Prophylaxis for Gonococcal and Chlamydial Ophthalmia Neonatorum By Richard B. Goldbloom Prepared by Richard B. Goldbloom, MD, FRCPC1 The term ophthalmia neonatorum applies in this chapter to acute conjunctivitis in the newborn from any cause. In 1979, the Canadian Task Force on the Periodic Health Examination concluded that there was good evidence to support prophylaxis with routine instillation of 1% silver nitrate solution into each eye at birth. Several important developments have occurred over the subsequent years: 1) Other antibiotics, notably tetracycline and erythromycin, have been evaluated as alternative agents for the prevention of gonococcal and chlamydial ophthalmia neonatorum; 2) The importance of Chlamydia trachomatis as a cause of neonatal conjunctivitis has been recognized; and 3) Concern has been expressed regarding the transient chemical conjunctivitis that may occur following instillation of the silver nitrate solution and the possibility that this complication will interfere with parent-infant attachment (“bonding”). The evidence does not demonstrate the superiority of any one prophylactic agent and in 1992<1> the Task Force recommended the use of 1% silver nitrate solution, 1% tetracycline ointment or 0.5% erythromycin ointment, primarily to prevent gonococcal ophthalmia. Separate chapters were prepared on screening for gonorrhea (Chapter 59) and Chlamydial infection (Chapter 60).
In the absence of preventive measures it is estimated that
gonococcal ophthalmia neonatorum will develop in approximately 28%of infants born to women with gonorrhea. Gonococcal conjunctivitis isusually severe, and N. gonorrhoeae can penetrate the intact cornealepithelium and cause microbial keratitis, ulceration and perforation. Maternal gonococcal infection is particularly common in developingcountries, where penicillin-resistant gonococci account for up to 60%of the strains isolated. Infection in such women is often asymptomatic. Since 1981 the rate of reported gonorrhea in Canada (about 230 per100,000) has been steadily decreasing: in 1989 there were 19,110 cases(73 cases per 100,000); 8,421 of the cases involved women aged 15 to59 years. The number of reported cases of penicillinase-producingNeisseria gonorrhoeae (PPNG) infection increased from 591 in 1988 to1,046 in 1989; 92% were reported in Ontario and Quebec.
1 Professor of Pediatrics, Dalhousie University, Halifax, Nova Scotia
In 1989 the Laboratory Centre for Disease Control, Ottawa,
received reports of 55,186 cases of chlamydial infection across Canada(excluding British Columbia and the Yukon Territory). In 1989-90
women aged 15 to 39 years accounted for 34,802 of the cases of
genital chlamydial infection (excluding British Columbia and the
Northwest Territories). Although chlamydial infection became
nationally notifiable in 1990, reporting practices may vary between
provinces and territories. More than 4 million cases of chlamydial
infection occur each year in the U.S., and 155,000 infants are born to
women with cervical infection. At a community health centre inMontreal, 7.1% of women presenting for a routine gynecologicexamination were found to have C. trachomatis infection. Chlamydialinfection can cause pseudomembranous or membranous conjunctivitisin the newborn that may result in conjunctival scarring and cornealinfiltrates. The recorded risk of conjunctivitis in infants born to womenwith C. trachomatis infection has varied from 18% to 50%.
In descending order of frequency, the infectious causes of
ophthalmia neonatorum are C. trachomatis, Staphylococcus, N. gonorrhoeae, Streptococcus, Hemophilus and, rarely, herpes simplexvirus, molluscum contagiosum virus and papilloma virus.
Instillation of 1% silver nitrate solution or antibiotic ointment
(0.5% erythromycin or 1% tetracycline) into the conjunctival sac of thenewborn soon after birth.
The establishment of legal requirements for silver nitrate
prophylaxis was followed by a dramatic reduction in the incidence ofblindness due to gonococcal ophthalmia neonatorum.<2,3> Otheragents have been evaluated in controlled trials of varying design.
In a prospective controlled clinical trial Lund and associates<4>
compared the effectiveness of 1% silver nitrate solution and 0.5%erythromycin ointment in the obstetric units of three hospitals inCapetown, South Africa. In the 13 months before the trial began, whenocular prophylaxis was not practised, the incidence of gonococcalophthalmia neonatorum in the study area was 273 per 100,000 livebirths. Twenty-eight cases of gonococcal ophthalmia neonatorum werediagnosed among 24,575 births during the 13-month pretrial period, ascompared with only five cases among 23,883 births during the12 months after the prophylaxis was introduced (p<0.001). Four of thefive infected infants had inadvertently not received prophylaxis. During
the same two periods the incidence rates of gonococcal ophthalmianeonatorum in three midwife obstetric units that did not practiseocular prophylaxis were unchanged (39 cases in the pretrial period vs. 38 in the trial period).
In a prospective clinical trial,<5> the efficacy of prophylaxis with
silver nitrate drops, tetracycline ointment and erythromycin ointmentwere compared among 12,431 infants born during the study period. Treatment was changed monthly. Gonococcal ophthalmia neonatorumoccurred in one infant in the silver nitrate group, three in thetetracycline group and four in the erythromycin group; thesedifferences were not statistically significant. Seven mothers of theseeight infants had received no prenatal care, and five were drug abusers. The respective risks of gonococcal ophthalmia neonatorum afterprophylactic treatment were 0.03%, 0.07% and 0.1%.
