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Graefes Arch Clin Exp Ophthalmol

DOI 10.1007/s00417-016-3506-8

PEDIATRICS

Apgar score and reduced vision in children aged 3 to 6 years


Chen-Wei Pan 1 & Deng-Juan Qian 1 & Hui Zhu 2 & Jia-Jia Yu 3 & Hu Liu 2

Received: 22 April 2016 / Revised: 11 August 2016 / Accepted: 3 October 2016


# Springer-Verlag Berlin Heidelberg 2016

Abstract
Purpose We aimed to examine the association between
the 5-min Apgar score and reduced vision in children 3
to 6 years of age.
Methods A total of 5834 preschool children aged 3 to 6 years
participated in this school-based eye survey. Reduced vision
was defined as unaided distance vision of 6/12 or worse in the
better-seeing eye. The 5-min Apgar scores of the participants
were retrieved from medical records.
Results The overall prevalence of reduced vision in this population was 6.63 % (95 % confidence interval [CI] 5.997.27).
In multivariate analysis, the presence of reduced vision was
associated with a low 5-min Apgar score at birth (<7 vs. 710;
odds ratio [OR] = 1.66, 95 % CI 1.483.05) after adjusting for
age, gender, parental history of myopia, maternal age, gestational age, and birth weight. In addition, both myopia and
amblyopia were associated with Apgar scores of less than 7
in multivariate analyses.
Conclusions Children with 5-min Apgar scores of less than 7
were more likely to have reduced vision at the age of 3 to 6 years.
Keywords Apgar score . Reduced vision . Epidemiology .
Children

* Hu Liu
liuhu66@163.com
1

Jiangsu Key Laboratory of Preventive and Translational Medicine for


Geriatric Diseases, School of Public Health, Medical College of
Soochow University, Suzhou, China

Department of Ophthalmology, the First Affiliated Hospital of


Nanjing Medical University, 300 Guangzhou Road, Nanjing, China

Department of Ophthalmology, Wuxi No.2 Peoples Hospital,


Wuxi, China

Introduction
Unaided reduced vision is a major health concern affecting
a large number of children [1]. In mainland China, the
number of such cases among children aged 718 years
is projected to reach approximately 150 million by the
year 2020, rising to 180 million by 2030 [2]. Childrens
quality of life and neurological development are strongly
dependent on adequate vision, with compromised vision
having serious implications for overall developmental
progress in children [3, 4]. These situations highlight the
pressing need to identify novel predictors of reduced vision, especially in early life, to guide clinical practice and
medical decision making.
Early life exposures have been linked to many health
disorders in later life, including obesity [5], diabetes [6],
chronic kidney disease [7], and asthma [8]. Reports have
recently suggested that environments in utero such as maternal nutrition or antenatal depression could impact fetal
gene expression and developmental plasticity through epigenetic pathways [9]. Vision development is an important
part of the early growth of the whole body, and thus could
be affected by early life exposures in utero. Therefore, understanding the association between early life factors and
vision outcomes may provide new insights into the etiology
of childhood vision disorders. The Apgar score, first described more than 60 years ago by Dr. Virginia Apgar, is
widely used as a standardized index of health status in the
immediate neonatal period, and a low score is associated
with many health disorders as well as short-term and longterm mortality [10]. It is unclear whether the Apgar score is
associated with vision problems later in life.
In this study, we examined the association between the
Apgar score and reduced vision in children ages 3 to 6 years
in an urban center in China.

