONCLUSIONS: The encephalopathy assessment described by the Thompson score at age 3-5 hours is a sensitive predictor of either an abnormal 6-hour aEEG or moderate-severe encephalopathy presenting within 72 hours after birth. An early Thompson score may be useful to assist with triage and selection of infants for therapeutic hypothermia.

HIV transmission to extremely low birth weight infants.

BACKGROUND: Prematurity increases the perinatal HIV transmission rate compared with term infants. There is sparse literature documenting the risk of transmission of HIV to extremely low birth weight (ELBW) infants. OBJECTIVE: To determine the risk of perinatal transmission of HIV to ELBW infants in a tertiary neonatal unit in South Africa. METHODS: A prospective database was maintained on all inborn ELBW infants over a 1-year period from March 2010 to February 2011. Survival and DNA HIV polymerase chain reaction results at 6 weeks were recorded. RESULTS: Of the 180 ELBW infants, 51 (28%) of these babies were HIV exposed. Of these 51 infants, 37 survived until 6 weeks of age. Polymerase chain reaction testing revealed 1 HIV-positive infant for a rate of 2.7% (95% confidence interval: 0.7-14.1%). Twenty-six (72%) of the 36 mothers received antiretroviral drugs, but only 16 (44%) had been treated for more than 1 month. CONCLUSIONS: The rate of HIV transmission in this cohort of ELBW infants is very low despite only 44% of the mothers receiving adequate antiretroviral drugs. We postulate that this is due to our high (89%) cesarean section rate, universal (100%) infant prophylactic antiretroviral drugs and the use of pasteurized breast milk.

Defining hypoxic ischemic encephalopathy in newborn infants: benchmarking in a South African population.

OBJECTIVES: There are few population-based studies of hypoxic ischemic encephalopathy (HIE) in sub-Saharan Africa, and the published criteria that are used to define and grade HIE are too variable for meaningful comparisons between studies and populations. Our objectives were (1) to investigate how the incidence of HIE in our region varies with different criteria for intrapartum hypoxia and (2) to determine how encephalopathy severity varies with different grading systems. METHOD: We reviewed the records of infants with a diagnosis of HIE born between September 2008 and March 2009 in public facilities in the Southern Cape Peninsula, South Africa.The incidence of HIE was calculated according to four definitions of intrapartum hypoxia and graded according to three methods. RESULTS: Depending on which defining criteria were applied,the incidence of HIE varied from 2.3 to 4.3 per 1000 live births, of mild HIE ranged from 0.4 to 1.3 per 1000 live births, and of moderate-severe HIE ranged from 1.5 to 3.7 per 1000 livebirths. Ninety-seven of the 110 (88%) infants reviewed had at least one intrapartum-related abnormality. Only 62 (56%) infants had a blood gas performed in the fi rst hour of life. CONCLUSION: The incidence and grade of HIE can vary more than 2-fold in the same population, depending on which defining criteria are used. Consensus definitions are needed for benchmarking.

Growth velocity of extremely low birth weight preterms at a tertiary neonatal unit in South Africa.

INTRODUCTION: There is wide variation in the feeding practices of extreme low birth weight (ELBW) preterms often guided by tradition and resources. The feeding regimen at Groote Schuur Hospital (GSH) nursery, a tertiary neonatal unit, follows a restricted use of parenteral nutrition and concentrates on early introduction of breast milk. There is a need to determine whether this approach achieves acceptable growth velocity. OBJECTIVES: This study aims to describe the growth velocity of ELBW babies at GSH. DESIGN: This was a retrospective cohort study. METHODOLOGY: Infant hospital records of all ELBW babies born at GSH from 1 March to 31 August 2010 were accessed from a previously collected database and relevant data extracted. Growth data were collected from birth to 8 weeks postnatal age or discharge, whichever came first. RESULTS: Ninety-one ELBW babies were born during the study period. Forty were excluded from the study. Thirty died before discharge, and 10 were excluded for other reasons. The mean (SD) gestation of the cohort was 28.5 (1.6) weeks, and the median (range) birth weight was 875 (640-995) g. The overall mean (SD) growth velocity was 14 (2.9) g/kg/day. There was no statistically significant association between the growth velocity and the type of feed given, days to establishing full enteral feeds, time to regaining birth weight, HIV exposure status, intra-uterine growth restriction or exposure to antenatal steroids. CONCLUSION: In our cohort of ELBW infants, growth velocity was within the range currently deemed acceptable by international consensus.

Therapeutic hypothermia and hypoxic ischemic encephalopathy: opinion and practice of pediatricians in South Africa.

BACKGROUND: Recent newborn resuscitation guidelines recommend therapeutic hypothermia (TH) as a treatment to reduce long-term neurological deficit in hypoxic ischemic encephalopathy (HIE) survivors. In South Africa, varied resource constraints may present difficulties in the implementation of TH. OBJECTIVE: To determine the opinions and practice of South African pediatricians, regarding TH and the management of HIE. METHODS: We invited 288 South African pediatricians and neonatologists to participate in a web-based survey by e-mail. Practitioners were identified using the Medpages™ database. RESULTS: Responses were received from 37.8% of the e-mails. Seventy-six percent of respondents stated that hypothermia was either effective or very effective while 4% stated TH was ineffective in the management of HIE. Only 42% of respondents offered TH and a further 9% transferred patients to other units for cooling. Twenty-four percent had not implemented TH nor planned to introduce it into practice in the near future. Ninety-eight percent of respondents stated TH should be the standard of care in tertiary neonatal units. CONCLUSION: Most pediatricians in South Africa who responded to the survey stated that TH is effective to reduce the neurological deficit in HIE, however, less than half offered it as a treatment.

