i
SHORT TERM SURVIVAL OF PREMATURE INFANTS
ADMITTED TO THE NEW BORN UNIT AT MOI
TEACHING AND REFERRAL HOSPITAL, KENYA
BY
MAKOKHA FELICITAS OKWAKO MBChB (UoN)
SM/PGCHP/01/11
A Thesis Submitted in Partial Fulfillment of Requirements of Master of
Medicine (Child Health and Paediatrics) of School of Medicine, Moi
University
2014
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DECLARATION
Student’s declaration
I declare that this research thesis is my original work and that it has not been presented for a
degree in any other university. No part of this thesis may be reproduced without the prior
written permission of the author and /or Moi University
Dr. Makokha Felicitas Okwako
SM/PGCHP/01/11
Sign………………………………...
Date…………………………………
Supervisors’ declaration
This research thesis has been submitted for examination with our approval as University
supervisors.
Prof. Winstone Nyandiko M.
Associate Professor and Pediatrician
Department of Child Health and Paediatrics, Moi University
Sign…………………………………
Date………………………………..
Dr. Eren Oyungu
Senior Lecturer and Pediatrician
Department of Medical Physiology, Moi University
Sign…………………………………
Date…………………………………
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DEDICATION
I would like to dedicate this thesis to my family: my husband Vincent and my sons Edgar,
Levinus and Brennan for being the pillar of my strength.
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ABSTRACT
Background: Prematurity is a major contributor to neonatal mortality globally and it
accounts for 28% of all neonatal deaths. Preterm infants are at an increased risk of neonatal
morbidity and mortality compared to full term infants. In order to achieve the fourth
Millennium Development Goal, there is need for reduction of neonatal deaths especially
those ascribed to prematurity. Data on hospital based survival rates for preterm infants is
important for decision making by obstetricians, neonatologists and hospital management in
predicting outcomes of care and development of interventions to improve outcomes of care.
Objective: To determine the proportion of premature infants admitted to the newborn unit at
Moi Teaching and Referral Hospital who survive to discharge.
Methodology: This was a prospective descriptive study conducted in the newborn unit at
Moi Teaching and Referral Hospital in Eldoret, Kenya. The study subjects were infants born
before 37 completed weeks of gestation. A minimum sample size of 175 premature infants
was required. Consecutive sampling was used to identify subjects. Data was collected using a
pretested structured questionnaire and analyzed using STATA version 10.0. Descriptive
statistics were used for continuous variables and frequency listing for categorical data. Cox
Proportional Hazards model was used to determine factors associated with survival and
Kaplan-Meier survival curves drawn.
Results: A total of 175 neonates were enrolled into the study and followed until discharge or
death. There were 82 (46.9%) male and 93 (53.1%) female infants. There were 27 (15.4%)
extremely preterm (less than 28 weeks), 54 (30.9%) very preterm (28 to less than 32 weeks)
and 94 (53.7%) moderate to late preterm (32 to less than 37 weeks) infants. Neonatal sepsis
(88.6%), hypothermia (67.4%) and respiratory distress syndrome (64.6%) were the main
diagnoses made. The overall survival to hospital discharge was 60.6% (95% CI 0.53-0.68).
The survival rate was 29.6% for infants born less than 28 weeks gestation, 50% for those
born at 28-31 weeks and 75.5% for those born at or above 32 weeks. Of the infants who did
not survive, 11 (15.9%) died within the first 24 hours while 56 (81.2%) died by the end of the
first week. Gestation age of 32 weeks (HR 0.39, 95% CI 0.18-0.8), birth weight >1000g (HR
0.27, 95% CI 0.20-0.78) and maternal antenatal care attendance (HR 0.52, 95% CI 0.3-0.9)
were associated with better survival. Caesarian section mode of delivery, versus spontaneous
vertex delivery, was associated with increased risk of death (HR 4.26, 95% CI 1.88-9.66).
Conclusions: Two thirds of premature infants admitted to MTRH new born unit survived to
discharge. The survival gestation age limit was 28 to less than 32 weeks category (50%
chance of survival as per WHO). Increasing gestation age, birth weight over 1000g and
maternal antenatal care clinic attendance were associated with better survival.
We therefore recommend that whenever possible preterm birth delivery should be delayed
until after 28 weeks gestation.
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TABLE OF CONTENTS
DECLARATION ........................................................................................................................................... i
DEDICATION .............................................................................................................................................. ii
ACKNOWLEDGEMENT ........................................................................................................................... vi
LIST OF TABLES ...................................................................................................................................... vii
LIST OF FIGURES ................................................................................................................................... viii
ACRONYMS/LIST OF ABRREVIATIONS .............................................................................................. ix
OPERATIONAL DEFINITIONS ................................................................................................................. x
CHAPTER ONE: INTRODUCTION ........................................................................................................... 1
1.1 Background Information ....................................................................................................... 1
1.2 Problem Statement ................................................................................................................ 4
CHAPTER TWO: LITERATURE REVIEW ............................................................................................... 6
2.1 Epidemiology of Prematurity ................................................................................................ 6
2.2 Factors associated with prematurity ...................................................................................... 6
2.3 Spectrum of disease and Management in Premature Infants ................................................ 8
2.4 Short term Survival of Premature infants ............................................................................ 17
2.5 Factors affecting Short term Survival of Premature infants ................................................ 18
CHAPTER THREE: RESEARCH QUESTION, OBJECTIVES AND JUSTIFICATION ....................... 21
3.1 Research Question ............................................................................................................... 21
3.2 Objectives ............................................................................................................................ 21
3.3 Justification of the Study ..................................................................................................... 21
CHAPTER FOUR: METHODOLOGY ...................................................................................................... 23
4.1 Study design ........................................................................................................................ 23
4.2 Study site ............................................................................................................................. 23
4.3 Study Population ................................................................................................................. 24
4.4 Sample Size ......................................................................................................................... 24
4.5 Sampling Technique ............................................................................................................ 25
4.6 Outcome measures .............................................................................................................. 25
4.7 Data Collection .................................................................................................................... 25
4.8 Study Execution .................................................................................................................. 26
4.9 Data management, data analysis and presentation .............................................................. 27
4.10: Ethical Considerations ..................................................................................................... 27
CHAPTER FIVE: RESULTS ..................................................................................................................... 29
5.1 Infant characteristics ........................................................................................................... 29
5.2 Maternal characteristics....................................................................................................... 30
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5.3 Short term Survival ............................................................................................................. 31
5.3 Causes of morbidity ............................................................................................................ 32
5.4 Interventions ........................................................................................................................ 34
5.5 Correlates of Mortality ........................................................................................................ 34
CHAPTER SIX: DISCUSSION ................................................................................................................. 40
Study Limitations ...................................................................................................................... 48
CHAPTER SEVEN: CONCLUSIONS AND RECOMMENDATIONS ................................................... 49
REFERENCES ........................................................................................................................................... 50
APPENDICES ............................................................................................................................................ 55
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ACKNOWLEDGEMENT
I wish to thank my supervisors Prof. Winstone Nyandiko and Dr. Eren Oyungu for their
guidance and support; and Dr Ann Mwangi for guiding me through statistical aspects of this
study. I also acknowledge my research assistant and staff of the new born unit who helped me
to identify the study participants and treated them during their stay in the unit. Lastly, I thank
my family and entire pediatrics and child health fraternity for their moral, intellectual and
material support.
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LIST OF TABLES
Table 1: Infant Characteristics ................................................................................................. 29
Table 2: Maternal Characteristics ............................................................................................ 31
Table 3: Gestational age specific survival rate ........................................................................ 31
Table 4: Causes of Morbidity .................................................................................................. 33
Table 5: Correlates of Mortality (Causes of morbidity) .......................................................... 33
Table 6: Correlates of Mortality (Infant characteristics) ......................................................... 38
Table 7: Correlates of Mortality (Maternal characteristics) .................................................... 39
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LIST OF FIGURES
Figure 1: Place of delivery ....................................................................................................... 30
Figure 2: Admissions and Survivors ........................................................................................ 32
Figure 3: Overall Survival curve .............................................................................................. 35
Figure 4: Birth weight specific survival curves ....................................................................... 36
Figure 5: Gestational age specific survival curves .................................................................. 37
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ACRONYMS/LIST OF ABRREVIATIONS
ANC
CI
Antenatal care
Confidence interval
Cm Centimeter
CPAP Continuous positive airway pressure
ELBW Extremely low birth weight
g Gram
GA
GBS
Gestational age
Group B Streptococcus
HIV Human Immunodeficiency Virus
IMR Infant mortality rate
IREC Institutional Research and Ethics Committee
IVH Intraventricular hemorrhage
HR Hazard ratio
KDHS Kenya Demographic Health Survey
Kg Kilogram
KNH Kenyatta National Hospital
LBW Low birth weight
LGA Large for gestational age
MNCH Maternal Newborn and Child Health
MTRH Moi Teaching and Referral Hospital
NBU New born unit
NEC Necrotizing enterocolitis
NICU Neonatal intensive care unit
PDA Patent ductus arteriosus
RDS Respiratory distress syndrome
SGA Small for gestational age
UNICEF United Nations Children’s Fund
UN-MDGs United Nations Millennium Development Goals
VLBW Very low birth weight
WHO World Health Organization
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OPERATIONAL DEFINITIONS
Neonate New born infant; less than 28 days old
Infant Child up to 12 months old
Prematurity A birth that occurs before 37 completed weeks of gestation.
