Comparison of morbidity and mortality of very low birth weight infants in a Central Hospital in Johannesburg between 2006/2007 and 2013
Ballot et al. BMC Pediatrics
Comparison of morbidity and mortality of very low birth weight infants in a Central Hospital in Johannesburg between 2006/2007 and 2013
Daynia E Ballot 0
Tobias Chirwa 2
Tanusha Ramdin 0
Lea Chirwa 0
Irma Mare 1
Victor A Davies 0
Peter A Cooper 0
0 Departments of Paediatrics and Child Health, University of the Witwatersrand , Johannesburg , South Africa
1 Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand , Private Bag 3, Wits, 2050 Johannesburg , South Africa
2 Department of Public Health, University of the Witwatersrand , Johannesburg , South Africa
Background: Health protocols need to be guided by current data on survival and benefits of interventions within the local context. Periodic clinical audits are required to inform and update health care protocols. This study aimed to review morbidity and mortality in very low birth weight (VLBW) infants in 2013 compared with similar data from 2006/2007. Methods: We performed a retrospective review of patients' records from a neonatal computer database for 562 VLBW infants. These neonates weighed between 500 and 1500 g at birth, and were admitted within 48 hours after birth between 01 January 2013 and 31 December 2013. Patients' characteristics, complications of prematurity, and therapeutic interventions were compared with 2006/2007 data. Univariate analysis and multiple logistic regression were performed to establish significant associations of various factors with survival to discharge for 2013. Results: Survival in 2013 was similar to that in 2006/2007 (73.4% vs 70.2%, p = 0.27). However, survival in neonates who weighed 750-900 g significantly improved from 20.4% in 2006/2007 to 52.4% in 2013 (p = 0.001). The use of nasal continuous positive airway pressure (NCPAP) increased from 20.3% to 62.9% and surfactant use increased from 19.2% to 65.5% between the two time periods (both p < 0.001). Antenatal care attendance improved from 54.4% to 70.6% (p = 0.001) and late onset sepsis (>72 hours after birth) increased from 12.5% to 19% (p = 0.006) between the two time periods. Other variables remained unchanged between 2006/2007 and 2013. The main determinants of survival to discharge in 2013 were birth weight (odds ratio 1.005, 95% confidence interval 1.003-1.0007, resuscitation at birth (2.673, 1.375-5.197), NCPAP (0.247, 0.109-0.560), necrotising enterocolitis (4.555, 1.659-12.51), and mode of delivery, including normal vaginal delivery (0.456, 0.231-0.903) and vaginal breech (0.069, 0.013-0.364). Conclusions: There was a marked improvement in the survival of neonates weighing between 750 and 900 g at birth, most likely due to provision of surfactant and NCPAP. Provision of NCPAP, prevention of necrotising enterocolitis, and control of infection need to be prioritised in VLBW infants to improve their outcome.
Infant; Very low birth weight; Premature; Neonatal mortality
In 2013, neonatal mortality accounted for almost 45% of
deaths in children younger than 5 years of age . Only
27 of 138 developing countries are likely to achieve the
fourth Millennium Development Goal of reducing
under-5 mortality by two thirds before 2015, and South
Africa is not among these countries . The neonatal
mortality rate in South Africa is lower than the global
average but is approximately five-fold that in some
European and Scandinavian countries . Preterm birth
is the most important cause of neonatal mortality . In
2013, complications relating to prematurity were the
second largest cause of death in children younger than
5 years old, with infectious causes accounting for
approximately half of these deaths . Most neonatal deaths occur
within the first week of life and two thirds could be
prevented by provision of adequate health care .
To achieve the Every Newborn target of less than 10
neonatal deaths per 1000 births by 2035, the most important
causes of neonatal death need to be determined . Very
low birth weight (VLBW) neonates (birth weight <1500 g)
comprise a high-risk group with considerable mortality.
Survival of VLBW infants in South Africa is reported to be
just over 70% [5,6]. Although this survival rate is better
than some other African countries, it is far worse than
other developing countries [7,8]. Efforts to reduce neonatal
mortality, and especially that of VLBW infants, must
become a health priority in South Africa.
