A Meta-analysis of the Efficacy of Ocular Prophylactic Agents Used for the Prevention of Gonococcal and Chlamydial Ophthalmia

Neonatorum
Elizabeth K. Darling, RM, MSc, and Helen McDonald, RM, MHSc
Introduction: Neonatal eye prophylaxis has been routine in North America for more than a century. Contextual changes justify reexamining this practice, and prompted a systematic review of the efficacy of prophylactic agents. Methods: We searched MEDLINE (1966–2008), EMBASE (1980–2008), CINAHL (1982–2008), and the Cochrane library (the first quarter of 2008) for relevant clinical trials and hand-searched the resulting reference lists. We independently evaluated eligibility and study quality. Meta-analyses were performed using a random effects model. Results: Each of the eight included studies had substantial methodologic weaknesses. Data to estimate the efficacy of prophylaxis in the prevention of gonococcal ophthalmia neonatorum (GON) were not available. One study found no differences in rates of chlamydial ophthalmia neonatorum (CON) when three agents were compared to no prophylaxis: silver nitrate (relative risk [RR] = 1.06; 95% confidence interval [CI], 0.55–2.02; 2225 newborns), erythromycin (RR = 0.93; 95% CI, 0.48–1.79; 2306 newborns), and tetracycline (RR = 0.82; 95% CI, 0.42–1.63; 2299 newborns). No statistically significant differences were found between agents in the prevention of GON. Erythromycin and povidone-iodine both decrease the risk of CON when compared to silver nitrate (RR = 0.71; 95% CI, 0.52–0.97; 4514 newborns, and RR = 0.52; 95% CI, 0.38–0.71; 2005 newborns, respectively). Discussion: Failure rates of universal eye prophylaxis support reexamination of this policy where the prevalence of maternal infection is low. J Midwifery Womens Health 2010;55:319–327 Ó 2010 by the American College of Nurse-Midwives. keywords: ophthalmia neonatorum, conjunctivitis, bacterial, infant, newborn, prophylaxis, systematic review, antibacterial agents, chlamydia, gonorrhea

INTRODUCTION When neonatal eye prophylaxis was introduced in the late 1800s, it led to a dramatic reduction in gonococcal ophthalmia neonatorum (GON) and prevented many cases of childhood blindness.1 Mandatory neonatal eye prophylaxis was soon legislated in much of North America,2 and it remains a routine part of care to this day in most areas of the United States and Canada. Over the years, the development of antibiotics and other advances in health care have significantly altered the context for this intervention. Most women who receive prenatal care are screened for chlamydia and gonorrhea and are successfully treated with antibiotics before giving birth if they are infected. Likewise, if a newborn develops ophthalmia neonatorum (ON) in a setting with adequate postpartum care, access to antibiotic therapy makes blindness extremely unlikely. Another change was the identification of Chlamydia trachomatis in 1907 and subsequent recognition in the 1930s and 1940s that it can also cause ON.3,4 This infection is much more prevalent in North American

Address correspondence to Elizabeth K. Darling, RM, MSc, Midwifery Group of Ottawa, 700-265 Carling Ave., Ottawa, ON K1S 2E1, Canada. E-mail: ldarling@laurentian.ca

women than gonorrhea (e.g., 543.6 per 100,000 vs. 123.5 per 100,000 in the United States in 2007).5 Chlamydial ON (CON) progresses more slowly than GON and is less likely to cause blindness. In wealthy countries, rates of ON are often extremely low. In the United States in 2002 the rate was 8.5 per 100,000 births.6,7 Several other countries no longer require universal prophylaxis (e.g., Britain, Australia, Sweden, Norway, and Denmark), with some abandoning prophylaxis completely and others offering parental choice.8 In settings where universal prophylaxis has been abandoned, prenatal screening and treatment of sexually transmitted infections along with selective neonatal prophylaxis are used to prevent ON. In Britain, where routine prophylaxis was abandoned in the mid-1950s, no cases of blindness resulting from GON were reported during the first 25 years after this change.8 A crude comparison of the rates of ON in Canada and Britain suggests that routine eye prophylaxis in Canada may have limited impact on the rate of ON.9 Rates of GON and CON in the United Kingdom in 2003 were 3.7 per 100,000 and 6.9 per 100,000, respectively,10,11 while in Ontario, Canada, the combined rate of GON and CON was 4.5 per 100,000 in 2004.12,13 Overall rates of chlamydial and gonorrheal infections were 161.5 per 100,000 and 41.9 per 100,000, respectively, in the United Kingdom in 2003,14
