Arch Iranian Med 2009; 12 (2): 135 139

Original Article

Perinatal and Neonatal Risk Factors for Neurodevelopmental

Outcome in Infants in Karaj
Farin Soleimani MD*, Roshanak Vameghi MD MPH*, Sahel Hemmati MD*,

Reza Salman-Roghani MD *
Background: Although it is well-known that the incidence of developmental delay in high-risk
infants is higher than in low-risk ones, little is known about the risk factors among Iranian infants.
The objective of this study was to determine the various pre-, peri-, and neonatal factors in
developmental delay in participants and to compare the incidence of each factor with that of the
normal population.
Methods: The Infant Neurological International Battery developmental assessment was
employed as the diagnostic tool by a team of experts. Neurological examinations were performed
and a questionnaire was completed as well. The subjects consisted of 6,150 infants divided into
two groups respectively, with normal and abnormal scores for the evaluation over a period of 12
months in city of Karaj (Tehran Province).
Results: The mean age of the participants was 39 weeks. Factors associated with a significant
increased risk of developmental delay in the studied population included postneonatal seizures
(OR=5.54, 95%CI: 3.1 9.6), neonatal seizures (OR=4.37, 95%CI: 1.7 10.8), preterm delivery
(OR=2.52, 95%CI: 1.3 4.7), and type II pneumonia (OR=2.39, 95%CI: 1.4 3.8).
Conclusion: To increase the survival rate of neonates and effectiveness of early intervention,
the above-mentioned risk factors could be considered as valuable clues. Routine
neurodevelopmental screening for neonates and infants for early detection of neurodevelopmental
delays is highly recommended. If economic limitations prevent mass-screening of neonates, at
least high-risk infants should be routinely re-evaluated.
Archives of Iranian Medicine, Volume 12, Number 2, 2009: 135 139.

Keywords: Child developmental delay infant morbidity

Introduction

bout 10 20% of all pregnancies and

9% of neonates are at risk.1 According
to international studies, 2.6 10% of
neonates with birth weight of <2000 g are at risk of
developmental disorders such as cerebral palsy up
to 30 times more than normal neonates.2,3 Among
the normal infant population, two per 1000
have developmental delay; however, the figure
increases to 60 per 1000 among the high-risk
Authors affiliation: *Pediatric Neurorehabilitation Research
Center, Social Welfare and Rehabilitation Sciences University,
Tehran, Iran.
Corresponding author and reprints: Reza Salman-Roghani
MD, Pediatric Neurorehabilitation Research Center, Social
Welfare and Rehabilitation Sciences University, Koodakyar Ave.,
University Blvd., Evin, Tehran 19834, Iran.
Tel: +98-218-855-5188, Fax: +98-218-855-5188
E-mail: farinir@yahoo.com
Accepted for publication: 23 July 2008

ones.4
According to previous studies,5 major causes of
infant developmental disorders contributing the
childhood morbidity are:
Congenital anomalies (e.g., cardiac, central
nervous system, and respiratory);
Congential malformations (e.g., chromosomal
and metabolic);
Preterm birth; and
Low birth weight (LBW, i.e., <2500 g).5
This study was conducted in the city of Karaj
(Tehran Province) with a population of two million. The objective of this study was to determine
the risk factors causing the developmental delay in
this specific population.

