Effect of Kangaroo Mother Care on Retinopathy of Prematurity in Neonates Less Than 1,800 g or Below 34 Weeks of Gestation

Chetan Singh1 , Sugandha Arya1, Harish Chellani1, Pratima Anand1 and Richa Singhal1

Abstract

Introduction: KMC (Kangaroo Mother Care) is an established intervention to reduce mortality and morbidity in low birth weight (LBW) neonates. A multitude of risk factors and preventive strategies for ROP (retinopathy of prematurity) have been studied, however, the effect of KMC on ROP has not been reported. This study aims to study the effect of KMC on
ROP in neonates with birth weights between 1,000 and 1,800 g.

Methods: The babies who received effective KMC (>6 hours per 24 hours for three consecutive days) were analysed in the intervention group and those with ineffective KMC were analysed in the control group. Variables significant in univariate analysis were entered into backward regression models in multivariate analysis. Odds ratios and 95% confidence intervals were calculated. P values < .05 are taken as significant.

Results: Of 783 neonates enrolled, 66 (8.4%) developed ROP (any stage). The incidence of ROP requiring intervention was 1.02%. Effective KMC reduced the risk of ROP by 95%, RR 0.05 (0.02–0.12) and number needed to treat = 5. The proportion of neonates with ROP in zone 1 and stage 3 was more in the ineffective KMC (42.4% vs. 1.5%) group than in the effective KMC group (51.5% vs. 0%) (P < .001). Ineffective KMC, gestation <30 weeks, small for gestation, obstetric complications, asphyxia, sepsis, higher initial PEEP and lack of breastfeeding were significant risk factors for developing ROP.

Conclusion: KMC, an effective intervention to improve the mortality and morbidity in LBW neonates, was significantly associated with the reduction of any stage ROP and ROP needing intervention, potentially preventing a significant cause of childhood blindness.

 

Keywords
Kangaroo Mother Care, retinopathy of prematurity, low birth weight, neonate, Received 20 October 2023; accepted 23 February 2024

 

Introduction

Retinopathy of prematurity (ROP) is a disorder of developing retina that occurs predominantly in premature neonates and is one of the leading causes of childhood blindness. The global burden of ROP is on the rise and with the increasing survival of extremely premature neonates, the incidence of ROP among screened infants is also increasing from 14.7% in 2000 to 19.8% in 2012.1,2 Not only ophthalmologic morbidity, but ROP has also shown to have a substantial maturational delay of the optic radiation, posterior limb of the internal capsule, external capsule and poor white matter,
hence associated with poor motor and cognitive outcomes at 18 months corrected age.2

Since ROP was first described over 75 years ago, there have been a conglomerate of papers that identify distinct putative risk factors and interventions to prevent ROP.3–13 Previous studies from the authors’ reported various risk factors of which significant ones were prematurity, low birth weight (LBW), and lack of antenatal steroids.14,15 Multiplegestation was also found to be an independent causative factor. for developing any stage ROP.14 Kangaroo Mother Care (KMC) is an effective intervention to reduce mortality and morbidity in LBW neonates.16 KMC stabilizes various physiological parameters including temperature, heart rate and respiratory rates in LBW neonates.17 Benefits of KMC like reduction of sepsis (65%), hypothermia (72%), hospital stay and provision of physiological stability are the same as factors which form the basis of target interventions used to reduce the ROP and its severity. Early stabilization by KMC would lead to lesser fluctuations in vital parameters including SpO2 and hence lesser oxygen exposure in the crucial initial few days.

Department of Pediatrics, Vardhman Mahavir Medical College &
Safdarjung Hospital, New Delhi, Delhi, India

Corresponding author:
Chetan Singh, Department of Pediatrics, Vardhman Mahavir Medical
College & Safdarjung Hospital, New Delhi, Delhi 110029, India.
E-mail: chetansingh2193@gmail.com

We hypothesized that clinical stability provided by KMC would lead to a reduction in any stage of ROP and severity of ROP in neonates who receive effective KMC during a hospital stay. This present study was conducted with an objective to analyse the effect of KMC on ROP in neonates with birth weights between 1,000 and 1,800 g.

Subjects and Methods

Study Design and Settings

In this prospective cohort study, neonates were enrolled after obtaining the institutional ethics committee clearance and informed written consent from the parents. The study was conducted from June 2018 to May 2019 amongst neonates with birth weights of 1,000 g to less than 1,800 g. The primary objective was to identify the effect of KMC on any stage of ROP. Describing the epidemiology and incidence of ROP were the secondary objectives. The study was conducted in a 2,500-bed tertiary care hospital with a 62-bed neonatal intensive care unit (NICU), with a 25,000 annual delivery rate and an average of 4,800 NICU admissions every year.

