I. General information
A total of 128 preterm infants with a mean gestational age of 31.62 ± 2.523 weeks (25+ 1–36+ 6 weeks) were included in this study (Table 1, Fig. 1). Among the preterm infants, 78 were boys and 50 were girls; the mean birth weight was 1709.41 ± 543.718 g (660–3200 g) (Table 2, Fig. 2).
Table 1
Gestational age distribution among the included preterm infants
Gestational age (week)
|
ARF group (%)a
|
Non-ARF group (%)a
|
Total (%)a
|
25+ 1–27+ 6
|
1 (3.3)
|
6 (6.1)
|
7(5.5)
|
28+ 1–30+ 6
|
13 (43.3)
|
22 (22.4)
|
35 (27.3)
|
31+ 1–32+ 6
|
7 (23.3)
|
42 (42.9)
|
42 (32.8)
|
33+ 1–36+ 6
|
9 (30)
|
28 (28.6)
|
28 (21.9)
|
Total
|
30 (100)
|
98 (100)
|
128 (100)
|
Note: a expressed as a number (percentage).
ARFs, amblyopia risk factors.
Table 2
Distribution of birth weight among the included preterm infants
Birth weight
|
ARF group (%)a
|
Non-ARF group (%)a
|
Total (%)a
|
500–1000 g
|
6 (20)
|
5(5.1)
|
11 (8.6)
|
1001–1500 g
|
12 (40)
|
32 (32.7)
|
34 (34.4)
|
1501–2000 g
|
6 (20)
|
33 (33.7)
|
38 (30.5)
|
2001–2500 g
|
4 (13.3)
|
17 (17.3)
|
21 (16.4)
|
2500–3001 g
|
2 (6.7)
|
9 (9.2)
|
11 (8.6)
|
> 3000 g
|
0 (0)
|
2 (2.0)
|
2 (1.6)
|
Total
|
30 (100)
|
98 (100)
|
128 (100)
|
Note: a expressed as a number (percentage).
ARFs, amblyopia risk factors.
II. Amblyopia risk assessment
The enrolled preterm infants were regularly followed up until 12 months of corrected gestational age. According to the Spot photoscreener, there were 30 participants in the amblyopia risk group (30/128, 23.4%), including 18 male individuals and 12 female individuals, and 98 participants in the non-amblyopia risk group (98/128, 76.6%), including 60 male individuals and 38 female individuals; there was no statistical difference in sex between the two groups (Table 3).
Table 3
Comparison of the general characteristics between the ARF and non-ARF groups
Demographic information
|
ARF group
|
Non-ARF group
|
Statistical value
|
P
|
Sex
|
M
|
18
|
60
|
0.014
|
0.904
|
F
|
12
|
38
|
Weeks of gestation (weeks)
|
|
31.40 ± 2.64
|
31.68 ± 2.49
|
0.537
|
0.592
|
Birth weight (g)
|
|
1533 ± 560.15
|
1763.41 ± 529.79
|
2.057
|
0.042
|
ARFs, amblyopia risk factors.
The mean gestational age was 31.10 ± 2.647 weeks in the amblyopia risk group and 31.68 ± 2.494 weeks in the non-amblyopia risk group, with no statistical difference in the gestational age between the two groups (Table 1, Fig. 2). The mean birth weight of 1533.00 ± 560.150 g in the amblyopia risk group was significantly lower than that of 1763.42 ± 529.794 g in the non-amblyopia risk group (P < 0.05) (Table 2, Fig. 3).
III. Risk classification of amblyopia in preterm infants at the corrected gestational age of 12 months
Thirty of the 128 children were at risk for amblyopia (23.4%). Further classification of the amblyopia risk revealed 20 cases of astigmatism (15.63%), eight cases of strabismus (6.25%), seven cases of refractive error (5.47%), four cases of hyperopia (3.13%), no cases of myopia (0.00%), and eight cases of mixed factors (6.25%). Based on the above data, astigmatism was found to be the major risk for amblyopia followed by strabismus (Table 4).
