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Research and Reports in Neonatology 2018:8 9–17
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ORIGINAL RESEARCH
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/RRN.S140889
Trend of head circumference as a predictor
of microcephaly among term infants born at a
regional center in Malaysia between 2011–2015
Rosnah Sutan1
May Luu Yeong1
Zaleha Abdullah Mahdy2
Ahmad Shuhaila2
Jaafar Rohana3
Shareena Ishak3
Khadijah Shamsuddin1
Aniza Ismail1
Idayu Badillah Idris1
Saperi Sulong4
1Department of Community
Health, 2Department of Obstetrics
and Gynecology, 3Department of
Pediatrics, 4Department of Medical
Records, Universiti Kebangsaan
Malaysia Medical Center, Kuala
Lumpur, Malaysia
Introduction: The aim of this study was to determine the trend of head circumference as
predictor of microcephaly among term infants born in a teaching hospital in Malaysia from
2011 to 2015.
Methodology: This was a cross-sectional study using data from the electronic birth census.
The independent variables were mothers’ age and height, parity, birth weight and birth length.
All term newborns, both alive and stillbirth, with 37–41 completed gestational weeks, and a
birth weight of at least 500 g was extracted from the census.
Results: A total of 26,503 newborns fulfilled the inclusion criteria (13,655 males, 12,840
females). The mean head circumferences for male and female newborns were 32.93 cm (± SD
1.32) and 32.56 cm (± SD 1.31). The average head circumference for Malaysian newborns was
found to be smaller than the World Health Organization Standard Growth Chart for Term Infant.
A total of 17.6% (n=4,669) of the total samples were observed to have microcephaly. Among
them, 73.2% (n=3,419) were non-proportionate microcephaly with normal birth weight of 2.5kg
and above. Bivariate analyses showed that all independent variables were significant predictors of
microcephaly. Both simple and multiple logistic regressions demonstrated that low birth weight
was the most significant predictors for microcephaly (adjusted OR 12.14, 95% CI 10.80, 13.65).
Conclusion: There is an increasing trend of microcephaly across the years and the low birth weight
was noted as the main predictor of microcephaly. Future studies are needed to determine the possible
cause of increasing microcephaly by controlling for birth weight and gestational age of the neonates.
Keywords: SGA, perinatal, growth chart, IUGR, birth parameter, occipito-frontal
Introduction
Birth parameters are important indicators of prenatal nutritional status and intrauterine
environment. In Malaysia, birth weight, length, and head circumference of all infants
are measured and recorded in the Child Health Record Book at birth and on clinic
visits. These indicators play an important role in monitoring growth and development
of the infants. For example, head circumference is used to monitor the growth of
brain volume and is known to be a significant predictor of cognitive and intelligence
development of a child.1 Abnormal head circumference has also been associated with
various medical conditions. Microcephaly and macrocephaly are associated with
intrauterine infection, toxic environmental exposure, congenital malformation, and
various genetic abnormalities.2 According to the definition by the Center of Disease
Control and Prevention (CDC), microcephaly is diagnosed when occipito-frontal
Correspondence: Rosnah Sutan
Department of Community Health,
Faculty of Medicine, Universiti
Kebangsaan Malaysia Medical Center,
Jalan Yaacob Latif, Bandar Tun Razak,
56000 Cheras, Wilayah Persekutuan
Kuala Lumpur, Malaysia
Tel +60 1 9321 2256
Email rosnah_sutan@yahoo.com
Journal name: Research and Reports in Neonatology
Article Designation: ORIGINAL RESEARCH
Year: 2018
Volume: 8
Running head verso: Sutan et al
Running head recto: Trend of microcephaly
DOI: http://dx.doi.org/10.2147/RRN.S140889
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(head) circumference (OFC) falls below the third percentile
compared to the appropriately age-matched normal standard;3
while macrocephaly is diagnosed when the head circumfer-
ence measurements are above the 97th percentile.