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German. 320 . Canada. and completeness of follow-up data. RESULTS Description of Studies The final literature searches were conducted on January 31. prophylaxis. It was decided a priori that if there were serious concerns about the validity of the results of any of the studies included in the metaanalysis because of other methodologic weaknesses (e. Twenty-three studies were identified in the searches in MEDLINE. a high proportion of participants lost for follow up). the single most comprehensively reported publication was included. but translation was only available for studies published in French. Where multiple publications of the same trial were identified. Articles were independently assessed for inclusion eligibility.17 and Ramirez-Ortiz et al. eight studies were eligible for inclusion in this review.g. and is an Assistant Professor in the Midwifery Education Program at Laurentian University. GON and CON were defined as the presence of ON symptoms plus positive culture. Two of these studies were excluded based on their abstracts. and the evidence from settings where this policy has been abandoned. further secondary analyses would be conducted excluding the studies of concern. Abstracts were eligible for inclusion if a full publication could not be identified through a MEDLINE search or contacting the authors. Responses were obtained from three authors (Fischer and Reta.8. Ontario. Ontario. 2008. Meta-analysis was conducted where possible. and 21 were retrieved for assessment. it seems reasonable to reevaluate the utility of this practice. Studies were eligible for inclusion if GON or CON was an outcome. conjunctivitis. and differences were resolved by consensus. Of the 26 publications retrieved. METHODS Studies were eligible for inclusion if they were randomized or quasirandomized controlled trials. infant. The reviewers then met to compare assessments of study eligibility and methodologic quality. Ontario. ON was defined as conjunctivitis occurring within the first 28 days of life. Statistical analyses were conducted using Review Manager software (v. 4. July/August 2010 Liz Darling is a registered midwife who practices in Ottawa. MEDLINE (1966–January 2008) was searched using the following MeSH terms and textwords: conjunctivitis. A random effects model was used because of its tendency to yield more conservative estimations of treatment effects and wider CIs.9 per 100. A systematic review of the efficacy and safety of agents used to prevent ON was conducted to facilitate one aspect of such an evaluation. respectively. Examination of funnel plots to assess for evidence of publication bias was planned. Outcomes are reported using relative risk (RR) for categorical data. and CINAHL using a similar strategy. Eligible interventions included one or more of the following comparisons: one prophylactic agent applied to the eyes of a newborn at or shortly after birth versus placebo. 4. trachoma.1 per 100.16–35 Four additional studies were identified from the reference lists of retrieved studies. inclusion. cannot tell. no prophylactic agent. Canada. blinding of interventions and outcomes. Helen McDonald is a registered midwife who practices in Hamilton. ophthalmia neonatorum.15 Given the contextual changes since the introduction of neonatal eye prophylaxis.. or a different prophylactic agent. and discharge. in Ontario in 2004. Each author independently assessed methodologic quality using standardized criteria to evaluate randomization. EMBASE. Canada. Reference lists of published systematic and narrative reviews and all included studies were reviewed to identify additional studies. with 95% confidence intervals (CIs).9.D). Canada. Agreement between the authors on evaluation of methodologic quality was assessed using calculations of weighted Kappa for three ordered categories (yes. and EMBASE. No. Copenhagen.40 All together.16 Isenberg et al. She is an Associate Professor in the Midwifery Education Program at McMaster University in Hamilton. She has a Master of Science degree in Health Research Methodology from McMaster University in Hamilton.. swelling.mp.18) and independently considered before comparison of the assessments of study quality. newborn. Attempts to resolve uncertainty about methodology were made by contacting the corresponding authors.mp.and 197. and Swedish. a total of 26 studies were retrieved for assessment. but clarification or additional information was requested from published authors. Both authors independently selected articles for retrieval from a literature search conducted by the primary author (E. allocation concealment. and clinical trial (publication type).K.000 and 28. Double data entry of outcome data was performed by the primary author and verified for accuracy by the second author.36–39 and one additional study was identified from the reference list of an evidence-based guideline on prophylaxis for ON. Study participants were newborns. Ontario. The Nordic Cochrane Center. Unpublished material was not solicited. Language restrictions were not applied to the search. Denmark). The objective of this review is to determine the efficacy of prophylactic agents used to prevent GON and CON and to compare the efficacy of different agents in the prevention of these infections. Many of the ineligible Volume 55. and no). Tests for heterogeneity were performed. Searches were also conducted in the Cochrane Central Register of Controlled Trials (CCRCT). prevention.2. bacterial. and was determined clinically by the presence of symptoms such as redness. the CCRCT.000.

