EFFECT OF HUMAN MILK ON DEVELOPMENT OF RETINOPATHY OF PREMATURITY.
Keywords: Formula milk, Human milk, Preterm babies, Retinopathy of prematurity.
Prematurity is defined as birth of babies before completed 37 weeks of gestation1. The preterm birth rate varies among developing and developed countries. It ranges from 5% in European countries to 18% in Malawi. In Pakistan preterm birth rate has been estimated as 15.8%2,3.
Premature infants may develop complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotising enterocolitis, intraventricular haemorrhage, hyper-bilirubinemia, patent ductus arteriosus and retinopathy of prematurity (ROP)4.
ROP is a preventable and treatable vascular proliferative disorder affecting immature retina in preterm babies. Prematurity, low birth weight, high flow oxygen therapy, inappropriate nutritional supplemen-tation, all contributes to the pathogenesis of ROP5,6. Neonates with ROP may develop visual complications including refractive errors, blind-ness, strabismus, visual field defects and abnor-mal colour vision7.
ROP prevalence varies, according to the availability of resources, from 5-8% in developed countries to 30% in developing countries8. Sohaila et al9 from Pakistan reported incidence of ROP in premature babies as 10.5% and in urban Punjab ROP incidence was reported as 24.6%10.
The risk factors which are associated with ROP are not fully understood, but prematurity, low birth weight and immature retina are the major risk factors. Other risk factors are oxygen administration, congenital heart disease, acidosis, anemia, septicemia and blood transfusions.
Human milk may protect against the development of ROP due to the antioxidant11 and immuneprotective12 properties of human milk. Human milk contains vitamin C, E, and b-carotene and has greater antioxidant properties as compared to formula13,14. In addition to antioxidant component of human milk it also contains some of immunomodulatory substances like secretory immunoglobulin A, lactoferrin, cytokines, lyzozymes and some cellular compo-nents14,15. These components influence immune system of babies and this may be the explanation for the lower risk of necrotizing enterocolitis (NEC) and septicaemia in breast fed babies and hence indirectly protect the development of retinopathy of prematurity16,17.
Pakistan is a developing country and because treatment and screening programs for ROP are not well developed and no large multicentre studies have been conducted, so exact incidence of ROP in Pakistan is not estimated. Moreover factors which may have protective role are not studied. Based on this review, we planned to conduct the study to determine the protective effect of human milk for the development of retinopathy of prematurity. This study will help in streng-thening the guidelines for earliest initiation of human milk in premature babies to prevent ROP and blindness in survivors.
PATIENTS AND METHODS
This observational study was conducted in the department of paediatrics King Edward Medical University Lahore (KEMU) from February 2016 to December 2016 after approval by Institutional Review Board.
An informed consent was taken from the parents. Neonates with birth weight <2.5kg and 60% of feed from mother, Formula fed group included those with exclusive formula feeding or >60% feed of formula milk.
Eye examination was performed minimally at 4 weeks of life and then serially according to eye examination findings by trained ophthal-mologist. Before the examination, eye drops containing 1% tropicamide and 0.5% pheny-lephrine were instilled three times (5 minute apart) to dilate the pupils. Indirect ophthalmo-scopy with indentation was performed using a binocular indirect ophthalmoscope. All examina-tion results were recorded using a predesigned form.
Data were analysed through SPSS 20.0. Quantitative variables (age, gestational age, maternal age, birth weight, duration of mecha-nical ventilation and duration of oxygen therapy) were presented as mean +- S.D and qualitative variables (sex, mode of delivery, socioeconomic status, type of feeding, stages of retinopathy) were presented as frequency and percentages. The chi square test was applied to determine the effect of breast milk for the development of ROP.
Table-I: Demographic characteristics of study population (n=142).
Variables###Categories###Frequency (% age)
###Lower class###135 (95.1%)
###Middle class###7 (4.9%)
Mode of delivery
Mechanical ventilation###15 (10.6%)
###Human milk###84 (59.2%)
###Formula milk###58 (40.8%)
###Stage I###1 (0.007%)
###Stage II###2 (0.01%)
Stages of ROP###Stage III###3 (0.02 %)
###Stage IV###2 (0.01%)
###Stage V###1 (0.007%)
Table-II: Comparison of ROP in relation to feeding pattern (n=142).