Although the head circumference at birth is recorded for
all newborns in Malaysia, there is no systematic reporting
system or analysis on head circumference or microcephaly
registry. The existing child health program has been focusing
on interventional measures and research on low birth weight
and premature infants. With the declaration of the Zika virus
as an international public health emergency on February 1,
2015,4 it is important for Malaysia to establish the baseline
information on the incidence and causes of microcephaly,
in order to formulate reference values for abnormal head
circumference. However, universal screening for all antenatal
mothers and babies will incur considerable cost. Therefore,
in order to develop a cost-effective microcephaly screening
program, the predictive or risk factors associated with micro-
cephaly should be evaluated first prior to planning any such
program. A valuable resource of data is a birth center where
birth data are recorded.
Zika virus is an arbovirus transmitted by mosquitoes of
the Culicidae family and the Aedes genus (sylvatic and urban
transmission) including Aedes aegypti (urban transmission).5
It is suspected to have a causal link to the spike of increase in
babies born with microcephaly and neurological conditions
in Brazil in 2015. Zika virus infections have been reported
in travelers who visited Thailand6 and Malaysia7 in recent
years. Although there was no report on Zika virus infection
among the local population, its vector, A. aegypti, is rampant
in the Southeast Asian region, transmitting dengue virus and
causing widespread dengue fever and dengue hemorrhagic
fever in this region.
The last published information on head circumference
among Malaysian newborns was in 1994.8 Therefore, the head
circumference measurement should be repeated to assess
the current birth trend. The Ministry of Health Malaysia has
adopted the WHO Standard Growth Curve Chart for head
circumference since its release in 2006 for better international
comparison.9 The WHO charts for standard growth describe
the growth of healthy children in optimal conditions.9 The
chart has been incorporated in the child home-based record
for child health monitoring.10 To date, there are no local
studies found in the literature that describe the growth of
children in Malaysia using this standard reference. The abil-
ity of the WHO standard to represent individual countries
and populations has been questioned.11 Notably, there was
no representative data from the East and Southeast Asian
countries, whose population constituted one-fifth of the
global population, during the development of the standard
charts. Moreover, studies from the East Asian countries have
demonstrated a trend of smaller head circumference and birth
weight.12,13 Similarly, a Malaysian study in 1994 revealed that
Malaysian infants were smaller than the standard reference.8
The predictors of head circumference of infants have
been widely studied. Maternal age, height, pregnancy weight
gain, socioeconomic background, lifestyle, and environmen-
tal exposure were identified as significant predictors.14–19
Advancing maternal age, mothers with short stature, and poor
weight gain during pregnancy were identified as contributing
factors to smaller infant head circumference.16–18 The aims of
this study were to establish the trend of head circumference
and incidence and predictors of microcephaly among Malay-
sian term newborns at the Universiti Kebangsaan Malaysia
Medical Center (UKMMC) from 2011 to 2015.
Methods
This is a cross-sectional study, using labor room electronic
birth census data from a regional hospital in Malaysia. Total
live births recorded in Malaysia for 2015 were 521,136 with
52% male infants.20 The UKMMC represents about 1% of
the total births in Malaysia each year. All birth data in this
center were recorded in both manual case records and an elec-
tronic data system. Information recorded includes mothers’
demographic data and obstetric profile, birth outcome, and
newborn profile. Birth outcome was summarized as newborn
fit to be discharged to mother, newborn requiring neonatal
intensive care unit (NICU) admission, and stillbirth. Details
of conditions of newborn such as genetic and chromosomal
abnormalities, growth restriction, and physical abnormali-
ties were not recorded in the electronic birth census. Other
information such as mothers’ medical history, comorbidity,
and previous obstetric history were also not recorded in the
electronic data system, but were available in the antenatal
record books or hospital medical records. Patient consent to
review medical records was not required as this was anony-
mous data retrieved from records with ethics approval.
The data extracted for this study were newborn birth
parameters (birth weight, head circumference, and length),
and maternal age, height, and parity. Head circumference of
newborn was identified as the dependent variable. The study
populations were all term live-born and stillborn delivered at
UKMMC from January 2011 to December 2015. The mea-
surement taken was based on the assessment of the newborn
at birth. No repeat measurement was made 24 hours after
birth. The criteria for term infant was birth at 37–41 com-
pleted gestational weeks and birth weight of ≥500 g. Cases
with incomplete recorded birth parameters were excluded
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Trend of microcephaly
from the study. Head circumference was classified into
microcephaly, normal head circumference, and macrocephaly
for descriptive analysis, and the statistical test for a trend
analysis was performed. Microcephaly is defined as having
OFC of less than the third percentile compared to appropri-
ate, age-matched, normal standards;3 whereas macrocephaly
is defined as head circumference above the 97th percentile.