e.34 one was a commentary. reported complete follow up after exclusions. Agreement between the reviewers in the assessment of study quality was good. Journal of Midwifery & Women’s Health  www.26 the majority of newborns did not complete scheduled follow-up appointments. and results of each trial is provided in Table 1. 95% CI.16–18. participants. The usual duration of hospital stay was not reported in most studies. In the remaining studies. Prevention of Chlamydial Ophthalmia Neonatorum Estimates of the efficacy of silver nitrate.03. In Fischer and Reta. it is probable that parents were unaware of the agent received by their newborn. was most vulnerable to bias that might be introduced by seasonal variation in the prevalence of maternal infections.16 a large portion of newborns did not receive their allocated treatment because those administering it disliked how ‘‘messy’’ it was. Secondary analyses excluding trials without true allocation concealment were not possible because all contributing studies were quasirandomized. the eight included trials report the outcomes of more than 26.00–1. Erythromycin.23 One of the included studies was published in French.16–18.26 or monthly37 basis. A summary of the study methods. 0...g. this study was not adequately powered to detect statistically significant differences in this outcome and provides poor quality evidence for such an estimate.. because prophylaxis is often administered outside of their presence.27..11.20.000 newborns.18 Brussieux et al. interventions. outcomes.org Follow Up Incomplete follow up was a significant issue in all trials.30 in their small study of 60 newborns born to mothers who had chlamydia. 0.17 did not schedule follow-up appointments but instead relied on parents to return for assessment if they observed signs of infection.41 Allocation Concealment Hammerschlag et al.. with the mean weighted Kappa for the five different questions being 0. and povidone-iodine are each compared to silver nitrate.38.29 one study did not investigate an eligible intervention. Blinding of some outcome assessment (e.39 Two publications were review articles32. erythromycin.24 and Laga et al. Chen.33.37 Rotation or randomization occurred on a daily. Together. and povidone-iodine is then compared to erythromycin.30 did not report if allocation concealment was achieved. Isenberg et al.25.24–26. but povidone-iodine drops will stain the skin and sclera. Chen37 included a no prophylaxis group but found no cases of GON (4544 newborns). as discussed below. the only observed cases of GON in this study occurred in these untreated newborns. In at least some of the trials. laboratory analysis) may have occurred in the remaining trials but was not reported.37 who used a monthly rotation of treatment.22.. Concealment of treatment allocation was not possible in any of the other trials.24 and the rest were published in English.21. 327 newborns) and between tetracycline and no prophylaxis (RR = 0.17 and Brussieux et al. Fischer and Reta16 did not report follow-up details. Randomization Hammerschlag et al.25and Chen37 did not report the number of participants that returned for scheduled follow-up appointments.8. Comparison of Efficacy: Gonococcal Ophthalmia Neonatorum Table 2 presents comparisons of prophylactic agents with respect to the prevention of GON.36.06.19 translation was not available for two publications (so eligibility could not be fully determined).16 However. Blinding of Outcome Measurement Isenberg et al. 95% CI.40 and the remaining two studies were secondary analyses of included studies.854.35 one study was an observational design.24 described some blinding of the assessment of outcomes.jmwh. which all used quasirandom allocation methods. Losses to follow up tended to occur after newborns were discharged from hospital. tetracycline. ‘‘quasi-random’’ treatment assignment).24 weekly. Efficacy of Neonatal Eye Prophylaxis Prevention of Gonococcal Ophthalmia Neonatorum No trials provided estimations of the efficacy of prophylactic interventions in the prevention of GON based on comparisons with participants assigned to a no prophylaxis group. Analysis based on actual treatment rather than intention to treat found no significant difference in the rate of GON between silver nitrate and no prophylaxis (RR = 0.01–2. In Ramirez-Ortiz et al. Hammerschlag et al.publications were excluded because they did not report GON or CON as an outcome. 214 newborns). Only Hammerschlag et al.06. alternate treatment allocation methods were used (i. and tetracycline in the prevention of CON are only 321 .30 reported that participants were randomized but did not specify the randomization method. Blinding of the Interventions Blinding of the interventions was not described in any trials. Methodologic Quality of Included Studies The included studies all had at least one area of substantial methodologic weakness.31.28. No statistically significant differences were found between these prophylactic agents in the prevention of GON.