Table 4
Amblyopia risk classification in preterm infants at the corrected gestational age of 12 months
ARFs
|
N
|
Percentage (%)
|
Hyperopia
|
4
|
3.13
|
Astigmatism
|
20
|
15.63
|
Myopia
|
0
|
0.00
|
Anisometropia
|
7
|
5.47
|
Strabismus
|
8
|
6.25
|
Mixed factors
|
8
|
6.25
|
Totals
|
30
|
23.4
|
ARFs, amblyopia risk factors.
IV. Single factor analysis of risk factors associated with the risk of amblyopia in the neonatal period in preterm infants at the corrected gestational age of 12 months
1. General perinatal risk factors
There were no statistical differences in the age of the mother or father, presence of gestational hypertension or GDM during the pregnancy, whether the children were born as twins, and birth weight less than the gestational age (SGA) or greater than the gestational age (LGA) between the two groups of children (Table 5).
2. Risks associated with complications during NICU stay
Regarding complications during hospitalization, children in the ARFs group had higher rates of asphyxia, preterm brain white matter injury, BPD, IVH, and sepsis during neonatal hospitalization than the non-ARF group, and the differences were statistically significant. The incidence of NRDS, hydrocephalus, neonatal NEC, ROP meningitis, and EEG abnormalities was not statistically different among the hospitalized children (Table 5).
3. Risks associated with various treatments during NICU stay
During NICU stay of preterm infants, the rates of treatment with PS, blood transfusion, invasive ventilator use, and levothyroxine use were significantly higher in the ARF group than in the non-ARF group, with statistically significant differences. However, there were no statistically significant differences between the two groups in terms of whether glucocorticoids were used, sequential invasive plus noninvasive ventilator use, or whether surgery was performed during hospitalization (Table 5).
Table 5
One-way comparison of the risk factors in the amblyopia risk group versus the non-amblyopia risk group of preterm infants with corrected gestational age of 12 months
|
Risk factor
|
ARF group
|
Non-ARF group
|
Statistical value
|
P
|
|
Number of cases
|
30
|
98
|
|
|
General perinatal
factors
|
Age of mother (years)a
|
32.66 ± 3.49
|
33.26 ± 3.77
|
0.773
|
0.441
|
Father's age (years)a
|
33.86 ± 3.91
|
34.94 ± 4.68
|
1.148
|
0.253
|
Maternal hyperemesisb
|
10 (33.3)
|
24 (24.5)
|
0.921
|
0.337
|
GDMb
|
7 (23.3)
|
37 (37.8)
|
2.118
|
0.146
|
Twin pregnanciesb
|
8 (26.7)
|
30 (30.6)
|
0.171
|
0.679
|
SGAb
|
5 (16.7)
|
6 (6.1)
|
3.251
|
0.071
|
LGAb
|
0 (0)
|
2 (2.0)
|
|
1.000
|
Complications during hospitalization
|
Neonatal asphyxiab
|
12 (40.0)
|
19 (19.4)
|
5.317
|
0.021*
|
NRDSb
|
17 (56.7)
|
57 (58.2)
|
0.021
|
0.885
|
BPDb
|
10 (33.3)
|
10 (10.2)
|
7.648
|
0.002**
|
IVHb
|
12 (40.0)
|
18 (18.4)
|
5.990
|
0.014*
|
Hydrocephalusb
|
1 (3.3)
|
0 (0)
|
|
0.234
|
Brain damage in white matterb
|
3 (10.0)
|
1 (1.0)
|
|
0.040*
|
Electroencephalogram abnormalitiesb
|
13 (43.3)
|
35 (35.7)
|
0.569
|
0.451
|
Septicaemiab
|
10 (33.3)
|
13 (13.3)
|
6.276
|
0.012*
|
Meningitisb
|
2 (6.7)
|
3 (3.1)
|
|
0.334
|
NECb
|
4 (13.3)
|
6 (6.1)
|
0.569
|
0.369
|
ROPb
|
5 (16.7)
|
6 (6.1)
|
6.276
|
0.012*
|
Treatment during hospitalization
|
Hormonesb
|
3 (10.0)
|
7 (7.1)
|
0.015
|
0.610
|
Blood transfusionb
|
10 (33.3)
|
16 (16.3)
|
4.104
|
0.043*
|
PSb
|
16 (53.3)
|
28 (28.6)
|
6.243
|
0.012*
|
Levothyroxineb
|
14 (46.7)
|
21 (21.4)
|
7.545
|
0.006**
|
Ventilator useb
|
23 (76.7)
|
71 (72.4)
|
0.209
|
0.647
|
Invasive ventilatorb
|
16 (53.5)
|
19 (19.4)
|
13.322
|
0.000***
|
Surgeryb
|
0(0.00)
|
6 (6.1)
|
|
0.335
|
Length of stay in hospital (days)a
|
38.36 ± 24.49
|
29.24 ± 19.33
|
-1.869
|
0.069
|
Note: a is represented by x̄±s, and the statistical value is the t value. B is expressed as the number of cases (%), and the statistical value is the ×2 value. P < 0.05 was considered statistically significant. * means P < 0.05, ** means P < 0.01, *** means P = 0.000. ARFs, amblyopia risk factors; GDM, gestational diabetes mellitus; SGA, small for gestational age; LGA, large for gestational age; NRDS, hyaline membrane disease of prematurity; PS, pulmonary surfactant; BPD, bronchopulmonary dysplasia; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis of the newborn; ROP, retinopathy of prematurity.