Therefore, by using the WHO standard growth curve for head
circumference,9 which has been implemented in Malaysia in
the child home-based card since 2006,10 the term newborns
with head circumference <32.1 cm for boys and <31.7 cm
for girls at birth were categorized as microcephaly, whereas
head circumference >36.9 cm for boys and >36.1 cm for girls
at birth were categorized as macrocephaly. Subsequently,
newborns with microcephaly and normal head circumfer-
ence were included for bivariate and multivariate analyses to
identify significant predictors. Birth weights were categorized
into low birth weights and normal birth weights for analysis.
Low birth weight has been defined by WHO as weight at birth
of <2.5 kg.21 Newborn lengths were categorized into short
and normal lengths. Newborns with birth lengths of less than
the third percentile (45 cm) according to the WHO Standard
Growth Chart9 were categorized as having short birth length.10
These birth parameters were measured at the time of
birth using standardized methods. Newborns were weighed
using an electronic weighing scale, and the weights were
rounded up to the nearest 0.01 kg. Head circumferences
were measured with a plastic measuring tape passing around
the widest horizontal OFC, and the lengths were rounded
up to the nearest 0.1 cm. Newborn recumbent lengths were
measured with knees and legs fully extended, and the lengths
were rounded up to the nearest 0.1 cm. Birth parameter
measurements were taken only once, by a midwife in the
labor room. Repeat measurement is not routinely required,
except for newborns with abnormal birth parameters. The
latest Perinatal Care Manual22 recommended that all new-
borns with head circumference and birth weight below the
tenth percentile to be referred for pediatric assessment. The
pediatric medical officer usually repeats the birth parameter
measurements for correlation with other clinical findings.
As such, we were unable to perform intra- or inter-observer
reliability tests in this study as no data were recorded for
repeat measures. Nevertheless, all nurses in Malaysia have
been trained with the same methods of infant anthropometric
measurements by using the Perinatal Care Manual22 as the
standard protocol. This manual is a comprehensive training
manual and the general reference for Malaysian health care
providers. Its use has received consensual approval from
both the Obstetrician and Pediatrician Committees under the
Malaysian Ministry of Health.22
Maternal height and weight were recorded in the system
using measurements taken at the first visit to UKMMC,
either during the antenatal period, or upon arrival for deliv-
ery if the mother had never had any antenatal clinic visits at
UKMMC. Therefore, pre-pregnancy weight, weight at first
antenatal booking, and serial measurements of weight gain
during pregnancy according to gestational week were not
available in the system, as most mothers had their antenatal
bookings done in the Ministry of Health Primary Health
Clinics. Data collected on maternal weight in the system
consisted of weights from a wide range of gestations, making
the data not suitable for analysis. Maternal age, height, and
parity upon admission to the labor room were also recorded
in the birth census. Maternal height was measured, and the
measurement was rounded up to the nearest 0.1 cm. In this
study, maternal age, height, and parity were categorized
into dichotomous variables based on the risk stratification
in the Perinatal Care Manual for analysis. A maternal age
≥35 years was classified as having higher risk of neonatal
resuscitation, whereas maternal height <145 cm, and parity
>5 were recorded as having higher risk of needing intrapar-
tum intervention. Hospital deliveries are required for mothers
with these high-risk profiles.
Statistical analyses were performed using Statistical Pack-
age for the Social Science (SPSS), version 21. Initial bivariate
analyses were done using chi square tests and simple logistic
regression to determine the associations between potential
variables and infants’ head circumference. Variables with
p-values <0.05 in the chi square tests were selected for multi-
variate analysis. Multiple logistic regression analysis was used
to calculate the odds ratio (OR) of each selected independent
variable on the infants’ head circumference at birth. The
statistical test for a trend in prevalence over time was used.