Low birth weight Weight at birth less than 2500g
Very low birth weight Weight at birth between 1000g and 1499g
Extremely low birth
weight
Weight at birth less than 1000g
Neonatal mortality Death occurring within the first 28 days of life
Moderate to late preterm Gestational age of 32 to less than 37 weeks
Very preterm birth Gestational age of 28 weeks to less than 32 weeks
Extremely preterm birth Gestational age below 28 weeks
Infant mortality Death occurring before the first birth day
Perinatal mortality Death occurring between 28 weeks gestational age and within
28 days of life
Post neonatal mortality Death after 28 days to 12 months of life
Under five mortality Death between birth and the fifth birthday
Day 1 The day of birth
Small for gestational age Weight less than 10 th
percentile for age
Large for gestation Weight more than 90 th
percentile for age
Hospital discharge Act of allowing a patient to leave hospital after recovery or
attaining recommended weight if the neonate had low birth
weight
Hypothermia Axillary skin temperature less than 35.5 degrees Celsius
Survival limit Gestational age and birth weight at which a prematurely born
fetus/infant has a 50% chance of survival
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CHAPTER ONE: INTRODUCTION
1.1 Background Information
Preterm birth is the leading cause of neonatal deaths and the second leading cause of death
after pneumonia in children under five years (1, 2). Mortality rates among premature
infants correlate with birth weight and gestational age with decreases in both associated
with poorer survival. Reliable data show that preterm births rates are increasing globally
(1, 2). An equivalent of 1 in every 10 children are born preterm and around one million
children die each year due to complications of preterm birth (1). In order to achieve the
fourth Millennium Development Goal (MDG) of reducing the under five mortality rate by
two thirds, there has to be a substantial reduction in neonatal deaths and especially those
ascribed to prematurity.
It has been shown that deaths from preterm birth complications can be reduced by over 75%
even without neonatal intensive care services (2). However, low coverage, poor quality, and
inequities in the provision of essential antenatal interventions remain a challenge in many
sub-Saharan African countries (3). With an average of only 42% of births occurring in health
facilities, there is a coverage gap for obstetric and newborn care that needs to be addressed
(4).The burden on health systems imposed by care of preterm infants in high-income
countries is considerable and well recognized. Indeed it was estimated that the cost of care for
a single preterm birth in the USA was US$ 51 600 in the year 2005 (5). This cost is
unachievable in low-income countries but is actually of greater magnitude as preterm birth
rates are higher and the resources available fewer, characterized by understaffed hospitals
with ill equipped or non-existent neonatal care units which ultimately result in higher
neonatal mortality rates (6).
Over 90% of babies born in low-resource settings before 28 weeks gestation die in the first
few days of life (< 10% die in high-income nations), a 10:90 survival gap. In developed
2
countries, 50% of babies born at 24 weeks survive, whereas in low-resource nations, this
survival rate is not achieved until 32 weeks of gestation (2).
Most published trials of neonatal care focus on incremental gains with high-technology care
for example changes in ventilation methods which in fact has limited relevance to the
resource limited settings where 99% of neonatal deaths occur (7).
Over 60% of preterm deliveries worldwide occur in Sub-Saharan Africa and South Asia
regions where resources for neonatal care are limited and progress to reduce neonatal
mortality has been slow (2, 7, 8).
It has also been shown that strengthening existing programs within health facilities could
prevent many deaths, even without high-tech equipment and supplies. Many newborn deaths
could be prevented with facility-based interventions such as neonatal resuscitation, thermal
care around the time of birth for all neonates, early and exclusive breastfeeding, baby hats,
blankets, infection prevention (basic hand washing with soap and clean environment), and
continuous positive airway pressure as well as antenatal steroids and Kangaroo Mother Care
for preterm babies (9).
Frieberg et al (10) argues that since low resource countries cannot be expected to scale up all
essential Maternal Neonatal and Child Health (MNCH) interventions simultaneously,
prioritization and phasing are required in order to generate success that will lead to increased
investment and trust in health systems. Using coverage of skilled attendance at birth as a
marker of health system access and equity of service delivery, Kenya was categorized in
middle health system context (skilled birth attendance 30-60%) which provided a framework
for assessment of priority MNCH interventions. In their model they demonstrated that
increasing coverage for essential MNCH interventions could lead to 85% reduction in
neonatal mortality in resource limited countries like Kenya. This study sought to determine
short term survival of preterm infants as baseline information that would be used to inform
Moi Teaching and Referral Hospital (MTRH) management, obstetricians, pediatricians,
3
neonatologists and other stakeholders on the current hospital based outcomes of preterm
infants. This information will be important for decision making on the new born unit’s
survival limit and expected outcomes of care.
Previous studies done Kenyatta National Hospital (KNH) and MTRH have focused on
neonatal survival rates of low birth weight infants. Although concordance exists between the
three low birth weight categories and the three prematurity categories, they are not
interchangeable since not all low birth weight infants are preterm hence need for this study
that specifically focuses on preterm infants.
Previous studies done in Kenya and other Sub Saharan countries have demonstrated high
neonatal mortality rates with extremely and very low birth weight babies having the lowest
survival rates. A prospective study done at KNH in 1996 showed an overall neonatal survival
rate of infants less than 2000 grams to be 62.2%. None of the 23 infants born weighing less
than 1000g survived to hospital discharge (11). In a prospective study done in MTRH in
1999, the seven day mortality rate of infants admitted to the special care nursery was reported
to be 19.7%. Fifteen percent of the neonates admitted to the special care unit at the time of
that study were preterm (12).
An unpublished study done in MTRH in the same special care unit in the year 2006 showed
that the neonatal mortality of low birth weight infants was 51.6%. This was at a time when
there was no continuous positive airway pressure (CPAP) for respiratory support. Similarly,
none of the infants born weighing less than 1000g survived to hospital discharge (13).
A retrospective study done in Nigeria reviewing records of infants born between 1998 and
2001 in a tertiary hospital without CPAP showed an overall neonatal mortality of 19.4% with
31.9% of the mortality being attributed to prematurity (14).
It has been shown that those countries with low neonatal mortality rate achieved it even
before the technological advancements seen today (15). Since preterm infants are more
vulnerable compared to term infants, determining their hospital based survival rate will
4
provide useful baseline data which future development of strategies to improve neonatal care
outcomes in MTRH would refer to.
1.2 Problem Statement
Globally 15 million babies are born prematurely and neonatal deaths account for forty
percent of all deaths occurring in children under five years of age (1, 2).
According to the Kenya Demographic Health Survey (KDHS) of 2008-09, Kenya has a high
neonatal mortality rate of 31/1000 live births with neonatal deaths accounting for 60% of the
infant mortality rate (16).
Some of the effective high impact interventions that have reduced child, infant and neonatal
mortality in developed countries are being implemented low income countries. But lack of
data and contextual information for priority setting in the resource-constrained settings has
hampered similar progress in developing countries.
MTRH is the second largest public hospital in Kenya, has the second largest public new born
unit in the country and serves as a referral centre for all health facilities in the Western part of
Kenya. The number of premature infants admitted to the new born unit has increased over the
last five years and according to a clinical audit done in the year 2011, in which third of the
infants admitted to the new born unit every month were preterm (12). In MTRH, there has
been improvement in staff training on neonatal resuscitation, infection prevention by hand
washing with soap and general hygiene, appropriate antibiotic treatment for neonatal sepsis,
Kangaroo mother care, thermal provision around the time of delivery and thereafter. In
addition CPAP respiratory support is now available for use in neonates with respiratory
distress syndrome (RDS). Those improvements coupled with additional space and human
resource were expected to improve short term neonatal survival in variance with the higher
neonatal mortality among low birth weight infants reported in the same hospital in the 2006
study (13). This study therefore sought to determine survival to hospital discharge of
5
premature infants admitted to the new born unit at MTRH following the expansion and
increase in the number of premature infants admitted to the unit.
6
CHAPTER TWO: LITERATURE REVIEW
2.1 Epidemiology of Prematurity
Birth weight and gestation age have traditionally been used as strong indicators of the risk of
neonatal death. World Health Organization (WHO) reported that 9.6% of all births were
preterm in 2005, which translated to about 12.9 million births. Approximately 85% of this
burden was concentrated in Africa and Asia, where 10.9 million births were preterm. About a
half a million preterm births occurred in Europe and the same number occurred in North
America (17).
Over the past two decades, the LBW rate has increased primarily because of increased
number of preterm births. In the United states, in 2008, about 12.3% of all live births were
less than 37 completed weeks gestational age and low birth weight infants accounted for
8.2% of live births in both 2007 and 2008 (18).
The KDHS report does not collect data on preterm births but reports data on low birth weight.
According to the KDHS 2008/09, it was reported that 6% of the live births weighed less than
2500g (16). MTRH new born unit offers neonatal care to premature infants born in the
hospital, those born at home and those referred from lower level health facilities.
2.2 Factors associated with prematurity
About two-thirds of preterm births are spontaneous; these births follow preterm premature
ruptured membranes and preterm labour or related diagnoses, such as cervical insufficiency.
Even though the primary and major determinant of birth weight is gestational age, there are
other secondary factors that either directly or indirectly determine the weight of a baby at
birth. It is difficult to separate completely factors associated with prematurity from those
associated with low birth weight.
In a retrospective study done in Northern Tanzania to determine risk factors associated with
low birth weight, it was found that gestational age below 37 weeks was strongly associated
7
with low birth weight. A strong positive correlation existed between preterm birth,
intrauterine growth restriction and low socioeconomic status (19).
Pregnant women from families with low socioeconomic status have been shown to have
higher rates of maternal under-nutrition, poor utilization of antenatal services, lower maternal
age, short interval pregnancies, pregnancy related illnesses and lower maternal education
level; most of which have been associated with preterm birth and low birth weight (19, 20).
In a retrospective review of 2,216 deliveries at the labour ward of the University of Nigeria,
Enugu for two years, maternal age <20 years and ≥ 35 years was associated with relatively
high incidence of low birth weight. Other factors identified as risk factors for delivery of
LBW infants in the same study included lack of antenatal care, female gender, grand
multiparty and multiple gestation (20).
Additionally, in a retrospective study done in Calabar, Nigeria to determine factors that
influenced the incidence of preterm births; previous induced abortion, nulliparity, out of
wedlock birth and lack of antenatal care were found to significantly increase the incidence of
preterm delivery. Women with multiple pregnancy or previous preterm birth were at an
increased risk of preterm delivery. Antenatal complications particularly malaria and anemia
were also noted to be risk factors (21).
In a South African study done to determine obstetric causes of very low birth weight
(VLBW) found that hypertension disease was present in 44.7% of the deliveries, spontaneous
preterm labour in 28.8% of the cases, preterm premature rupture of membranes and
congenital anomalies in 9.5% and 1.3% respectively (22).
Utilization of antenatal services in Kenya has been good with the proportion of women
seeking ANC services from a trained medical provider in their most recent birth rising from
88% to 92% in the past five years. But only 15% of the mothers received ANC care during
the first trimester (16).