Patients and Methods

The city of Karaj (Tehran Province) is 20 km

Archives of Iranian Medicine, Volume 12, Number 2, March 2009 135

Perinatal and neonatal risk factors for development

west of Tehran (the capital). The majority of the

inhabitants are immigrants from all over the
country, which has created a sociocultural
diversity.
The city is divided into three health districts
with an overall population of 18,000 infants four to
18 months old. A total number of 6,150 (3129
males and 3021 females) apparently healthy infants
with no overt abnormalities such as congenital
anomalies, chromosomal, metabolic, and neurodegenerative disorders were assessed during the
well-being check-ups over a 12-month period.
Using a stratified sampling method, the children
were chosen from all three districts proportionately
to their population.
The Infant Neurological International Battery
(INFANIB) developmental assessment test
validated in Iran7 was employed. INFANIB has 20
items that assesses the infants motor development
in supine, prone, standing, and suspended positions
for reflexes and French angles as well as muscle
tone and body posture.6 The validity of this test has
been reported with 90% sensitivity and 83%
specificity, and a high reliability.7 The INFANIB
test sets out the definitions of normal,
abnormal, and transient (undetermined). To
decrease false- negative results, the two latter
groups underwent neurological examinations by a
pediatric neurologist as well.
To detect high-risk infants, a questionnaire was
completed by the pediatrician (trained in
developmental assessment) and a team of
trained/experienced developmental assessment
occupational therapists.
The completion of questionnaire was based on
thorough evaluation of the children's medical
records and statements of their mothers. Data such
as delivery-related issues (preterm), perinatal
information (gender, parental consanguinity,
mother's age, drug use during pregnancy,
multiparity, history of handicapping condition in
the family, miscarriages, and pregnancy
complications), birth method, head circumference
at birth, Apgar score, LBW, neonatal and postneonatal
seizures,
pneumonia,
and
hyperbilirubinemia leading to phototherapy or
blood exchange transfusion were obtained.
Neonatal respiratory disorders can be broadly
classified into two groups in terms of outcome:
Treatable, that is mild and self-limited (type
I).
Potentially life-threatening, that is of longer

duration and need more intensive treatment

(type II).8
Statistical analyses were performed by SPSS
and included descriptive statistics, 2 ,and risk
estimates. A significance level of P values <0.05
was used in all analyses.
In ethical terms, the following issues were
considered:
The parents of the children participated in this
study voluntarily.
There were no obstacles/restriction for
nonparticipants
in
receiving
usual
health/medical services.
Informed consent was obtained from the
parents.
Children diagnosed with abnormality in our
study were referred to the rehabilitation center
of Karaj for further therapeutic interventions.

Results
A total of 6,150 infants (3,129 males and 3,021
females), with a mean birth weight of 3,180 g and
mean age of 39 weeks were assessed in this study.
Neonatal and postnatal seizures; preterm birth;
LBW;
type
II
pneumonia;
pregnancy
complications (preeclampsia, gestational diabetes,
vaginal bleeding, X-ray exposure, and cervical
incompetency); and history of miscarriage were
factors found to have significant correlation with
infant developmental delay (Table 1). Other
factors studied, had no significant correlation with
developmental delay.

Discussion
Neurodevelopmental problems occur two to
five times more frequently in LBW compared to
normal birth weight infants.911 In western
countries, the prevalence of major neurodevelopmental disorders in infants with birth weight of
1500 2500 g is 8% and rises to 15% in those with
birth weight of 1001 1500 g.1214 However, our
study showed a decrease by a factor of 0.64 in
developmental delay for every 1000 g increase in
birth weight. These findings, however, were not as
significant as reported in other studies. High
mortality rate among those with LBW in Iran,
different etiologies of LBW (which could not be
determined like in many other studies),
uncontrollable coexisting factors are among other
contributory factors.

136 Archives of Iranian Medicine, Volume 12, Number 2, March 2009

F. Soleimani, R. Vameghi, S. Hemmati, et al.

Table 1. Risk factors associated with neurodevelopmental delay.

Risk factors
Preterm birth (<37 weeks)
Pregnancy complications
Miscarriage
Low birth weight (<1500 g)
Type II pneumonia
Neonatal seizure
Postnatal seizure