New developments in neonatal care are associated with
improved survival in preterm infants. These include in
utero transfer, antenatal steroids, early surfactant therapy
and extubation to nasal continuous positive airway pressure
(NCPAP) , promotion of breastfeeding, and kangaroo
mother care (KMC). Neonatal networks, such as the
Vermont Oxford Network (VON) , have been
developed to improve the standard and safety of neonatal care
through clinical audits and quality control. South Africa is
a middle-income country with limited health resources,
resulting in rationing of care to extremely low birth weight
infants, many of whom are not offered mechanical
ventilation. Newborns who weigh <900 g are not routinely
provided with intermittent positive pressure ventilation (IPPV)
in our institution, based on anticipated poor outcome,
prolonged ventilation, and high use of resources. However, less
costly and invasive measures, such as INSURE
(IntubateSURfactant-Extubate) and NCPAP have been shown to
significantly improve survival in this group of neonates .
Ongoing clinical audits, incorporating regional neonatal
and obstetric services within a perinatal network, provide
current, local statistics that can be used to inform and
monitor interventions to improve neonatal outcome. The
Perinatal Problem Identification Programme  is a
South African national audit of neonatal deaths, which
considers the obstetric and neonatal causes of death, as
well as avoidable factors. Additional information on other
outcomes and interventions is beneficial. Therefore, an
integrated approach, incorporating regional neonatal and
obstetric services, would be helpful in developing integrated
perinatal care programmes. Although the VON 
considers this information, certain data, such as maternal
human immunodeficiency virus (HIV) and syphilis status, are
lacking, which are of great local importance. Therefore, a
locally relevant system of clinical audits needs to be
Health care protocols need to be regularly reviewed
and modified to accommodate new therapies and
address specific issues in a particular setting. This is
especially relevant in low- and middle-income countries with
limited health resources, insufficient equipment, and a
lack of adequately skilled staff. Interventions shown to
improve outcomes in a high-income setting may not be
as effective in low- and middle-income countries. There
is limited information regarding the care and outcome
of VLBW infants in sub-Saharan Africa. A study
conducted in the Charlotte Maxeke Johannesburg Academic
Hospital (CMJAH) neonatal unit in 2006/2007 showed a
survival rate of 70.5% with birth weight, NCPAP,
necrotising enterocolitis (NEC), hypotension, sex, and place of
birth as significant predictors of survival . NCPAP
was introduced in the unit in June 2006 and was initially
only provided to a few neonates weighing >900 g.
Neonates with a birth weight <900 g were not provided with
ventilatory support or surfactants at the time. INSURE
and NCPAP have gradually become first-line therapies
for all VLBW babies >750 g at birth with hyaline
membrane disease (HMD) in the CMJAH neonatal unit. The
2006/2007 study also identified other areas for
improvement, such as attendance at antenatal care and the use
of antenatal steroids.
The present study aimed to review the morbidity and
mortality of VLBW infants at the CMJAH in 2013 and
to compare these data with data from 2006/2007 in the
same unit. The acquired information would be useful for
revising and updating health care protocols to improve
outcomes in this group of neonates in sub-Saharan
This study was a retrospective review of patients records
that were obtained from the CMJAH neonatal computer
database, which is kept for clinical audit. All neonates
who weighed between 500 and 1500 g, who were born
between 01 January 2013 and 31 December 2013, and
who were admitted to the CMJAH neonatal unit within
48 hours of birth, were eligible for inclusion. The
primary outcome was survival to discharge from hospital.
Secondary outcomes were rates of complications and
therapeutic interventions and risk factors for mortality.
