From the Special Care Baby Unit, Royal Hospital, PO Box 1331, CPO Seeb, PC 111, Sultanate of Oman.
Reprint requests: Dr. Arun Kumar Nair, Senior Specialist and Neonatologist, Department of Child Health, Royal Hospital, PO Box 1331, CPO Seeb, PC111, Sultanate of Oman.E-mail: [email protected]

Manuscript received: March 18, 1999;
Initial review completed: June 24, 1999;
Revision accepted: September 14, 1999

Survival of very low birth preterm babies has been a spectacular achievement of the modern era but despite all the advances in the care of preterm babies in the recent years, many a problem afflicting them has not yet been well understood. Necrotising enterocolitis (NEC) continues to remain one area where the etiology still remains elusive. Obviously the problem is multifactorial. The immaturity of the gut of the extreme premature baby is probably the most important basic problem and ischemia of the gut brought about by various stress factors does seem to play the crucial role.

The first case report on the association between the stress of ophthalmological exa-mination and NEC was published in 1973(1). Reports of isolated cases have since appeared in literature from time to time. At the neonatal unit of Royal hospital in Oman, routine screen-ing for retinopathy of prematurity (ROP) is the standard practice in all babies weighing below 1500 g. While cases of NEC have been occur-ring sporadically, the possible association of ROP screening with feed intolerance and NEC was only realized when we reviewed our cases.

A retrospective analysis of all the cases of very low birth weight (below 1500 g) admitted in our unit during a period of two years from January 1995 to December 1996 was done. We had a total of 1403 admissions during this period. Two hundred and twenty of these infants were below 1500 g in birth weight. Eye examination for ROP screening is routinely done for these babies, at about the sixth week of life.

For eye examination the pupils were dilated by the topical administration of the available mydriatics, in appropriate concentration, one hour before the eye examination, after consultation with the Ophthalmologist. The dose used was one drop to each eye and repeated twice at ten minutes intervals. The procedure involved moving the babies into an adjacent darkened room and out of the incubator into an open cot. Retina was visualized using the standard Keeler indirect ophthalmoscope. Lids were retracted by the infant size Barriaquer wire speculum after anesthetizing with topical Novesin (benoxinate Hcl 0.4%). The whole procedure took an average fifteen to twenty minutes after the pupils were fully dilated. No prior sedation was given to the babies. Feeds were withheld one hour prior to the procedure.

For diagnosis and classification of the stages of NEC we use the standard modified Bells’ criteria(2). Pediatric surgical consultation was sought for each case. Conservative management of NEC at our center involves intravenous antibiotic (ampicillin, amikacin and metronida-zole), nil by mouth, and total parenteral nutrition for seven to fourteen days.

We had 41 cases of NEC (stage II or III) during the study period; of these, four developed NEC within 24 h of ROP screening, that is around the sixth week of life. The average age at onset of NEC for the rest of our cases was 12.7 days (range 3 days - 26 days). Doubtful cases (NEC stage I or transient feed intolerance) were excluded from analysis for want of clear cut diagnosis.

Table I summarizes the profiles of the four cases who developed NEC after ROP screening. All the four patients were born to Omani parents. The first three patients were outborn and transferred to our center for intensive care. They had mild respiratory distress which required only nasal CPAP (Continuous Positive Airway Pressure). The second and third case developed PDA (Patent Ductus Arteriosus) in the second week. The former needed two courses of indomethacin while the latter was not treated as the ductus was asymptomatic. The fourth case was born at our hospital and had developed severe respiratory distress syndrome. The baby was treated with artificial surfactant and needed ventilatory support for twelve days. His initial course was complicated by pneumothorax and he needed total parenteral nutrition for fourteen days.

Table I - Profile of the Cases Developing NEC Following ROP Screening

All the four babies were free from any illness, stable, feeding and growing satis-factorily for at least a couple of weeks prior to the eye check. All of them were predominantly on breast milk, multivitamin and iron, with occasional supplementation with preterm formula. All the babies survived and were thriving at follow up except for the first, who has developed severe visual handicap. This baby is now three and a half years old, she is just able to perceive light shown into her right eye and left eye is totally blind. Besides these four cases there were six other neonates during this period who developed feed intolerance transiently which resolved without progressing on to full fledged NEC.

The occurrence of cases of NEC following mydriatic eye drops and ophthalmological examination have been described previously(1). The adverse effects of the drugs used for mydriasis (Cyclopentolate and phenylephrine hydrochloride) in neonates have been reported(1,3,4). It has been shown that there is a significant risk of feeding intolerance following ophthalmological examination of preterm neonates(5). The possible mechanism involves a combination of: (i) The toxic effects of the eye drops (cyclopentolate - parasym-patholytic, atropine like activity on the gut and phenylephrine - sympathomimetic, probably causing splanchnic vasoconstriction) and (ii) the stress of ophthalmological examination itself on the immature gut. It is well known that during examination many of the tiny infants undergo abrupt temperature changes, crying, aerophagia, substantial vagal stimulation and increased intra cranial pressure changes(6).

It has been shown that the incidence of feed intolerance can be reduced significantly by withholding feeds for two hours before and four hours after the eye examination(7). Other measures suggested in literature to reduce the toxic effects of the drugs include: (a) Use of only one drop of cyclopentolate in each eye with or without phenylephrine hydrochloride and repeating the dose only once if satisfactory pupillary dilatation has not occurred, as judged by the examining ophthalmologist; (b) Direct pressure on the puncta of the nasolacrimal ducts, to prevent the drug trickling down into the nostrils and subsequently getting absorbed through the nasal mucosa; (c) Dripping in a way such that the drug flows from the medial to the lateral corner of the eye and mopping up the excess drug along with tears if any, soon after instillation(4); (d) To restrict the concentration of the drugs - Cyclopentolate to 0.5% and phenylephrine to 2.5%; (e) Use of microdrops (5 microliters) instead of the standard (26 microliters)(8); and (f) Use of tropicamide 0.5% instead of cyclopentolate along with phenylephrine 2.5%(9).

We have looked into the various possible reasons for the occurrence of NEC follow- ing eye examination in our patients. We had problems with regular supply of ideal eye drops; different preparations were available during the study period, the concentrations of the drug used also varied and at times the drugs had to be prepared and diluted to the required con-centration in our hospital pharmacy. However every time ophthalmologist had been consulted before the instillation of the drops and quality check was performed as per the protocols by the pharmacist whenever dilutions had to be made. Although no direct causal relationship between the eye examination and NEC can be proven in these cases but the temporal sequence of events and the fact that all of them were hemo-dynamically stable, feeding and apparently thriving well at least two weeks prior to the eye examination give credence to our observation that the process of eye examination did indeed play a significant role in the etiology of NEC.

This case series demonstrates the hazards involved in the eye examination of tiny preterm babies and emphasizes the need for strict adherence to the safety precautions.

Contributors: AKN was chief investigator who initiated the study, collected the data and drafted the manuscript. MGP and DDC were involved in the literature search and management of the subjects during their illness. (SMK) was overall incharge, guided the preparation of the manuscript and overall design of the study.

Funding : None.
Competing interests: None stated.

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3. Borromeo-McGrail V, Borduik JM, Keitel H. Systemic hypertension following ocular adminis-tration of 10% phenylephrine in the neonate. Pediatrics 1973; 51: 1032-1036.

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