This study was approved by the Universiti Kebangsaan
Malaysia Research Ethics Committee (FF-2016-031) and
supported by the University Research Grant (GUP-2014-089).
Results
A total of 33,292 births were recorded between January 2011
and December 2015. Of the total, 26,503 births (13,655 male
and 12,840 female births) that fulfilled the study criteria of
term newborn with a birth weight >500 g were included for
analyses. Nine stillbirths were recorded during the study
period. All except eight newborns had complete information
on birth parameters. The demographic breakdown of ethnicity
among the mothers was 77.8% Malay, 17.2% Chinese, 2.5%
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Indian, and 2.5% of other races. The mean head circumfer-
ence was 32.93 cm (±SD 1.32) for boys and 32.56 cm (±SD
1.31) for girls.
Table 1 shows the number of term newborns with micro-
cephaly, normal head circumference, and macrocephaly
from 2011 to 2015. The total number of term newborns with
microcephaly was 4,669 (17.6%) within the 5-year period.
An increasing trend was observed over the period of time,
with the highest number with microcephaly recorded in 2015,
comprising 20.0% of all term newborns (n=1,058). Among
the newborns with microcephaly, 26.8% (n=1,250) had
proportionately small head circumference and birth weight,
while 73.2% (n=3,419) of term newborns had disproportion-
ate microcephaly with a normal birth weight. In terms of
birth outcomes of newborns with microcephaly, 91.8% with
proportionate microcephaly and 98.8% with disproportionate
microcephaly were well and allowed discharge to postnatal
wards with the mother, after routine assessment by the
pediatric medical officer. Table 2 shows the trend analysis
of mean head circumference over the years. There is a sig-
nificant difference noted for mean of head circumference of
babies by years of delivery. Table 3 shows a comparison of
average head circumference percentiles between our study
and a previous study by Boo et al8 in 1994, with reference to
the WHO Child Growth Standards for Term Infant.9 Gener-
ally, Malaysian newborns have smaller head circumference.
The head circumference at the third percentile for Malaysian
newborns in our study was 30.5 cm for boys and 30.0 cm for
girls, which were both smaller than the WHO Child Growth
Standards for Term Infant. According to the recommended
growth standard, newborns with head circumference <32 cm
are considered microcephaly, which is equivalent to the 25th
percentile of head circumference of all Malaysian newborns
in this study (Table 3). Compared to the findings by Boo
et al,8 the head circumference of male newborns from the
10th to 90th percentile and the head circumference of female
newborns from the 50th to 90th percentile were smaller in this
study. Table 4 shows the bivariate analysis of the independent
variables and head circumference of newborns using chi
square test. All independent variables were significant pre-
dictors of microcephaly in newborns (p<0.01). Therefore, all
independent variables were included in the logistic regression
model to assess their OR.
Table 5 shows the results of simple logistic regression and
multiple logistic regression analysis of head circumference
of newborns and the associated independent variables. All
factors were significantly associated with the head circum-
ference of infants (p<0.01) in the simple logistic regression.
Birth weight seemed to be the most significant predictor of
head circumference of newborns. Newborns with low birth
weight were 12 times more likely to have microcephaly than
newborns with normal birth weight. This was followed by
newborn length, where newborns with a length below the
third percentile (45 cm) were 1.82 times more likely to have
microcephaly. Our study also shows that mature mothers
aged >35 years were 28% less likely to have newborns with
microcephaly than younger mothers. Multiple logistic regres-
sions reaffirmed that birth weight was the most significant
Table 1 Trend of head circumference among term infants in UKMMC from 2011 to 2015
Head circumference 2011 2012 2013 2014 2015 Total
n % n % n % n % n % n %
Microcephaly 857 15.4 778 14.7 942 18.5 1,034 19.6 1,058 20.0 4,669 17.6
Normal HC 4,617 82.8 4,389 83.2 4,053 79.7 4,182 79.1 4,161 78.8 21,402 80.8
Macrocephaly 103 1.8 108 2.0 90 1.8 70 1.3 61 2.0 432 1.6
Total 5,577 100 5,275 100 5,085 100 5,286 100 5,280 100 26,503 100
Abbreviations: UKMMC, Universiti Kebangsaan Malaysia Medical Center; HC, head circumference.