8
In a study done in rural South Africa, maternal human immunodeficiency virus (HIV)
infection was shown to cause small for gestation infants but not preterm births. However,
infants of HIV positive mothers in this study had a 3-fold significantly increased hazard to
infant death (23).
However, in a study done in Rural Mozambique between 2003 and 2006, there was no
statistical difference observed in adverse pregnancy outcomes such as low birth weight,
spontaneous abortion, preterm birth and still birth between HIV positive and negative
mothers (24).
2.3 Spectrum of disease and Management in Premature Infants
Premature infants are at risk for developing short-term complications that result from
anatomic or functional immaturity during the neonatal period.
The risk of complications increases with decreasing gestational age with serious morbidities
occurring in the extremely premature infants. Immature organs of a premature infant have
functional limitations leading to many physiologic challenges when adapting to the extra-
uterine environment.
2.3.1 Respiratory
Respiratory distress syndrome (RDS) – occurs in 60-80% of premature infants less than 28
weeks gestation, 15-30% of those between 34-36 weeks and 5% of term babies (25).
Deficient synthesis or release of surfactant, together with small respiratory units and a
compliant chest wall in preterm babies, produces atelectasis and results in perfused but not
ventilated alveoli, which causes hypoxia.
In a study done in KNH new born unit in 1996 to determine survival of infants weighing less
than 2000g at birth, it was reported that 43% developed RDS (11).
9
Another study conducted in the same unit, four years later, to quantify morbidity and
mortality of low birth weight infants showed that the leading diagnosis on admission or
discharge of low birth weight infants was respiratory distress syndrome at 69% (26).
For these reasons, preterm birth deliveries in MTRH are attended by clinicians experienced
in neonatal resuscitation, mostly pediatrics residents.
Most effective prevention of RDS is prolongation of gestation and prevention of extreme
prematurity whenever possible.
The management of RDS involves use of antenatal steroids, postnatal supplemental oxygen,
exogenous surfactant and ventilatory support. Surfactant therapy for preterm infants with or
at risk of RDS improves survival and reduces risk of pneumothorax (25).
Exogenous surfactant and mechanical ventilatory support are the two interventions that are
not available in MTRH newborn unit.
Nasal bubble CPAP is the main respiratory support modality for premature neonates with
RDS in MTRH new born unit.
Apnea is a common problem in preterm infants that may be due to immaturity of the
respiratory centre or an associated illness. Apneic spells are considered clinically significant
if the episodes are greater than twenty seconds duration or when shorter episodes are
accompanied by hypoxia and/or bradycardia. Several theories exist regarding the
pathogenesis of apnea of prematurity, none of which have been confirmed as being the single
cause to date. One theory describes the role of adenosine as a central respiratory inhibitor.
Adenosine is a nucleoside component of compounds such as adenosine triphosphate and
cyclic adenosine monophosphate, which are crucial to numerous biochemical processes. In
term infants, apnea is always worrisome and demands immediate diagnostic evaluation.
Periodic breathing must be distinguished from prolonged apneic pauses because the latter
may be associated with serious illnesses. Apnea is a feature of many primary diseases that
affect neonates. These disorders produce apnea by direct depression of the central nervous
10
system's control of respiration (hypoglycemia, meningitis, drugs, hemorrhage, seizures),
disturbances in oxygen delivery (shock, sepsis, anemia), or ventilation defects (pneumonia,
RDS, persistent pulmonary hypertension of the newborn , muscle weakness).
In a retrospective study in KNH using records of low birth weight infants admitted from
January to December 2000, 42% of the infants experienced apneic attacks during the
admission period (26).
Because of limited availability of pharmacotherapeutic agents such as caffeine in MRTH new
born unit, apnea is managed using menthylxanthine, aminophyline.
2.3.2 Cardiovascular
Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in
premature infants. Prematurity has been identified as the major predisposing factor to patent
ductus arteriosus (PDA). In a prospective cohort study done at the University College
Hospital, Ibadan, 35% of the preterm babies were found to have PDA compared to the overall
incidence of 24.5% amongst all admissions (27).
In infants born prior to 28 weeks of gestation, a haemodynamically significant PDA can
cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need
for assisted ventilation and increase the risk of bronchopulmonary dysplasia, intraventricular
hemorrhage, renal dysfunction, cerebral palsy and mortality (25).
Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen remain the mainstay of
medical therapy for PDA, and can be used both for prophylaxis as well as for rescue therapy
to achieve PDA closure. Surgical ligation is also effective and is used in infants who do not
respond to medical management. Although both medical and surgical treatment have proven
efficacy in closing the ductus, both modalities are associated with some adverse effects.
Because the ductus does undergo spontaneous closure in some premature infants, early
identification of infants with a symptomatic PDA in MTRH new born unit is done through
11
clinical examination and echocardiography. Both medical management by clinicians and
ligation of PDA by cardiothoracic surgeon is available at MTRH.
2.3.3 Hematologic
Anemia of prematurity occurs in low birth weight infants 1–3 mo after birth, is associated
with hemoglobin levels below 7–10 g/dL, and is clinically manifested as pallor, poor weight
gain, decreased activity, tachypnea, tachycardia, and feeding problems. Repeated phlebotomy
for blood tests, shortened red blood cell survival, rapid growth, and the physiologic effects of
the transition from fetal (low PaO2 and hemoglobin saturation) to neonatal life (high partial
pressure of oxygen and hemoglobin saturation) contribute to anemia of prematurity. The
oxygen available to neonatal tissue is lower than that in adults, but a neonate's erythropoietin
response is attenuated for the degree of anemia and, as a result, hemoglobin and reticulocyte
count levels are low. In MTRH, anemia of prematurity is managed by transfusing packed red
blood cells based on the available transfusion guidelines.
Folic acid and iron supplementation is started after two weeks and four weeks respectively to
prevent anemia of prematurity. Transfusion is thought to improve oxygen transport and
cardio-respiratory function thus reducing need for oxygen use and ventilatory support.
However packed red cell transfusion in preterm infants has been shown to increase the risk of
necrotizing enterocolitis. In a retrospective study in the USA, the infants who received
packed red cell transfusion had increased adjusted odds of developing NEC compared with
infants who did not receive a transfusion (28).
2.3.4 Gastrointestinal
Hyperbilirubinemia –Preterm infants are at a greater risk of developing jaundice compared
to term or normal birth weight infants.
Premature babies are prone to hyperbilirubinemia due to increased load of bilirubin to be
metabolized by the liver (polycythemia, shortened red cell life as a result of immaturity or
12
transfused cells, increased enterohepatic circulation due to slow gastric movement, infection)
and reduced ability to conjugate bilirubin due activity of the liver transferases due to
prematurity.
In a Swedish population based study conducted to determine morbidity in moderately preterm
infants, that is, infants born at 30 to 34 completed gestational weeks, 59% of the infants had
hyperbilirubinemia (29).
A systematic review of nine studies to evaluate the efficacy of prophylactic phototherapy in
preterm infants found that it helped to maintain a lower serum bilirubin concentration and
may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental
impairment. However, it was recommended further well-designed studies that could enable to
determine the efficacy and safety of prophylactic phototherapy on long-term outcomes
including neurodevelopmental outcomes be done (30).
In MTRH new born unit, pathological neonatal jaundice is treated using phototherapy and
exchange transfusion depending on the bilirubin levels and the clinical characteristics of the
patient in reference to standard normograms.
Necrotizing Enterocolitis
Necrotizing enterocolitis (NEC) is the most common cause of gastrointestinal-related
morbidity and mortality in the neonatal intensive care unit (NICU). The incidence of NEC is
1–5% of infants in neonatal intensive care units (25).
NEC is rare in term infant whereas in preterm infants it begins at 10-15 days after birth. The
cause of NEC remains unclear but is most likely multifactorial. The risk factors for
developing NEC are prematurity, enteral feeding, ischemia, infective agents and bacterial
colonization of the gut. In a retrospective study done in Tel Aviv, Israel to determine short-
term effects in human milk fed versus formula fed preterm infants; it was found that the rates
of NEC were lower in the group of infants that were fed on human milk (31).
13
Preterm infants receiving certain treatments have been shown to have increased incidence of
developing NEC. In a retrospective controlled cohort study conducted in the USA, preterm
infants from 23 to less than 31 weeks who had received more packed red cell transfusions and
more weeks of antibiotic therapy for nosocomial infection developed NEC than did infants
who had not (32). Almost all preterm infants in MTRH newborn unit are fed on breast milk
and whenever NEC is suspected, enteral feeding is stopped and the infant put on parenteral
antibiotics. Complicated cases of NEC are managed by pediatric surgeons.
Nutritional problems
Preterm nutrition contributes significantly to their short term and long term outcomes.
Premature infants born weighing less than 1500 grams are not able to coordinate sucking,
swallowing, and breathing. Feeding into the gastrointestinal tract (enteral feeding) helps with
gastrointestinal tract development and growth (25).
The introduction of enteral feeds for very low birth weight (VLBW) infants may however be
delayed due to severe respiratory distress or concern that early introduction may not be
tolerated and may increase the risk of necrotizing enterocolitis.
Delay in enteral feeding may diminish the functional adaptation of the immature
gastrointestinal tract and prolong the need for total parenteral nutrition which is not available
in most resource limited new born units like MTRH. Early trophic feeding by giving infants
very small volumes of breast milk during the first week after birth, may promote intestinal
maturation, enhance feeding tolerance and decrease time to reach full enteral feeding.
According to WHO guidelines on optimal feeding of low birth weight infants in low and
middle income countries, LBW infants including those with VLBW should be fed on their
mother’s own milk and that is what is being implemented in MTRH new born unit (33).
14
2.3.5 Metabolic
Hypothermia — Premature infants are at greatest risk for hypothermia immediately after
birth in the delivery room and even during admission in the NBU.
Rapid heat loss occurs in premature infants because of their relatively large body surface
area, thin skin and inability to produce enough heat. Heat is lost by conduction, convection,
radiation, and evaporation. Hypothermia may contribute to metabolic disorders such as
hypoglycemia or acidosis. In extremely premature infants of less than 26 weeks gestation,
hypothermia is associated with increased mortality and, in survivors, pulmonary
insufficiency.
In a population-based cohort study of 8782 very low birth weight infants born in California
neonatal intensive care units in 2006 and 2007, 56.2% of the infants were found to be
hypothermic. Low birth weight, cesarean delivery and a low Apgar score were associated
with hypothermia in that study (34).
