The Relationship between Hyperglycemia and Retinopathy of Prematurity in Very Low Birth Weight Infants

Sung Keun Kim; Jin Wan An; Seung Hyun Lee; Yeon Kyun Oh

doi:10.14734/PN.2017.28.4.127

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Kim, An, Lee, and Oh: The Relationship between Hyperglycemia and Retinopathy of Prematurity in Very Low Birth Weight Infants

Original Article

Perinatology 2017;28(4):127-133.

Published online: 19 January 2017

DOI: https://doi.org/10.14734/PN.2017.28.4.127

The Relationship between Hyperglycemia and Retinopathy of Prematurity in Very Low Birth Weight Infants

Sung Keun Kim, MD, Jin Wan An, MD, Seung Hyun Lee, MD, Yeon Kyun Oh, MD

Department of Pediatrics, Wonkwang University School of Medicine, Iksan, Korea

Correspondence to Yeon Kyun Oh, MD Department of Pediatrics, Wonkwang University School of Medicine, 460 Iksan-daero, Iksan 54538, Korea Tel: +82-63-859-1510 Fax: +82-63-853-3670 E-mail: oyk5412@wonkwang.ac.kr

Received 30 June 2017 Revised 26 August 2017 Accepted 20 September 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

We aimed to investigate if hyperglycemia is a risk factor of retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants.

Methods

One hundred forty-seven VLBW infants during the years 2011 through 2015 were included in this retrospective study. Glucose levels were analyzed with whole blood for three weeks after birth. Hyperglycemia was defined as the blood glucose level over 125 mg/dL. ROP patients were compared with non-ROP patients. Variables significantly related to ROP including glycemic characteristics were evaluated in a multivariate analysis.

Results

ROP occurrence was associated with perinatal factors like birth weight (BW), gestational age, 5-minute Apgar score and premature rupture of membranes. It was also significantly related to neonatal factors like respiratory distress, surfactant use, bronchopulmonary dysplasia, congenital heart disease, transfusion, surgical operation, apnea, aminophylline or caffeine use, ventilator days, and admission days. In glycemic characteristics, hyperglycemia duration, average and maximum glucose level for 3 weeks after birth showed statistical significance. But, in a multivariate analysis, only BW and surfactant use were independently associated with ROP, while glycemic characteristics were not. In comparisons based on ROP severity, hyperglycemia duration, average blood glucose level of 3rd week after birth, and insulin use showed significant difference, but they were not independent factors.

Conclusion

In this study, hyperglycemia duration, average and maximum blood glucose level during three weeks after birth were statistically significant, but they were not independent factors associated with ROP development.

Keywords: Hyperglycemia, Retinopathy of prematurity, Infant, Very low birth weight

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Table 1.

Perinatal Risk Factors for Development of ROP in Very Low Birth Weight Infants

N	Non-ROP (n=123)	ROP (n=24)	P-value
GA (weeks)	30.5±2.7	27.3±1.5	<0.0001
BW (g)	1,240±219	952±199	<0.0001
Male	65 (52.8)	9 (47.2)	0.167
Apgar score
1 minute	4.4±1.8	3.8±1.6	0.151
5 minutes	6.7±1.6	6.0±1.3	0.014
IUGR	25 (20.3)	2 (8.3)	0.134
Maternal hypertension	31 (25.2)	2 (8.3)	0.120
PPROMs	31 (25.2)	11 (45.8)	0.048
C-sec	82 (66.7)	18 (75)	0.415

Values are presented as mean±standard deviation or number (%). Abbreviations: ROP, retinopathy of prematurity; GA, gestational age; BW, birth weight; IUGR, intrauterine growth retardation; PPROMs, preterm premature rupture of membranes; C-sec, cesarean section.

Table 2.

Neonatal Risk Factors for Development of ROP in Very Low Birth Weight Infants

	Non-ROP (n=123)	ROP (n=24)	P-value
Respiratory distress	76 (61.8)	21 (87.5)	0.009
Surfactant use	73 (59.3)	20 (83.3)	0.019
Air leak syndrome	5 (4.1)	2 (8.3)	0.404
BPD	31 (25.2)	13 (54.2)	0.006
PDA	20 (16.3)	11 (45.8)	0.003
CHD	24 (19.5)	11 (45.8)	0.009
IVH	35 (28.5)	17 (70.8)	<0.0001
PVL	12 (9.8)	3 (12.5)	0.692
Sepsis	11 (8.9)	4 (16.7)	0.282
NEC	8 (6.5)	2 (8.3)	0.751
Transfusion	75 (61)	22 (91.7)	0.001
Operation	4 (3.3)	4 (16.7)	0.008
UAC	10 (8.1)	4 (16.7)	0.224
Apnea	76 (61.8)	23 (95.8)	<0.0001
Aminophylline use	18.7±23.9	46.2±40.0	<0.0001
Ventilator days	8.1±13.2	32.7±52.5	<0.0001
Admission days	51.3±20.9	83.6±49.1	<0.0001
Hyperoxia days	2.0±2.7	2.4+2.6	0.497

Values are presented as number (%) or mean±standard deviation. Abbreviations: ROP, retinopathy of prematurity; BPD, bronchopulmonary dysplasia; PDA, patent ductus arteriosus; CHD, congenital heart disease; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; NEC, necrotizing enterocolitis; UAC, umbilical artery catheterization.

Table 3.

