The prevalence of premature birth and low birth weight was 6.2% in 2018 in Indonesia.

Premature birth and birth weight were health indicator of the newborn and one of the challenges
of the health care.1 World Health Organization health statistics in 2012 showed the birth rate of
LBW around the world reached 15% of total births with 17% mortality. 2 Preterm is defined as
babies born alive before 37 weeks pregnancy are completed. There are sub-categories of preterm
birth based on gestational age, moderate-late preterm (32 to <37 weeks), very preterm (28 to <32
weeks), and extremely preterm (<28 weeks), with decreasing gestation age at birth associated
with increase risk of mortality.3
Low birth weight infants define as birth weight less than 2500 grams regardless the
gestational age. World Health Organization classified low birth weight infant into 3 categories,
low birth weight (LBW) infant if the birth weight less than 2500 grams, very low birth weight
(VLBW) infant if the birth weight less than 1500 grams, and extremely low birth weight
(ELBW) if the birth weight less than 1000 grams.4 In United States, the prevalence of VLBW
infant was 1.46%, there was no data in Indonesia, which more than 50% of VLBW experience
death or disability.5 Based on birth weight and gestational age neonate can be classified using
Lubchenco curve into appropriate for gestational age, small for gestational age, large for
gestational age.6 In this case, patient was born preterm with an estimated gestational age of 31
weeks and very low birth weight (1300 grams). The birth weight, birth height, and head
circumference were on 10th – 90th percentile of Lubchenco curve.
Neonatal pneumonia is defined as pulmonary infection occurring within the first 28 days of
life. Transmission of infection may occur in utero, during birth, or after birth. 8 Neonatal
pneumonia is a serious respiratory infectious disease caused by a variety of microorganisms,
mainly bacteria, with the potential of high mortality and morbidity. Worldwide neonatal
pneumonia is estimated to account for up to 10% of childhood mortality, with the highest case
fatality rates reported in developing countries. Incidence of neonatal pneumonia ranging from 1
to 35 %, 1 percent for term infants and 10 percent for preterm infants. Neonatal pneumonia is
mostly caused by bacteria Group B Streptococcus, Staphylococcus aureus, Staphylococcus
epidermidis, E coli, Pseudomonas, Serratia marcescens dan Klebsiella. 9 Risk factors for neonatal
pneumonia including prolonged rupture of membranes, prematurity, MAS, and therapeutic
cooling. The signs and symptoms of neonatal pneumonia are often nonspecific and may include
respiratory distress, temperature instability, and hypothermia. The radiographic findings for
neonatal pneumonia are variable. Pulmonary opacities can be focal but are more often diffuse
and bilateral. Chest radiographs can show hazy opacities similar to those associated with
surfactant deficiency disorder (SDD), coarse irregular opacities similar to those associated with
meconium aspiration syndrome (MAS), or reticular opacities similar to those associated with
transient tachypnea of the newborn. Patients are often treated empirically with antibiotics.
Definitive diagnosis is based on blood or respiratory culture, though cultures are often negative. 8
In this case, patient was born preterm with respiratory distress occured after birth. Chest X-ray
showed infiltrate patterns in accordance with neonatal pneumonia.