Standard newborn care in the delivery room to prevent hypothermia in MTRH new born unit
is achieved by maintaining the room temperature at a minimum of 25ºC, drying the baby
thoroughly immediately after birth then removal of any wet blankets and use of pre-warmed
radiant heaters if resuscitation is needed.
Premature low birth weight neonates <1500g are nursed in incubators warmer to avoid
hypothermia in MTRH new born unit. Since the incubators are limited, when available
patients exceed the incubator numbers, Kangaroo mother care is utilized. Triaging is done
based on the gestation age, birth weight and other clinical symptoms.
Hypoglycemia
Premature babies are prone to hypoglycemia due to inadequate glycogen stores. Since
glycogen is deposited during the third trimester of pregnancy, infants born prematurely have
diminished reserves. There is evidence that hypoxemia and ischemia may potentiate the role
of hypoglycemia in causing permanent brain damage (25).
15
In MTRH newborn unit, premature neonates born before arrival have a random blood sugar
level taken and appropriate interventions in form of intravenous dextrose solution or feeding
started as soon as possible.
2.3.6 Renal
Electrolyte imbalance
Premature infants are prone to developing hyponatremia due to urinary losses of sodium
disproportionate to the intake and daily requirement.
In a comparative cohort study conducted in KNH in 1998 to evaluate the impact of early
neonatal morbidity on serum sodium levels, sick preterm infants were found to develop
significant hyponatremia more often than their healthy counterparts (35).
This justifies the analysis of serum electrolytes and other renal function markers in preterm
infants during admission.
The smallest sickest infants are at greatest risk of metabolic bone disease due to
hypocalcaemia. Progressive osteopenia with demineralized bones and occasionally
pathologic fractures may develop. The major cause is inadequate intake of calcium to meet
the requirements for growth. Poor intake of phosphorus and vitamin D are additional risk
factors. Contributing factors include prolonged parenteral nutrition, vitamin D and calcium
malabsorption, intake of unsupplemented human milk, immobilization, and urinary calcium
losses from chronic diuretic use (25).
In MTRH new born unit, supplementation of vitamin D is done using multivitamin
formulation containing vitamin D that is given from two weeks of age helps to prevent rickets
of prematurity.
16
2.3.7 Central Nervous System
Intraventricular hemorrhage
Intraventricular hemorrhage (IVH) is a major complication of prematurity. IVH typically
occurs in the germinal matrix, which is a richly vascularized collection of neuronal-glial
precursor cells in the developing brain. It increases in frequency with decreasing gestational
age and birth weight. The etiology of IVH is multifactorial and is primarily attributed to the
intrinsic fragility of the germinal matrix vasculature and the disturbance in the cerebral blood
flow. Severe intraventricular hemorrhage is noted in approximately 25% of infants 501–750
g; in 12% between 751 and 1,000 g; in 8% between 1,001 and 1,250 g; and in 3% between
1,251 and 1,500 g (25).
In a prospective study conducted in Nigeria between 1992 and 1994, transfontanelle
ultrasound scans were performed on 93 very low birth weight neonates. Twenty two percent
of the neonates had mild IVH, whereas 7.5% had moderate to severe IVH (36). There is no
routine screening for IVH using cranial ultrasound in MTRH new born unit as it done in
developed countries.
2.3.8 Infectious disease
Neonatal sepsis
Premature babies are prone to sepsis due to immature immune system and under developed
natural barrier mechanisms. Two patterns of neonatal sepsis have been described: early-onset
disease, which presents at <3 days of age, and late-onset disease, which presents at 3 days of
age or later. In the 1990s, widespread implementation of maternal chemoprophylaxis led to a
65% decrease in the incidence of early-onset neonatal Group B Streptococcus (GBS) disease
in the USA; from 1.7/1,000 live births to 0.6/1,000 live births, whereas the incidence of late-
onset disease remained stable at 0.4/1,000 (25). Clinical presentation of sepsis in premature
infants is subtle and non-specific; therefore a high index of suspicion is very important. Signs
17
and symptoms of sepsis include temperature instability, respiratory distress, apnoea, feed
intolerance, jaundice, lethargy or irritability. Clinical diagnosis of suspected neonatal sepsis
as a cause of morbidity is done in Kenya as demonstrated in a study done in KNH where 41%
of the infants had a clinical diagnosis of neonatal infection (11).
Similarly, in a retrospective conducted in KNH to quantify morbidity and mortality among
low birth weight infants admitted in the year 2000, 37% had suspected sepsis out of which
only 14% had a blood culture done to confirm the diagnosis (31).
The first line treatment of infants with suspected sepsis is broad-spectrum antimicrobial
agents; Benzyl penicillin and an aminoglycoside. Once a pathogen is identified, after culture
and sensitivity results, antimicrobial therapy is narrowed.
Prevention strategies include strict compliance with hand washing and universal precautions,
limiting nurse-to-patient ratios and avoiding crowding, minimizing the risk of catheter
contamination, meticulous skin care, encouraging early appropriate advancement of enteral
feeding, education and feedback to staff, and surveillance of nosocomial infection rates in the
new born unit (25).
2.4 Short term Survival of Premature infants
Estimates of the probability of survival of very preterm infants admitted to NICU care are
vital for counseling parents on expected outcomes of care and in planning to improve
neonatal services. Survival rates of preterm infants have improved over the last five decades especially in developed countries and trends well documented (2).
Developed countries have higher survival for newborns with birth weights above 1000g at
94% (20). In developed countries there were major changes in both obstetric and neonatal
care during the 1990s. These changes were associated with decreases in mortality and
morbidity for VLBW infants. In these such countries, they are currently concentrating on
18
improving outcome of babies with birth weight 500g to 1000g and they are already reporting
good survival as exemplified by survival rates of 55% and 88% for neonates between 501-
750 g and 751-1000g surviving respectively in the USA (25).
In Kenya and other Sub-Saharan countries, survival rates of very low birth weight and who
mostly are premature infants are still low. A prospective study done at KNH in 1996 showed
overall survival to hospital discharge for infants less than 2000 grams to be 62.2%. None of
the 23 infants born less than 1000g survived the neonatal period in that study (11). In a
prospective study done in MTRH in 1999, the perinatal mortality of neonates admitted to the
special care nursery was 19.7% (12). An unpublished study done in MTRH in the same
special care nursery in 2006 showed overall survival for neonates below 2000g was 48.4%
(13). A retrospective study in Nigeria reviewing records of children born between 1998 and
April 2001 in a tertiary hospital without CPAP had an overall mortality of 19.4% with 31.9%
of the mortality attributed to prematurity (14).
All these studies demonstrated low survival rates for premature infants especially the
extremely preterm babies.
2.5 Factors affecting Short term Survival of Premature infants
2.5.1 Fetal factors
Gestational age and birth weight are the most important determinants of premature infant
short term survival. Mortality rates amongst premature infants correlate with birth weight and
gestational age with decreases in both associated with poorer survival (25). Thus infants born
with the lowest gestational age and birth weight have the largest impact on infant mortality
because they have the greatest risk of death. In two different studies conducted in KNH and
MTRH new born units, the neonatal mortality rate among infants weighing less than 1000g
was 100% (11, 13). The gestation age specific survival rate in the KNH study was low for
the extremely preterm infants with only 9% of those born less than 28 weeks gestation
19
surviving (11). Male gender and low Apgar score at 5 minute have also been associated with
poor survival.
In a study done by in South Africa to determine survival of very low birth weight infants,
male gender and low Apgar score at 5 minutes, were associated with poor survival (37).
Birth weight-specific neonatal diseases such as grade IV intraventricular hemorrhage,
neonatal sepsis (severe group B streptococcal pneumonia or meningitis), and neonatal
malformations e.g. pulmonary hypoplasia also contribute to a poor outcome (25).
2.5.2 Maternal factors
Lack of antenatal care clinic attendance by pregnant mothers has been associated with poor
preterm infant survival. In a study done to determine survival of very low birth weight infants
in a public hospital in South Africa, infants whose mothers did not attend ANC had poor
survival (37). Mode of delivery has been shown to affect survival of infants with spontaneous
vertex delivery having higher mortality compared to Caesarean section as reported in studies
done in KNH, MTRH and South Africa (26, 37).
Maternal antenatal use of steroids by pregnant women has been associated with lower
incidence of RDS and better survival (25).
2.5.3 Level of care
Premature infants are more likely to survive if they are born in high level neonatal intensive
care than in lower level hospitals with limited facilities.
The new American Association of Pediatrics neonatal levels of care consist of four levels
with no subdivisions:
Level I: Provides basic neonatal care for term babies; can perform neonatal resuscitation at
every delivery and care for infants born at 35-37 weeks gestation who remain physiologically
stable.
20
Level II: Provides specialty care for newborns at 32 weeks’ gestation or more and weighing
1,500 grams or more with problems expected to resolve rapidly or who are convalescing from
a higher level of intensive care.
Level III: Provides sub-specialty care for high-risk newborns needing continuous life support
and comprehensive care for critical illnesses. This includes infants weighing less than 1,500
grams or who were less than 32 weeks’ gestation at birth.
Level IV: Includes capabilities of a level III neonatal intensive care unit (NICU) as well as
the ability to provide on-site pediatric medical and surgical subspecialists to care for infants
with complex congenital or acquired conditions, coordinate transport systems, and provide
outreach education within their catchment area. Level IV intensive care units have the highest
neonatal survival rates. The relative risk of neonatal mortality for infants born with very low
birth weights was twofold higher in Level II centers than in Level III centers (5).
Improvements in newborn intensive care, including the use of surfactant treatment and
antenatal steroid therapy to prevent and treat neonatal respiratory distress syndrome, have
resulted in decreased mortality rates of preterm infants, except in those who are at the limit of
viability (17).
In a retrospective cohort study conducted in a South African tertiary public hospital, in a level
II NICU focusing on deliveries conducted from the year 2000 to 2002, low survival to
hospital discharge of the extremely preterm infants was attributed to the lack or limited
availability of exogenous surfactant and mechanical ventilation. (37). The level of care
provided at MTRH new born unit given the available facilities is at level II since there is no
exogenous surfactant and no facilities for continuous ventilatory support like conventional
mechanical ventilation.