A similar study was conducted in the CMJAH unit
from 1 July 2006 to 30 June 2007 . The definition
used for VLBW infants at that time considered all
neonates weighing 1500 g or less and neonates were
enrolled within 24 hours of birth. The current study used
the definition of VLBW infants as defined by the VON
 as neonates with a birth weight between 500 and
1500 g. To have a valid group for comparison, neonates
with the same inclusion criteria as the current study
were extracted from the initial data set (i.e., those who
were admitted to the neonatal unit within 48 hours of
birth between 1 July 2006 and 30 June 2007 with a birth
weight of 5001500 g). Therefore, this dataset was
slightly different from that in the previously published
article  and was used as the baseline in the current
Hospital facilities and services
The neonatal unit at the CMJAH has a six-bed labour
ward nursery, where newborns are initially admitted and
stabilised. There is a 35-bed high-care nursery where
intravenous fluids, antibiotics, NCPAP, surfactant
therapy, supplemental oxygen, and phototherapy are
provided. Additionally, this hospital also has a 20-bed ward
where neonates await weight gain for discharge and a
15-bed kangaroo mother care (KMC) ward. IPPV is
provided in a shared 14-bed paediatric/neonatal intensive
care unit. High-frequency ventilation, paediatric
cardiology, paediatric neurology, and paediatric surgery are
available within the facility. High-flow oxygen therapy
was not used in the unit at the time. The neonatal and
obstetric services are referral centres for the surrounding
midwife obstetric units and district hospitals. Neonates
whose current weight was above 1000 g were sent to
KMC just prior to discharge when they were clinically
stable, off supplemental oxygen, and tolerating full
enteral feeds. Whenever possible, these neonates were
transferred out to KMC facilities in regional hospitals.
Neonates were discharged home from the CMJAH once
they had achieved a current weight of 1600 g, were
taking full feeds from either the breast or cup, and
maintaining body temperature and blood glucose levels.
Neonates were occasionally discharged home on
Neonates were managed according to standard unit
protocols by attending neonatologists and paediatric
registrars. All neonates, irrespective of birth weight, received
warmth, supplemental oxygen via low-flow nasal
cannulae, intravenous fluids, phototherapy, and antibiotic
therapy as required. Cranial ultrasound was performed on
all VLBW infants within the first week of life. Screening
for retinopathy of prematurity (ROP) was performed by
an ophthalmologist at the later age of either 4 to 6 weeks
of chronological age or at 31 to 33 weeks corrected
gestational age. Packed red cell transfusions were provided
if the neonate showed symptoms of anaemia with a
haemoglobin (Hb) level below 8 g%, at an Hb level
below 10 g% if the neonate was receiving supplemental
oxygen, or at an Hb level below 12 g% if the neonate
was receiving IPPV.
Because of limited resources, the neonatal unit has a
policy of rationing ventilatory support according to birth
weight . Rescue surfactant therapy that was
administered as INSURE and NCPAP was provided as a
firstline therapy in all VLBW infants >750 g at birth with
HMD who showed signs of respiratory failure.
Ventilation (IPPV) was provided to those infants >900 g who
showed evidence of respiratory failure on NCPAP or
became apnoeic. Newborns who were below the weight
cut-off were occasionally provided with support at the
discretion of the attending medical staff.
Neonatal database and ethical approval
Detailed information, including birth factors, therapeutic
interventions, complications of prematurity, and clinical
outcome, was collected upon discharge from hospital for
each patient. This information was entered into a neonatal
database that was maintained for the purpose of clinical
audits and quality control. This database was managed using
Research Electronic Data Capture tools hosted at the
University of the Witwatersrand . Data for each eligible
VLBW patient were obtained from the computer database
and analysed. Each case was de-identified for the purpose
of confidentiality. Ethical approval for the study was
obtained from the Human Research Ethics Committee of the
University of the Witwatersrand.
Standard definitions as per the VON  were used. NEC
was considered as modified Bells stage 2 or 3  and
peri-intraventricular haemorrhage (IVH) was classified
using Papiles staging . At the time of the study, the
neonatal unit of the CMJAH did not submit data to the
VON. Maternal HIV referred to mothers who were HIV
positive and not necessarily those on anti-retroviral
treatment or those who had AIDS. Chorioamnionitis was
defined as premature and/or prolonged rupture of the
membranes, fever, and foul-smelling liquor in mothers.
Neonates were considered to be small for gestational age
if the birth weight was below the 10th percentile on the
Fenton growth charts . Resuscitation at birth was
defined as the need for bag mask ventilation, chest
compressions, or intubation and ventilation. Severe IVH was
considered to be either grade 3 or 4. Sepsis was classified
as culture-proven bacterial or fungal sepsis only; suspected
sepsis or clinical sepsis was classified as no sepsis. Birth
defects were defined as life-threatening anomalies at birth.