Comparison of Glycemic Characteristics between ROP Group and Non-ROP of Prematurity Group in Very Low Birth Weight Infants

	Non-ROP (n=123)	ROP (n=24)	P-value
Mean daily glucose (mg/dL)
1st week	112.84±42.03	130.59±39.37	0.033
2nd week	130.21±38.70	169.65±52.70	0.003
3rd week	119.85±27.68	140.10±36.30	0.030
Maximum daily glucose (mg/dL)
1st week	209.57±197.32	265.87±118.24	0.005
2nd week	196.96±90.43	274.22±114.82	0.004
3rd week	185.10±92.70	239.42±125.16	0.033
Days of Hyperglycemia
>125 mg/dL (mild)	4.8±5.4	10.1±6.5	<0.0001
>150 mg/dL (modera	te) 3.5±4.7	8.0±6.4	0.001
>200 mg/dL (severe)	1.6±2.8	4.1±4.5	0.002
Insulin use	2 (1.6)	1 (4.2)	0.421

Values are presented as mean±standard deviation or number (%). Abbreviation: ROP, retinopathy of prematurity.

Table 4.

Multivariate Analysis for Risk Factors in Development of Retinopathy of Prematurity by Severity of Hyperglycemia in Very Low Birth Weight Infants

	Mild (>125 mg/dL)			Moderate (>150 mg/dL)			Severe (>200 mg/dL)
	OR	95% CI	P-value	OR	95% CI	P-value	OR	95% CI	P-value
GA	0.618	0.33-1.13	0.122	0.627	0.34-1.14	0.128	0.590	0.32-1.09	0.093
BW	0.993	0.98-0.99	0.016	0.993	0.99-1.00	0.016	0.993	0.99-1.00	0.016
PPROMs	3.238	0.69-15.19	0.136	3.152	0.66-15.00	0.149	3.436	0.70-16.97	0.130
Respiratory distress	3.495	0.16-76.56	0.427	3.252	0.15-72.11	0.456	3.333	0.13-82.25	0.462
Surfactant use	0.028	0.001-0.71	0.031	0.030	0.001-0.71	0.030	0.023	0.001-0.65	0.027
PDA	0.285	0.04-2.01	0.209	0.272	0.04-1.93	0.192	0.196	0.02-1.58	0.126
CHD	3.941	0.59-26.28	0.157	3.755	0.55-25.55	0.176	4.979	0.70-35.33	0.108
Transfusion	1.093	0.11-10.37	0.939	0.930	0.10-8.86	0.950	0.999	0.10-10.46	0.999
Operation	5.821	0.33-102.63	0.229	5.655	0.31-100.18	0.237	7.186	0.37-138.2	0.191
IVH	2.890	0.56-14.91	0.205	2.995	0.66-14.96	0.181	2.755	0.57-13.39	0.209
Apgar score 5min	1.237	0.69-2.20	0.470	1.254	0.70-2.24	0.445	1.202	0.66-2.20	0.549
Ventilator days	0.989	0.93-1.04	0.701	0.991	0.94-1.05	0.755	0.997	0.94-1.06	0.933
Admission days	1.012	0.96-1.06	0.658	1.012	0.96-1.07	0.663	1.016	0.96-1.08	0.599
Aminophylline use	1.018	0.98-1.05	0.304	1.017	0.99-1.05	0.301	1.020	0.99-1.05	0.221
Days of Hyperglycemia	0.991	0.80-1.21	0.928	0.989	0.81-1.22	0.915	0.796	0.58-1.09	0.151
Mean daily glucose	1.011	0.97-1.04	0.510	1.016	0.98-1.06	0.419	1.022	0.99-1.06	0.225
Max. daily glucose	0.996	0.98-1.01	0.420	0.995	0.98-1.01	0.339	0.997	0.99-1.01	0.571

Abbreviations: OR, odds ratio; CI, confidence interval; GA, gestational age; BW, birth weight; PPROMs, preterm premature rupture of membranes; PDA, patent ductus arteriosus; CHD, congenital heart disease; IVH, intraventricular hemorrhage; Max., maximum.

Table 5.

Glycemic Characteristics of Severe Retinopathy of Prematurity defined as requiring any Operation

	No operation (n=139)	Operation (n=8)	P-value
Mean daily glucose (mg/dL)
1st week	115.00±41.93	129.67±43.41	0.306
2nd week	136.14±42.83	159.54±59.73	0.260
3rd week	121.25±26.11	159.01±54.81	0.028
Maximum daily glucose (mg/dL)
1st week	209.58±190.59	262.75±116.92	0.122
2nd week	213.16±97.51	242.43±130.22	0.471
3rd week	189.28±89.99	285.43±183.39	0.122
Days of Hyperglycemia
>125 mg/dL (mild)	5.36±5.70	11.75±6.88	0.008
>150 mg/dL (moderate)	3.94±4.94	9.88±7.51	0.019
>200 mg/dL (severe)	1.88±3.02	5.00±5.78	0.105
Insulin use	1 (0.7)	1 (12.5)	0.005

Values are presented as mean±standard deviation or number (%).

Table 6.

Multivariate Analysis for Risk Factors in Development of Severe Retinopathy of Prematurity requiring any Operation in Very Low Birth Weight Infants

	OR	95% CI	P-value
GA	1.058	0.58-1.94	0.855
BW	0.995	0.98-1.00	0.114
Apgar score 5 minutes	1.314	0.65-2.66	0.448
Operation	4.066	0.30-55.11	0.292
Ventilator days	1.011	0.97-1.06	0.610
Admission days	0.999	0.95-1.05	0.960
Insulin use	7.516	0.28-204.20	0.231
Days of Hypoglycemia	1.088	0.80-1.48	0.586
Days of Hyperglycemia (>125 mg/dL)	1.024	0.81-1.29	0.840
3rd week mean glucose	1.038	0.97-1.10	0.207

Abbreviations: OR, odds ratio; CI, confidence interval; GA, gestational age; BW, birth weight.

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