An analysis of neonates with surgical diagnoses admitted to the neonatal intensive care unit at Charlotte Maxeke Johannesburg Academic Hospital, South Africa.

BACKGROUND: The burden of neonatal surgical conditions is not well documented in low- to middle-income countries (LMICs). These conditions are thought to be relatively common, with a considerable proportion of neonates admitted to the neonatal intensive care unit (NICU) requiring surgical intervention. OBJECTIVES: To review neonates with surgical conditions admitted to the NICU in our hospital setting. METHODS: This was a retrospective, descriptive study of neonates with surgical conditions admitted to the NICU at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), South Africa, between 1 January 2013 and 31 December 2015. The characteristics and survival of these neonates were described using univariate analysis. The NICU at CMJAH is combined with a paediatric intensive care unit, to a total of 15 beds, and serves as a referral unit. RESULTS: Of 923 neonates admitted to the NICU, 319 (34.6%) had primarily surgical conditions. Of these 319 neonates, 205 survived (64.3%). There were 125/319 neonates (39.2%) with necrotising enterocolitis (NEC), 55 of whom survived (55/125; 44.0%), making the presence of NEC significantly associated with poor outcome (p<0.001). Other significant predictors of poor outcome were the patient being outborn (p=0.029); the presence of late-onset sepsis (p<0.001), with Gram-negative organisms (p=0.005); and lesser gestational age (p=0.001) and lower birth weight (p<0.001). Major birth defects were present in 166/319 neonates (52.0%). The abdomen was the most prevalent site of surgery, with 216/258 procedures (83.7%) being abdominal, resulting in a mortality rate of 76/216 (35.2%). CONCLUSIONS: Neonates with major surgical conditions accounted for one-third of NICU admissions in the present study. The study highlights the considerable burden placed on paediatric surgical services at a large referral hospital in SA. Paediatric surgical services, with early referral and improvement of neonatal transport systems, must be a priority in planned healthcare interventions to reduce neonatal mortality in LMICs.

A prospective observational study of developmental outcomes in survivors of neonatal hypoxic ischaemic encephalopathy in South Africa.

BACKGROUND: Neonatal hypoxic ischaemic encephalopathy (NHIE) is an important cause of long-term handicap in survivors. There is limited information on the burden of handicap from NHIE in sub-Saharan Africa. OBJECTIVES: To determine the developmental outcomes in survivors of NHIE in South Africa (SA). METHODS: In this prospective observational study, the developmental outcomes in 84 infants who had survived hypoxic ischaemic encephalopathy (the NHIE group) were compared with those in 64 unaffected infants (the control group). The Bayley Scales of Infant Development version III were used for assessment of developmental outcomes. RESULTS: Significant differences were found between the developmental outcomes of the two groups, with a significantly lower composite language score and higher proportions with language, motor and cognitive developmental delays in the NHIE group than in the control group. Cerebral palsy (CP) was present in 13 of the infants with NHIE (15.5%) and none in the control group (p<0.001). CP was associated with developmental delay, and also with the severity of NHIE. Therapeutic hypothermia (TH) was administered in 58.3% of the study group, but although it was associated with lower rates of CP and developmental delay than in the group without TH, the only significant difference was for delay on the language subscale. CONCLUSIONS: Survivors of NHIE in SA are at risk of poor developmental outcomes.

A review of antenatal corticosteroid use in premature neonates in a middle-income country.

BACKGROUND: Antenatal corticosteroid (ANS) use in premature neonates has become a standard of practice. However, there is low ANS coverage in low- to middle-income countries (LMICs). Recent studies have questioned the efficacy of ANSs in such countries. OBJECTIVE: To review the use of ANSs in preterm neonates at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), South Africa. METHODS: This was a retrospective observational study of all neonates with a birth weight of 500 - 1 800 g born at CMJAH between 1 January 2013 and 30 June 2016. Neonatal and maternal characteristics of neonates exposed to ANSs were compared with those of neonates who were not exposed. RESULTS: The ANS coverage of the final sample was 930/2 109 (44.1%). The mean (standard deviation (SD)) birth weight was 1 292.4 (323.2) g and the mean gestational age 30.2 (2.9) weeks. Attending antenatal care and maternal hypertension were associated with increased use of ANSs, whereas vaginal delivery was associated with decreased use. In neonates weighing <1 500 g, the use of ANSs was associated with decreased mortality, decreased intraventricular haemorrhage and decreased patent ductus arteriosus. There was no association between ANSs and respiratory distress syndrome, necrotising enterocolitis, sepsis or need for respiratory support in all premature neonates, and no association with improved outcomes in those weighing ≥1 500 g. CONCLUSION: The benefits of ANSs in terms of neonatal morbidity in this study were not as marked as those published in high-income countries. A randomised controlled trial may be indicated in LMICs.