Respiratory failure was defined as oxygen saturation below
88% in 60% supplemental oxygen, respiratory acidosis (pH
<7.25 with PaCO2 > 60 mmHg), or clinical marked
respiratory distress. Ventilatory support referred to the most
invasive level each neonate received (i.e., those who were
treated with both NCPAP and IPPV were classified in the
IPPV group). Neonates who were transferred out to
regional hospitals for KMC were classified as survivors.
Statistical analysis was performed using SPSS (IBM Corp
released 2013 IBM SPSS Statistics for Windows Version
22.0, Armonk NY). Data are described using standard
statistical methods. Frequency tables and percentages
with 95% confidence intervals were used for categorical
variables. Continuous variables (normally distributed)
are summarised using mean and standard deviation
(SD). Results are reported as mean (SD). Obstetric and
labour room information is reported per neonate (not
per mother) to allow for multiple pregnancies and to
concur with the aim of the study. Univariate analysis
was performed using cross tabulations with the chi
square test to compare categorical variables. Continuous
variables were normally distributed and thus compared
using unpaired t-tests. A p value less than 0.05 was
considered significant. Various demographic and birth
factors, complications of prematurity, and therapeutic
interventions were compared between 2006/2007 and
2013. Ventilatory support was different among the
various birth weight categories. Therefore, neonates were
stratified into weight groups as follows: <750 g, no
ventilatory support (no IPPV or NCPAP); 750900 g, NCPAP
only if required; 9001500 g, NCPAP and IPPV if
required. These weight groups were then compared for
IPPV, surfactant use, NCPAP, and survival.
Further analysis was performed considering the 2013
data only. Univariate analysis was performed to
determine significant associations of various factors with
survival at discharge. A multiple logistic regression model
with survival as the binary outcome variable, using a
forward entry conditional model, was then performed.
Variables that were significantly associated with survival in
univariate analysis were included in the model. Logistic
regression was repeated excluding neonates with less
than 750 g birth weight to control for possible selection
bias because these neonates did not receive ventilatory
The sample comprised 562 VLBW infants, including 20
who died in the delivery room. The mean birth weight was
1120.0 (248) g in 2013 and 1127.0 (233) g in 2006/2007,
with no difference between the two time periods (p = 0.64).
Mean gestational age was significantly lower in 2013 than
in 2006/2007 (29.3 [2.8] vs 29.9 [2.9] weeks, p < .001).
The mean duration of hospital stay was 28.2 (21.8) days
in 2013 and 25.8 (22.1) days in 2006/2007, with no
difference between the two time periods (p = 0.08). Thirty-two
(5.6%) neonates were transferred to regional step-down
facilities. The mean birth weight of these neonates was
1166.6 (195.7) g (p = 0.92 compared with the main
sample) and the mean gestational age was 29.9 (2.16) weeks
(p = 0.98 compared with the main sample).
Demographic and birth characteristics are shown in
Table 1. The mean maternal age was 28.1 (6.1) years.
Fifteen (2.7%) mothers were teenagers and 165 (29.4%)
were primiparous. Attendance at antenatal care
significantly improved from 54.4% to 70.6% (p = 0.001) and the
number of neonates who were born SGA decreased
from 37.6% to 30.9% in 2006/2007 to 2013 (p = 0.038).
Complications of prematurity and therapeutic
There was a significant increase in the number of
neonates with HMD from 63.7% in 2006/2007 to 83.6% in
2013 (p < 0.001, Table 2). Figure 1 shows IPPV by birth
weight for neonates with HMD. Significantly fewer
neonates with HMD received IPPV in 2013 (20.9%) than in
2006/2007 (32.9%). Figure 2 shows NCPAP use by birth
weight in neonates with HMD and Figure 3 shows
surfactant use in neonates with HMD by birth weight.
There was a significant increase in NCPAP use for
neonates >750 g and in surfactant use in all weight
categories between 2006/2007 and 2013. There was a marked
increase in the use of NCPAP and surfactant between
2006/2007 and 2013. Significantly fewer neonates with
HMD received NCPAP and were provided with
surfactant in 2006/2007 than in 2013 (both p < 0.001). Most
neonates who were treated with NCPAP (94.6%; 335/
354) received surfactant therapy. There was also a
significant increase in late onset sepsis from 12.5% in 2006/
2007to 19% in 2013 (p = 0.006). One neonate was
discharged home on oxygen.