Odds ratio

Coefficient

P value

2.52
1.94
1.63
0.64
2.39
4.37
5.54

0.926
0.663
0.495
-0.440
0.874
1.476
1.713

0.004
0.023
0.004
0.006
<0.007
0.001
<0.001

The small for gestational age (SGA) fraction of

LBW usually have lower rates of motor deficiencies and higher rates of minimal brain damage,
which would be detected at the preschool and
school age, whereas our screening tool (INFANIB)
mainly assessed motor development in four to 18
months old infants.
Hypoxic-ischemic encephalopathy (HIE) is
often characterized by signs of fetal or neonatal
distress, or both, and sometimes by neurologic
abnormalities that may include sedation, coma,
hyperirritability, and seizures.15 Seizures occur in
approximately 50% of patients with HIE and are
indicative of moderate or severe encephalopathy.
The most important causes of neonatal seizures
include HIE (50 60%), intracranial hemorrhages
(10%), and intracranial infections (5 10%).16 The
risk of subsequent epilepsy after neonatal seizures
secondary to perinatal asphyxia is approximately
30%.17
HIE is a cause of neonatal seizures as well as
the etiology of later developmental delay among
Iranian infants. If it is not associated with any
metabolic disorders.
Apgar scores are routinely determined at
deliveries. One- and five-minute Apgar scores
alone, however, did not predict developmental
outcome. The extended Apgar scores, nonetheless,
are more valuable in predicting neurological
outcome.18
Unfortunately, in Iran the Apgar score is only
assessed and registered at one and five minutes
after birth and without sufficient precision. Thus,
in this study, in concordance with some others, no
relationship between low five-minute Apgar scores
(in those who did not need resuscitation) and infant
developmental delay was found. However, some
other studies, such as Moster and colleagues,19
have reported that infants with five-minute Apgar
scores of 0 3 had an 81-fold increased risk for
cerebral palsy compared with infants who had
scores of 7 10. Other studies have shown that
low Apgar at 20 minutes and after, increases the

95% CI
Lower limit

Upper limit

1.33
1.09
1.17
.471
1.47
1.77
3.17

4.76
3.44
2.29
.879
3.89
10.80
9.69

potential for developmental disorders and cerebral

palsy.
Our study also showed a significant correlation
between infant developmental delay and preterm
birth. Preterm neonates admitted to the NICUs in
Iran do not undergo routine cranial ultrasonography for detecting intraventricular hemmorhage
(IVH) and periventricular leukomalacia (PVL), and
thus the correlation with developmental delays
with IVH and PVL could not be directly assessed
in our study, but we found a significant correlation
between preterm delivery and developmental
delay. One can consider this as indirect evidence
for the possible relation of hemorrhage into the
germinal matrix tissues and IVH with coexisting
preterm birth risk factors in Iranian preterm infants
with the occurrence of later developmental
delays.20,21
Singer et al. found no difference in intelligence
between infants with bronchopulmonary dysplasia
(BPD) and age-matched premature controls at
three years of life, but motor function was
significantly impaired.22 Hack and associates also
followed a group of extremely premature infants
who received exogenous surfactant at birth and
found that type II pneumonia was among the most
significant predictors of an abnormal motor
developmental index (OR: 2.18) and neurological
abnormalities (OR: 2.6).23 Several more recent
follow-up studies have confirmed that a diagnosis
of BPD continues to be associated with a higher
risk for abnormal neurodevelopmental outcome in
premature infants.2425
However, infants developing type II pneumonia
are often the smallest and the sickest patients in the
NICU and consequently can develop other
conditions which also appear to be important
variables in determining developmental outcome.24
In this study, a significant correlation between
type II pneumonia and neurodevelopmental delay
was detected but in type I pneumonia this
correlation was not found. This is specifically true
and concordant with other similar studies, due to

Archives of Iranian Medicine, Volume 12, Number 2, March 2009 137

Perinatal and neonatal risk factors for development

the fact that infants were mainly assessed for motor

development. In terms of intelligent quotient (IQ),
longitudinal follow-up studies yet needed to be
performed.
The ordinary physiologic jaundice of infancy
should not produce any particular stress on the
newborn. Long-term recovery from hyperbilirubinemia is generally very good.8,26,27 In present
study, no significant correlation between
developmental delay and hyperbilirubinemia
leading
to
phototherapy/blood
exchange
transfusion was revealed.
The need for early diagnosis of developmental
delay is the healthcare providers major responsibility. In other words, identifying risk factors and
close monitoring can be a preliminary clue for
physicians to detect delays and disorders in highrisk group infants at an early stage.
We suggest that Iranian physicians and those of
the other developing countries consider the abovementioned factors along with constant monitoring
of the affected newborns, as an important and
valuable clue for detecting any subtle signs of
neurodevelopmental delays at the earliest stage.
We also suggest that neurodevelopmental screening be carried out in Iran routinely. However, if
any economic problem prevents the massscreening of neonates and follow-ups, it should at
least be done for high-risk infants.

Acknowledgment

6
7

9
10

11
12
13

14

15
16
17

We would like to express our appreciation to

the healthcare providers of Karaj network for their
valuable cooperation in carrying out this study,
Prof. Christa Einspieler for her critical reading of
the paper, and Mrs. Nadereh Compani for her
throughness in editing the manscript.

18

19

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