A comparison of high versus low dose recombinant human erythropoietin versus blood transfusion in the management of anaemia of prematurity in a developing country.

The purpose of this study was to evaluate the effectiveness of early treatment with erythropoietin (EPO) in two different treatment regimes (high vs. low dose) in comparison to the conventional treatment of packed red blood cell (PRBC) transfusions in the management of anaemia of prematurity in a country with limited resources. An open controlled trial was conducted on 93 preterm infants (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group. EPO was administered subcutaneously three times a week and all infants received 6 mg/kg iron orally from study entry to endpoint of therapy. Haematological parameters were measured and compared. The success was defined as an absence of transfusions and a haematocrit that did not fall below 30 per cent during the time period that the infants were in the study. The three groups were statistically comparable at study entry with respect to gestational age, birthweight, Apgar scores, and haematological values. Over the period that the infants were in the study, 75 per cent of the low dose group and 71 per cent of the high dose group met the criteria for success compared with 40 per cent in the control group (p < 0.001). However, there was no significant difference in the number of transfusions when the low and high EPO dose groups (9.5 per cent) were combined and compared with the control group (26.7 per cent) p = 0.0587. It was concluded that in stable infants, 900-1500 g, where phlebotomy losses are minimized and stringent transfusion guidelines are adhered to, EPO does not significantly decrease the number of transfusions. A conservative approach in the management of anaemia of prematurity, is a viable alternative in areas with limited resources.

Hematological reference ranges in black very low birth weight infants.

This study compared hematological reference ranges in black very low birth weight infants to previously published values established predominantly on white subjects. Ninety-four healthy, black, premature babies with a birth weight of 800 to 1500 g at 2-7 days of age were enrolled as part of a study comparing blood transfusions and high- versus low-dose recombinant erythropoietin in anaemia of prematurity. Peripheral venous blood was collected for a full blood count and differential, fetal hemoglobin and erythropoietin levels. The hematological parameters observed in black very low birth weight neonates are similar to previously published reference ranges, except that lower limits of normal were observed for hemoglobin and the red cell indices.

Is prophylaxis of early-onset group B streptococcal disease appropriate for South Africa?

BACKGROUND: Early-onset group B streptococcal (GBS) disease in neonates can be prevented by the use of intrapartum chemoprophylaxis. There are two prevention strategies, one based on risk factors and the other on culture screening for GBS. This study sought to establish whether GBS chemoprophylaxis is appropriate in a developing country such as South Africa. METHODS: All neonates with early-onset GBS disease born at Johannesburg Hospital between 1 January 1995 and 21 December 1997 were reviewed. Data were collected prospectively between 1 January and 31 October 1998. Data included demographic information, obstetric information, disease characteristics, admission details and mortality. The approximate cost of implementing both strategies was determined. RESULTS: The overall incidence of early-onset GBS was 1.16 per 1,000 live births. The rate was significantly greater in 1998 compared with the previous years. Most of the babies were born preterm (70%), and 60% required admission to the neonatal intensive care unit (ICU) (a total of 81 ICU days). Twelve of the babies died. Assuming that chemoprophylaxis would reduce the number of ICU days by half, this would save an amount of R52,000. Culture-based chemoprophylaxis would cost R10 million, whereas an approach based on risk factors would cost R31,140. CONCLUSION: In conclusion, we feel that early-onset GBS disease is sufficiently prevalent in our unit to justify the implementation of a chemoprophylaxis strategy based on risk factors. Whether other units should adopt a similar approach would depend on the local incidence of early-onset GBS.

Serial interleukin 6 measurements in the early diagnosis of neonatal sepsis.