V. Multifactorial analysis of risk factors in the neonatal period in children born prematurely for the corrected risk of amblyopia at 12 months of gestational age
On the basis of the risk factors found in Table 6 in the neonatal period, multifactorial logistic regression analysis was performed and the results revealed that the presence of BPD (odds ratio [OR] 8.355, 95% confidence interval [CI] 1.492, 46.786), brain white matter injury in preterm infants (OR 16.742, 95% CI 0.684, 409.804), treatment with levothyroxine (OR 2.859, 95% CI 0.946, 8.639), and use of an invasive ventilator (OR 2.983, 95% CI 0.942, 9.445), were independent risk factors for the corrected risk of amblyopia at 12 months of gestational age; hormone therapy (OR 0.055, 95% CI 0.004, 0.737) was found to be protective factors.
Table 6
Multifactorial logistic regression analysis of risk factors for amblyopia
Risk factor
|
Regression coefficient
|
Standard error
|
Wals value
|
P
|
OR
|
95% CI
|
Hormone regimen
|
-2.893
|
1.320
|
4.803
|
0.028
|
0.055
|
0.004–0.737
|
Invasive breathing (medicine)
|
1.093
|
0.588
|
3.453
|
0.063
|
2.983
|
0.942–9.445
|
BPD
|
2.123
|
0.879
|
5.833
|
0.016
|
8.355
|
1.492–46.786
|
White matter damage
|
2.818
|
1.632
|
2.983
|
0.084
|
16.742
|
0.684–409.804
|
Levothyroxine
|
1.051
|
0.564
|
3.468
|
0.063
|
2.859
|
0.946–8.639
|
Constant
|
-1.686
|
0.340
|
24.561
|
0.000
|
0.185
|
|
BPD, bronchopulmonary dysplasia; OR, odds ratio; CI, confidence interval.
VI. Relationship between the amblyopia risk and neurological development in preterm infants with corrected gestational age of 12 months
Developmental abnormalities were present in nine (30%) children in the ARF group and 13 (13.27%) in the non-ARF group. The proportion of children with fine motor abnormalities was significantly higher in the ARF group than in the non-ARF group, with a significant difference (P = 0.034 < 0.05). There were no differences in the rates of adaptive, gross motor, language, and personal social abnormalities between the two groups of children. See Table 7 for details.
Table 7
Relationship between the risk factors for amblyopia and neurological development
Gesell Developmental Scales
|
ARF group (%)
|
Non-ARF group (%)
|
Chi-square (math.)
|
P
|
Adaptive
|
8 (26.7)
|
16 (16.3)
|
1.612
|
0.204
|
Large scale movement
|
12 (40.0)
|
22 (22.4)
|
3.627
|
0.057
|
Fine-motion
|
9 (30.0)
|
13 (13.3)
|
4.519
|
0.034*
|
Language
|
14 (46.7)
|
32 (32.7)
|
1.959
|
0.162
|
Personal social
|
8 (26.7)
|
15 (15.3)
|
2.011
|
0.156
|
Note: *P < 0.05 denotes statistical significant. ARFs, amblyopia risk factors.