The unit admits all sick and LBW neonates below 1,800 g in the NICU. As per WHO guidelines, once LBW neonates are stabilizing (minimal or no oxygen requirement, on partial/ full feeds), short sessions of KMC are initiated inside the NICU. Once the neonate is stable, that is, on full feeds and is off respiratory support, they are shifted to the KMC ward where continuous KMC is encouraged. However, many neonates are either not shifted to the KMC ward or stay there for short periods of time, due to the non-availability of beds in KMC wards for many days.

It is a unit policy to examine all the neonates eligible for ROP screening either prior to discharge or in follow-up.

 

Eligibility and Enrolment

At our unit, screening for ROP is done for (a) all neonates born at 34 weeks or less gestational age, (b) all infants weighing 1,800 g or less at birth and (c) all preterm infants >34 weeks’ gestational age/1,800 g having risk factors (prolonged oxygen requirement, cardiorespiratory support, respiratory distress syndrome, chronic lung disease, blood transfusion, intraventricular haemorrhage, sepsis and exchange transfusion, apnoea). These screening criteria are country-specific and differ from certain international screening recommendations.18 All live-born neonates with birth weight between 1,000 and 1,800 g were enrolled and followed up. The presence of major congenital malformation in neonates was the exclusion criteria. The demographic and clinical course of the neonate were recorded in a predefined structured proforma on a daily basis. Effective KMC for the purpose of this study was defined as any KMC provided for more than 6 hours in 24 hours, for three consecutive days during the stay in the hospital.19 The definitions of various factors analysed in the cohort are provided in Appendix A. Neonates who were discharged prior to the recommended timing of screening of three to four weeks of postnatal age were called for follow-up at the ROP clinic at our unit. The neonates who did not come for follow-up visits were defined as lost to follow-up.

Outcomes

The eligible neonates as per the criteria were screened by the ophthalmologists who were formally trained in ROP screening and diagnosis, by indirect ophthalmoscope. After standard preparation for ROP examination, an anterior segment examination was carried out to look for tunica vasculosa lentis, pupillary dilation and media clarity followed by, the posterior pole and peripheral examinations of all clock hours to inspect for vascularization and presence of zone and stage of ROP. ROP was classified as per the Revised Intervention Classification of ROP20 and follow-up was planned as decided by the initial stage. ROP needing intervention was done with LASER and or anti-VEGF as indicated.

 

Statistical Analysis

Taking the prevalence of ROP of 13.67% of screened infants21 from a previous study from the same centre, alpha error of 0.05 and power of 80%, the number of babies required to be screened was calculated to be 750. Data was collected through a predesigned proforma and final data was collated in an Excel spreadsheet. Analysis was done in the statistical software package SPSS 21.0 version. Mean ± SD was calculated for continuous variables and frequency tables and percentages were calculated for categorical variables. Predictors of ROP were assessed using univariate and multivariate logistic regression analysis. Variables significant in univariate analysis were entered into backward stepwise regression models in multivariate analysis. Odds ratios and 95% confidence intervals were calculated for variables that were significant. All P values were two-tailed and values <.05 were taken as significant.

Results

Of the 28,474 live births during the study period between June 2018 and May 2019, 1,359 live neonates were between birth weights 1,000 and 1,800 g and 783 neonates were enrolled in the study. Appendix B describes the flow of enrolment of neonates. The mean birth weight of the cohort was 1,460 ± 190 g with a mean gestation of 31.58 ± 1.49 weeks. Approximately two-thirds of enrolled neonates were preterm and 48.7% were females. Multiple pregnancies (twins) comprised 18% of the cohort. A total of 66 neonates developed any stage ROP (8.4%) which either needed further screeningor intervention. Overall, eight neonates (1.02%) needed intervention for ROP in the form of LASER. None of the neonates above 34 weeks developed ROP. Of the 66 neonates who
developed ROP, 19 (28%) were multiple gestation (twin). The incidence of ROP was higher in gestation less than 32 weeks (6.0%) compared to gestation between 32 and 34 weeks (2.4%). Similarly, birth weight less than 1,500 g had a higher incidence of 6.2% compared to 2.1% in birth weight above 1,500 g.