Not all neonates were screened for IVH or ROP. Cranial
ultrasound was performed in 52.8% (297/562) of patients
and only 25.6% (144/562) were screened for ROP. Many
neonates did not have a cranial ultrasound for a number of
reasons. Some of them died early before ultrasound could
be performed, some were well and were sent to KMC early
before having ultrasound, and shortages of staff and
equipment sometimes resulted in cranial ultrasound being
unavailable. Many neonates did not have screening for ROP
because they were discharged prior to the required age for
Born outside a health facility
Resuscitation at birth
160 (28.5)[24.9 32.3]
6 (1.1) [0.4 2.3]
220 (39.1)[35.2 43.3]
397 (70.6)[66.7 74.3]
14 (2.5) [1.6 4.1]
130 (23.1)[19.8 26.8]
472 (84)[80.7 86.8]
33 (5.9) [4.2 8.1]
311 (55.4) [51.2 59.4]
174 (30.9))[27.3 34.9]
203 (36.1)[32.2 40.3]
308 (54.8)[50.7 58.9]
119 (25.7)[21.6 29.8]
11 (2.4) [1.1 3.9]
172 (37.1)[32.6 41.5]
252 (54.4)[49.4 59]
378 (81.6) [78.7 85.7]
34 (7.3) [5.0 9.6]
238 (51.4) [46.1 58.5]
174 (37.6) [33.3-42.1]
152 (32.8) [28.5 37.1]
238 (53.2)[48.3 57.7]
The overall survival rate was 413/562 (73.4%; 95%
confidence interval 69.677%). The primary cause of death is
shown in Figure 4. The most common cause of death was
extreme multi-organ immaturity in 56/149 (37.5%)
patients. The survival of VLBW infants in 2013 was not
different from that in 2006/2007 (325/463 [70.2%]; 95%
confidence interval 65.974.2; p = 0.27). However, survival
of neonates weighing 750900 g significantly improved
from 20.4% in 2006/2007 to 52.4% in 2013 (p = 0.001),
while survival in the other birth weight categories remained
unchanged (Figure 5). The duration of hospitalisation was
significantly longer in survivors than in non-survivors
(35.52 [19.89] days vs 7.77 [12.57] days, p = 0.001). The
majority of deaths (111/149, 74.49%) occurred in the early
Ligation of Patent Ductus Arteriosus (PDA)
Cystic periventricular leukomalacia (PVL)
Discharged on human milk feeds
*percentage of babies screened.
**percentage of those discharged.
368 /470 (78.3)[74.4 81.8]
98/470 (20.9) [17.4 24.8]
354/470 (75.3) [71.2 79.0]
3 (0.5) [0.18- 1.5]
146 (26) [22.8 29.8]
107 (19) [16 22.5]
41 (7.3) [5.4 9.8]
10 (1.8) [0.97 3.3]
11 (2.0) [1.1 3.4]
4 (0.7) [0.28 1.8]
22/297 (7.4)*[4.9 11]
2 /297(0.6)* [0.12 2.7]
3/144 (2.1)* [0.71 5.9]
126/413 (30.5)** [26.3 35.1]
97/295 (32.9) [27.8 38.4]
94 /470(31.9) [26.8 37.4]
26 (5.6) [3.9 8.1]
106 (22.9) [19.2 26.6]
58 (12.5) [9.1 16.6]
26 (5.6) [3.7 7.8]
20 / 321(6.0)* [3.9 9.1]
4 /321(1.2)* [0.3 2.5]
Figure 2 NCPAP use in VLBW infants with HMD by birth weight at two time periods. There was a significant increase in NCPAP use
between 2006/2007 and 2013 for the weight categories of 750900 g and >900 g (both p < 0.001).
Figure 1 Mechanical ventilation by birth weight category in VLBW infants with HMD at two time periods. Significantly fewer babies who
weighed > 900 g were ventilated in 2013 compared to 2006/2007 (p = 0.008).
neonatal period. There were 20 delivery room deaths.
These neonates had a mean birth weight of 870.8 (271) g
and a gestational age of 26.7 (3.6) weeks. The cause of
death was extreme multi-organ immaturity in 11 (55%),
hypoxia in four (20%), HMD in three (15%), and congenital
abnormalities in two (10%) neonates.