Table 2 Trend analysis of mean head circumference over years
Year N Mean SD SE 95% Condence interval t statisticsa (df)p-value
Lower bound Upper bound
2011 5,474 32.858 1.3679 0.0185 32.822 32.894 39.366
(426,066)
<0.001
2012 5,167 32.883 1.3145 0.0183 32.847 32.919
2013 4,995 32.671 1.2846 0.0182 32.636 32.707
2014 5,216 32.682 1.3053 0.0181 32.647 32.718
2015 5,219 32.640 1.3013 0.0180 32.605 32.675
Total 26,071 32.748 1.3197 0.0082 32.732 32.764
Note: aOne way ANOVA.
Abbreviations: ANOVA, analysis of variance; SD, standard deviation; SE, standard error.
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Trend of microcephaly
Table 3 Comparison of head circumference percentile between Malaysian term infants and WHO Child Growth Standards for Term
Infant
Head circumference
percentile
Malaysian term infant
delivered in UKMMC, cm
Malaysian term infant
(Boo et al8), cm
WHO Child Growth Standards
for Term Infanta, cm
Boys Girls Boys Girls Boys Girls
3rd 30.5 30.0 – – 31.9 31.5
5th 31.0 30.5 – – 32.5 32.5
10th 31.0 31.0 31.4 30.8 33.0 33.0
25th 32.0 32.0 32.4 31.9 33.6 33.8
50th 33.0 32.5 33.4 32.9 34.6 34.8
75th 34.0 33.5 34.4 33.9 35.8 36.0
90th 34.5 34.0 35.3 34.8 37.0 37.0
95th 35.0 35.0 – – 37.5 37.5
97th 35.5 35.0 – – 38.0 38.2
Note: aAdapted from World Health Organization. Child growth standards. Available from: http://www.who.int/childgrowth/en42
Abbreviation: UKMMC, Universiti Kebangsaan Malaysia Medical Centre.
Table 4 Bivariate analysis of the determinants of HC of infants (n=26,071)
Variables Microcephaly Normal HC X2df p-value
n % n %
Maternal age (years) ≤35 4,087 87.5 17,878 83.5 46.23 1 <0.001
>35 582 12.5 3,524 16.5
Maternal race Malay 3,642 78.0 16,636 77.7 17.90 3 <0.010
Chinese 744 15.9 3,742 17.5
Indian 140 3.0 514 2.4
Other 140 3.1 510 2.4
Maternal height (cm) ≤145 98 2.1 192 0.9 50.33 1 <0.001
>145 4,571 97.9 21,210 99.1
Parity <52,321 49.7 13,286 62.1 244.00 1 <0.001
≥52,348 50.3 8,116 37.9
Birth weight (kg) <2.5 1,250 26.8 540 2.5 3,424.61 1 <0.001
≥2.5 3,419 73.2 20,862 97.5
Birth length (cm) <45 377 8.1 191 0.9 927.68 1 <0.001
≥45 4,292 91.9 21,211 99.1
Note: p<0.05 as signicant determinants.
Abbreviation: HC, head circumference;
Table 5 Simple logistic regression and multiple logistic regression of determinants associated with microcephaly (n=26,071)
Independent
variable
SLogRaMLogRb
Crude OR (95% Cl) p-value Adjusted OR (95% Cl) Wald p-value
Mother’s age (years) ≤35 1.00
>35 0.72 (0.66, 079) <0.01 0.76 (0.69, 0.84) 28.68 <0.01
Mother’s race Malay 1.00
Chinesec0.91 (0.83, 0.90) 0.03 0.87 (0.79, 0.95) 9.22 0.02
Indianc1.24 (0.13, 0.51) 0.02 1.08 (0.88, 1.34) 0.539 0.463
Otherc1.28 (1.06, 1.55) 0.02 1.23 (1.00, 1.51) 3.893 0.05
Mother’s height (cm) ≤145 2.73 (1.85, 3.03) <0.01 2.16 (1.64, 2.484) 30.15 <0.01
>145 1.00
Parity <51.00
≥51.66 (1.55, 1.77) <0.01 1.59 (1.48, 1.70) 169.47 <0.01
Birth weight (kg) <2.5 14.13 (12.69, 15.72) <0.01 12.14 (10.80, 13.65) 1,746.47 <0.01
≥2.5 1.00
Birth length (cm) <45 9.76 (8.17, 11.65) <0.01 1.82 (1.7, 2.27) 29.21 <0.01
≥45 1.00
Notes: aSimple logistic regression (outcome as head circumference, cm). bMultiple logistic regression (Nagelkerke R2=0.171); the model ts reasonably well; model
assumptions are met; there are interactions between parity and mother’s age and between parity and birth weight; however no multicollinearity problem was found. cWald
test for SLogR: Chinese, 4.77; Indian, 5.06; other, 6.60.