silver nitrate.29).53–0. July/August 2010 Table 1. tetracycline vs.93 (0.72 (0.55–2. RR = relative risk. No.66 (0. 1.55) Outcome: CON—tetracycline vs. povidone-iodine. silver nitrate. Kenya Gonococcal ON U U U U U U U No Prophylaxis Chlamydial ON Silver Nitrate Erythromycin Tetracycline 322 Volume 55. 0. 3. no prophylaxis..70 (0. silver nitrate. tetracycline vs.Chloramphenicol Povidone-Iodine Author and Date Ramirez-Ortiz et al.16 1988 Hammerschlag et al. NaN = not a number. 0. 0. Taiwan.57 (0.48–1.05–1.30 1980 U U U U U U N = infinity. erythromycin vs. tetracycline vs. 0.25–1. GON = gonococcal ophthalmia neonatorum.03) Outcome: CON—povidone-iodine vs. WA. a In the comparisons with these results. all newborns born to mothers with chlamydia at the time of birth U U U Hammerschlag et al. 1. interventions rotated weekly RCT. 2. interventions randomly assigned weekly Quasi-RCT....25 1989 U U U U Laga et al.06 (0.37 1992 Quasi-RCT. all newborns born to mothers with chlamydia at the time of birth. RCT = randomized controlled trial. 0. China U U U U U Brussieux et al.. RR = N (NaN–N)a Outcome: GON—RR not possible to calculate (no cases in either group) Outcome: CON—erythromycin vs. silver nitrate. RR (95% CI) Outcome: CON—chloramphenicol vs.27–24. there were no cases in one of the intervention groups. silver nitrate.41).82 (0. silver nitrate.36) Outcome: GON—RR not possible to calculate (no cases in either group) Outcome: CON—erythromycin vs. 0.41–32.57 (0. silver nitrate.27 (0. silver nitrate. no prophylaxis. silver nitrate.73–7. 0.36–1. interventions rotated weekly Participants and Setting 2004 newborns from three rural hospitals in Southern Mexico 3117 newborns in a hospital setting in Kikuyu.26–1.66) Outcome: GON—tetracycline vs.29 (0.72). CI = confidence interval. 0.26 1988 Quasi-RCT. France 230 newborns in a hospital setting in Brooklyn. interventions rotated monthly 4544 newborns in a hospital setting in Taichung. no prophylaxis.51 (0. 2007 Isenberg et al. 4.38–0. 2.24 1991 Quasi-RCT. silver nitrate.19) Outcome: CON—silver nitrate vs. 0. interventions randomly assigned daily Quasi-RCT. silver nitrate.17 1995 18 Methods Quasi-RCT.71). randomization method not specified U U U Fischer and Reta.60–6.. CON = chlamydial ophthalmia neonatorum. Characteristics of Included Studies Interventions Outcomes Summary of Findings. erythromycin vs. secondary analysis reported GON in all 12431 newborns born during the study period (alternating treatments were given to all) 2732 newborns in a hospital setting in Nairobi. 0 (0–NaN)a Outcome: GON—RR not possible to calculate (no cases in either group) U U U U U U U Chen.66 (0.31–1.63). NY. silver nitrate.02).55 (0. Kenya 450 newborns in a hospital setting in northeastern Zaire 60 newborns in a hospital setting in Seattle.79) Outcome: GON—RR not possible to calculate (no cases in any group) Outcome: CON—tetracycline vs.31) Outcome: GON—erythromycin vs. erythromycin vs. interventions alternated weekly 900 newborns in a hospital setting in Saint-Germain-en-Laye. interventions rotated weekly Quasi-RCT.94 (0.42–1. .93) Outcome: GON—povidone-iodine vs.

