FP727 : Retinopathy of Prematurity – Intersibling Variability of Risk Factors Among Twins.

Dr. N S. Sudeep, Dr. Kavitha C.V., Dr.Pavana Acharya

AIM:

  1. 1. To know the incidence of ROP in twins
  2. To study the difference in the risk factors of ROP between first and second twin.

MATERIALS AND METHODS:

A prospective study was done on 32 paired twins at Hassan. All twins admitted to NICU with low birth weight (LBW) <2000grms and/or gestational age<34weeks during December 2015 to April 2016 were screened for ROP using  RETcam.Twin1 and 2 were categorized based on order of delivery. Both maternal and neonatal risk factors were analyzed.

RESULTS:

Among 32pairs 22pairs had ROP(68%).

In twin1 preterm (100%), LBW(68%), Respiratory distress syndrome(27%), LSCS(22%), PIH(22%), Neonatal jaundice(18%),  Intra ventricular haemorrhage(1%) were significant risk  factors for ROP.

For twin 2  preterm(100%), LBW(45%), LSCS(22%), PIH(22%) were significant risk factors.

CONCLUSION:

The incidence of ROP among twins is 68%.Twin 1 is more susceptible to post natal risk factors for ROP.

Introduction and need for the study:

Retinopathy of prematurity (ROP) is a consequence of an arrest in normal retinal neural and  vascular development, which determines the aberrant retinal regeneration1,2.

Retinopathy of prematurity (ROP) is a disease process mostly reported in preterm neonates with a wide spectrum, ranging from mild, transient changes in the retina with regression to severe progressive vasoproliferation, scarring, detachment of retina and blindness and it is common blinding disease in children and a major cause of vision loss among preterm infants3.Today it is well known that oxygen therapy is not the single causative factor, but many other risk factors play a causative role in the pathogenesis of ROP4,5.

The risk factors for ROP include oxygen administration, hypoxia, hypercapnia, blood transfusion exchange transfusion, apnea ,sepsis and total parenteral nutrition. The incidence of ROP has been reported to be similar in multiple and singleton births6,7,8. Twin studies show that from 70% to 80% of the susceptibility to ROP is conditioned by genetic factors 9,10

Recent years have witnessed an increasing number of multiple pregnancies which is due to higher age at first pregnancy, extensive use of hormones and development of new methods for treatment of infertility. Very low birth weight is 10 times higher in multiple compare to singleton pregnancies. For the first time 1956, the relative risk for cicatricial ROP was reported 3 times higher in multiple pregnancy compared to singleton, by performing regression analysis Bossi et al reported that twin are higher risk of  ROP in 1993.

Hence this study is to find out the incidence of ROP in twins in a tertiary care centre in a developing country. It also attempts to identify the difference in risk factors among twins which predispose to ROP in a large population of Neonatal Intensive Care.

Materials and methods:

All preterm twin neonates born after Dec. 2015 in srichamarajendra Hospital, Hassan and all preterm twins admitted to NICU with birth weight <2000grmsand/or gestational age <34 weeks were evaluated for ROP screening and recruited into the study.

Method of collection of data:

Study was initiated after obtaining approval from the Institutional Ethics Committee, Hassan institute of medical sciences, Hassan. All preterm twin neonates are screened UK screening guideline using RET fundus  camera for ROP under routine screening and will be examined weekly or biweekly until retinal vasculature reaches zone 3 and established ROP regression. Fundus is examined after full pharmacological dilation using cyclopentolate 0.5% and staging done according to revised International Classification of ROP, including the extent, zone and presence or absence of plus disease. Treatment is laser implemented when the disease progressed to stage 3 above and stage 2 with plus disease.

Inclusion criteria:

All twins birth weight less than 2000 grams and/or gestational age less than 34 weeks admitted to NICU of Hassan Institute of Medical Sciences, Hassan.

Exclusion criteria: Neonates with incomplete data and twins with birth weight more than 2000 grams and gestational ageMore than 34 weeks.

Antenatal risk factors

Maternal diseases; preeclampsia, gestational diabetes mellitus,

IVF, Use of antenatal steroids, preterm premature rupture of membranes, LSCS.

Neonatal risk factors

Oxygen administration, hypoxia, hypercapnia ,blood transfusion ,exchange transfusion,

Apnea ,sepsis, intraventricular hemorrhage and total parenteral nutrition.

Study design: Prospective study.

Study period: Study conductedfrom dec2015 to april2016.

Statistical Analysis:   Data were analysed using Epidata. Estimates are calculated independently by pregnancy order(Twin 1 or Twin 2).

Results:

Among 32pairs 22 pairs had ROP (68%).

Among 44 infants Stage1 ROP developed in 28 (64%) infants [twin 1-16 (58%), twin 2-12(42%)]; Stage2 ROP developed in 15(34%) infants [twin 1-6 (40%), twin 2-9(60%)] and Stage3 ROP developed in 1(2%) twin 2.

There were 30 male (68%) and 14 female (32%) subjects. The mean GA was 30.4 weeks {28 weeks to 34 weeks} and the mean BW was 1145 Gms {1000 gms to 1650gms}.