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predictor for microcephaly (adjusted OR 12.14), followed
by maternal height (adjusted OR 2.16), baby’s birth length
(adjusted OR 1.82), and multiparity (adjusted OR 1.59).
However, Indian and other races were not significant predic-
tors in this logistic model.
Two pairs of independent variables were noted to have
interaction, that is, between parity and birth weight, and
between parity and maternal age. However, there was no
multicollinearity among these independent variables. Hosmer
and Lemeshow goodness-of-fit test demonstrated that our
data set fitted well with the logistic model. This model was
able to predict correctly 84.8% of infants with microcephaly
and explained 17.1% of variation in the outcome variable.
Table 6 shows the results of simple linear regression and
multiple linear regression analyses of head circumference of
infants and the associated independent variables. All variables
had significant linear relationship with the head circumfer-
ence of infants (p<0.01). Thus, infants with maternal age of
1 year had larger head circumference by 0.033 cm (95% CI:
0.030, 0.037). In a multivariable analysis, it was found that
all five independent variables had significant independent
effect on newborn head circumference. The models explain
67.7% of variation in head circumference of newborns in the
study sample (R2= 0.677).
Discussion
The World Health Organization (WHO) launched new growth
standards for infants and children23 in 2006. It was based on
the WHO Growth Reference Study on singleton term infants
without health, environmental, or economic constraints on
growth from India, Brazil, Norway, United States, Ghana,
and Oman. However, infants from East and Southeast Asia
were not included in the standards development. The WHO
assumed that all economically advantaged children who were
breastfed as infants grew similarly.9 Hence, these standards
have been adopted for use internationally to depict how
normal children should grow when free from diseases and
fed according to recommendations.
The reliability of the standard growth chart for use
in this region has been widely studied.11–13 Results from
these studies showed that our newborns have smaller birth
parameters compared to the WHO standard. For example,
Japanese breastfed infants are significantly shorter and lighter
throughout almost the first 24 months12 compared to the
WHO growth standard, and infants in Hong Kong are shorter
at 36 months.11 A Singaporean study demonstrated similar
findings.24 Among both male and female Singaporean infants
at the 38th gestational week, the 10-50-90th percentile values
for head circumference were 1–2 cm smaller than the WHO
growth standard.25 Another study on a birth cohort in Jakarta
from 2010 to 2011 also found that Indonesian infants were
smaller in all three birth parameters than the WHO standard
from birth up to 12 months.11 The studies in Singapore25 and
Jakarta, Indonesia,11 in the Southeast Asian region concluded
that the WHO growth chart does not reflect the current growth
of the infant cohort and may have overestimated the birth
parameter measurements for gestational age and the diagnosis
of microcephaly. As a whole, the results from these studies
were similar to our findings on Malaysian infants. Hong Kong
and Singapore have adopted their own local reference charts
for infant growth monitoring.26,27
On the other hand, a Turkish study28 reported no disparity
in their infant head circumference percentile when compared
to Belgian and American infant head circumference percen-
tiles at birth. The United States adopts the WHO standard
for child growth from 0 to 24 months, and the subsequent
growth is referred to the CDC growth chart for up to 59
months. Deviations from the WHO growth standard should
prompt clinicians to identify whether there are suboptimal
environmental conditions and to correct the causes of sub-
optimal growth. Nevertheless, the lack of East Asian and
Southeast Asian data in the WHO growth standard could