77. Prophylaxis (either silver nitrate or erythromycin) was then introduced at three hospitals. and in most settings it would now be considered unethical to randomize newborns at risk of acquiring GON to receive no prophylaxis because this intervention is generally accepted as highly effective. 95% CI.97–3.92–6.52–0.77 (0.17 Povidone-iodine vs.26 These findings are in line with the results of a very large prospective before/after observational study conducted in Cape Town.41. 0.93.37 who included a no prophylaxis group. 138 newborns.a RR (95% CI) 2.17 respectively).71. Studies of this size are difficult to conduct. 2306 newborns). 95% CI.85 (0.02. silver nitrate Studies No.94 (0. 323 . respectively). a Random effects model.37 Hammerschlag et al.79.. 2004 newborns). 95% CI.17 Isenberg et al. Erythromycin and povidone-iodine both decreased the risk of CON when compared to silver nitrate (RR = 0. the risk of GON was significantly reduced (RR = 0.a RR (95% CI) 4514 6008 2005 2188 2004 0.17 but there was a nonsignificant trend toward a higher risk of CON when povidone-iodine was compared to chloramphenicol (RR = 1. the trials included in this review provide no high-quality evidence regarding the effect size of prophylactic agents Journal of Midwifery & Women’s Health  www..02–0. Comparison of Efficacy of Various Agents in the Prevention of Gonococcal Ophthalmia Neonatorum Comparison Erythromycin vs.54–1. 95% CI. both silver nitrate and tetracycline led to a significant reduction in GON (RR = 0.19. Studies Hammerschlag et al.38–0.52–0. 2299 newborns). silver nitrate Povidone-iodine vs. vaginal swabs were collected at delivery from historical controls and from mothers of newborns enrolled in the trial.17 No. 95% CI.. 95% CI.17 Povidone-iodine vs.03. When compared to no prophylaxis. povidone-iodine was associated with a nonsignificant trend towards a reduced risk of CON (RR = 0.71 (0.52 (0.07–0.48–1.03) Table 3.60–6.37 Comparison of Efficacy: Chlamydial Ophthalmia Neonatorum Table 3 presents comparisons of prophylactic agents used to prevent CON. erythromycin Isenberg et al.17 Tetracycline vs.37 and RR = 0. chloramphenicol Ramirez-Ortiz et al. 2005 newborns.98) 0. 0.71) 0. In both cases this is related to a lack of adequate power.org in the prevention of GON nor do they provide adequate data to compare the efficacy of the various agents in the prevention of GON. 0. silver nitrate Brussieux et al. 0.. only newborns that were seen for follow-up visits were included. The authors compared rates of infection in exposed newborns in each treatment group with exposed newborns in the historical control group. 0.30 DISCUSSION Gonococcal Ophthalmia Neonatorum There is little doubt that silver nitrate significantly reduced the incidence of GON when it was introduced.22) Chen. 0.54–1. and RR = 0.22.10) 0. South Africa.37 Hammerschlag et al.03) 1. silver nitrate Tetracycline vs.26 compared rates of infection to historical controls.18 CI = confidence interval.004 11.30) 1. 0.. silver nitrate Povidone-iodine vs.18 Secondary analyses were not conducted because allocation concealment was not reported in the one randomized study contributing data to these analyses. RR = relative risk. 0.35–2.52. erythromycin CI = confidence interval.42–1. 2005 newborns).71. available from Chen.30.38–0. 95% CI. When prophylaxis was compared to no prophylaxis.45–1. erythromycin (RR = 0.97–3.29.82.40 During the ‘‘pre-trial’’ period.54 (0. 95% CI. In this study. 2225 newborns). 95% CI.30 Isenberg et al.004 2005 2188 Effect Size. 133 newborns.74. 0.25 Laga et al.06.97) 0. a Random effects model.24 Chen. 4514 newborns17.25. no prophylaxis was being used.17 Povidone-iodine vs. silver nitrate Isenberg et al. None of the interventions made a significant difference in the rate of CON when compared to no prophylaxis: silver nitrate (RR = 1.72 (0. When the prevalence of maternal gonorrhea is low.25 Hammerschlag et al..25 Isenberg et al.55–2. Estimations of the efficacy of various agents in the prevention of GON therefore cannot be determined solely on the data available from randomized participants.25 Isenberg et al. very large numbers of participants are required to show a statistically significant reduction in the incidence of GON. of Participants Effect Size.29) 0.74 (0. Compared to erythromycin.08–6. of Participants 10.07.26 Isenberg et al.70 (0. Comparison of Efficacy of Various Agents in the Prevention of Chlamydial Ophthalmia Neonatorum Comparison Erythromycin vs.17.97. and tetracycline (RR = 0. RR = relative risk.jmwh.63. However. Laga et al.Table 2.17 Hammerschlag et al.