21
CHAPTER THREE: RESEARCH QUESTION, OBJECTIVES AND
JUSTIFICATION
3.1 Research Question
What proportion of premature infants admitted to the new born unit at Moi Teaching and
Referral Hospital survive to discharge?
3.2 Objectives
3.2.1 Primary Objective
To determine the proportion of premature infants admitted to the newborn unit at Moi
Teaching and Referral Hospital who survive to discharge.
3.2.2: Secondary Objectives
1. To determine the survival in the different gestational age categories; less than 28
weeks, 28 to less than 32 weeks and 32 to less than 37 weeks.
2. To describe the factors that are associated with short term survival of premature
infants admitted to the new born unit at MRTH.
3.3 Justification of the Study
Neonatal survival data has been utilized by countries and NICUs to demonstrate trends in
preterm birth outcomes over the years (2). It is difficult to formulate appropriate interventions
to improve neonatal care and outcomes without reliable data on survival rate.
In KNH and MTH earlier studies done focusing on survival of low birth weight infants
reported poor survival of very low birth weight and extremely low birth weight infants most
of whom are known to be preterm (11,13).
In MTRH, there has been significant increase in the number of preterm infants admitted to
the new born unit following the expansion of the unit. However, both the short term and long
term survival of preterm infants admitted to the new born unit had not been documented (12).
22
Facility specific data on survival of preterm infant and causes of morbidity and mortality
would help the MTRH management to develop interventional strategies aimed at improving
outcomes of this vulnerable group of patients. The findings will be useful to obstetricians,
paediatricians and neonatologists when making decisions on delivery and care of these
preterm infants and when counseling parents on expected outcomes. Findings of this study
may also be used for advocacy to improve neonatal services at MTRH and other public
facilities in the country taking care of preterm infants.
Lastly, this information will help advice the peripheral facilities on appropriate referral of
mothers with preterm labour to MTRH given the viability limit findings from this study.
We projected that at the current rate of preterm birth deaths and with few years remaining,
Kenya is unlikely to achieve the fourth MDG target of reducing under five mortality rate by
the year 2015 and even beyond 2015 (16).
23
CHAPTER FOUR: METHODOLOGY
4.1 Study design
This was a prospective descriptive study. Study participants were recruited at admission by
the principal investigator and followed during their stay in the unit, taking note of all
significant clinical events until either discharge home or death. There was no intervention by
research team.
4.2 Study site
The study was conducted in the newborn unit of MTRH which is located in Eldoret town,
about 300km from Nairobi, in Uasin Gishu County, Kenya. The hospital is an 800 bed
capacity tertiary hospital that serves as a referral hospital for the western part of Kenya, with
a catchment population of about 13 million people - 33% of Kenyan population. The hospital
provides various services ranging from primary to specialized care and serves urban, peri-
urban and rural populations from near and far counties. The hospital also serves patients from
neighboring countries; Uganda, Sudan, South Sudan and Rwanda.
The hospital’s new born unit is located in the Riley Mother and Baby hospital wing, a new
extension of the hospital that was opened in 2009. The NBU has a capacity of fourteen
incubators, forty eight cots and is able to provide basic neonatal services and non invasive
respiratory support using nasal bubble CPAP. The unit does not have a neonatal intensive
care unit (NICU) and does not provide mechanical ventilation and exogenous surfactant for
preterm babies.
The staffs allocated to the unit include two neonatologists, three pediatricians, thirty five
nurses, a nutritionist, paediatrics resident doctors, medical officer interns and clinical officer
interns.
All premature low birth weight neonates weighing less than 1700g, born in the MTRH labour
ward, born at home or referred from lower level health facilities in the catchment area are
24
admitted to the MTRH new born unit. They are managed using the basic Pediatric protocol in
Kenya which has been adopted from the WHO guidelines.
4.3 Study Population
Premature neonates admitted to the MTRH new born unit from December 2012 to August
2013 who met the inclusion criteria were recruited. This included premature neonates born in
MTRH labour ward, those referred from other health facilities and those born at home.
Inclusion Criteria
a) Neonates who were born at less than 37 completed weeks gestational age.
b) Preterm neonates whose mothers gave informed consent to have their infants enrolled
in the study.
Exclusion Criteria
a) Preterm infants with congenital malformations not compatible with life.
4.4 Sample Size
The Fischer’s formula for calculating the sample size for a simple random sample without
replacement was used as follows; N= Z 2
α P (1-P) W 2
Where:
Z α is the standard normal deviate and =1.96 for a 95% confidence level
P is the expected proportion of premature infants who survive to discharge in
MTRH, 50%. In studies done in similar resource-poor settings birth weight
(not gestational age) has often been used as a proxy measure for maturity, thus
getting short term survival proportion as an outcome measure is difficult. This
study therefore used a median value of 50% since the exact outcome
proportion is unknown.
W is the desired width of the confidence interval and = 0.05
25
Thus: Replacing these values in the above formulae:
=384
Adjusting for finite population for premature infants admitted to MTRH new born unit based
on the 2011 hospital medical records where an average of 30 premature neonates were
admitted per month, for 9 months: 270
Thus:
; N=270 (N= the population size while nf = is the finite sample size)
= 158.6; ≈ 159
Adjusting for transfer outs, an additional 10% more were recruited giving a final sample size
of 175 premature infants.
4.5 Sampling Technique
Consecutive sampling of premature neonates admitted to MTRH new born unit was done.
Every next study subject meeting the inclusion criteria was recruited until the desired
minimal sample size of 175 was attained.
4.6 Outcome measures
The primary outcome measure was the proportion of premature infants who survived to
hospital discharge. The secondary outcome was the length of hospital stay.
4.7 Data Collection
Data was collected by the principal investigator using a pretested standard questionnaire and
follow up data collection form. The demographic data, neonatal and maternal characteristics
were entered in the data collection form at admission. Gestation age was calculated using two
26
methods; the last menstrual period (LMP) as an entry point and then New Ballard score
method for analysis. For most of the infants, there was no significant difference between
gestational age by LMP and that by new Ballard score. Infants’ anthropometric
measurements; weight, length and head circumference were taken by the PI or research
assistant. Any missing maternal data was obtained through maternal interview and by
checking the ANC attendance booklet.
4.8 Study Execution
The clinicians working in the new born unit were sensitized about the study to enable them
inform the principal investigator and research assistant, a NICU nurse, whenever preterm
infants were admitted in the new born unit. The research assistant identified infants born at
less than 37 completed weeks by LMP and informed the principal investigator. Mothers’ of
premature infants were identified in the postnatal ward or hostel and informed written
consent was obtained from those whose babies met the inclusion criteria.
The gestational age was determined by calculating the number of weeks from the first day of
the last menstrual period and confirmed using the new Ballard score within 48 hours of
admission (38).The infant’s demographic data, maternal antenatal and delivery data and the
clinical characteristics were collected by the principal investigator at admission through an
interview of the mother and physical examination of the baby.
Information on whether the mother had started attending ANC and their HIV serology status
was obtained. Presence of any antenatal and perinatal maternal morbidity was noted.
Anthropometric measurements taken at admission were birth weight in grams (g), length and
head circumference in centimeters. Weight was measured using electronic digital weighing
scale, SECA model 728 to the nearest 1g.
The diagnosis made and interventions started at admission were recorded. The participants
received standard newborn care based on the diagnosis made as per the new born care
27
protocol. Daily ward rounds were done by the health care providers in NBU and appropriate
investigations done to diagnose any new causes of morbidity suspected.
The principal investigator followed up the study subjects and collected information on the
significant events; causes of morbidity and interventions received during hospitalization and
updated the information in the follow up data collection form until discharge or death. . The
length of stay and final outcome were noted.
Discharge was decided by the clinicians taking care of the subjects in the new born unit upon
recovery or achieving the recommended weight for discharge.
4.9 Data management, data analysis and presentation
Data collected was coded to maintain confidentiality and then entered into a Microsoft access
data base. Data was then checked for consistency by providing validation checks in Microsoft
access. Data was then exported to STATA version 10.0 for analysis.
The data was analyzed at 95% level of confidence. Descriptive statistics such as mean and
median were used for continuous variables. Frequency listings and percentages were used to
describe categorical variables. Survival analysis was done using Cox Proportional Hazards
model was used to determine factors associated with survival and Kaplan-Meier Survival
curves drawn. Significant correlation was when the confidence interval did not contain 1 and
p-value was less than 0.05. Data was presented in prose, tables, figures and curves.
4.10 Ethical Considerations
Approval to conduct the study was granted by Institutional Research and Ethics Committee
(IREC) and the management of MTRH. Patients details obtained were handled confidentially
by use of computer password known by the principal investigator only. All patients received
the necessary standard treatment regardless of their willingness or unwillingness to
participate in the study. No incentives or inducements were used to convince mothers to
28
allow their babies to participate in the study. Informed and written consent was emphasized.
Findings of this study will be shared with MTRH management.
29
CHAPTER FIVE: RESULTS
A total of 175 preterm infants were studied from December 2012 to August 2013. There were
82 males and 93 female infants giving a male to female ratio of about 1:1.13.
5.1 Infant characteristics
The mean gestation age was 31.94 weeks (±3.06) and the mean birth weight was 1342g
(± 355.5). Among the infants recruited 14.9% (26) were extremely low birth weight, 46.3%
(81) were very low birth weight whereas 38.9% (68) were low birth weight.
Table 1: Infant Characteristics
Characteristic Frequency (n=175) %
Gender: Male 82 46.9
Female 93 53.9
Gestation age: <28weeks 27 15.4
28-31weeks 54 30.9
32-36 weeks 94 53.7
Mode of delivery: SVD 138 78.8
EMCS 22 12.6
SBD 15 8.6
30
Figure 1: Place of delivery
5.2 Maternal characteristics
The median maternal age was 24 years (range from 14 to 42 years). Twenty percent of the
mothers were teenagers. The majority of mothers, 117 (67.2%) were married while 56
(32.2%) were single. Most of the mothers whose infants were studied were primigravidae, 85
(48.6%). Sixty four percent of the mothers had attended antenatal clinic at least once. All
mothers had their HIV status known with the most of them, 164 (93.7%) being HIV negative.
Sixty nine percent of the mothers reported to have developed spontaneous preterm labour.