Graefes Arch Clin Exp Ophthalmol

Methods
Study population
The Nanjing Pediatric Vision Project, conducted from 2011 to
2012, was a school-based survey aimed at estimating the burden and predictors of common pediatric ocular disorders
among preschool children aged 3 to 6 years in the Yuhuatai
District, Nanjing, China. The study method has been described elsewhere [11]. In brief, all kindergartens located in
Yuhuatai district were included in the sampling frame. From
an initial list of all names of children provided by the principals in each kindergarten, an age-stratified random sampling
procedure was adopted to select half of the names in the list.
Ultimately, 5980 children were selected using this sampling
strategy, and informed consent was obtained from parents or
legal guardians of 5884 children. Among these, 5862 (98 %)
participated in ocular examinations. After data cleaning, 28
children were excluded from data analyses, since 20 were
found to be beyond the age range of 3 to 6 years at the time
of ocular examination, and eight had missing unaided distance
VA data. Thus, 5834 (97.5 %) preschool children aged 3 to
6 years, including 3123 boys (54 %) and 2711 girls (46 %),
were included in this analysis.
The study was approved by the ethics committee of
Nanjing Medical University, and followed the tenets of the
Declaration of Helsinki. Informed consent was obtained from
all parents after the nature of the study was explained.
Ocular examinations
Clinical ocular examinations were performed by trained pediatric ophthalmologists. If children wore spectacles, ocular
tests were performed with and without refractive correction.
For all children, distance visual acuity (VA) was measured in
both eyes, with or without spectacles, using the Early
Treatment Diabetic Retinopathy Study (ETDRS) VA chart
(Precision Vision, LaSalle, IL, USA) at a distance of 4 m.
For children with a distance VA (both aided and unaided) of
less than 6/12 or a difference of two or more lines detected
between eyes, subjective refraction was subsequently performed to obtain the best-corrected VA. The refractive status
of children with abnormalities found in examinations of ocular
alignment, ocular movement, or distance VA was further evaluated after cycloplegia. For cycloplegic refraction, one drop of
topical 1.0 % cyclopentolate was administered twice to each
eye at a 5-min interval. Fifteen minutes later, if the pupil size
was less than 6 mm or if the pupillary light reflex was still
present, a third drop was administered. Refraction was performed using a handheld autorefractor (SureSight; Welch
Allyn, Skaneateles Falls, NY, USA). In addition to cycloplegic
refraction, children with abnormalities of ocular alignment,
ocular movement, or distance VA underwent testing that

included a stereopsis screening using random-dot stereograms, slit-lamp examination, and fundus examination.
Reduced vision in this study was defined as unaided distance
vision of 6/12 or worse in the better-seeing eye. The use of
unaided distance vision as the criterion for defining reduced
vision is helpful for understanding the Bnature state^ of childrens visual function and its relationship to early life factors.
Assessment of risk factors
Clinical information regarding early life factors including maternal age, birth weight, gestational age, delivery mode, intensive care at birth, 5-min Apgar score, and maternal medication
intake during pregnancy were retrieved from medical records.
A face-to-face interview was administered by a research assistant using a comprehensive questionnaire to collect information on history of feeding patterns, parental education level,
parental history of smoking during pregnancy, and family history of myopia.
The 5-min Apgar score [12] is an aggregate score of five
readily identifiable neonatal characteristics including skin color, heart rate, respiratory effort, muscle tone, and reflexes.
Each category is assigned a score of 0, 1, or 2, depending on
the observed condition. The Apgar test is usually performed
5 min after delivery and may be repeated later if the score is
low. Scores of 7 and above indicate Bgenerally normal^,
scores of 4 to 6 Bfairly low^, and scores of 3 and below are
considered Bcritically low^ [12]. The primary aim of the test is
to rapidly determine whether a newborn needs immediate
medical care in the delivery room [13].
Statistical analyses
The prevalence of reduced vision, defined as unaided distance
vision of 6/12 or worse in the better-seeing eye, was estimated
for the overall sample, and then stratified by age and sex. Chisquare tests were performed to examine variations in prevalence among different age and sex groups. Binary logistic
regression models were fitted to examine the association between early life factors and reduced vision. For multivariate
analysis, only age, sex, and factors with a p value of less than
0.10 in univariate comparisons or factors of scientific importance were retained in the model. The cut-off for the p value
was set at 0.10 in univariate analyses so as not to miss any
important risk factors of marginal significance. All analyses
were performed using SPSS software (PASW Statistics 18;
SPSS Inc., Chicago, IL, USA).

Results
The mean age of the children included in the analysis was
4.90 0.74 years (4.91 0.74 years for boys and 4.89