Second. First.32.42 Given the failure rates of prophylaxis.23. and arbitrarily assume that the RR of CON with prophylaxis is 0. 95% CI.4 per 100. Finally.. which may vary from one setting to another. and through potential bias in comparison between intervention groups if there were differences between groups in follow-up rates. Laga et al. these data suggest that prophylaxis fails to prevent CON 23% to 32% of the time. and may also prevent other adverse outcomes for mother Volume 55. 300 newborns. in the United States in 2002.07–0.11–0. 0. There was no significant change in the rate of GON during this time at three midwifery obstetric units where prophylaxis was not introduced (17928 newborns).25—in which all included newborns were born to mothers with known chlamydial infection and received prophylaxis— the overall rates of CON were lower than the rates of infection found in a cohort of newborns whose mothers had chlamydia and did not receive prophylaxis (11–20% vs. However. the finding of no significant reduction in risk does not fit with other available evidence. a newborn might self-inoculate the eye via their hands if the oropharynx is colonized. Cases of GON acquired through contact spread (e.000. prenatal detection and treatment of maternal chlamydia and gonorrhea is ideal.8 Systemic rather than topical antibiotic therapy is recommended for treatment of GON and CON. This review provides fair evidence that both erythromycin and povidone-iodine are significantly more effective than silver nitrate in the prevention of CON. and demonstrated some effect in reducing the risk of CON: when compared to historical controls who received no prophylaxis. including the oropharynx.50. the study was quasirandomized. both silver nitrate and tetracycline led to a significant reduction in CON (RR = 0. the results of this study must be interpreted with caution given the methodologic weakness of the trial. For example. Despite ocular prophylaxis. four of the five newborns that presented with GON during the trial period had inadvertently not received prophylaxis.26 compared trial findings with 324 data from historical controls as described above. Laga et al. Another possible reason for the failure of prophylaxis is that there are other portals of entry for infections during birth.6% in the group without prophylaxis. Estimations of efficacy are impacted by compliance with treatment protocols.80 to detect a 75% reduction in the risk of CON compared to the risk of 1. in Hammerschlag et al.37 This study found that none of the agents significantly reduced the risk of CON. 0.17–0.60.g.6.000. and that the RR of GON is 0. During the before/after study.40 It is possible that with better adherence to treatment protocols. Overall. Note that these assumptions are conservative—they are likely to lead to lower estimations of the number needed to treat when compared to the estimations of the efficacy of prophylaxis from clinical studies. Implications for Practice Parents should be informed of the limitations of eye prophylaxis and should be instructed to report any signs of eye infection. but the reduction is not as substantial as the reduction in the risk of GON. While the sample size of this study had a power of 0. the rate of GON was 1. which logically would not exist if all the agents have no effect.40 Another way of framing these RRs is to say that prophylaxis fails to prevent GON approximately 7% to 19% of the time. via contaminated fingers or towels) have been documented. In other words. 0. respectively). 30530 newborns).95% CI. and RR = 0. No. the effectiveness of prophylactic agents will be higher than the estimates provided by the studies above. very large numbers of newborns will need to be given prophylaxis to prevent a single case of ON. 4. The accuracy of this estimation of effect size is limited by possible bias inherent in a nonrandomly allocated control group.26 noted that three of the cases of GON in newborns who received prophylaxis occurred early in the study when the research nurses were not yet familiar with the technique for applying prophylaxis. suggesting no natural variations in prevalence during the study. and it is not clear how many newborns were seen for complete follow up. 33%).20.05 with prophylaxis. Incomplete follow up in the studies contributing to these findings limits the accuracy of estimations of effect size through possible underestimation of the frequency of outcomes. blinding was not reported. the results of this review show statistically significant differences between different agents in the prevention of CON. 3378 newborns need to receive prophylaxis to prevent one case of CON and 4785 newborns need to receive prophylaxis to prevent one case of GON.7 One might generously estimate the effectiveness of prophylaxis to be slightly better than the estimations from historical control data discussed above. these data suggest that prophylactic agents lead to some reduction in the risk of CON. 312 newborns. While it is plausible that eye prophylaxis is not as effective in the prevention of CON as it is in the prevention of GON. Number Needed to Treat In settings with low rates of maternal gonorrheal and chlamydial infections at birth. 95% CI. July/August 2010 . and the rate of CON was 7. The risks of long-term sequelae from GON or CON are minimal when there is adequate postpartum follow up and prompt access to antibiotic therapy upon diagnosis.1 per 100. Several types of evidence suggest that prophylactic agents do have some effect on reducing the risk of CON. Based on these conditions.8 Chlamydial Ophthalmia Neonatorum Only one of the studies included in this review contributed data to examine how effectively prophylactic agents reduce the risk of CON.46.