Mothers who had obstetric complications prior to delivery included 24 with preeclampsia, 13
with Ante partum hemorrhage and 8 with premature rupture of membrane. Most mothers who
delivered through caesarian section had antenatal complications with 14 (63.6%) having
preeclampsia.
111, 64%
37, 21%
27, 15%
MTRH
OTHER FACILITY
HOME
31
Table 2: Maternal Characteristics
Characteristic Frequency (n=175) %
Age (Years): <20 36 20.6
20-25 73 41.7
26-30 34 19.4
31-35 15 8.6
>35 17 9.7
Employment status: Unemployed 113 64.6
Self employment 49 28.0
Formal employment 13 7.4
5.3 Short term Survival
The overall proportion who survived to hospital discharge was 60.6% (95% CI 0.53-0.68).
Of the babies who did not survive, 11 (15.9%) died within the first 24 hours with 56 (81.1%)
dying by the end of the first week. Only two infants died after the end of the neonatal period.
The mean length of stay for the infants who survived to hospital discharge was 25.8days
(±16.1) whereas for those who died it was 6.2 days (±7.6).
Table 3: Gestational age specific survival
Gestation age
in weeks
Admissions Survivors at
discharge
Survival %
< 28 27 8 29.6
28-31 54 27 50.0
32-36 94 71 75.5
Total 175 106 60.6
32
Figure 2: Admissions and Survivors
5.3 Causes of morbidity
The diagnoses made at admission for majority of the study participants were prematurity, low
birth weight and respiratory distress syndrome. Various clinical diagnoses made by the
clinicians during the infant stay in the new born unit were noted.
Although 155 (88.6%) infants were suspected to have neonatal sepsis, only 24 (15.5%) had
blood cultures done. The organisms species that were isolated included: Klebsiella (10),
Coagulase negative staphylococcus (4), E. coli (1), Enterococcus (1) and Citrobacter (1). Two
cultures had no growth obtained and five had no results back by the time of the patient death
or discharge home. Hypothermia (HR 2.87, 95% CI 1.06-7.73, p-value 0.00), apnoea (HR
26
81
68
3
48
55
Less than 1000g 1000-1499g 1500-2449g
Admissions Survivors
33
5.3, 95% CI 2.58-10.98, p-value 0.04) and respiratory distress syndrome (HR 2.92, 95% CI
1.29-6.60, P-value 0.01) were significantly associated with higher hazard of dying.
Table 4: Causes of Morbidity
Diagnosis Frequency %
Suspected Neonatal sepsis 155 88.6
Hypothermia 118 67.4
Neonatal jaundice 115 65.7
Respiratory distress syndrome 113 64.6
Apnoea 76 43.4
Anemia 71 40.6
Necrotizing enterocolitis 13 7.4
Hypoglycemia 8 4.6
Table 5: Correlates of Mortality (Causes of morbidity)
Variable HR 95%CI p-value
Neonatal Sepsis 0.46 0.15 1.43 0.18
Anemia 0.86 0.51 1.44 0.57
Neonatal Jaundice 0.35 0.21 0.58 0.00
Hypothermia 2.87 1.06 7.73 0.04
Hypoglycemia 2.31 0.88 6.06 0.09
Neonatal Enterocolitis 1.19 0.59 2.37 0.63
Apnoea 5.30 2.58 10.89 0.00
RDS 2.92 1.29 6.60 0.01
34
5.4 Interventions
All preterm babies were started on IV fluids, intramuscular vitamin K injection and
tetracycline eye ointment at admission. Antibiotics were used in 98.9% of the study subjects.
The first line antibiotics were Benzyl penicillin and gentamicin, second line was a third
generation cephalosporin and amikacin and third line was a fourth generation cephalosporin
or meropenem and vancomycin. A total of 71(40.6%) infants were diagnosed to have anemia,
42 (73.2%) of those received blood transfusion.
Babies weighing less than 1500g were nursed in incubators. Eighty infants (45.7%) were
nursed in incubator during their stay in the newborn unit.
5.5 Correlates of Mortality
Infant characteristics
The proportion of infants who survived to discharge increased with increasing gestation age
and birth weight with those born weighing over 1500g having the highest survival proportion
of 80.9%. The hazard of dying was low among low birth weight infants compared to
extremely low birth weight infants (HR 0.4, 95% CI 0.20-0.78, p-value 0.003).
The hazard of dying was low for preterm infants born after 31 weeks gestation compared to
those born at or less than 28 weeks gestation (HR 0.39, 95% CI 0.18-0.82, p-value=0.013).
The hazard of dying was higher for premature infants born through cesarean section
compared to those born via spontaneous vertex delivery (HR 4.25 95% CI 1.875-8.662; p-
value=0.001)
35
Figure 3: Overall Survival curve
0 .0
0 0
.2 5
0 .5
0 0
.7 5
1 .0
0
P ro
p o
rt io
n s
u rv
iv in
g
0 20 40 60 80 Length of stay (days)
Kaplan-Meier estimate
36
Figure 4: Birth weight specific survival curves
0 .0
0 0
.2 5
0 .5
0 0
.7 5
1 .0
0
P ro
p o
rt io
n s
u rv
iv in
g
0 20 40 60 80 Length of stay (days)
Below 1000
1000-1499
1500-2500
Kaplan-Meier estimate by birthweight
Log Rank Test (p-value=0.000)
37
Figure 5: Gestational age specific survival curves
0 .0
0 0
.2 5
0 .5
0 0
.7 5
1 .0
0
P r o
p o
r ti
o n
s u
r v
iv in
g
0 20 40 60 80 Length of stay (days)
Below 28 weeks
28-31 weeks
32-36 weeks
Kaplan-Meier estimate by gestation age
Log Rank Test (p-value=0.000)
38
Table 6: Correlates of Mortality (Infant characteristics)
Variable HR 95%CI P-value
Place of delivery
Facility vs MTRH 1.91 0.72 5.10 0.20
Home vs MTRH 2.48 0.87 7.11 0.09
GA in weeks
28-31 vs <28 0.74 0.37 1.49 0.4
32-36 vs <28 0.39 0.18 0.82 0.013
Sex: Male vs Female 1.50 0.92 2.47 0.108
Mode of delivery
SBD vs SVD 1.62 0.76 3.45 0.209
EMCS vs SVD 4.26 1.88 9.66 0.001
Birth weight in g
1000-1499 vs <1000 0.40 0.20 0.78 0.008
1500-2500 vs <1000 0.27 0.11 0.64 0.003
Age at admission in hours
1-6 vs <=1 0.59 0.24 1.42 0.238
6-12 vs <=1 1.99 0.23 17.22 0.532
12-24 vs <=1 0.87 0.22 3.51 0.849
>24 vs <=2 0.24 0.03 1.93 0.18
Apgar score
4-5 vs 3 2.29 0.77 6.80 0.137
6-7 vs 3 0.78 0.29 2.15 0.636
8-10 vs 3 0.50 0.24 1.04 0.065
39
Maternal characteristics
The hazard of dying was lower for premature infants whose mothers attended ANC compared
to those whose mothers didn’t (HR 0.52 95% CI 0.3-0.9; P-value=0.02).
Maternal age, education level, marital status and HIV status were not significantly associated
with short term survival as shown in table 7 below.
Table 7: Correlates of Mortality (Maternal characteristics)
Variable HR 95% CI P-value
Age 20-25 vs <20 1.13 0.59 2.17 0.716
25-30 vs <20 1.12 0.50 2.48 0.786
30-35 vs <20 0.99 0.34 2.91 0.981
>35 vs <20 0.32 0.09 1.18 0.087
Education: Post primary vs primary 1.25 0.71 2.20 0.440
Marital status- Married vs Single 0.89 0.48 1.64 0.704
ANC attendance-Yes vs No) 0.52 0.30 0.90 0.020
Parity >0 vs 0 1.18 0.67 2.06 0.571
HIV status-Pos vs Neg 1.57 0.55 4.54 0.403
40
CHAPTER SIX: DISCUSSION
Demographic data
In this study the male and female subjects were basically the same which is similar to the
findings of Kramer in his 1987 meta analysis which found no overall difference in sex
distribution in low birth weight infants (39). There was a slight female preponderance among
infants surviving to hospital discharge however the difference was not statistically significant.
Simiyu in a study done in KNH found a similar gender difference in survival of low birth
weight infants which was explained by death of more male newborns but the difference was
also not statistically significant (26). A study by Velaphi et al on survival of very low birth
weight infants in South Africa showed that male gender was significantly associated with
poor neonatal survival (37). The finding in this study suggests that gender has no role in
determination of survival; however this question seems not to be conclusively answered
because other studies have reported significant difference.
Short term Survival
Preterm newborns are known to have greater risk of both morbidity and mortality compared
to term neonates. There are not many studies in Africa that have looked specifically at
mortality among preterm infants. Majority of the studies looked at overall neonatal mortality
and prematurity was reported a leading cause of neonatal mortality in most of the studies. In
this study, two thirds of preterm infants survived to hospital discharge which is similar to
findings by Were et al in a prospective study that looked at 163 infants weighing less than
2000g and found a 62.2% survival to hospital discharge (11). The survival rate in this study is
slightly higher than what Simiyu in a study done in the year 2000 which reported neonatal
mortality low birth weight infants to be 57.4% in the new born unit of KNH (26). That was a
retrospective study in a setting where 23 % of the files were missing and hence this could
have introduced bias.
41
Kasirye-Bainda et al reported an overall neonatal mortality rate of 24.6% in KNH and
reported that LBW and prematurity accounted for 95.6% of the mortality (40).
In a Tanzanian tertiary referral hospital, neonatal mortality rate of 19% was reported by
Klingenberg et al and gestation less than 31 weeks accounted for 67% of the mortality (41).
Survival was different for the three birth weight categories with the low birth weight having
the best outcome and extremely low birth weight the worst outcome.
This is similar to findings by Kasirye- Bainda et al who reported survival of 48.7% among
babies with birth weight less than 1500g while Were et al in the same hospital reported zero
survival of newborns less than 1000g and two thirds survival for bigger ones (11, 40).
Increasing survival proportion with increasing birth weight is also true of gestation age as
shown in this study finding that the hazard of dying was significantly lower for infants with
gestational age 32 to less than 37 weeks compared to those below 28 weeks.
Were et al reported 69% survival among those with gestation 32 to 35 weeks and only 9% for
those less than 28weeks gestation (11).