Graefes Arch Clin Exp Ophthalmol

0.73 years for girls; P = 0.41), which was not significantly different from that of the non-responders (P =
0.35). The overall prevalence of reduced vision in this
population was 6.63 % (95 % confidence interval [CI]
5.997.27), with no difference by age (P = 0.60) or sex
(P = 0.11). The prevalence of reduced vision was
7.80 % (95 % CI 5.769.84), 6.53 % (95 % CI 5.56
7.50), 6.35 % (95 % CI 5.377.34), and 7.03 % (95 %
CI 4.259.82) in children aged 3, 4, 5, and 6 years,
respectively (Table 1).
In univariate analysis, the presence of reduced vision
was associated with self-reported parental history of myopia (having two myopic parents vs. no myopic parents;
P < 0.001), low birth weight (<2.5 kg vs. 2.5 kg; P =
0.05), low gestational age (<37 weeks vs. 37 weeks; P =
0.003), low 5-min Apgar score at birth (<7 vs. 710;
P < 0.001). Other factors including age, sex, height, parental age when pregnant, parental education level, delivery
mode, intensive care at birth, feeding pattern, parental
smoking history, and maternal medication intake during
pregnancy showed no association (all P > 0.10). In multivariate analysis adjusting for age, sex, and factors that
were significantly different in univariate comparisons
(P < 0.10) or factors of scientific importance (e.g. maternal
age), the presence of reduced vision was associated with a
low 5-min Apgar score (<7 vs. 710; odds ratio [OR] =
1.66, 95 % CI 1.48to 3.05; Table 2). A subgroup analysis was performed in children aged 5 to 6 years, and the
association between 5-min Apgar score and reduced vision
was still significant in multivariate analysis (< 7 vs. 710;
OR = 1.47, 95 % CI 1.093.11).
Refractive error and amblyopia were the two major causes
of reduced vision in this study. Table 3 shows the results of
multivariate analyses of the association between early life factors and myopia or amblyopia. Both myopia and amblyopia
were associated with an Apgar score of less than 7 in multivariate analysis.
Table 1

Prevalence of reduced vision by age and sex


N

All children
Sex
Boys
Girls
Age (years)
3
4
5
6
a

Prevalence

P valuea

Children with
reduced vision
(n)

% (95 % CI)

5834

387

6.63 (5.997.27)

3123
2711

192
195

6.15 (5.316.99)
7.19 (6.228.17)

0.11

667
2495
2345
327

52
163
149
23

7.80 (5.769.84)
6.53 (5.567.50)
6.35 (5.377.34)
7.03 (4.259.82)

0.60

P values were calculated using a chi-square test

Table 2

Multivariate analyses of risk factors of reduced vision


Multivariate analysis*
OR

Parental history of myopia


No myopic parents

95 % CI

Reference group

One myopic parent

1.07

0.93

1.45

0.20

Two myopic parents


Maternal age (per year increase)

1.80
1.02

1.35
0.99

2.95
1.04

<0.001
0.28

1.18

0.73

1.88

0.50

2.48

0.01

Birth weight
<2.5 kg
2.5 kg
Gestational age at birth
37 weeks
<37 weeks
Apgar score at 5 min
710
<7

Reference group
Reference group
1.66

1.11

Reference group
1.48
1.02
3.05

0.006

OR odds ratio, CI confidence interval


*Adjusted for age and gender of the children

Discussion
In this study of more than 5000 Chinese preschool children
aged 3 to 6 years, we found that the presence of reduced vision
was associated with a 5-min Apgar score of less than 7, after
adjusting for a wide range of confounders. These observed
associations highlight the importance of the fetal and perinatal
periods for eye growth and vision development.
To the best of our knowledge, this was the first study
to assess the association between low Apgar score and the
risk of reduced vision in childhood. Our study demonstrates that children with a 5-min Apgar score of less than
7 had a higher likelihood of developing reduced vision at
age 3 to 6 years compared to those with an Apgar score
of 710 (within the normal range), although the underlying biological mechanism remains unclear. Low Apgar
scores have been reported to be related to increased risk
of neonatal and infant neurological disorders such as cerebral palsy, epilepsy, and cognitive impairment [14]. In
embryology, eyes are part of the wider base of
neurodevelopment, and thus the effects of low Apgar
score on neurodevelopment and eye growth may share
common pathophysiological pathways. Further welldesigned cohort studies are needed to confirm this finding,
and basic research is needed to explore the biological
mechanism behind this association. From a clinical perspective, the Apgar score may serve as a clinical predictor
of visual outcome later in life. However, reduced vision is
caused by various eye disorders. In our previous report,
refractive errors and amblyopia were found to be the

Graefes Arch Clin Exp Ophthalmol


Table 3 Multivariate analyses of
risk factors of myopia and
amblyopia

Myopia*
OR

Amblyopia*

95 % CI

OR

95 % CI

Parental history of myopia


No myopic parents

Reference group

One myopic parent

1.33

1.03

1.85

0.02

0.95

0.45

1.97

0.68

Two myopic parents


Maternal age (per year increase)

