154 Paediatrica Indonesiana, Vol. 45, No.

7-8 July - August 2005

Paediatrica Indonesiana
VOLUME 45 NUMBER 7-8 July - August 2005
Original Article
From the Department of Child Health, Medical School, Padjadjaran
University, Hasan Sadikin Hospital, Bandung, Indonesia.
Reprint requests to: Stanza Uga Peryoga, MD, Department of Child
Health, Medical School, Padjadjaran University, Hasan Sadikin Hospital,
Jl. Pasteur No. 38, Bandung 40161, Indonesia. Tel. 62-22-2034426; E-
mail: bikaup@bdg.centrin.net.id, office@pediatry.fk.unpad.ac.id.
The risk for delayed development in low birth weight,
appropriate for gestational age preterm infants
Stanza Uga Peryoga, MD; Abdurachman Sukadi, MD; Sambas Wiradisuria, MD
ABSTRACT
Background Preterm infants, particularly those who have had
severe asphyxia, hyperbilirubinemia, and sepsis, tend to be at risk
for neurodevelopmental impairment.
Objective The purpose of this study was to assess the risk for de-
layed development in low birth weight (LBW), appropriate for gesta-
tional age (AGA) preterm infants compared to that in term, non-LBW
infants, and to investigate the roles of severe asphyxia, sepsis, and
hyperbilirubinemia as potential risk factors for delayed development.
Methods This was a hospital-based retrospective cohort study
involving preterm, LBW and term, non-LBW infants conducted in
Hasan Sadikin Hospital, Bandung. The Bayley Infant
Neurodevelopmental Screener (BINS) test was performed to as-
sess the risk of delayed development at 3 months of corrected age
for the preterm infants and at 3 months of chronological age for the
term infants. Bivariate analysis using the chi-square test and mul-
tivariate analysis using logistic regression were performed.
Results One hundred and twelve infants fulfilled eligibility criteria,
consisting of 52 preterm, LBW and 60 term, non-LBW infants. Based
on the BINS test, of the preterm, LBW infants, 32 (61%) were at
low risk, 11 (21%) at moderate risk, and 9 (17%) at high risk for
delayed development. Of the control infants, 49 (82%) were at low
risk, 10 (17%) at moderate risk, and 1 (1.7%) at high risk for de-
layed development. Logistic regression analysis showed signifi-
cant association between accompanying diseases such as sepsis
(OR=25.60; P=0.001) and hyperbilirubinemia (OR=16.07; P=0.001)
with delayed development. Despite more than twofold odds for
delayed development in infants with severe asphyxia (OR=2.51)
and LBW-prematurity (OR=2.47), the association was statistically
insignificant (P=0.20 and P=0.15, respectively).
Conclusions In preterm infants appropriate for gestational age,
prematurity and low birth weight alone may or may not predispose
to delayed development at 3 months of age. However, the risk for
delayed development in such infants is increased when sepsis or
hyperbilirubinemia is present [Paediatr Indones 2005;45:154-
159].
Keywords: preterm, low birth weight, developmen-
tal delay, Bayley Infant Neurodevelopmental Screener
D
elayed development in high-risk infants is
caused either by existing biological,
psychosocial environment, or social economic
risk factors.
1
Preterm infants are at risk for delayed
development due to the immaturity of their organs.
2
The occurrence of delayed development may also be
a consequence of accompanying diseases such as
asphyxia, hyperbilirubinemia, sepsis, periventricular
hemorrhage, and chronic lung disease.
3,4
Aside from infectious diseases and malnutrition,
low birth weight (LBW) is a significant cause of child
morbidity and mortality, as well as a risk factor for
delayed development in later life.
5
In Indonesia, the
incidence of LBW is still high, both in rural (10%) or
urban (20%) areas.
6
However, the outcome of infants
with birth weight of 1500-2499 g is less frequently
reported than that of those weighing less than 1500 g
at birth. In Indonesia, the risk for delayed develop-
ment is predicted to be different from that in devel-
oped countries, considering the abundance of biologi-
cal and environmental risk factors. The incidence,
mortality, and morbidity of LBW infants in Indonesia
Paediatrica Indonesiana, Vol. 45, No. 7-8 July - August 2005 155
Stanza Uga Peryoga et al: The risk for delayed development in preterm infants
are still high.
6,7
To assess an infants developmental
status, an early developmental screening test needs
to be done periodically.