The groups of effective versus ineffective KMC differed regarding the need for resuscitation, initial PEEP and FiO2 requirement, breastfeeding rates and presence of sepsis (P < .05). The mean duration of KMC (hours per day) was 9 hours (±2.82 SD) ineffective KMC group, which was significantly higher than the duration in ineffective KMC group (1.5 ± 2.12). Effective KMC is associated with reduced risk of ROP (any stage), by 95% (1.04% vs. 20.1%), RR 0.05 (0.02–0.12) and for every five neonates between 1,000 and 1,800 g receiving effective KMC, one ROP was prevented, that is, number needed to treat is 5.

The profile of ROP ineffective KMC versus the ineffective KMC groups was also different. Out of the 8 neonates with ROP needing intervention, 2 (3% of any ROP) were ineffective KMC compared to 6 (10% of any ROP) in the ineffective KMC group (P < .001). In ROP not needing intervention, but further screened, the proportion of neonates with ROP in zone 1 or stage 3 was higher in the ineffective KMC group compared to the effective KMC group (42.4% vs. 1.5%) and (51.5% vs. 0%), respectively (P < .001).

Effective KMC showed a protective effect on ROP. Besides effective KMC, other known factors that may affect the development of ROP were analysed. Maternal obstetric and medical complications, prematurity, LBW, female gender, SGA, Apgar score (need for resuscitation), higher initial PEEP and FiO2 requirement, sepsis and lack of breastfeeding were found to be
significantly associated with the presence of ROP.

To eliminate the effect of confounding factors, a multivariate analysis was done. On multivariate analysis, apart from ineffective KMC, gestation less than 30 weeks, small for gestation, presence of obstetric complications, asphyxia (need for resuscitation), presence of either clinical or culture positive sepsis, PEEP of 5 cm H20 in the first 72 hours and lack of breastfeeding was significantly associated with the presence of ROP.

Discussion

This prospective observational study finds that a mean KMC duration of 6 hours (i.e., effective KMC) reduces the incidence of any stage ROP needing repeat screening or intervention. The incidence of any stage ROP in the cohort of neonates between 1,000 and 1,800 g was noted to be 8.4% and ROP requiring intervention was 1.0%. Also, the severity of ROP with respect to of zone and stage of ROP was less in the effective KMC group as compared to the ineffective KMC group, though the sample size for this outcome was underpowered.

The incidence of ROP reported in India varies between 2.4% and 42% among screened infants, with study population varying from less than 32 to 34 weeks and birth weight less than 1,500 to 2,000 g.4–15 The special neonatal care units (SNCUs), which are the cornerstone of sick and LBW neonates in India report a 15% incidence of sight-threatening (STROP), that is, ROP requiring intervention.6 Globally the reported incidence is between 15.2% and 42.7%.22 This wide variation in ROP incidence reflects the characteristics of neonatal care units in terms of care being provided, for example, adherence to evidence-based practices like oxygen titration, use of blenders, optimal delivery room management, pulse oximetry and alarm limits monitoring, asepsis
and prevention of infection and breastfeeding rates. Awareness of healthcare providers also affects the timely screening and therefore prevention of severe ROP or ROP requiring intervention.

The 8.4% incidence of any ROP in the current study and especially the 1.02% incidence of ROP requiring intervention is lower than that reported from various units in our country. This incidence is also lower than the incidence of 13.67% reported in neonates less than 1,800 g from our centre enrolled in 2011–2012.21 It is noteworthy, however, that the enrolled population does not include neonates less than 1,000 g who are at highest risk of developing ROP. Our unit follows adherence to the use of oxygen strictly as per indication and continuous pulse oximetry monitoring in sick neonates, apart from other evidence-based practices.

ROP is preventable to a large extent through modification of certain risk factors. Primary prevention of ROP can be done by preventing preterm births, however, other modifiable risk factors for ROP have also been studied in the existing literature. A systematic review in 2018 identified around 300 articles on ROP analysing various risk factors such as gestational age, birth weight and oxygen requirement being the major factors whereas maternal, obstetric, medical factors and neonatal factors as alternative factors.1 The study from our centre in 2011–2012 reported multiple
gestations, antepartum haemorrhage, blood transfusions, mechanical ventilation, pregnancy-induced hypertension and Apgar at 1 minute to be independently associated with the incidence
of ROP.21 In the present study, independent risk factors found significant on multivariate analysis apart from ineffective KMC include the presence of obstetric complications, asphyxia (need for resuscitation), sepsis, SGA, gestation <30 weeks and higher PEEP requirement in the first 72 hours of life and lack of breastfeeding. A higher PEEP requirement is indicative of higher oxygenation in babies developing ROP.