Stage of ROP Twin 1 Twin 2 Total
Stage1 16 12 28
Stage 2 6  ( 2A-5 & 2P-1) 9 15
Stage 3 0 1 1
Total 22 22 44

In twin1- Among 22 pairs  preterm 22 (100%), LBW 15(68%), Respiratory distress syndrome 6(27%), LSCS 5(22%), PIH 5(22%), Neonatal jaundice 4(18%),  Intra ventricular haemorrhage 2(1%) were significant risk  factors for ROP.

For twin 2  preterm 22(100%), LBW 10(45%), LSCS 5(22%), PIH 5(22%) were significant risk factors.

Risk factor Twin 1 Twin 2 Total
Preterm 22 22 44
Low birth weight 15 10 25
Caesarean section 5 5 10
Neonatal jaundice 4 4
Respiratory distress syndrome 6 6
Pregnancy induced hypertension 5 5 10
Intraventricular hemorrhage 2 2

Discussion:

In a twin pair study by Azad et al. [10], it was shown that there were no significant differences n both GA and BW (? = 1.00 forGA, = 0.39 for BW) among the twins with severe ROP (mean GA of 29.3 weeks and mean BW of 1239) compared to those with less severe ROP (mean GA of 29.3 and mean BWof 1297).In our study GA (100%) is significant risk factors for ROP compared to BW (68%).

Blumenfeld et al [1]study showed that there is no significant difference in stage of ROP between infants of single vs multiple gestation pregnancies.Frilling et al [8] showedThere was no significant difference in the incidence of ROP between the twins and the singletons and second-born twin seemed at higher risk for developing ROP, but logistic regression showed that the lower birth weight of the second twin, Our study showed incidence of getting ROP inmultiple pregnancies is quite significant and more advanced stages of ROP found in twin 2 compared to twin 1.

There were discrepancies in the susceptibility of postnatal risk factors for ROP between the twins despite exposure to similar postnatal conditions. Twin 1 was more likely to develop ROP when exposed to the following factors that were found to be independent ROP risk factors in Twin 1 but not Twin 2: presence of Respiratory distress syndrome, Neonatal jaundice, and Intra ventricular haemorrhage.

CONCLUSION:

The incidence of ROP among twins is 68%.In twin1antenatal risk factors like preterm (100%), LBW(68%), LSCS(22%), PIH(22%) & post natal risk factors like Respiratory distress syndrome(27%),Neonatal jaundice(18%),  Intra ventricular haemorrhage(1%) were significant for ROP.

For twin 2 only antenatal risk factors like preterm (100%), LBW (45%), LSCS (22%), PIH (22%) were significant & postnatal risk factors not found.

Advanced stages were seen more in twin 2 but it is statistically not significant.

Conflict of Interests

The authors declared no potential conflict of interests withrespect to the research, authorship, and/or publication of thispaper.

Acknowledgement : Thanks to NarayanaNethralaya Bangalore for the conduction of ROP screening at HIMS, Hassan.

References:

1.A. Hellstrom, L. E. H. Smith, and O. Damman, “Retinopathy of prematurity,” The Lancet, vol. 26, pp. 1445–1457, 2013.

2.J. Chen,A. Stahl,A.Hellstrom, and L. E. Smith, “Current update on retinopathy of prematurity: screening and treatment,” Current Opinion in Pediatrics, vol. 23, no. 2, pp. 173–178, 2011Chen J, Smith LE. Retinopathy of prematurity. Angiogenesis 2007; 10: 133–140.

3.Hammer ME, Mullen PW, Fergusson JG, Poi S, Cosbox C. Jackson KL. Logistic analysisof risk factors in acute retinopathy of prematurity. Am J Ophthalmol 1986; 102: 1-6.

4.Seiberth V, Linderkamp O. Risk factors in retinopathy of prematurity. A multivariatestatistical analysis. Ophthalmologica 2000; 214: 131-135.

5.Schaffer DB, Palmer EA, Plotsky DF, Metz HS, Flynn JT, Tung B, Hardy RJ (1993)

6.Prognostic factors in the naturalcourse of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology100:230–237

7.Blumenfeld LC, Siatkowski RM, Johnson RA, FeuerWJ,Flynn JT (1998) Retinopathy of Prematurity in multiplegestationpregnancies. Am J Ophthalmol 125:197–203

8.Friling R, Rosen SD, Monos T, Karplus M, Yassur Y (1997)Retinopathy of prematurity in Multiple-gestation, very lowbirth weight infants. J Pedi Ophthalmol Strabismus 34:96– 100

9.M. J. Bizzarro, N. Hussain, B. Jonsson et al., “Genetic susceptibility to retinopathy of Prematurity,” Pediatrics, vol. 118, no. 5,pp. 1858–1863, 2006.

10.R. Azad, P. Chandra, S. D. Patwardhan, and A. Gupta, “Profileof asymmetrical Retinopathy of prematurity in twins,” IndianJournal of Ophthalmology, vol. 58, no. 3, pp.209–211, 2010.

FP1082 : Normative Biometric Data in Pediatric Eyes from Birth To 2 Years of Age

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