Univariate analysis of predictors of survival for 2013
Birth weight was significantly lower in non-survivors
(911.4  g) than in survivors (1191.3  g, p <
0.001). Similarly, gestational age was significantly lower
in non-survivors (27.4 [2.5] weeks) than in survivors
(29.9 [2.6] weeks, p < 0.001). Temperature at admission
was significantly lower in non-survivors than in
survivors (35.1 [1.7] C vs 35.8 [1.2] C, p < 0.001). The
neonates sex was not associated with outcome. Other
significant predictors of survival at discharge are shown
in Tables 3 and 4. Place of birth, antenatal care,
antenatal steroids, maternal hypertension, maternal HIV
infection, mode of delivery, resuscitation at birth, and
major birth defects were significantly associated with
outcome (Table 3). IPPV, NCPAP, surfactant therapy,
patent ductus arteriosus, and NEC were significantly
associated with outcome (Table 4). Fifty-one percent of
neonates received KMC, and KMC was strongly
associated with survival. Five of the 237 babies (1.7%) who had
KMC died as compared to 118 of the 237 babies (49.8%)
who did not have KMC (p < 0.001). However, there was
marked selection bias because neonates in this study
were sent to KMC just prior to discharge. Therefore,
KMC was not included in the multivariate analysis.
Major birth defects were predictive of survival in
Figure 3 Surfactant use in VLBW infants with HMD by birth weight category between two time periods. There was a significant increase
in surfactant use for all weight categories (<750 g, p = 0.024; 750900 g, p < 0.001; >900 g, p < 0.001).
univariate analysis, but were also excluded from
multivariate analysis because only life-threatening defects
were considered. Other factors, including the duration
of ventilation, the duration of nasal CPAP, the age of
receiving surfactants, hypoglycaemia, atelectasis,
pulmonary haemorrhage, pneumothorax, blood transfusion,
exchange transfusion, and sepsis (both early and late
onset), were not significant predictors of mortality.
Multiple regression analysis
Results of multiple regression analysis for the whole
group are shown in Table 5. Significant predictors of
mortality were birth weight, resuscitation at birth,
NCPAP, NEC, and mode of delivery. Multiple logistic
regression excluding neonates <750 g at birth (no
NCPAP or IPPV) showed that significant predictors of
mortality were birth weight (p < 0.001), maternal HIV
status (p = 0.024), resuscitation at birth (p = 0.002),
NCPAP (p = 0.028), and NEC (p = 0.002).
The number of VLBW infants is increasing, with an
increase of 18.5% of VLBW admissions to the CMJAH in
2013 compared with 2006/2007. Care of these infants
should become a health priority in the coming decade.
Regular review of outcomes and adjustment of health
protocols are essential to ensure the best possible
outcome of patients. There was a marginal improvement in
the overall survival of VLBW infants in this unit, from
70.2% in 2006/2007 to 73.4% in 2013, but this did not
reach statistical significance. These survival rates are
similar to those in Korea (6), but remain below those of
high-income countries (14, 15). Different interventions
are provided for different birth weights in the CMJAH
neonatal unit. In the current study, stratifying for birth
weight showed that survival of VLBW infants weighing
750900 g significantly improved from 20.4% in 2006/
2007 to 52.4% in 2013, whereas that for infants <750 g
and those who weighed 9001500 g did not change. The
Primary cause of death
Figure 4 Primary cause of death in VLBW infants at the CMAJH in 2013.
<750 grams 750-900 grams >900 grams
Figure 5 Survival of VLBW infants by birth weight category at two time periods. Survival of VLBW infants who weighed 750900 g at birth
significantly improved between 2006/2007 and 2013 (p = 0.001).