Neonatal sepsis is one of the main problems in LBW with a high mortality rate. The
incidence of neonatal sepsis globally reached 25% and in cases with LBW reaches 50%, whereas
in our hospital was reported by 5% with a mortality of 28.3% in 2008.12 Neonatal sepsis is a
clinical syndrome of systemic illness accompanied by bacteremia occurring in the first month of
life. The overall incidence of primary sepsis is 1–5 per 1000 live births. The incidence is much
higher for VLBW infants (birthweight <1500 g). Onset of neonatal sepsis is based on the onset,
classified as early-onset sepsis (EOS) if perinatal infections occur in the early post natal period
(<72 hours) and late onset sepsis (LOS) if perinatal infection occurs after 72 hours post natal
period, that obtained from the surrounding environment or hospital organism. 8 Neonatal sepsis
criteria based on history (including maternal and neonatal risk factors) as shown in Table 1,
clinical features, and laboratory findings. Clinical signs of neonatal sepsis is often non-specific
and relate to the characteristics of microba and the body response to the microba, such from
central nervous system (lethargy, weak suck reflex, high pitch cry, irritable, convulsions),
cardiovascular (pallor, cyanosis, cold), respiratory (tachypnea, apnea, moaning, retractions),
gastrointestinal (vomiting, diarrhea, abdominal distension), hematology (bleeding, jaundice),
skin (rash, ptechiae).13 Laboratory evaluation can help confirm the diagnosis of sepsis. Positive
blood culture is the gold standard for diagnosing sepsis. Hematologic examinations should
performed serially in order to see the changes that occur during infection. 13 Other commonly
used non-culture based diagnostic was, leukocyte count (normal between 5,000 / uL up to
30,000/uL), platelet count (normal >150,000 / uL), I/T ratio (normal neutrophil ratio of immature
to total neutrophils <0.2), procalcitonin (Normal <0.05 mg / mL; suspected bacterial infection of
>10 ng/mL).14 In this case, patient diagnosed as clinically early onset sepsis, due to 1 major risk
factor (mother fever during intrapartum period with temperature >38 0C) and 3 minor risk factors
for sepsis (gestational age < 37 weeks, vaginal discharge, and birth weight 1300 grams). Clinical
findings and septic marker support the presence of sepsis but no growth of bacteria from blood
cultures. The clinical diagnosis of sepsis is confirmed by clinical symptoms and laboratory in
accordance with the description of sepsis.
Table 1. Risk factors for neonatal sepsis
Major risk Minor risk
1. Rupture of membranes >24 hours 1. Rupture of membranes >12 hours
2. Mother fever during intrapartum 2. Mother fever during intrapartum period with
period with temperature >380C temperature >37,50C
3. Chorioamnionitis 3. Low APGAR score (minute 1<5, and
4. The fetal heart rate >160 minute 5 <7)
beats/minute 4. Very low birth weight infants (<1500 gram)
5. Green amniotic fluid 5. Gestational age <37 weeks
6. Multiple pregnancy
7. Vaginal discharge
8. Urinary tract infections
Source: Aminnulah A, 2008

Treatment of neonatal infections can be divided into antimicrobial therapy for the
suspected (empirical) or known (definitive) pathogens. Antimicrobial therapy administration
should not be delayed for suspected early onset sespsis cases, delayed antimicrobial therapy will
increase the morbidity. Initial empirical treatment of early-onset bacterial infections should consist
of ampicillin and an aminoglycoside.15 Neonates initiated on empirical antibiotics for EOS who
have sterile cultures, with no signs of infection, and normal screening laboratory exams should
have antimicrobials stopped. In a single center study of over 3000 patients admitted to the NICU
who had a blood culture obtained in the first postnatal hour, and a complete blood count (CBC)
obtained in the first postnatal hour and again at 8 – 12 hours, none of the 1539 neonates (49%)
who had 2 normal immature to total neutrophil (I:T) ratios and a negative blood culture at 24
hours subsequently developed sepsis. Therefore, if no early test was abnormal, the culture is
sterile, the neonate is well, antibiotics should be stopped. Antimicrobials can continue until 7
days if there are clinical signs of infection that persisted over 24 hours or clinical signs initially
absent, but became apparent after first postnatal hours and persisted more than 24 hours. 16 In this
case, the patient was born vigorously but had respiratory distress immediately after birth and
need oxygen that persisted more than 24 hours, and the patient was given antimicrobial therapy
(ampicillin and amikacin) for 8 days.