The objective of the present study was to evaluate serial interleukin 6 (IL6) levels in the early diagnosis of neonatal sepsis. Subjects included 255 neonates from the Neonatal Unit of Johannesburg Hospital evaluated for suspected sepsis between February and May 1998. All infants had IL6, full blood count (FBC), C reactive protein (CRP) and blood cultures done at presentation. CRP and IL6 were repeated after 24 h. Infants were categorized into groups according to the likelihood of infection on the basis of clinical presentation, CRP, FBC and culture results, i.e., group 1 (no infection) to group 4 (definite infection). IL6 was compared between the groups by the U-test of Mann-Whitney; stepwise logistic regression was done to establish the best predictors of infection, sensitivity, specificity, positive and negative predictive values were determined. The initial IL6 level was significantly raised in those infants with possible infection [880.67 pg/ml (2966.04), p value 0.0104], probable infection [422.62pg/ml (4077.7), p value 0.0021] and definite infection [11164.39pg/ml (24139.77), p value 0.0000] as compared to those infants without infection [58.65 (182.4)]. The best predictors of infection were the combination of the initial IL6 value and CRP value after 24 h (goodness of fit 97.7 per cent). An initial IL6 value below 20 pg/ml gave a negative predictive value of 90.18 per cent. It is concluded that an IL6 value done at the time of presentation of signs and symptoms suggestive of infection is useful in the early diagnosis of neonatal sepsis. In particular, an initial IL6 value below 20 pg/ml may allow antibiotics to be withheld in a number of infants evaluated for sepsis. There is no benefit in serial determination of IL6 in the diagnosis of neonatal sepsis.

Use of C-reactive protein to guide duration of empiric antibiotic therapy in suspected early neonatal sepsis.

BACKGROUND: Serial C-reactive protein (CRP) measurements have been shown to be useful for guiding duration of antibiotic therapy in neonates. This study sought to determine whether this is a safe and practical approach in a developing country. METHODS: The study was conducted at the Johannesburg Hospital between September 15, 1998, and January 15, 1999. Subjects included all neonates evaluated for suspected sepsis in the first 24 h of life who had negative initial and repeat CRP values (< or = 10 mg/l) [corrected]. Repeat CRP measurements were performed between 24 and 48 h after birth. Antibiotic therapy was stopped in these infants at 24 to 48 h, and they were observed until 72 h, when the final blood culture results were available. The number of positive blood cultures in this group was determined. RESULTS: The repeat CRP estimation correctly identified 99 of 100 infants in the study as not requiring further antibiotic therapy (negative predictive value, 99%; 95% confidence intervals, 95.6 to 99.97%). The 1 infant with a positive blood culture was premature with a gestational age of 31 weeks. Eight babies required repeat evaluation for suspected sepsis, 4 presented on Day 3 to 4 and one of these babies died. All these neonates were of < or =33 weeks gestation. CONCLUSION: The use of serial CRP measurements to guide antibiotic therapy is a safe and practical approach in neonates with suspected sepsis in a developing country.

Factors associated with poor prognosis in very-low-birth-weight infants.

OBJECTIVE: To evaluate predictors of poor outcome, including the CRIB (Clinical Risk Index for Babies) score, in a local population of very-low-birth-weight (VLBW) infants, in order to provide guidelines for selection of these babies for expensive tertiary care. SUBJECTS: Two hundred and thirty-one neonates born at less than 31 weeks' gestation and/or weighing between 1001 g and 1500 g, enrolled prospectively as part of a multicentre study evaluating the CRIB score. DESIGN: Univariate analysis (chi-square/t-tests) and multivariate analysis (stepwise logistic regression) on the above sample to determine predictors of poor outcome. SETTING: Neonatal Unit, Johannesburg Hospital. OUTCOME MEASURES: Death or impairment (namely oxygen therapy > 28 days, grade 3 or 4 intraventricular haemorrhage, or ventricular enlargement). RESULTS: Poor outcome was predicted by birth weight, lowest oxygen requirement in the first 12 hours (which are two components of the CRIB score), and maximum partial arterial carbon dioxide pressure (PaCO2) in the first 72 hours. Other factors, including the full CRIB score, were not predictive of outcome. CONCLUSIONS: One method of selection of infants for expensive tertiary care is on the basis of predicted outcome. Birth weight remains a reasonable basis for this selection, but the inclusion of other factors, such as oxygen requirement, would improve accuracy. The CRIB score was not a suitable means to select infants in the local context, but may be of value in international comparisons.