Table 3 Obstetric and birth-related factors associated with survival to discharge for VLBW infants in 2013
Variable (number) Died/survived Mortality percentage [95% CI]
Inborn (472) 121/351 25.6 [21.9 29.7]
Born Outside Health facility (33) 17 /16 51.5 [35.2 67.5]
Born at another hospital (36) 6 /30 16.6 [7.9 31.9]
Born at Midwife obstetric unit (19) 5/14 26.3 [11.8 48.8]
Yes (397) 92/305 23.1 [19.3 27.6]
No (140) 47 /93 33.5 [26.3 41.7]
Yes (220) 44 /176 20 [15.3 25.8]
No (288) 95/193 32.9 [27.8 38.6]
Yes (126) 24 /106 18.4 [12.7 26]
No (366) 105 /261 28.6 [24.3 33.5]
Yes (160) 47 /113 29.3[22.9 36.9
No (362) 76 /286 20.9[17.1 25.5]
Mode of delivery
NVD (221) 87/134 39.3[33.2 45.6]
Vaginal breech (18) 9 /9 50 [29 71]
CS elective (15) 3 /12 20 [7 45.2]
CS emergency (296) 48/248 16.2 [12.5 21]
Yes (174) 30/144 17.2 [12.4 23.5]
No (384) 112/272 29.1 [24.8-33.9]
Resuscitation at birth
Yes (203) 93/110 45.8 [39.1 52.7]
No (344) 53/291 21.7 [17 27.3]
Major birth defect
Yes (12) 7/5 58.3 [31.9 80.7]
No (536) 140 / 396 26.1 [22.6 30]
Table 4 Complications of prematurity and therapeutic
interventions significantly associated with survival in
VLBW infants in 2013
Died/survived Percentage mortality P value
38.8 [29.7 48.7]
21.3 [17.6 25.5]
21 [16.7 26.1]
40.9 [29.5 53.5]
32.8 [26.5 36.8]
32.8 [26.5 39.8]
25.1 [21.4 29.2]
43.9 [29.9 59]
22.4 [19 26.3]
reason for this finding can be attributed to the
introduction of NCPAP and INSURE for the group of neonates
weighing 750900 g, whereas the management of
neonates in the other weight groups remained unchanged
between the two time periods. During 2006/2007, only
6.8% of neonates with HMD who weighed 750900 g at
birth were offered NCPAP compared with 94.8% in
2013. The number of neonates who weighed >900 g with
HMD requiring IPPV significantly decreased from 35.1%
in 2006/2007 to 24.6% in 2013. Importantly, NCPAP is a
cheaper therapeutic option than mechanical ventilation
with its attendant difficulties and complications. Based
on this markedly improved survival of ELBW infants,
perhaps physicians should review the birth weight
cutoff for NCPAP and INSURE, and offer this to all
neonates with RDS, regardless of their birth weight.
Provision of available therapeutic interventions to every
Table 5 Multivariable logistic regression for factors
associated with survival to discharge for VLBW infants in
Resuscitation at birth
Odds ratio (95%CI)
1.005 (1.003 1.007)
0.456 (0.231 - .0.903)
0.069 (0.013 0.364)
2.673 (1.375 5.197)
0.247 (0.109 0.560)
4.555 (1.659 12.510)
neonate, irrespective of birth weight, is a major factor in
better survival rates of VLBW infants in high-income
compared with low- and middle-income countries .
The most significant predictor of survival in the
present study in 2013 was birth weight, which is
consistent with previous findings in 2006/2007. Other
significant predictors of survival in the present study were
NCPAP, NEC, resuscitation at birth, maternal HIV
status, and mode of delivery. These findings are slightly
different to those in 2006/2007 where hypotension, sex,
and birth outside a health facility were associated with
outcome, but these factors were not associated in the
2013 study. However, NCPAP and NEC remained
significantly associated with outcome in both time periods.
Other significant differences between the two time
periods were an increase in attendance at antenatal care,
HMD, and late onset sepsis, with a decrease in neonates
who were SGA. The significant increase in the number
of neonates with HMD between the two time periods
was unexpected, but may be associated with the
decrease in the number of neonates who were SGA .
Despite this increase in HMD, the survival rate increased
over time (as discussed above).
Some authors have suggested that there is little
additional benefit in using other predictors of outcome over
birth weight in resource-constrained settings .
However, both studies at the CMJAH showed other
modifiable factors to be significantly associated with survival,
with particular emphasis on NEC and NCPAP. Survival
of VLBW infants in the local context can be improved
with low technology and relatively inexpensive
interventions (e.g., NCPAP) in a regional hospital setting,
provided there is adequate equipment and properly
trained staff. Health protocols at the CMJAH should be
developed to include promotion of breastfeeding,
adequate neonatal resuscitation, prevention of
mother-tochild transmission of HIV, and provision of NCPAP.