Apnea of prematurity is a condition where the breath stopped for more than 20 seconds,
associated with the presence of bradycardia or cyanosis in infants with gestational age less than
37 weeks. Incidence of AOP increases proportionally with the gestational age. The most
common cause is immaturity of respiratory center and coordination of respiratory muscles
(diaphragm and intercostal muscle) in controlling breathing. Onset of AOP is usually at the age
of 2 until 7 days. Apnea that occur at the first 24 hours or more than 7 days, should be considered
caused by other causes. The AOP classification consists of central apnea, obstructive apnea, and
mixed apnea. Management of AOP includes the use of methylxanthine and CPAP.
Methylxanthine preparations recommended as standard therapy is caffeine citrate. It is useful in
reducing recurrence of apnea and is better tolerated by the gastrointestinal tract. Side effects like
tachycardia are also less than other preparations, such as aminophylline.19 The problem is its
availability because it is only available on certain place. Another methylxanthin preparation that
can be used is aminophylline. It has wider availability throughout Indonesia. In this case, the
patient had AOP on 1st day of treatment and received intravenous aminophylline therapy (loading
dose continued with maintenance dose). Aminophylline was well tolerated by the patient and no
side effects such as vomiting or tachycardia were present.
Hyperbilirubinemia is a common and in most cases benign problem in first month of
life which is often physiologic and intervention is not usually necessary. Jaundice appears during
the first week of life in approximately 60% of term and 80% of preterm infants. Common
etiology of hyperbilirubinemia in preterm infants are prematurity and infection. 17 Preterm infants
develop more significant jaundice due to poor bowel motility, decreased oral intake, and
immaturity of the hepatic conjugating system. Consequently, prematurity is a significant risk
factor for developing hyperbilirubinemia and requiring therapy. Hyperbilirubinemia in preterm
infants is more prevalent, more severe, and its course more protracted than in term neonates, as a
result of exaggerated neonatal red cell, hepatic, and gastrointestinal immaturity. 18 In this case,
patient experienced hyperbilirubinemia within 1 week of life, that normally can be caused by
prematurity, since there was no evidence of bacterial growth from blood culture that led to early
onset sepsis as the etiology of hyperbilirubinemia.
 The preterm nutrition at the age less than 34 weeks provided through enteral or
parenteral. The best nutrition for premature infant is human milk that contained immune
protection with risk of growth failure, developmental delays, necrotizing enterocolitis, and late-
onset sepsis increasing with decreasing gestational age and birth weight. Milk from women who
deliver prematurely differs from that of women who deliver at term. Preterm milk is initially
higher in protein, fat, free amino acids, and sodium, but over the first few weeks following
delivery these levels decrease. The mineral content (including trace minerals) of preterm milk is
similar to that of term milk, with the following exceptions: calcium is significantly lower in
preterm milk than term milk and does not appear to increase over time while copper and zinc
content are both higher in preterm milk than term milk and decrease over the time of lactation.
Human milk must be fortified for small premature infants to achieve adequate growth. 19,20 The
purpose of early aggressive nutrition is to reduce the cumulative caloric and protein deficits in
acute stage to a minimal degree and hence to prevent EUGR (extra uterine growth retardation)
and associated abnormal cognitive and neurodevelopmental outcomes. This strategy involves
initiating early parenteral and enteral nutrition. The initiation of minimal enteral feedings (with
initially small amounts 10-20 ml/kg/day, and then advancing, within the first 5 days of life. First
week protein and energy intake are associated with 18 month developmental outcomes in very
preterm infants.21 In growing care stage, the goal of growth should approximate the rate of
growth and composition of weight gain for a normal fetus of the same post menstrual age. From
return to birth weight through discharge, the goal of enteral nutritional management of these
infants should include requirements for catch-up growth, and should be set for weight gain 10-15
g/kg/day and head circumference increase up to 0.8 cm/week, because this growth rate was
associated with better neurodevelopmental and growth outcomes. Nutritional intervention to
promote growth during the intermediate period while the infants are still in hospital are
commonly slowly advanced to full enteral nutrition, including multinutrient fortification of
human breast milk for breastfed infant (fortified human milk) and nutrient-enriched formula for
formula-fed infants (preterm infant formulas).20 Two major strategies are in common clinical use:
multinutrient fortification of human breast milk for breastfed infants and nutrient-enriched
formula for formula-fed infants.22 In this case, patient got breast milk and human milk fortifier,
the body weight was increased 10-15 g/kg/day.