Selection of paediatric patients for intensive care.

OBJECTIVES: To determine characteristics of older infants and children admitted to the paediatric intensive care unit (PICU) at Johannesburg Hospital; and to evaluate an admission score based on the PRISM score (an index of severity of illness) as a possible means for selection of patients for admission to the PICU. DESIGN: Retrospective review of patient records and calculation of admission score from data. SETTING: Paediatric intensive care unit at Johannesburg Hospital. SUBJECTS: All patients older than 3 months of age admitted to the PICU from July 1993 to 31 March 1994. RESULTS: There were 117 admissions during the study period with a mean age of 4,6 years. The mortality rate was 29.1%. The mean duration of ICU stay was 4,2 days. A review of requests for admission showed that over a 7-month period, 53 patients (> 3 months) could not be accommodated. In 71 patients with complete data, the admission score was significantly higher in non-survivors than survivors. The area under the ROC curve for predicting mortality from the admission score was 0.73 (SE 0.054). An admission score > or = 16 predicted mortality with a sensitivity of 42% and a specificity of 98%. CONCLUSIONS: PICU facilities at Johannesburg Hospital are insufficient to meet the demand. An admission score based on the PRISM score could assist in the selection of patients for these limited PICU facilities.

Reasons for failure to administer antenatal corticosteroids in preterm labour.

A retrospective review of 101 preterm infants delivered at Johannesburg Hospital was conducted to determine the use of antenatal corticosteroids (ACs). Overall there were 38 opportunities for the use of ACs of which 18 were missed. Of the remaining mothers, 32 presented in advanced labour, 22 presented with obstetric emergencies and 6 were managed as inevitable abortions. There was a significant association between lack of antenatal care and presentation in advanced labour. Therefore, although only 20% of mothers received ACs, there was no opportunity for their use in the majority of patients. The use of a safe and cost-effective measure such as ACs should not be ignored in a country with limited health resources. Better antenatal care as well as increased awareness among obstetricians is required to improve the situation.

The introduction of surfactant replacement therapy into South Africa.

Within the context of limited financial and physical resources in South Africa, academic neonatologists have established strict criteria for ventilation of neonates with hyaline membrane disease (HMD). In the private sector neonatal care is less structured. Following the introduction of the artificial surfactant (Survanta) in November 1991 it was considered important to monitor its use in the public and private sectors. In collaboration with the marketing company a data sheet containing demographic information and clinical details was drawn up to be completed in each case where Survanta was administered to babies with HMD. Data from 155 babies treated at 10 hospitals were included in the final analysis (70 babies from 4 State-funded academic hospitals and 85 from 6 privately funded hospitals). Within the group of private hospitals there were some which treated large numbers of babies weighing > 2,000 g, while in a few others there was a relative excess of babies weighing < 1,000 g. There was a higher incidence of patent ductus arteriosus and intraventricular haemorrhage, and a higher mortality rate at the academic hospitals. Poor outcome at these institutions may largely have been due to poor antenatal care.

The selection of infants for surfactant replacement therapy under conditions of limited financial resources.

The cost of surfactant replacement therapy (SRT) will restrict its use under conditions of limited health resources. Before the local advent of SRT, infants ventilated for hyaline membrane disease (HMD) had an overall survival rate of 87% and an incidence of bronchopulmonary dysplasia of 6.4%. This, together with the cost of SRT, prompted a study to identify those infants who would benefit the most from SRT. Twenty-two infants assessed as having severe HMD were randomised to receive SRT at 3 - 4 hours (9) or at 6 - 8 hours (13) after birth. Two infants (15%) in the latter group did not require SRT. The outcome of these two groups was the same. Of 56 infants assessed as having moderate HMD, only 24 (43%) qualified for SRT from 6 hours of age. The outcome of the SRT and non-SRT infants was comparable. The group of infants with moderate HMD had a significantly better outcome than those with severe HMD. A limited period of observation to assess the severity of illness did not compromise outcome in this group of 78 infants with moderate to severe HMD.

The cost and effectiveness of surfactant replacement therapy at Johannesburg Hospital, November 1991-December 1992.