###Any stage ROP
Type of feed
The study population consisted of 142 preterm newborns. Mean age at the time of enrol-ment was 11.22 +- 16.48 days. Mean gestational age was 33.1 +- 13.06 weeks and 69% babies were born at >32 weeks of gestation. There was male predominance with 86 (60.6%). Mean birth weight recorded was 1.7 +- 0.43 kilograms. Among total cases, 135 (95.1%) belong to poor socioeconomic status and 7(4.9%) were of middle class status. Regarding mode of delivery, 95 (66.9%) were delivered by spontaneous vaginal delivery (SVD) and 47 (33.1%) were born by C section. Changes compatible with ROP were found in 9 (6.3%) cases. Among ROP cases, one baby had stage I disease, 2 babies had stage II disease, 3 cases were of stage III, 2 cases of stage IV and one case was in stage V disease (table-I). Mean duration of oxygen therapy was 3.7 +- 3.79 days.
Babies were assessed regarding type of feeding. Out of total 142 cases, 84 (59.2%) babies were on human milk and 58 (40.8%) babies were taking formula milk. Mean weight of babies with ROP was 1.2kg (range 0.8-1.8kg) and mean gestation age of these cases was 31.5 weeks (range 27-36 weeks). Five cases of ROP were born at <32 weeks of gestation. Among human milk fed, 3 babies (3/84 = 3.57%) developed ROP and in formula fed babies, 6/58 (10.3%) developed changes of ROP. Thus, the risk of developing ROP was higher in formula milk fed babies compared to human milk feeding babies. However this observation was not statistically significant (p-value=0.103).
ROP is a multifactorial disease and risk factors like oxygen therapy, prematurity and low birth weight are associated with its pathogenesis. The frequency of ROP in our study was lower as compare to Khalid et al18, this observation may be due to inclusion of preterm less than 37 weeks in our study. Our study was conducted to deter-mine whether human milk is protective against development of ROP. Our results are comparable to the findings from meta-analysis by Zhou et al19 that breast feeding potentially plays a strong role in protecting preterm babies from any stage and severe ROP. Manzoni et al20 and Ginovart et al21 observed that exclusive breast feeding is associa-ted with lower rate of ROP. Maayan-Metzger et al22 and Okamoto et al23 detected lower incidence of ROP in preterm born between 24-28 weeks who were breast fed but authors found no differences among infants born before gestational week23.
Porcelli et al24 reported that extremely low birth weight infant who received breast milk in second week of life but not on 4th week of life, were at lower risk of ROP, suggesting that earlier intake of breast milk is associated with lower risk of ROP. However, our study did not address the difference between early and late feeding.
The results from our study favour the protec-tive role of human milk for the development of ROP. In contrast, infants in study by Keraan et al25 who were exclusively breast fed were more likely to develop ROP. This finding is unusual but is not justified by the authors in their circumstances. Our findings are not favouring this observation.
To summarize, in this study, we have attempted to fill some of the gaps in our local population. If breast feeding does lower the risk of development of ROP then it is more likely to be effective when infants are expose to high level of oxidant stress and at that time antioxidant component of human milk protect retina from injury. Our findings suggest a protective effect of human milk for the development of ROP. However, there are conflicting reports regarding effect of breast feeding with the development of ROP. Possible sources of variations include the gestational age, age of initiation of enteral feeding and amount of breast milk fed to infant.
The study was limited to one tertiary care centre with limited sample size. Furthermore, the medical benefits of breast milk and routine recommendation of breast milk as preferred feeding for the preterm infants limited this study as observational study instead of randomized trial. Long term follow up was not made for visual dysfunction. If it would have been done, the results might have been different.
The frequency of retinopathy of prematurity was 6.3%. Although human milk protect the preterm babies from development of retinopathy of prematurity, but the protective effect was statistically not significant.
The authors are thankful to the parents of preterm newborns who volunteered for the study. The authors also acknowledge the contri-bution of residents and staff who cooperated in conducting this study.
CONFLICT OF INTEREST
This study has no conflict of interest to declare by any author.
1. Oza S, Lawn JE, Hogan DR, Mathers C, Cousens SN. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013. Bull World Health Organ 2015; 93(1):19-28.
2. Stoll BJ, Hansen NI, Bell EF. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126(3): 443-56.
3. Blencowe H, Cousens S, Oestergaard M, Chou D, Moller AB, Narwal R, et al. National, regional and worldwide estimates of preterm birth. Lancet 2012; 379(9832): 2162-72.
4. Waldemar A. Carlo. The high risk infants. In: Kliegman RM, StGeme JW, Schor NF. Nelson Text book of Paediatrics. 20th ed. Philidilphia: Elsevier; 2016: 818-31.
5. Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med 2012; 367(26): 2515-26.
6. Hellstrom A, Smith LE, Dammann O. Retinopathy of prematurity. Lancet 2013; 382(9902): 1445-57.
7. Blencowe H, Lawn JE, Vazquez T, Fielder A, Gilbert C, et al. Preterm associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. Pediatric Research 2013; 74: 35-49.
8. Gergely K. Gerinec A. Retinopathy of prematurity-epidemics, incidence, prevalence, blindness. Bratislavskelekarskelisty 2010; 111(9): 514-7.
9. Sohaila A, Tikmani SS, Khan IA, Atiq H, Akhtar ASM, et al. Frequency of Retinopathy of Prematurity in Premature Neonates with a Birth Weight below 1500 Grams and a Gestational Age <32 Weeks: A Study from a Tertiary Care Hospital in a Lower-Middle Income Country. PLoS ONE 2014; 9(7): e100785.
10. Jamil AZ, Tahir MY, Ayub MH, Mirza KA. Features of retinopathy of prematurityin a tertiary care hospital in Lahore. J Pak Med Assoc 2015; 65(2): 156-58.
11. Cloetens L, Panee J, Akesson B. The antioxidant capacity of milk - The application of different methods in vitro and in vivo. Cell Mol Biol (Noisy-legrand) 2013; 59(1): 43-57.
12. Perrin MT, Fogleman A, Allen JC. The nutritive and immuno-protective quality of human milk beyond 1 year postpartum: Are lactation duration based donor exclusions justified? J Hum Lact 2013; 29(3): 341-49.
13. Elisia I, Kitts DD. Differences in vitamin E and C profile between infant formula and human milk and relative susceptibility to lipid oxidation. Int J VitamNutr Res 2013; 83(5): 311-19.
14. Aycicek A, Erel O, Kocyigit A, Selek S, Demirkol MR. Breast milk provides better antioxidant power than does formula. Nutrition 2006; 22(6): 616-19.
15. L'Abbe MR, Friel JK. Superoxide dismutase and glutathione peroxidase content of human milk from mothers of premature and full-term infants during the first 3 months of lactation. J Pediatr Gastroenterol Nutr 2000; 31(3): 270-74.
16. Herrmann K, Carroll K. An exclusively human milk diet reduces necrotizing enterocolitis. Breastfeed Med 2014; 9(4): 184-90.
17. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364(3): 255-64.
18. Khalid A, Haider AA, Fatima N, Tahira F, Amna, Siddique L et al. Retinopathy of prematurity; An experience at a tertiary care hospital. Pak Pediatr J 2017; 41(2): 97-102.
19. Zhou J, Shukla VV, John D, Chen C. Human milk feeding as a protective factor for retinopathy of prematurity:A Meta-analysis. Pediatrics 2015; 136: e1576-86.
20. Manzoni P, Stolfi L, Pedicino R, Vangarelli F, Mosca F, Pungi L et al. Human milk feeding prevents retinopathy of prematurity in preterm VLBW neonates. Early hum dev 2013; 89: S64-68.
21. Ginovart G, Gich I, Verd S. Human milk feeding protects very low-birth-weight infants from retinopathy of prematurity: a pre- post cohort analysis. J Matern Fetal Neonatal Med 2016; 1-6.
22. Maayan-Metzger A, Avivi S, Eisen IS, Kuint J. Human milk versus formula feeding among preterm infants: short-term outcomes. Am J Perinatol 2012; 29: 121-6.
23. Okamoto T, Shirai M, Kokubo M. Human milk reduces the risk of retinal detachment in extremely low-birthweight infants. PediatrInt 2007; 49: 894-7.
24. Porcelli PJ, Weaver RG. The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants. Early Hum Dev 2010; 86: 391-6.
25. Keraan Q, Tinley C, Horn A. Retinopathy of prematurity in a cohort ofneonates at Groote Schuur Hospital, CapeTown, South Africa. SAMJ 2017; 107: 64-9.
|Printer friendly Cite/link Email Feedback|
|Publication:||Pakistan Armed Forces Medical Journal|
|Date:||Apr 30, 2019|
|Previous Article:||ANALYSIS OF HYPERTENSION PERCEPTION OUTLOOK IN A RURAL HYPERTENSIVE POPULATION: AT THE BASIC HEALTH UNIT LEVEL.|
|Next Article:||POSTMENOPAUSAL BLEEDING - A STRONG INDICATOR OF ENDOMETRIAL CARCINOMA.|