Notably, administration of antenatal steroids  and
prevention of hypothermia  should also be
addressed, even though these factors were not significant
in multiple regression analysis. The rate of late onset
sepsis (LOS) significantly increased from 12.5% in 2006/
2007 to 19% in 2013. This finding might be due to
overcrowding and overuse of broad spectrum antibiotics.
Surprisingly, LOS was not a significant cause of
mortality in the current study. This finding may be due to a
strong association between NEC and nosocomial
infection because 42% of neonates who died of NEC had
nosocomial infection. Although LOS was not a risk for
mortality, control of infection should also be prioritised
because LOS is associated with increased costs of care,
prolonged hospitalisation, and an adverse outcome .
Although vaginal delivery is associated with a poor
outcome, it may not be feasible to deliver all preterm
infants by caesarean section, particularly in a
In the current study, notably, several factors did not
improve over time. Administration of antenatal steroids
remained low. Many mothers present late in labour and
do not attend antenatal care. Therefore, there may be
limited opportunities for obstetricians to administer
steroids . Maternal HIV infection remains a major
problem, affecting almost one third of mothers.
Certain complications of prematurity in the current
study were low, including pneumothorax, cystic
periventricular leukomalacia, severe peri-intraventricular
haemorrhage P-IVH, and ROP. This may reflect the relatively
poor survival of ELBW infants, but many of the
neonates in the present report were not screened. Therefore,
these figures may be under-reported. Reliable
information on long-term outcome (not only survival) is
essential. Therefore, protocols must be put in place to ensure
that all neonates are screened for ROP and have cranial
ultrasound performed. The presence of ROP, IVH, and
periventricular leukomalacia can be used as proxy
indicators of a long-term poor outcome.
The mortality rate of VLBW infants did not significantly
change between 2006/2007 and 2013. The greatest
improvement in survival was observed in VLBW infants who
weighed 750900 g at birth. This most likely reflects the
provision of surfactants and NCPAP to this weight category
of infants. Health protocols, including simple, inexpensive
interventions (e.g., adequate neonatal resuscitation, NCPAP,
prevention of mother-to-child transmission of HIV, and
measures to prevent NEC), should improve survival to
discharge in VLBW infants. Although LOS is not associated
with mortality, there is an alarming increase in LOS, and
infection control measures must also be prioritised. These
interventions will not only improve the survival of VLBW
infants but also result in lower costs in the care of these
CS: Caesarean section; CMJAH: Charlotte Maxeke Johannesburg Academic
Hospital; ELBW: Extremely low birth weight; Hb: Haemoglobin; HIV: Human
immunodeficiency virus; HMD: Hyaline membrane disease; INSURE:
IntubateSURfactant-Extubate; IPPV: Intermittent positive pressure ventilation;
IVH: Intraventricular haemorrhage; KMC: Kangaroo mother care; LOS: Late onset
sepsis; NCPAP: Nasal continuous positive airways pressure; NEC: Necrotising
enterocolitis; PDA: Patent ductus arteriosus; PVL: Periventricular leukomalacia;
ROP: Retinopathy of prematurity; SGA: Small for gestational age; VLBW: Very low
birth weight; VON: Vermont Oxford Network.
The authors declare that they have no competing interests.
DEB conceptualised the study, collected and analysed the data, and wrote
the manuscript. TC assisted with the design of the study and data analysis,
and reviewed drafts of the manuscript. LC and TR assisted with data
collection and reviewed drafts of the manuscript. IM assisted with data
collection and analysis and reviewed drafts of the manuscript. VAD assisted
with the design of the study and writing the manuscript, and reviewed
drafts of the manuscript. PAC assisted with the design of the study and
writing the manuscript, and reviewed drafts of the manuscript. All authors
read and approved the final manuscript.
We thank Mr Lebogang Rapola, Mr Milton Reineke, and Miss Patricia
Hanrahan for their assistance in data collection, without which the study
would not have been possible.
This study was funded by a research grant from the SPARC fund of the
University of the Witwatersrand.
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