2.04
1.01

1.35
0.98

2.95
1.04

<0.001
0.35

1.25
1.03

0.92
0.99

2.37
1.07

0.26
0.59

1.25

0.79

2.46

0.46

1.12

0.70

2.62

0.65

Birth weight
<2.5 kg
2.5 kg

Reference group

Reference group

Reference group

Gestational age at birth


37 weeks
<37 weeks
Apgar score at 5 min

Reference group
1.36
1.01
2.23

710

Reference group

<7

1.38

1.01

0.03

Reference group
2.03
1.41
3.15

<0.001

Reference group
2.25

0.02

1.65

1.03

2.55

<0.001

OR odds ratio, CI confidence interval


*Adjusted for age and gender of the children

principal causes of reduced vision in this cohort [11]. In


this study, we found that low Apgar scores predicted both
myopia and amblyopia. However, we believe that the
mechanisms linking Apgar score to myopia and amblyopia
may be different, and thus warrant further study.
The age-related changes of reduced vision in our study
were inconsistent with the findings of most previous studies in children of similar ages. In previous studies, the
percentage of children failing the VA tests tended to decrease with age, at least until the prevalence of myopia
increased, which is generally after the age of 6 [3, 1517].
However, our study found no significant age-related prevalence of reduced vision. The reason for this observation
warrants further clarification. We found that the prevalence
of untreated strabismus was higher in the older age group
in our study. For example, the prevalence of untreated
strabismus was 4.5 % in children aged 3 to 4 years, and
increased to 6.6 % in those aged 5 to 6 years [18]. In
addition, although the overall prevalence of myopia in this
population was not high (4 %), most myopic children
were in the older age group (56 years). Thus, the higher
prevalence of untreated strabismus and myopia may have
resulted in greater rates of reduced vision in the older age
group. More specifically, although there was little difference in the prevalence of reduced vision between the older
and younger age groups in this cohort, the causes of vision reduction were quite different. In younger children,
reduced vision may be related to performance issues, simply due to cognitive limitations, whereas in the older age
group in this study, vision reduction was driven by a
higher prevalence of untreated strabismus and myopia.

The strengths of our study include its large, populationbased sample, with an extremely high participation rate,
such that the study sample may be well representative of
the target population. The studys major limitation was
that ocular measurements such as VA and subjective refraction may not have been accurate, given the age range
of the study participants. Younger children may have
greater difficulty in achieving good VA test scores simply
because of cognitive and ocular developmental limitations.
Thus, younger children who failed the standard VA test
may not have actually had impaired vision, and the prevalence of reduced vision in the younger age group may
have been overestimated in the current analysis, which
could obscure the age-related trend in reduced vision. In
addition, if a significant proportion of children with reduced vision actually had age-appropriate vision, the association between risk factors such as Apgar score and reduced vision observed in this study would likely be reduced and on occasion obscured. However, in the subgroup analysis of older children aged 56 years, the association between Apgar score and reduced vision was still
significant, indicating that the Apgar score may be a reliable predictor of reduced vision in children.
In summary, a 5-min Apgar score of less than 7 was associated with a higher prevalence of reduced vision in children,
indicating that early life factors might regulate eye growth and
affect visual outcome later in life. Further studies are needed to
confirm this association. Our study highlights the importance
of the Apgar score and of alerting clinicians to the need for
careful monitoring of vision development in premature infants
with low Apgar scores.

Graefes Arch Clin Exp Ophthalmol


Compliance with ethical standards
Funding The National Natural Science Foundation of China (grant no.
81502824) and the Science and Technology Projects in Nanjing (grant no.
201001110) provided financial support in the form of research funding.
The sponsors had no role in the design or conduct of the research.
Conflict of interest All authors certify that they have no affiliations
with or involvement in any organization or entity with any financial
interest (such as honoraria; educational grants; participation in speakers
bureaus; membership, employment, consultancies, stock ownership, or
other equity interest; or expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials
discussed in this manuscript.

6.

7.

8.

9.
10.

Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the
institutional and/or national research committee and with the 1964
Helsinki declaration and its later amendments or comparable ethical
standards.
Informed consent Informed consent was obtained from all individual
participants included in the study.

11.

12.
13.

14.

References
15.
1.

2.

3.

4.

5.