Laga and colleagues<2> compared the efficacy of 1% silver
nitrate drops and 1% tetracycline ointment in a controlled trialinvolving 2,732 newborns in Kenya. The prevalence rate of intrapartumgonococcal infection was 6.4%; the frequency of multiresistant strainswas high. The drugs were alternated every week for 15 months andwere administered within 30 minutes after birth. To evaluate theprotective efficacy of the two regimens mother-infant transmissionrates were compared with those observed in a cohort study at thesame hospital before prophylaxis was given at birth. After the silvernitrate and tetracycline prophylaxis the prevalence rates of gonococcalophthalmia neonatorum were 0.4% and 0.1% respectively (differencenot statistically significant). Attack rates in newborns exposed to N. gonorrhoeae at birth were 7.0% among those who received the silvernitrate and 3.0% among those who received the tetracycline (95%confidence interval: 3.4% to 11.4%). Thus, compared with the ratesamong the historical controls, the incidence of gonococcal ophthalmianeonatorum was 83% lower among infants treated with silver nitrateand 93% lower among those treated with tetracycline. Two factorsmay have contributed to the higher attack rates in the silver nitrategroup. First, three of the five cases of infection occurred during thefirst week of the study, before nurses were fully familiar with thetechnique for applying the silver nitrate drops. Second, a substantialnumber of patients were lost to follow-up: 31% by day 7 and 57% byday 28.
In summary, the available evidence indicates that 1% silver
nitrate solution, 1% tetracycline ointment and 0.5% erythromycin
ointment have comparable efficacy in preventing gonococcal infection.
On the basis of cost estimates and the attack rates reported in the
Kenyan trial, tetracycline is more cost-effective than silver nitrate.
Unfortunately, the only costs considered were those of the antibiotics
used in prophylaxis and treatment. Given this limitation as well as thedifferences in 1) the price and availability of antibiotics or silver nitrate
ampoules; and 2) the prevalence of gonococcal infection and PPNGstrains, these results cannot be generalized to Canada.
The evidence supporting the efficacy of any of the currently
available agents (silver nitrate, erythromycin or tetracycline) inpreventing chlamydial ophthalmia neonatorum is conflicting andinconclusive.<2,5-7>
Chemical Conjunctivitis Due to Prophylaxis
Randomized clinical trials have shown that the use of silver
nitrate in the delivery room decreases eye openness and inhibits visualresponses within the first hour after birth. A comparison of times andplaces indicated that the use of single-dose wax ampoules reduced theaccidental instillation of high concentrations of silver nitrate solution(as a result of evaporation of water). However, in a large case series,silver nitrate instillation (by ampoule, with or without rinsing) withinthe first hour after birth caused conjunctivitis in 90% of infantsbetween 3 to 6 hours of age; the ocular reaction subsided within24 hours in most cases. Topically applied antibiotics resulted inchemical conjunctivitis in less than 10% of cases and compared withsilver nitrate have been associated with a 2.5 to 12-fold reduction inthe incidence of such ocular reactions. This finding is consistent withthe results of controlled trials, but its clinical significance has not beendetermined. The possibility that chemical conjunctivitis after silvernitrate prophylaxis might impair parent-infant bonding, by interferingwith eye contact, was one of the main reasons for introducing a topicalantibiotic ointment. This led to widespread abandonment of silvernitrate prophylaxis in the 1980s in favour of the more expensiveantibiotic ointments.
In a randomized clinical trial Butterfield, Emde and Svejda<8>
compared the effect on bonding of silver nitrate prophylaxis givenimmediately after birth and 1 hour after birth. Although mothers inthe first group noted diminished eye openness it did not alter theirbaby-focused attention or prevent their pleasure and excitement in theinitial encounter. For fathers the increased eye openness associatedwith delayed prophylaxis appeared to encourage more affectionateattention. These observations suggested that there might be somemerit in delaying silver nitrate prophylaxis for a short time after birthbut did not indicate any significant effect on ultimate parent-infantattachment.
The availability of effective ocular prophylaxis for gonococcal
ophthalmia neonatorum does not diminish the importance of prenatal
screening for and appropriate treatment of maternal gonorrheal andchlamydial infection (see Chapters 59 and 60). Indeed, several Westerncountries depend on universal prenatal care and contact tracing rather
than on ocular prophylaxis to prevent gonorrheal ophthalmia. In the
case of chlamydial ophthalmia, prenatal screening currently appears to
offer better prospects for prevention than topical ocular prophylaxis in
The ideal prophylactic agent would be both nontoxic and highly
effective in preventing gonococcal, chlamydial and nongonococcal,
nonchlamydial ophthalmia neonatorum. Since gonococcal ophthalmiaposes the greatest threat to a child’s vision it is generally believed thatthe principal goal of ocular prophylaxis should be the prevention ofgonococcal infection.