Is the attendance of paediatricians at all elective caesarean sections an effective use of resources?

OBJECTIVES: To determine the need for resuscitation at the birth of babies delivered by elective caesarean section (CS) and to record the time spent by doctors attending such deliveries. METHODS: Data were collected prospectively on all elective CSs performed at Groote Schuur Hospital over a 3-month period. Data collected included: total time involved for paediatrician from call to leaving theatre, management of infant (requiring any form of resuscitation), Apgar scores and neonatal outcome (e.g. admission to nursery). The CSs were classified as low-risk or high-risk (multiple pregnancy, prematurity, growth restriction, abnormal lie, general anaesthetic or known congenital abnormality). RESULTS: Data were recorded for 138 deliveries. Three were excluded as they were not elective CS. One hundred and fifteen deliveries were classified as uncomplicated and 20 as high-risk. Only 1 of the babies born from the 115 low-risk CSs needed brief resuscitation, whereas 9 of the 20 high-risk deliveries resulted in newborn resuscitation. The reasons for low-risk CS were: previous CS (81); infant of diabetic mother (IDM) and previous CS (16); IDM alone (6); estimated big baby (10); and other (2).The average time spent at each elective CS by the pediatrician was 37 minutes. CONCLUSION: For low-risk CS, the same medical attendance (i.e. a midwife) as for an uncomplicated NVD would be appropriate; this can free a doctor for other duties, and assist in de-medicalising a low-risk procedure.

Increased lung water and tissue damage in bronchopulmonary dysplasia.

OBJECTIVES: To test the hypothesis that high and asymmetrical water content persists in infants with bronchopulmonary dysplasia (BPD) and that this is associated with nonuniform lung damage. STUDY DESIGN: Magnetic resonance imaging was used to assess lung water content in 20 infants and tissue injury in 35 infants of 23 to 33 weeks' gestational age (15 with severe BPD, 13 with mild BPD, and 7 without BPD). Relative proton density provided an index of water content and distribution. The location and extent of focal densities and cyst-like appearances indicating lung damage were defined. RESULTS: Proton density was significantly higher in dependent regions. Average proton density, proton density gradient, and severity of lung damage were greater in infants with severe BPD. Indicators of damage were greatest in dorsal lung regions. BPD was associated with a higher lung water burden and gravity-dependent atelectasis and/or alveolar flooding. Lesions were more common in dorsal lung regions in infants with severe lung damage. CONCLUSIONS: Infants with BPD have increased lung water and are susceptible to gravity-induced collapse and/or alveolar flooding in the dependent lung. Focal tissue damage appears to be distributed inhomogenously.

T2 relaxation values in the developing preterm brain.

BACKGROUND AND PURPOSE: MR imaging is increasingly used to assess maturation and disease in the preterm brain. Knowledge of the changes in T2 values with increasing postmenstrual age (PMA) will aid image interpretation and help in the objective assessment of maturation and disease of the brain in infants. The aim of this study was to obtain T2 values in the preterm brain from 25 weeks' gestational age (GA) until term-equivalent age in infants who had normal neurodevelopmental findings at a minimum corrected age of 1 year. METHODS: The study group consisted of 18 preterm infants, born at 33 weeks' GA or sooner. The median GA of the infants at birth was 27 weeks (range, 23-33 weeks), and the median PMA at imaging was 31 weeks (range, 25-41 weeks). T2 measurements were obtained using a 1.0-T MR system and a four-echo pulse sequence (TR/TE, 2500/ 30, 60, 110, and 600). T2 values were measured in the thalami, lentiform nuclei, frontal white matter, occipital white matter, and central white matter at the level of the centrum semiovale. RESULTS: A significant negative linear correlation between T2 values and PMA was demonstrated in the lentiform nuclei (P =.003), frontal white matter (P <.0001), occipital white matter (P <.0001), and central white matter at the level of the centrum semiovale (P <.0001). T2 values were not significantly reduced with increasing PMA in the thalami (P =.06). CONCLUSION: T2 values decrease with increasing PMA in the preterm brain.

Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality.

OBJECTIVE: The most common finding on magnetic resonance imaging (MRI) of the brain in preterm infants at term-equivalent age is diffuse excessive high signal intensity (DEHSI) in the white matter. It is unclear whether DEHSI represents a biological abnormality. This study used diffusion-weighted imaging (DWI) to compare apparent diffusion coefficient (ADC) values in DEHSI with infants with normal imaging and those with overt brain damage to determine whether DEHSI shows the diffusion characteristics of normal or abnormal tissue. METHODS: MRI, using conventional and diffusion-weighted imaging (DWI), was performed in 50 preterm infants at term-equivalent age using a 1.5 Tesla MR scanner. The infants were divided into 3 groups on the basis of their MRI results: 1) normal white matter, 2) DEHSI, or 3) overt white matter pathology. ADC values were measured in the frontal, central, and posterior white matter at the level of the centrum semiovale. ADC values in the 3 groups of preterm infants were compared using a 1-way analysis of variance with a Bonferroni test for multiple comparisons. RESULTS: ADC values were significantly higher in infants with DEHSI and infants with overt white matter pathology than in infants with normal white matter. There was no significant difference between ADC values in infants with DEHSI and those with overt white matter pathology. CONCLUSIONS: This study provides objective evidence that DEHSI represents diffuse white matter abnormality.