Increasing gestational age and birth weight is associated with better respiratory maturity
which enables preterm infants to adapt better to extra-uterine life.
The survival proportion observed in this study is much lower than the one reported in
countries with advanced neonatal care. In South Africa, Velaphi et al reported survival to
hospital discharge of 32% among premature infants born at gestation below 28 weeks (37).
However, the best survival has been reported in the developed countries where survival for
newborns with birth weights above 1000g is above 94% (42, 43). In deed research in
developed countries is currently concentrating on improving outcome of babies with birth
weight 500g to 1000g and they are already reporting good survival as exemplified by survival
rates of 55% and 88% for neonates between 501-750 g and 751-1000g surviving respectively
reported in the USA (44). Changes in obstetric care and availability of advance neonatal
intensive care facilities have led to better outcomes in developed countries.
42
The risk of developing RDS in infants born less than 28 weeks gestation age is 60-80% (25).
Therefore in a resource limited new born unit without exogenous surfactant and ventilatory
support like in this study site, survival of infants born at less than 28 weeks remains low.
It has been shown that 25 – 45% of neonatal mortality occurs within the first 24 hours mainly
as a result of birth asphyxia and acute complications of prematurity. Of the infants who did
not survive in his study, a tenth died within the first 24 hours while cumulatively four fifths
died during the first seven days of life. Other studies reported higher deaths within the first 24
hours, Simiyu (36%), Were et al (28%) and Ezechukwu et al (64.5%) in tertiary hospitals in
Kenya and Nigeria respectively (11, 14, 26). Similar findings were reported by Kasirye-
Bainda et al where 86.8% of the neonatal deaths in a study done in KNH occurred within the
first week of life (40). Notably those studies were done in hospitals without continuous
positive airway pressure (CPAP) facilities and in an era where were exogenous surfactant and
antenatal steroids were not widely used; factors which may explain the current finding of a
lower proportion that died in MTRH in the first 24 hours with availability of CPAP and use
of antenatal steroids. The higher numbers of preterm infants dying during the first week of
life could be due to acute complications of prematurity occurring in a setting with limited
neonatal intensive facilities to support the preterm infants especially those with RDS and
early onset neonatal sepsis.
Extremely low birth weight infants who survived to hospital discharge had long length of
hospital stay. This is similar to findings by Simiyu et al in a study to quantify the morbidity
and mortality of low birth infants in KNH (26). This could be attributed to morbidity
associated with complications of extreme prematurity and time taken to gain recommended
weight before discharge more so in a setting where there is no total parenteral nutrition for
these infants for infants who can’t tolerate enteral feeds.
This study showed that the limit of viability in MTRH newborn unit was 28 to less than 32
weeks gestation category. Although the WHO has established the upper limit of viability at
43
37 completed weeks of gestation they have not set the lower limit. The lower limit is defined
by fetal organ maturity and advances in high risk obstetrics care and neonatal intensive care.
The USA currently defines this lower limit as about 25 weeks or weight above 500g (43).
Compared the developed countries, our viability limit is still high, a finding that could be
explained by limitation in high risk obstetric care and neonatal intensive care.
The mortality rate of preterm infants admitted in MTRH new born unit is still high especially
for the very preterm and extremely preterm infants.
Factors associated with survival:
Infant characteristics
In this study, there was a significant improvement in the proportion of premature infants
surviving to hospital in the gestation age 32 to 36 weeks category compared to less than 28
weeks or 28 – 31 weeks gestation category. Studies done in KNH and MTRH before reported
similar findings, showing a positive correlation between gestation age and survival (11, 13).
Indeed it has been stated that the most significant public health intervention to reduce
neonatal mortality is reduction in rate of preterm deliveries by prolongation of gestation age
whenever possible. This study suggests that efforts should not only aim at reducing preterm
births but at increasing gestation age by maximum possible days. This approach is likely to
bear more benefit in low resource settings where neonatal intensive care is often inadequate
or absent.
The finding that Caesarian section was associated with significant higher hazard of dying was
unexpected. This finding was contrary to other studies where caesarian section was
associated with better survival (11, 12, 37). In a retrospective audit of births that occurred in
MTRH labour ward between 2004 and 2011, Yego et al reported that majority of early
neonatal deaths followed vaginal deliveries (45).
44
We postulated that this finding could partly be explained by the fact that two thirds of
mothers who delivered through cesarean section in this study had severe preeclampsia which
could have increased the risk of poor outcome. However there could be other reasons and
therefore the area needs to be explored in future studies.
Infants born in MTRH had better probability of survival compared to those born either in
outside facility or at home, however after adjusting for other factors, difference was not
statistically significant. This finding is in agreement with those by Simiyu in KNH, by
Welbeck et al in a study done in Accra Ghana. However, it is different from findings from a
study done by Udo et al in Nigeria where survival of neonates born in the tertiary hospital
facility had better survival than those born in outside the facility (26, 46, 47). The poor
outcome in the infants born before arrival in the Ghana study was attributed to delay in
transportation of neonates to the tertiary hospital and inappropriate transportation which
adversely affected the neonates.
In this study, two thirds of the infants were born in MTRH and whereas those born at lower
level facility or at home were fewer likely contributing to statistical insignificance. However
studies that look at how babies born outside are transported to our facility and cared for
during transport may offer insights into practices that could have improved survival.
Babies with Apgar score above 3 at five minutes were more likely to survive compared to
those with lower and in addition this probability was directly proportional to the score with 8
to 10 having the best survival; however the benefit was not statistically significant after
adjusting for other factors. In South Africa, Velaphi et al reported that Apgar score less than 6
at 5 minutes was associated with poor survival. Increase in Apgar scores was reported to have
better survival to hospital discharge in preterm infants, which is in agreement with findings in
our study (37). Birth asphyxia in premature infants worsens the respiratory insufficiency due
to RDS and makes short term survival poor.
45
Maternal characteristics
Two thirds of mothers of the infants who were studied had attended ANC clinic at least once
before giving birth. This proportion is lower than 92% reported in KDHS of 2008-09 and
could be explained by the fact that a significant number of mothers start attending ANC late
in the 2 nd
and 3 rd
trimester thus those who had extremely and very preterm deliveries had not
yet started attending ANC (16).
Babies whose mothers attended at least one ANC had a lower hazard of dying compared to
those whose mothers didn’t. This is similar to findings by Velaphi et al in a study where
infants whose mothers attended ANC were one and half times more likely to survive (37).
Antenatal clinic attendance has been shown to be one of the major contributors to improved
neonatal survival in the USA (41). Antenatal care is useful in reducing preterm births by
aiding identification of mothers at risk for preterm delivery; offers an opportunity for timely
monitoring, intervention and admission to the new born unit. This study did not however look
at the optimum number of antenatal visits that were associated with improved survival. It has
been estimated that improving the quality of prenatal care would decrease prematurity
associated deaths by 75% (2).
Maternal age and parity were not found to be statistically significant in contributing to
neonatal survival. This is similar to findings by Welbeck et al in a study done in a tertiary
teaching hospital in Accra Ghana where maternal parity and age were not found to
significantly contribute to survival of at risk neonates (46). However, Yego et al reported that
a significantly higher number of early neonatal deaths occurred for infants whose mothers’
were in the age group of 15 to 24 years (45). This finding was due to by high rate of preterm
labour and late admission to hospital among young mothers. The difference in findings
between this study and our study could be attributed to the sample selection because our
study excluded term newborns. Those with preterm labour tend not to delay in seeking care
as observed in term labour. Additionally, this could be explained by the fact that after
46
gestational age and birth weight, the next important determinant of short term survival of
preterm infants is the level of neonatal care service in the unit which is independent of
maternal demographic characteristics.
Maternal HIV status was not significantly associated with survival to hospital discharge in
this study. In studies done in rural Mozambique and South Africa by Ndirangu et al and
Nianiche et al respectively, maternal human immunodeficiency virus (HIV) infection was
shown to cause small for gestation infants but not preterm births (23, 24). The findings in our
study similar to those two studies suggest that HIV infection does not worsen the neonatal
survival. This could be attributed to the natural history of vertically transmitted HIV whereby
there is no significant immunosuppression in the first month of life and the neonate has
maternal antibodies.
It is important to note that in this study the number of HIV positive mothers was few which
was comparable to the general prevalence of HIV amongst pregnant women (6.4%) reported
in the Rift valley region in the KDHS report (16). Implementation of prevention of mother to
child transmission of HIV interventions has also reduced the risk of vertical transmission and
hence reduced morbidity and mortality for sero-exposed infants.
Causes of morbidity and Interventions
In this study, respiratory distress syndrome was one of the most common diagnoses made and
it was associated with higher hazard of dying. In a study done in KNH new born unit in 1996
to determine birth weight specific survival of infants weighing less than 2000g at birth, 43%
developed RDS (11). Another study conducted in the same unit, four years later, to quantify
morbidity and mortality of low birth weight infants showed that the leading diagnosis on
admission or discharge of low birth weight infants was respiratory distress syndrome at 69%
(26). The high rates of respiratory distress syndrome were expected as a consequence of lung
47
immaturity and perhaps lack of timely prenatal steroid intervention and lack of exogenous
surfactant in MTRH new born unit.
This study found that although majority of the infants were suspected to have sepsis and
started on antibiotics, most of them did not have blood cultures done. We observed that it was
not routine to have all premature infants suspected to have neonatal sepsis have blood
cultures done. This was partly due to stock out of blood culture specimen collection bottles
and also due to clinicians prioritizing only infants who were very sick and or not responding
to initial antibiotic therapy. Simiyu, in two retrospective studies conducted in KNH on
newborn babies admitted to the new born unit and the general pediatric wards reported that
37% and 71%had suspected sepsis yet only 14% and 8.4% had confirm sepsis diagnosis
respectively (26, 48). One common finding in these studies was use of antibiotics without
laboratory confirmation of sepsis. This posed a risk for development of antibiotic resistance.
Meticulous infection control and treatment interventions are required to reduce morbidity due
to sepsis. It is possible that improvement in newborn intensive care technology will not
necessary improve short term outcomes unless there is reduction in the risk of sepsis.