OBJECTIVE: To assess the impact of surfactant replacement therapy (SRT) on the outcome of hyaline membrane disease (HMD) and to assess the cost implications of a policy of selective administration of artificial surfactant. DESIGN: The short-term outcome of 103 newborns ventilated for HMD (61 selected for SRT according to initial and/or ongoing oxygen requirements) was compared with that of a historical control group of 173 infants ventilated for HMD before the introduction of SRT. MAIN OUTCOME MEASURES: Mortality and morbidity of HMD including death, bronchopulmonary dysplasia, pneumothorax, pulmonary haemorrhage, patent ductus arteriosus and intraventricular haemorrhage. RESULTS: There were significant demographic differences between the treatment and control groups (black patients 74% v. 28%, P < 0.0001; unbooked mothers 72% v. 15%, P < 0.0001) as well as evidence of more severe lung disease in the treatment group (pressor support 44% v. 27%, P < 0.005; and paralysis during ventilation 38% v. 25%, P < 0.005). Pneumothorax was reduced in the SRT group (7% v. 17%, P < 0.01). There were no significant differences between the two groups in the incidence of BPD or mortality. The use of SRT added to the total cost of treating a patient ventilated for HMD. CONCLUSION: The selective use of SRT had the effect of converting severe disease into moderate disease rather than achieving maximal benefit in all cases of HMD through routine use of the product. A policy of restricting use may result in cost savings where resources are limited.

The late administration of surfactant.

Current recommendations for surfactant replacement therapy (SRT) in the treatment of hyaline membrane disease (HMD) are to administer the drug as soon as possible after starting ventilation in order to prevent ventilator lung damage. We present a review of 18 infants (gestational age 32.4 +/- 1.9 weeks and birth weight 1,795 +/- 427 g) who received the initial dose of SRT after they were 12 hours old. Fourteen infants were assessed as having HMD and 4 as having congenital pneumonia. Overall there was a significant and sustained improvement in oxygenation as measured by arterial/alveolar oxygen ratios. The outcome of these infants was good, with a duration of ventilation of 7.9 +/- 4.3 days and a duration of hospitalisation of 26.2 +/- 12.6 days. No infant developed bronchopulmonary dysplasia. Of particular interest is that 3 infants weighing > 2,400 g with congenital pneumonia responded to a single delayed dose of SRT. Late SRT is effective and there may be a place for SRT in the treatment of conditions other than HMD.

Congenital syphilis as a notifiable disease.

A review of the notification of congenital syphilis at Johannesburg Hospital from 1 May 1991 to 30 April 1992 was conducted to evaluate the effect of the recently introduced notification programme. A total of 209 Wassermann reaction (WR)-positive mothers were delivered during this time; 12 pregnancies (5.7%) resulted in stillbirths and 8 (3.8%) in incomplete abortions, and there were 2 (0.96%) early neonatal deaths. Only 45 (21.5%) of this group of WR-positive mothers had received antenatal care, and of these 9 (20%) had had adequately documented treatment. There were thus 200 potentially notifiable cases of congenital syphilis according to the Centers for Disease Control classification, of which 24 (12.0%) were actually notified. The goals of the notification programme, namely to increase awareness of congenital syphilis among health care providers and to evaluate the extent of the problem accurately, are clearly not being met.

Does hypoxemia prevent brain damage in birth asphyxia?

The clinical syndrome of hypoxic ischemic encephalopathy (HIE) which occurs in association with birth asphyxia, is thought to represent a reperfusion injury consequent upon the generation of cytotoxic oxygen derived free radicals. It has recently been suggested that resuscitation of asphyxiated infants with unrestricted oxygen may aggravate the brain damage by causing hyperoxia and increased free radical production. To determine whether sustained hypoxemia may be protective in birth asphyxiated infants, we investigated the relationship between HIE and persistent pulmonary hypertension of the neonate (PPHN). The latter condition is also related to intrauterine and intrapartum birth asphyxia but is associated with persistent hypoxemia in the infant. In a retrospective analysis of 39 asphyxiated neonates admitted to the neonatal intensive care unit, we found that 28 had HIE, 10 had PPHN and only 1 had both HIE and PPHN. We therefore suggest that the hypoxemia due to PPHN may limit the production of oxygen derived free radicals in asphyxiated neonates and hence protect against the development of HIE. These findings lend support to current research into air vs. oxygen resuscitation for infants with birth asphyxia.