Meta-analysis on interventions to reduce ROP by Fang et al. included 67 studies enrolling 21,819 infants in their analysis. 22 Lower oxygen saturation targets and aggressive parenteral nutrition reduced any stage ROP. Vitamin A, E, or inositol supplementation and breast milk feeding were found to be beneficial in observational studies. Thus, there is abundant literature on risk factors and ROP prevention,4,14–23 however, none of the published studies till now have studied the effect of KMC on ROP.

KMC is an evidence-based intervention to reduce mortality and morbidity in LBW neonates. Cochrane Review 2016 on 21 studies on KMC including 3,042 infants reports a 40% reduction in mortality, a 65% reduction in sepsis and a 72% reduction in hypothermia by KMC.16 The benefits of KMC in clinical outcomes are mainly by virtue of physiological changes that take place during KMC. Metanalysis of 23 studies by Mori et al. analysed the effect of KMC on heart rate, SpO2 and temperature which revealed the stabilizing effect of KMC on temperature and heart rate.17 Similarly, the effect of KMC on respiratory rate, heart rate, SpO2 and temperature on 265 mother-baby pairs showed improvement in all three parameters over three consecutive days in the hospital.24 The present study finds, in our sample, a statistically significant reduction in any stage ROP in the group undergoing effective KMC of a mean duration of 9 hours per day for three consecutive days during a hospital stay. It also describes the protective effect of KMC on the profile of ROP regarding the stage and zone of ROP as well as ROP requiring intervention, which
has not been reported till date.

In the present cohort, nearly 40% (303/783) of neonates received ineffective KMC (less than 6 hours per day) (median of 3 hours per day and mean of 1.5 hours per day). The inability of timely shifting of stabilized neonates to KMC wards and early discharge due to the unavailability of beds in KMC wards may have affected the duration of KMC in these neonates. Though short sessions are continued in the NICU, unlike the KMC ward absence of the mother’s continuous presence makes it difficult to continue KMC beyond a few hours.

Also, it is noted in the univariate analysis that the ineffective KMC group had a significantly higher number of neonates with asphyxia, sepsis and other factors which are some of the identified risk factors for ROP. These factors, as evidenced by multivariate analysis also, are independent risk factors for developing ROP apart from ineffective KMC, prematurity, SGA and lack of breastfeeding.

The strength of our study is that it is the first study analysing the effect of KMC on ROP. The sample size of 783 neonates who underwent screening for ROP was consistent with varying incidence rates of ROP reported from our country and also from the same institute in past. The target population in the present study, that is, 1,000–1,800g was selected in view of the operational aspect and feasibility of implementation of KMC in this group. The study included 1,000–1,800 g neonates considering the most commonly followed NICU/SNCU admission criteria of 1,800 g, which would make it more generalizable in the country. Various confounding factors were considered in both effective and ineffective KMC groups as well as in ROP and no ROP groups for evaluation. The significant difference in any stage ROP between the two groups (1.04% ineffective vs. 20.1% in ineffective KMC) provides rational conviction to derive reasonable inference despite the low rate of any stage ROP.

Reduction in ROP needing intervention through preventive measures is an important finding for application in resource-limited countries where trained ophthalmologists are scarce to provide laser therapy. Therefore, prevention of severe or ST ROP would prove to be more effective than treating severe ROP. Furthermore, laser therapy is not without its harms and long-term adverse effects, including unfavourable visual acuity, anisometropia and strabismus.25,26 These findings of the added benefit of KMC on reduction in ROP would have a pivotal impact on care provision invarious neonatal units especially in resource-limited countries.

Conclusion

KMC, which is an evidence-based effective intervention to improve the mortality and morbidity of LBW neonates, was significantly associated with the reduction of any stage ROP and ROP needing intervention, thus potentially preventing a significant cause of blindness in childhood. Thus, it is crucial to implement and disseminate this intervention effectively in neonatal centres across the country.

Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Ethical Approval
The study was approved by the Institutional Ethics Committee.

Funding
The authors received no financial support for the research, authorship and/or publication of this article.

Presentation at a Meeting
Pediatric Conference of North India & North India Pediatric Infectious Disease, New Delhi, 2 December 2020.

 

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