 Preterm infants are at higher risk for hypothermia because of several unique
characteristics. Preterm infants can only maintain core temperatures in a narrow range of
environmental temperatures. They have a greater ratio of skin surface to body weight, almost 4
times that of adults, compared with term infants, who have a ratio 3 times that of adults. This
larger skin surface area leads to more radiant heat loss and eventually, more insensible losses.
Transepidermal water loss varies inversely with the gestational age; preterm infants can lose as
much as 15 times more water per kilogram of body weight compared with term neonates. Brown
fat may not be well-developed until 26 to 30 weeks of gestation.10
There is a close association among temperature maintenance, oxygen consumption, and
glucose utilization. Cold stress leads to increased oxygen consumption, which can result in tissue
hypoxia and metabolic acidosis. Metabolic acidosis can, in turn, inhibit the formation of
surfactant. The norepinephrine that is released from brown fat can cause systemic and pulmonary
vasoconstriction. Pulmonary vasoconstriction can lead to increased pulmonary vascular
resistance with decreased oxygen delivery to the cells and tissues. Hypothermia can lead to
increased glucose consumption, and result in exhaustion of glycogen stores. Increased insensible
heat loss can lead to dehydration, fluid electrolyte imbalance, hypotension, irritability and poor
feeding. Untreated hypothermia eventually leads to altered physiology and may cause seizure
activity or even death.11 To prevent these morbidities, it is imperative to recognize cold stress as
soon as possible.
Incubators are designed to minimize heat loss and provide a neutral thermal environment
requiring minimal metabolic effort by the baby to maintain thermoregulation. However,
incubators lack the maternal-preterm bond and are expensive, especially in middle- and low-
income countries. Public hospitals across the country are facing a crisis over the shortage of
incubators for preterm babies as the number of mothers delivering in hospitals increases. In some
instances, the hospital staff sometimes place two or more preterm babies in the same incubator
despite the risk of cross-infections. Therefore, an economical, efficient and effective method is
needed as an alternative to an incubator. In this case, intermittent KMC is performed as an
alternative substitute for an incubator, where the mother's body will become a thermoregulator
for her baby, preventing hypothermia, facilitating breastfeeding, stimulation, bonding, and
protecting against infection.
 In preterm infants receiving oxygen therapy, retinopathy of prematurity (ROP) is the
most common visual impairment. The incidence of retinopathy of prematurity in very preterm
infants (<32 weeks) and low birth weight infants (<1,500 grams) in Indonesia ranged from 11.9–
30.5%.30 In this case, patient was born preterm (31 weeks) and very low birth weight (1450
grams) with respiratory distress syndrome, using CPAP support with total oxygen use more than
seven days. concluding the patient is at risk for ROP. Screening of ROP had been performed and
the result was bilateral immature retina. The patient planned for re-evaluation of ROP two weeks
after first screening.
The premature infant tend to develop negative iron balance due to a number of factors.
Iron is mostly accumulated during the third trimester of gestation. Total body iron and
hemoglobin (Hb) contents, and serum and storage iron concentrations are lower in preterm
infants. Conditions such as severe maternal iron deficiency, intrauterine growth restriction, and
chronic blood loss during gestation can further compromise fetal iron endowment. 7 Postnatally,
the meager iron stores can be rapidly depleted during the first 6–8 weeks, coinciding with the
onset of erythropoiesis and rapid catch-up growth. The Hb nadir is lower and occurs earlier in
more premature (gestational age 28–32 weeks) infants when compared with those born at a
gestational age of 33–36 weeks. However, beginning at 9 weeks and continuing until 12 months
of age, Hb concentrations are comparable in the two gestational age groups, implying the need
for a more robust erythropoiesis and therefore, greater iron requirement in the more prematurely
born infants.8 The effects of iron deficiency are pervasive and involve multiple organ systems.