8
To date, no study has been
reported on the risk for delayed development at an
early age (3 months) in LBW, appropriate for gesta-
tional age (AGA) infants using the Bayley Infant
Neurodevelopmental Screener (BINS) as screening
instrument. The purpose of this study was to assess
the risk for delayed development in LBW (1500-2499
g), AGA preterm infants compared to that in term,
non-LBW infants. The roles of accompanying condi-
tions, such as severe asphyxia, sepsis, and hyperbiliru-
binemia as potential risk factors for delayed develop-
ment were also investigated.
Methods
This was an observational study with a retrospective
cohort design involving LBW, AGA preterm infants
born in March-August 2003 and term, non-LBW
infants born in June-July 2003 at Hasan Sadikin
Hospital, Bandung. The subjects were recruited at
birth by consecutive sampling. Subjects included in
the LBW, preterm group were singleton, appropriate
for gestational age preterm infants with birth weight
of 1500-2499 g at 3 months of corrected age. The
control group consisted of term infants appropriate
for gestational age with birth weight of > 2,500 g at 3
months of age, who had no history of illness since birth.
All infants had to be in good health. We obtained
parental written informed consent from all subjects.
Exclusion criteria were major congenital anomaly (e.g.,
Down syndrome, meningocele), congenital infection
(TORCH), hyaline membrane disease, and history of
exchange transfusion, prior hospital admission,
seizures, and head trauma. To assess the risks for
delayed development, the Bayley Infant Neuro-
developmental Screener (BINS) test was performed.
The BINS test was administered during home visits
or at the outpatient Growth and Development Clinic
of Hasan Sadikin Hospital.
All data were recorded, tabulated, and analyzed
using SPSS version 10.0 for Windows. To determine
the association between prematurity, low birth weight,
and its accompanying diseases with the risk for de-
layed development, we performed bivariate analysis
using the chi-square test. To determine the influence
of other independent variables such as severe asphyxia,
sepsis, and hyperbilirubinemia, we performed multi-
variate analysis using logistic regression. In bivariate
and multivariate analysis, the risk for delayed devel-
opment was divided into low, moderate, and high risk.
A P value of <0.05 was considered statistically sig-
nificant. Odds ratio (OR) with 95% confidence in-
tervals 95% were calculated. Probabilities of risk for
delayed development from various risk factors were
estimated using the logistic regression model.
Ethical approval for this study was obtained from
the Research Ethics Committee of the Medical
School, Padjadjaran University.
Results
According to the perinatology medical records in
March-August 2003, 85 infants fulfilled the inclusion
criteria for the LBW, preterm group. We were unable
to locate the homes of 33 of these infants. At the end
of the study, there were 52 infants in the preterm,
LBW group, of which 38 were examined in the clinic
and 14 were home visited. Developmental examina-
tion in this group was conducted in July 2003 to
January 2004. In the control group there were 60
infants. Examination in this group was performed at
the clinic in September-November 2003.
Table 1 shows the characteristics of subjects in
both groups, which appear to be similar. The risks for
delayed development in both groups are shown in
Table 2. In bivariate analysis, significant difference
was found between both groups in the proportions of
infants with low risk (P=0.02) and high risk
(P=0.001) for delayed development. However, such
a difference was not found for moderate risk (P=0.54).
Table 3 depicts the performance of infants in
each group on each item of the BINS examination.
Using chi square test, significant differences between
both groups were found in the ability to hold the head
erect and steady for 15 seconds (P=0.001), to adjust
the head to ventral suspension (P=0.04), and to sit
with slight support for 10 seconds (P=0.001). Sig-
nificantly less infants in the preterm, LBW group than
in the control group were able to perform these items.