The American Academy of Pediatrics and the U.S. Centers for
Disease Control (CDC) recommend administering ointment or dropscontaining tetracycline or erythromycin, or 1% silver nitrate solution,to the eyes of all infants shortly after birth. The CDC and theAmerican College of Obstetricians and Gynecologists recommendobtaining endocervical cultures for N. gonorrheae in all pregnantwomen during their first prenatal visit; a second culture isrecommended late in the third trimester for women at high risk ofacquiring sexually transmitted diseases.
The U.S. Preventive Services Task Force has recommended that
endocervical culture for gonorrhea be performed at the first prenatalvisit in all pregnant women in high-risk categories.<9> Further, anophthalmic antibiotic (erythromycin 0.5% or tetracycline 1%ophthalmic ointment) should be applied topically to the eyes of allnewborns immediately after birth.
Prenatal screening for gonorrheal and chlamydial infections,
particularly among high-risk women, should play a major role in theprevention of ophthalmia neonatorum.
There is good evidence to support the use of universal ocular
prophylaxis for gonococcal ophthalmia, at least in the absence ofuniversal prenatal screening for gonorrhea. Prophylaxis should beadministered as soon as possible (within 1 hour) after birth; 1% silvernitrate solution, 1% tetracycline ointment and 0.5% erythromycinointment are approximately comparable in efficacy.
The occurrence of transient chemical conjunctivitis in some
infants after silver nitrate prophylaxis is a minor disadvantage. The riskcan be reduced to some degree through the use of single-dose
ampoules. Alternatively, tetracycline or erythromycin ointment can beused. Additional considerations in choosing a prophylactic agent areindividual preference, cost and the theoretic possibility that chemicalconjunctivitis due to silver nitrate prophylaxis might adversely affectparent-infant bonding.
There is poor evidence to support the use of neonatal ocular
prophylaxis with any agent for chlamydial ophthalmia neonatorum.
The ideal form of topical prophylaxis would be equally effective
in preventing both gonococcal and chlamydial ophthalmia, free of sideeffects such as chemical conjunctivitis and no more expensive thansilver nitrate. The search for agents that fulfil these criteria is aworthwhile objective for future research.
The literature was identified with a MEDLINE search up to
September 1991, using the following MESH heading: ophthalmianeonatorum.
This review was initiated in March 1990 and recommendations
were finalized by the Task Force in September 1990. A report with afull reference list was published in November 1992 (see reference#1 below).
The Task Force thanks Alexander C. Allen, MD, FAAP, FRCPC,
Peds., Professor of Pediatrics and of Obstetrics and Gynaecology,Dalhousie University, Halifax, NS; Robert A. Bortolussi, MD, FRCPC,Associate Professor of Pediatrics, Dalhousie University, Halifax, NS;Scott A. Halperin, MD, FRCPC, Peds., Associate Professor ofPediatrics and of Microbiology, Dalhousie University, Halifax, NS; andMichael J. Vincer, MD, FRCPC, Peds., Assistant Professor of Pediatrics,Dalhousie University, Halifax, NS, for reviewing the draft chapter andproviding useful comments.
Canadian Task Force on the Periodic Health Examination: Theperiodic health examination, 1992 update: 4. Prophylaxis forgonococcal and chlamydial ophthalmia neonatorum. Can MedAssoc J 1992; 147: 1449-1454
Laga M, Plummer FA, Piot P, et al : Prophylaxis of gonococcaland chlamydial ophthalmia neonatorum. A comparison of silvernitrate and tetracycline. N Engl J Med 1988; 318: 653-657
Laga M, Meheus A, Piot P: Epidemiology and control ofgonococcal ophthalmia neonatorum. Bull World Health Organ1989; 67: 471-477
Lund RJ, Kibel MA, Knight GJ, et al : Prophylaxis againstgonococcal ophthalmia neonatorum. A prospective study. S AfrMed J 1987; 72: 620-622
Hammerschlag MR, Cummings C, Roblin PM, et al : Efficacy ofneonatal ocular prophylaxis for the prevention of chlamydial andgonococcal conjunctivitis. N Engl J Med 1989; 320: 769-772
Hammerschlag MR, Chandler JW, Alexander ER, et al :Erythromycin ointment for ocular prophylaxis of neonatalchlamydial infection. JAMA 1980; 244: 2291-2293
Bell TA, Sandstrom KI, Gravett MG, et al : Comparison ofophthalmic silver nitrate solution and erythromycin ointment forprevention of natally acquired Chlamydia trachomatis. SexTransm Dis 1987; 14: 195-200
Butterfield PM, Emde RN, Svejda MJ: Does the earlyapplication of silver nitrate impair maternal attachment?Pediatrics 1981; 67: 737-738
U.S. Preventive Services Task Force: Guide to ClinicalPreventive Services: an Assessment of the Effectiveness of169 Interventions. Williams & Wilkins, Baltimore, Md, 1989:147-150
MANEUVER EFFECTIVENESS LEVEL OF EVIDENCE RECOMMENDATION <REF> Gonococcal infection:
erythromycin ointment(single-dose ampoules
have comparableefficacy, but evidencefor efficacy of anyagent is inconclusive.
nitrate prophylaxisdoes not significantlyaffect parent-infantbonding.
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