Poor physical growth, gastrointestinal disturbances, thyroid dysfunction, altered immunity and
temperature instability has been attributed to iron deficiency in very low birth weight (VLBW,
birth weight <1500 g) infants. Anemia is typically a late sign and suggests significant depletion
of iron stores. A major concern of early iron deficiency is its effect on the developing brain.9
Dietary iron deficiency during early infancy is associated with long-term
neurodevelopmental impairments that appear to be irreversible in spite of iron supplementation.
Long-term cognitive abnormalities have also been demonstrated in full-term infants with iron
deficiency in the neonatal period.8 A limited number of studies suggest that early iron deficiency
may also adversely affect neurologic function and neurodevelopment in preterm infants.
Compared with non-anemic, iron-replete infants, preterm infants with anemia (Hgb ≤ 9 g/dL)
and low iron stores (serum ferritin ≤ 76 μg/L) had an increased number of abnormal neurologic
reflexes at 37 wk postmenstrual age.10 Iron is essential for neural metabolism and functioning.
Iron deficiency anemia results in changes in energy metabolism within the brain with defects in
neurotransmitter function and myelination. Therefore, infants and young children with iron
deficiency anemia are at risk of developmental difficulties involving cognitive, social-emotional,
and adaptive functions.11 We want to know what is the optimal timing to administer prophylactic
enteral iron supplementation in preterm and very low birth weight infants, and we performed
journal searching and obtain evidence-based journal entitled "Early and late iron
supplementation for low birth weight infants: a meta-analysis" by Jin HX et al., from Italian
Journal of Pediatrics, 2015. Evidence based analysis from this journal showed valid, important,
and applicable, with the level of evidence 1a, and grade of recommendation A. Conclusion of the
journal is early iron supplementation increased hemoglobin levels and iron reserves, and reduced
the risk of iron-deficiency anemia. In this case, this patient was given iron supplementation at 2
weeks.
The infant mortality rate due to low birth weight is between 60 to 80% of the total
number of perinatal deaths. Skin of preterm newborns is immature partially due to the absence of
vernix and partial development of stratum corneum without proper architecture. High
environmental load of pathogenic organisms and malnutrition are two important contributors of
mortality of preterm in developing countries. Oil massage is a traditional practice in Indian
subcontinent for centuries. The putative benefits of oil application as well as the massage
induced tactile kinesthetic stimulation to the newborn skin in the form of improved skin barrier
function to decrease neonatal sepsis of late-onset type, thermoregulation and also possible
positive effect on growth and weight gain. It was also associated with a higher level of serum
vitamin D3 and a better neurodevelopmental outcome. Supplementation of essential fatty acid by
the emollient (helps in skin maturity), prevention of insensible water loss (less latent heat and
hence, less hypothermia) and stimulation during application (better neurodevelopment and
prevention of apnea) may be responsible for these findings.12
We want to know efficacy of cocounut oil application on the skin of preterm baby, and
we performed journal searching and obtain evidence-based journal entitled " Effect of Virgin
Coconut Oil Application on the Skin of Preterm Newborns: A Randomized Controlled Trial "
by Konar MC et al., from Journal of Tropical Pediatrics, 2019. Evidence based analysis from
this journal showed valid, important, and applicable, with the level of evidence 1a, and grade of
recommendation A. Conclusion of the journal is Use of coconut oil helps in dermal maturity and
better neurodevelopmental outcome. In this case, this patient was given virgin coconut oil
application on the skin.

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