The proportions of infants with accompanying
morbidities at birth, such as asphyxia, hyperbilirubine-
mia, and sepsis can be seen in Table 4. Severe asphyxia
Paediatrica Indonesiana
156 Paediatrica Indonesiana, Vol. 45, No. 7-8 July - August 2005
TABLE 1. SUBJECT CHARACTERISTICS
Characteristic Group
Preterm, LBW Term, Non-LBW
(n= 52) (n= 60)
Sex
Male 26 (50%) 24 (40%)
Female 26 (50%) 36 (60%)
Gestational age (weeks)
Mean (SD) 34.8 (1.4) 38.8 (1.0)
Range 32-36 37-41
Birth weight (g)
Mean (SD) 2038.6 (246.1) 3178.9 (324.1)
Range 1500-2450 2500-4000
Birth length (cm)
Mean (SD) 43.5 (3.4) 49.2 (2.2)
Range 30-52 43-53
TABLE 2. THE RISK FOR DELAYED DEVELOPMENT IN BOTH GROUPS
Risk for delayed Group
development Preterm, LBW Term, Non-LBW P
N % N %
Low 32 61.5 49 81.7 0.02*
Moderate 11 21.2 10 16.7 0.54
High 9 17.3 1 1.7 0.001*
TABLE 3. RESULTS OF BINS EXAMINATION
Item on BINS (%) P
Preterm, LBW Term, Non-LBW
Non- optimal Optimal Non- optimal Optimal
1. Eyes follow ring 1.9 98.1 1.7 98.3 0.72
2. Reaches for suspended ring 75 25 58.3 41.7 0.06
3. Holds head erect and steady for15 seconds 25 75 3.3 96.7 0.001*
4. Adjusts head to ventral suspension 7.7 92.3 - 100 0.04*
5. Demonstrates optimal muscle tone in upper - 100 - 100 -
extremities
6. Demonstrates optimal muscle tone in lower 1.9 98.1 - 100 0.46
extremities
7. Sits with slight support for 10 seconds 57.7 42.3 28.3 71.7 0.001*
8. Regards pellet-conjugate gaze 5.8 94.2 6.7 93.3 0.58
9. Vocalizes two different sounds 15.4 84.6 5.0 95.0 0.07
10. Fingers hands in play 36.5 63.5 36.7 63.3 0.99
11. Demonstrates coordinated movement of 1.9 98.1 - 100 0.46
extremities
TABLE 4. ACCOMPANYING MORBIDITY
Morbidity LBW Non-LBW P
N % N %
Without asphyxia 21 40.4 39 65.0 0.01
Mild to moderate asphyxia 18 34.6 17 28.3 0.47
Severe asphyxia 13 25.0 4 6.7 0.01
Hyperbilirubinemia 9 17.3 11 18.3 0.89
Sepsis 11 21.2 2 3.3 0.001
Paediatrica Indonesiana, Vol. 45, No. 7-8 July - August 2005 157
Stanza Uga Peryoga et al: The risk for delayed development in preterm infants
(P=0.01) and sepsis (P=0.001) was significantly more
prevalent in the preterm, LBW group than in the con-
trol group. Such a difference was not found for mild to
moderate asphyxia and hyperbilirubinemia.
From bivariate analysis, we obtained a statisti-
cally significant association between sepsis and hyper-
bilirubinemia with the risk for delayed development
(P=0.001). However, there was no significant asso-
ciation between severe asphyxia and the risk for de-
layed development (P=0.15).
On logistic regression analysis, it was shown that
sepsis (OR=25.60, 95%CI 2.61; 251.22) and hyper-
bilirubinemia (OR=16.07, 95%CI 3.80; 67.98) were
significantly associated with the risk for delayed de-
velopment. Low birth weight-prematurity (OR=2.47)
and severe asphyxia (OR=2.51) potentially increased
the odds for delayed development by more than two-
fold, but in the population the effects of these two
factors may vary (95%CI 0.72;8.42 and 0.62;10.22,
respectively) (Table 5).
Discussion
In this study, the number of participants examined in
the preterm, LBW group were less than initially
planned because we could not find the residences of
some patients. There were no participants with very
low birth weight (<1500 g), despite our knowledge
that approximately 50% of these infants are at risk for
delayed development.
9
From medical records, we
found that most of these very low birth weight
(VLBW) infants died during hospitalization; those
who survived died after they had been discharged.
The Bayley Infant Neurodevelopmental
Screener (BINS) is designed to identify infants be-
tween the ages of 3 to 24 months who are develop-
mentally delayed of have neurological impairments.
It is not an abbreviated form of the Bayley Scales of
Infant Development-Second Edition (BSID-II), but
rather a tool for screening infants to identify them
for further diagnostic testing.
10
The results of devel-
opmental screening test using BINS showed differ-
ences in the degree of risk for delayed development
between both groups. A larger proportion of LBW,
preterm infants were at high risk (17%) compared
to non-LBW, term infants (2%). We found that the
proportion of LBW, preterms at high risk for delayed
development was higher than that in the United
States (8%, 95%CI 5;20%). In the United States it
was also found that LBW, preterm infants had 2-5
times higher risk for delayed development than non-
LBW, term infants.