Table 6 Determinants of head circumference (cm) of infants among the study population for continuous data (n=26,071)
Independent variable SLRaMLRb
bc(95% Cl) p-value Unadjusted bd(95% Cl) t-stat p-value
Maternal age 0.033 (0.030, 0.037) <0.01 0.200 (0.017, 0.023) 13.901 <0.01
Maternal height (cm) 0.300 (0.270, 0.330) <0.01 0.008 (0.006, 0.010) 7.111 <0.01
Maternal weight (kg) 0.015 (0.014, 0.016) <0.01 −0.002 (−0.003, −0.001) −3.952 <0.01
Birth weight (kg) 2.110 (2.080, 2.140) <0.01 2.148 (2.111, 2.185) 113.389 <0.01
Birth length (cm) 0.206 (0.200, 0.212) <0.01 −0.014 (−0.021, −0.008) −4.515 <0.01
Notes: aSimple linear regression (outcome as head circumference, cm). bMultiple linear regression (R2=0.677; The model ts reasonably well; model assumptions are met;
there was no interaction between independent variables, and no multicollinearity problem). cCrude regression coefcient. dUnadjusted regression coefcient.
Abbreviations: SLR, simple logistic regression; MLR, multiple logistic regression.
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Trend of microcephaly
have contributed to the variance of birth parameters for these
countries. There is a possibility that comparison with the
WHO growth standard have contributed to the high propor-
tion of microcephaly infants in our study. Besides, >90% of
microcephaly newborns in our study did not have any gross
abnormalities recorded at birth to suggest any possibility due
to congenital anomaly. However, the results obtained were not
interpreted in relation to the gestational age of the newborns,
birth weight, birth length, and other clinical case findings.
Therefore, there might be a possibility that these newborns
have intrauterine health problems which might cause growth
and survival problems later. In our hospital delivery system,
all newborns were screened by pediatricians before discharge,
and those with identified problems in birth parameters were
followed up by the pediatricians in our clinic.
Our study on head circumference of newborns at birth did
not show any substantial difference compared to the study by
Boo et al8 in 1994. Boo et al8 conducted a longitudinal study
with a sample size of 10,000 healthy infants born between
1990 and 1991, which demonstrated significant variation in
head circumference among the three main ethnic groups.
Malay and Chinese newborns were found to have significantly
larger head circumference compared to Indian newborns in
the birth cohort. In our study using birth cohorts from 2011
to 2015, different races were associated with different risks of
microcephaly. Chinese infants were found to have less risk of
microcephaly compared to others. However, both the studies
were based on data from a single tertiary center in an urban
setting, which may not be representative of all Malaysian
infants, which is the limitation of the present study.
Contrary to our study, the study by Boo et al8 excluded
infants with abnormalities and infants whose mothers had
comorbidities. There are debates on whether the data should
be generated from a non-selected population sample or from
selected “healthy” subjects with no known factors affecting
their growth during the construction of the gestation-specific
growth standard. Cole29 reasoned that it is not logical to con-
struct a reference standard that is targeted at infants who are
excluded, by definition, from the reference sample, when one
of the important applications of the growth standard is to enable
clinicians to identify subjects with growth problems. Nonethe-
less, it is doubtful whether a reference that truly represents
“healthy” growth could ever be constructed because many
factors that affect fetal growth remain unidentified. In this
study, the authors did not exclude infants with antenatal factors
that affect fetal growth; hence, the birth parameters provide a
neutral baseline for comparison without any assumptions being
made with regard to the quality change to measurement of the
antenatal growth of the infants.26 Despite the different sampling
methods used, the findings in our study were not substantially
different from those by Boo et al8 25 years ago.