Robaei D, Rose K, Ojaimi E, Kifley A, Huynh S, Mitchell P (2005)


Visual acuity and the causes of visual loss in a population-based
sample of 6-year-old Australian children. Ophthalmology 112(7):
12751282. doi:10.1016/j.ophtha.2005.01.052
Sun HP, Li A, Xu Y, Pan CW (2015) Secular trends of reduced
visual acuity from 1985 to 2010 and disease burden projection for
2020 and 2030 among primary and secondary school students in
China. JAMA Ophthalmol 133(3):262268. doi:10.1001/
jamaophthalmol.2014.4899
Dirani M, Zhou B, Hornbeak D, Chang BC, Gazzard G, Chia A,
Ling Y, Selvaraj P, Young TL, Varma R, Wong TY, Saw SM (2010)
Prevalence and causes of decreased visual acuity in Singaporean
Chinese preschoolers. Br J Ophthalmol 94(12):15611565.
doi:10.1136/bjo.2009.173104
Wong HB, Machin D, Tan SB, Wong TY, Saw SM (2009) Visual
impairment and its impact on health-related quality of life in adolescents. Am J Ophthalmol 147(3):505511 e501. doi:10.1016/j.
ajo.2008.09.025
Mueller NT, Whyatt R, Hoepner L, Oberfield S, Dominguez-Bello
MG, Widen EM, Hassoun A, Perera F, Rundle A (2015) Prenatal

16.

17.

18.

exposure to antibiotics, cesarean section and risk of childhood obesity. Int J Obes (Lond) 39(4):665670. doi:10.1038/ijo.2014.180
Nielsen JH, Haase TN, Jaksch C, Nalla A, Sostrup B, Nalla AA,
Larsen L, Rasmussen M, Dalgaard LT, Gaarn LW, Thams P, Kofod
H, Billestrup N (2014) Impact of fetal and neonatal environment on
beta cell function and development of diabetes. Acta Obstet
Gynecol Scand 93(11):11091122. doi:10.1111/aogs.12504
Yim HE, Yoo KH (2014) Early life obesity and chronic kidney
disease in later life. Pediatr Nephrol. doi:10.1007/s00467-0142922-4
Sevelsted A, Bisgaard H (2012) Neonatal size in term children is
associated with asthma at age 7, but not with atopic dermatitis or
allergic sensitization. Allergy 67(5):670675. doi:10.1111/j.13989995.2012.02805.x
Bird A (2007) Perceptions of epigenetics. Nature 447(7143):396
398. doi:10.1038/nature05913
Iliodromiti S, Mackay DF, Smith GC, Pell JP, Nelson SM (2014)
Apgar score and the risk of cause-specific infant mortality: a
population-based cohort study. Lancet 384(9956):17491755.
doi:10.1016/S0140-6736(14)61135-1
Pan CW, Chen X, Gong Y, Yu J, Ding H, Bai J, Chen J, Zhu H, Fu
Z, Liu H (2015) Prevalence and causes of reduced visual acuity
among children aged three to six years in a metropolis in China.
Ophthalmic Physiol Opt. doi:10.1111/opo.12249
Apgar V (1953) A proposal for a new method of evaluation of the
newborn infant. Curr Res Anesth Analg 32(4):260267
Casey BM, McIntire DD, Leveno KJ (2001) The continuing value
of the Apgar score for the assessment of newborn infants. N Engl J
Med 344(7):467471. doi:10.1056/NEJM200102153440701
Ehrenstein V (2009) Association of Apgar scores with death and
neurologic disability. Clin Epidemiol 1:4553
Friedman DS, Repka MX, Katz J, Giordano L, Ibironke J, Hawes P,
Burkom D, Tielsch JM (2008) Prevalence of decreased visual acuity among preschool-aged children in an American urban population: the Baltimore Pediatric Eye Disease Study, methods, and results. Ophthalmology 115(10):17861795. doi:10.1016/j.
ophtha.2008.04.006, 1795 e1781-1784
Multi-Ethnic Pediatric Eye Disease Study G (2009) Prevalence and
causes of visual impairment in African-American and Hispanic
preschool children: the multi-ethnic pediatric eye disease study.
Ophthalmology 116(10):19902000 e1991. doi:10.1016/j.
ophtha.2009.03.027
Tarczy-Hornoch K, Cotter SA, Borchert M, McKean-Cowdin R,
Lin J, Wen G, Kim J, Varma R, Multi-Ethnic Pediatric Eye
Disease Study G (2013) Prevalence and causes of visual impairment in Asian and non-Hispanic white preschool children: Multiethnic Pediatric Eye Disease Study. Ophthalmology 120(6):1220
1226. doi:10.1016/j.ophtha.2012.12.029
Chen X, Fu Z, Yu J, Ding H, Bai J, Chen J, Gong Y, Zhu H, Yu R,
Liu H (2016) Prevalence of amblyopia and strabismus in Eastern
China: results from screening of preschool children aged 3672
months. Br J Ophthalmol 100(4):515519. doi:10.1136/
bjophthalmol-2015-306999

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