In comparison, in the United States, morbidity due to sepsis has decreased remarkably and
currently the main causes of morbidity and mortality in preterm infants are respiratory
distress syndrome and intraventricular hemorrhage (41). In this study we did not find any
diagnosis of intraventricular hemorrhage which could be explained by the low index of
suspicion among clinicians and lack of routine IVH screening in MTRH new born unit.
Apnoea and hypothermia were associated with increased hazard of dying. These are acute
complications of prematurity which occur more often in critically ill infants. This finding was
similar to findings by Simiyu in a study done in KNH where apnoea was occurred in 29% of
the patients, it was managed with rectal aminophylline but only 12% of these infants survived
(26). Lack of conventional drugs such as caffeine citrate in the unit could have contributed to
higher mortality in neonates with apnoeic attacks.
48
Hypothermia occurred in two thirds of the study participants. This proportion is higher than
that reported by Simiyu in a KNH study where hypothermia occurred in 27% of the patients
(26). The higher incidence could be attributed to the limited number of incubators available
in the unit leading to nursing of premature infants in open cots with space heaters where
thermal control was poor. Implementation of Kangaroo mother care in the unit was not
routinely performed and therefore, from the findings of this study, there is need to scale up
and formally implement KMC in the unit. Infants born before arrival were also noted to have
hypothermia at admission, especially those transported by private means. Referring health
facilities and the general public too need to be sensitized on use of KMC when referring
preterm infants to higher level facilities like MTRH new born unit and that could reduce the
incidence of hypothermia.
Study Limitations
Assumption that survival probabilities are the same for study subjects recruited into
the study at different times during the study period.
Estimating the gestational age: use of last menstrual period and New Ballard score,
without first trimester ultrasound; each of them is not ideal but combining the two
improves accuracy.
49
CHAPTER SEVEN: CONCLUSIONS AND RECOMMENDATIONS
CONCLUSIONS
Two thirds of premature infants admitted to MTRH new born unit survived to
discharge.
Majority of the infants died within the first seven days.
The survival limit was the 28 to less than 32 weeks gestational age category.
Increasing gestation age, birth weight over 1000g and maternal antenatal care clinic
attendance were associated with better survival.
Caesarean section mode of delivery was associated with poor survival.
RECOMMENDATIONS
1. Whenever possible preterm birth delivery should be delayed until after 28 weeks
gestation.
2. More effort should be put in increasing early antenatal care clinic attendance.
3. Further studies are needed to evaluate why caesarean mode of delivery of preterm
infants was associated with poor survival and audit the efficacy of current
interventions being implemented in the unit.
4. A study that follows premature infants after discharge to determine intermediate and
long term survival rates.
50
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55
APPENDICES
APPENDIX 1: DATA COLLECTION FORM
Demographic data:
Serial No……………………… IP No………………………..
Date of admission……/……/……. Date of discharge/death…/……/
Residence district……………… Place of delivery: MTRH…..H/Facility… Home….
Infant characteristics
Gestational age--------wks by LMP/-------wks by Ballard Sex: Male….Female……..
Mode of delivery: SVD…..SBD….AVD……..EMCS………ELCS…………
Birth weight…………g Age at the time of admission……..Hrs
Apgar score at 5min------/10
Maternal characteristics
Age:………….Years Level of education: None…Primary……….Post primary…….
Employment status: Unemployed…..Self employment….Formal employment……….
Parity: PARA……+…… Interval between this last birth and Conception………Months
ANC attendance: Yes/No HIV Serology Neg/Pos
Antenatal Complications Yes/No, If Yes specify……………………………………………..
Clinical characteristics
Diagnosis on admission……………………………………
Causes of Morbidity during admission Interventions on admission
o Neonatal Sepsis IV fluids
o Anemia IV antibiotics
o Neonatal jaundice Blood product transfusion
o Hypothermia Phototherapy
o Hypoglycemia Anticonvusants
o Necrotizing enterocolitis Oxygen
o Apnoea CPAP
Outcome: 1) Discharge home 2) Death
Length of stay…………days
56
APPENDIX 2: NEW BALLARD SCORE FOR ASSESSMENT OF GESTATIONAL
AGE AT BIRTH.
PHYSICAL MATURITY
SIGN SCORE SIGN
SCORE -1 0 1 2 3 4 5
Skin
Sticky,
friable,
transparent
gelatinous,
red,
translucent
smooth
pink,
visible
veins
superficial
peeling
&/or rash,
few veins
cracking,
pale
areas,
rare
veins
parchment,
deep
cracking,
no vessels
leathery,
cracked,
wrinkled
Lanugo
None sparse abundant thinning bald
areas
mostly
bald
Plantar
Surface
heel-toe
40-50mm: -1
<40mm: -2
>50 mm
no crease
faint red
marks
anterior
transverse
crease only
creases
ant. 2/3
creases
over entire
sole
Breast Imperceptible barely
perceptible
flat areola
no bud
stippled
areola
1-2 mm
bud
raised
areola
3-4 mm
bud
full areola
5-10 mm
bud
Eye /
Ear
lids fused
loosely: -1
tightly: -2
lids open
pinna flat
stays
folded
sl. curved
pinna;
soft; slow
recoil
well-
curved
pinna; soft
but ready
recoil
formed
& firm
instant
recoil
thick
cartilage
ear stiff
Genitals
(Male)
scrotum flat,
smooth
scrotum
empty,
faint rugae
testes in
upper
canal,
rare rugae
testes
descending,
few rugae
testes
down,
good
rugae
testes
pendulous,
deep rugae
Genitals
(Female)
clitoris
prominent &
labia flat
prominent
clitoris &
small labia
minora
prominent
clitoris &
enlarging
minora
majora &
minora
equally
prominent
majora
large,
minora
small
majora
cover
clitoris &
minora
TOTAL PHYSICAL MATURITY SCORE
57
NEUROMUSCULAR MATURITY
SIGN SCORE SIGN
SCORE -1 0 1 2 3 4 5
Posture
Square
Window
Arm
Recoil
Popliteal
Angle
Scarf
Sign
Heel To
Ear
TOTAL NEUROMUSCULAR SCORE
Maturity Rating
Score Weeks
-10 20
-5 22
0 24
5 26
10 28
15 30
20 32
25 34
30 36
35 38
40 40
45 42
50 44
58
APPENDIX 3: FOLLOW UP FORM
At
birth
D2 D3 D4 D5 D6 D7 WK
2
WK
3
WK
4
WK
5
Weight (g)
Minimum wt (g)
No. of days to
minimum wt
No. of days to
recover birth wt
Length (cm)
Head circumference
Morbidity
Respiratory distress
syndrome
Neonatal sepsis -
confirmed
Neonatal sepsis -
suspected
Anemia
Physiologic
Neonatal Jaundice
Pathologic NNJ
Hypoglycemia
Apnoea
Necrotizing
enterocolitis
Hypothermia
Interventions
1 st line antibiotics
2 nd
line antibiotics
3 rd
line antibiotics
Lab investigations
Continuous positive
airway pressure
Blood transfusion
Imaging
Surgery
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APPENDIX 4: CONSENT TO PARTICIPATE IN THE STUDY
SERIAL NUMBER ………..
Background
You are being asked to participate in a research study. Before you decide, it is important for
you to understand why the research is being done and what it will involve. Read the
following information carefully and ask us if there is anything that is not clear or if you
would like more information. Please take time to decide whether you want to take part in this
study. The
purpose of this study is to determine the proportion of premature infants surviving to
discharge at MTRH and the factors that influence their survival. Our study is for research
purposes but we hope that the information obtained will be used to inform the hospital and
other policy formulators which will result in improved healthcare service delivery.
Study Procedure
The study involves filling out a questionnaire capturing you and your baby’s biodata and the
presenting symptoms and signs at admission in the NBU. A record will be kept of the
anthropometric measurements and causes of morbidity during hospitalization. The findings
during subsequent assessments cannot be linked to your baby and are completely anonymous
and confidential since we shall be using serial numbers.
Risks
There are no risks involved in this study. This study will be anonymous. The baby will
receive treatment as per the diagnosis made based on the hospital and Ministry neonatal
protocols.
Benefits
There are no direct medical benefits to your child for participating in this study. A potential
benefit of the study will be improved healthcare service delivery based on the
recommendations of this study.
Alternative Procedures
You may choose your baby not to participate in this study
Confidentiality
This research will be conducted in accordance with all the Kenyan laws and regulations that
protect rights of human research subjects. All records and other information obtained will be
kept strictly confidential and your baby’s protected health information will not be used
without permission. All data collection tools will be identified by number or otherwise coded
to protect any information that could be used to identify your baby. Results of this study may
be published, but no names or other identifying information will be released.
Person to Contact
If you have questions, complaints or concerns about this study, you can contact the
investigator from Moi University, School of Medicine, department of Child Health and
Paediatrics, Postgraduate progarmme ; Dr. Makokha Felicitas Okwako +254722622651
email drmakfelis@gmail.com
Institutional Review Board
This study has been approved by the Institutional Research and Ethics Committee (IREC) of
Moi University/Moi Teaching and Referral Hospital. Contact IREC if you have questions
60
regarding your child’s right as a participant, and also if you have complaints or concerns
which you do not feel you can discuss with the investigator.
Contact IREC using the address ; The Chairman IREC, Moi Teaching and Referral Hospital,
PO BOX 3, Eldoret, Kenya. Tel. 33471/2/3
Voluntary Participation
It is up to you to decide whether your baby takes part in this study. Refusal to participate or
the decision to withdraw from this research will involve no penalty or loss of benefits to
which your child is otherwise entitled. This will not affect your relationship with the
investigators.
Right of investigator to withdraw
The investigator can withdraw your baby form the research without your approval.
Costs and Compensation to participants
There is no cost to you, and there is no compensation to subjects for participation in this
study.
Number of Participants: 175 babies
Authorization for use of your protected health information
This study that does not entail the use of your baby’s protected health information.
Thank you for your baby’s participation in this research and we truly appreciate your help.
CONSENT
By signing this consent form, I confirm I have read the information in this consent form and
have had the opportunity to ask questions. I will be given a signed copy of this consent form.
I voluntarily agree to take part in this study.
Name of Caregiver ………………………………Signature/Mark…………..
Date…………..
Name of Investigator ……………………………Signature………………….
Date…………..
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APPENDIX 5: IREC APRROVAL
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APPENDIX 6: HOSPITAL APPROVAL