11
Premature and low birth weight infants tend to
have higher risk for neurological disorder and delayed
development.
12
Moreover, they often have subnormal
growth and inferior health conditions.
13
Dunn et al
revealed that motor disorders often correlate with
prematurity.
14
From Table 3, we see that delayed de-
velopment in motor-neurologic aspects (holding head
erect and steady for 15 seconds, adjusting head to
ventral suspension) and expressive aspects (sitting
with slight support, vocalizes sound) were profound
in the LBW, preterm group.
Lenke
15
found that the prevalence of motor disor-
ders was 35% in LBW infants (1501-2000 g) and 60-
70% in VLBW infants (<1500 g). The types of motor
disorders were increased or decreased muscle tone, im-
paired automatic reaction, persistent primitive reflex, and
asymmetric neuromotor development. All these condi-
tions gradually improved and became normal at 8-10
months corrective age. Transient dystonia, a transient
motor disorder resolved in the first year of life.
15
Premature infants often experience other condi-
tions such as sepsis, severe asphyxia, hyperbilirubinemia,
intraventricular hemorrhage (IVH), and cerebral infarc-
TABLE 5. LOGISTIC REGRESSION ANALYSIS ON THE ASSOCIATION BETWEEN
POTENTIAL RISK FACTORS AND THE RISK OF DELAYED DEVELOPMENT
Risk factor SE P OR CI 95%
LBW-prematurity 0.90 0.63 0.15 2.47 0.72;8.42
Severe asphyxia 0.92 0.72 0.20 2.51 0.62;10.22
Sepsis 3.24 1.17 0.001* 25.60 2.61;251.22
Hyperbilirubinemia 2.78 0.74 0.001* 16.07 3.80;67.98
: regression coefficient; constant: -2.545; accuracy: 85.7%
Paediatrica Indonesiana
158 Paediatrica Indonesiana, Vol. 45, No. 7-8 July - August 2005
tion. All these conditions can aggravate neurological
impairments. In our study we did not have any data on
IVH or infarct due to lack of supporting devices (USG).
Fifteen percent of term infants who experience
hypoxic ischaemic encephalopathy (HIE) due to severe
asphyxia will have persisting brain function impairment
and develop cerebral palsy or mental retardation.
13
In
this study, severe asphyxia had no significant correlation
with delayed development. Similarly, Gottoff
16
wrote that
only 10% infants with cerebral palsy had experienced
severe asphyxia. This might be because most infants with
severe asphyxia had died before the study. It is still being
debated whether it is justified to use the Apgar score as
a sole determinant for severe asphyxia, and then associ-
ate it with the risk for delayed development.
In this study, prematurity alone was not a risk
factor for delayed development. However, if this con-
dition is accompanied with sepsis and/or hyperbiliru-
binemia (>15mg/dl), the risk became profound. Sep-
sis had the strongest correlation with delayed devel-
opment, whereas hyperbilirubinemia had significant
correlation in multivariate analysis.
To detect the possibility of delayed development
at later age, we recommend all subjects who had high
risk for delayed development to have a repeat develop-
mental assessment 2 weeks after the first assessment.
We also referred them for neuropediatric, ENT, and
eye examinations, as well as rehabilitation if needed.
5
Subjects who had moderate risk were recommended
to undergo developmental examination every 3 months.
The subjects should be followed until the age 18-24
months to diagnose delay and enable prompt interven-
tion. Assessment before school entry is needed to evalu-
ate minor disorders, particularly in fine motor ability,
visuomotor aspect, and learning behavior.
We conclude that preterm, AGA, LBW infants
are not necessarily at risk for delayed development at 3
months corrected age. Conditions which increase the
risk for delayed development were sepsis and hyperbi-
lirubinemia. Our findings underline the importance of
providing best perinatal care to prevent postnatal com-
plications that may lead to delayed development.
Acknowledgments
We are indebted to the subjects and their parents who provided all
the information for this study. We thank Prof. Herry Garna, MD,
PhD; Prof. Dedi Subardja, MD, PhD; and Prof. Abdurachman
Sukadi, MD, PhD for providing valuable advice, correcting the
manuscript, and giving the support which made this study possible.
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