Apart from the possible overestimation due to the use of
the WHO Growth Standard for comparison, healthy newborns
with microcephaly in this study could also be explained by the
concept of proportionality of head size30 and late manifesta-
tion of abnormality.31 Hagen et al31 reported that the majority
of children with microcephaly presented with neurological
symptoms at a mean age of 7–8 months. The proportionality
of head size refers to its measurement in relation to body size
(eg, a child who is short with a small head circumference is
probably normal). A study that supported this concept was
the Seattle school study, which showed that children whose
head circumferences were proportionate had significantly
higher mean academic achievement scores compared to chil-
dren whose head sizes were relatively small. The IQ scores
however did not differ.32
Many research articles have shown that advancing age,
maternal parity, and shorter maternal height were associ-
ated with smaller infant head circumference.16–18,33 A cross-
sectional study from Iran reported that the length and head
circumference of the neonates increased significantly with
maternal age and parity.17 A study by Kirchengast and Hart-
mann on the birth outcome of adolescent mothers showed
that the offspring of extremely young mothers of age 12–16
years were significantly smaller in all body dimensions com-
pared to the offspring of older adolescent mothers or adult
mothers.15 Lira et al18 also reported in their cohort study that
Brazilian children from taller mothers tended to have a larger
head circumference at birth.
However, our study reported an unexpected finding that
advanced maternal age was associated with a lower risk of
microcephaly. This may be due to the role of UKMMC as a
premier fertility center, providing advanced fertility treatment
to many mothers aged above 35 years. These mothers were
under meticulous pre-pregnancy and antenatal care, leading
to good birth outcomes. Apart from this, our findings on
maternal height and parity influence on the head circumfer-
ence of infants were similar to other studies.
The strength of this study is in using an electronic
database covering one single institution of health care that
practices the same protocol over years. Having 5 years’
data allows observation of the trend of microcephaly in the
center. Using singleton term babies for analysis helps in
controlling the influence of multiple pregnancy and preterm
birth on head circumference measurement. The limitation
of our study lies in being unable to explore the relationship
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Sutan et al
between head circumference and other important risk factors.
For example, maternal pre-pregnancy and antenatal weight
gain, socioeconomic position, dietary status, lifestyle, and
environmental exposures such as smoking, alcohol, and lead
exposure14,15,19,34–37 are important predictors of birth outcomes.
The electronic birth census at our center was not designed
to capture information on maternal activities and antenatal
progression outside the hospital. The data obtained for the
present study were anonymous based on data recorded in the
labor room. Hence, there is a limitation of assessing informa-
tion after babies who have been discharged from the labor
room to the postnatal ward.
Conclusion
This study provides updated reference values for the size
of head circumference among Malaysian term newborns
at 37–41 completed gestational weeks. The risk factors
associated with microcephaly are also reported, which can
help health care providers monitor the child who is at risk.
These reference values are useful for infant care as head
circumference at birth is often related to the future health of
the newborns.1,18,38–41 However, the cross-sectional anthro-
pometric data in this study do not reflect the intrauterine
growth of the fetuses and thus are not suitable for use in the
evaluation of fetal growth velocity, growth predictors, and
long-term outcome. The addition of the variable of birth
head circumference in the birth certificate recorded by the
registration department will be valuable data for monitor-
ing its trend nationwide rather than being institution-based.
Further study is recommended exploring infant growth pat-
tern, cognitive function, and milestones among babies noted
to have head circumferences below the third centile. We
propose that a longitudinal method with thorough antenatal
records, laboratory testing of biomarkers for smoking, and
heavy metal exposure are required to explore the relation-
ship between maternal environmental exposure and infant
anthropometry in Malaysia. Further assessment of the trend
of increase in the number of babies born with microcephaly
in the hot spot area of dengue virus in Malaysia, using
available data on birth head circumference, birth length,
and gestational age, is needed in view of the emergence of
the Zika virus. Studies on the relationship between dengue
and chikungunya infections during pregnancy and their
effects on pregnancy outcome, need to be explored. This
is because the Zika virus comes from the same arbovirus
group, with the same vector, Aedes mosquitoes, as these
other viruses. Retrospective and follow through studies of
confirmed microcephaly cases may help determine their
causal factors and the potential complications for public
health intervention planning, as the majority of Zika virus
infections are asymptomatic.
Acknowledgments
We thank the support staff from the labor room and NICU
who were committed to completing the record keeping.
Disclosure
The authors report no conflicts of interest in this work.
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