When additional evidence is also considered. Despite weaknesses in the available evidence.34 This claim is plausible—a systematic review by the primary author found povidone-iodine to significantly reduce the risk of infectious ON (all causes) when compared to silver nitrate. and a reexamination of this policy is warranted. 0. Settings with high maternal infection rates at birth would be most appropriate. Sex Transm Dis 1996. adverse effects. and most appropriate concentration of povidone-iodine is a priority. because parents have no legal right to refuse prophylaxis in most North American jurisdictions. Proponents argue that it is the most effective agent in the prevention of all causes of infectious ON. 95% CI.131:193–6. povidone-iodine appears to be the best agent for neonatal eye prophylaxis in these settings. the benefits of this information do not warrant the costs of conducting the large high-quality trial that would be required. Future trials should ensure adequately powered sample sizes and prioritize the complete follow up of participants. selection of the most effective method of prophylaxis will be of benefit. 5. with various CIs ranging from 2% to 50% for GON and from 11% to 60% for CON. Budai I. Where maternal infection rates are high. Finally. Atlanta. Taking cost. Thomas Parran Award Lecture. Acta Microbiol Immunol Hung 2007.19 Povidone-iodine has proven antibacterial properties.9 Povidone-iodine may be less acceptable than antibiotic ointment to some parents because it causes temporary staining of the skin and sclera. The history of nongonococcal urethritis. Such analyses should compare the implications of universal prophylaxis with those of alternative strategies for the prevention of GON and CON. Erythromycin is more appropriate than silver nitrate for comparisons with povidone-iodine because erythromycin is more effective than silver nitrate in the prevention of CON. the evidence suggests that current North American laws mandating universal neonatal eye prophylaxis have limited benefit. Tetracycline-resistant gonococci have led to a shift away from use of tetracycline for prophylaxis. 2. Povidone-iodine ophthalmic solutions designed for neonatal use and approved by the US Food and Drug Administration are not yet available in the United States. It is important to understand that neonatal eye prophylaxis has a significant failure rate. 3. REFERENCES 1. but there was inadequate power to confirm a difference when povidone-iodine was compared to erythromycin (RR = 0. it appears that prophylaxis does reduce the risks of both GON and CON. Silver nitrate prophylaxis. 4. Evidence regarding efficacy from this review might inform both economic analyses and risk–benefit analyses that could be used to determine the best approach within a given context. and maternal chlamydial infections are much more prevalent globally than gonorrheal infections.. midwives should familiarize themselves with the legal requirements for prophylaxis in their jurisdiction (e. Chlamydia trachomatis: Milestones in clinical and microbiological diagnostics in the last hundred years: A review. Limitations This analysis was limited to an examination of efficacy and did not explore the safety or cost-effectiveness of prophylactic agents. Can Med Assoc J 1984. Klauss V. Sexually transmitted disease surveillance 2007. and early identification and treatment of newborns infected with either GON or CON will also be necessary to prevent adverse outcomes caused by these infections. Centers for Disease Control and Prevention.70– 1. there is sufficient evidence available such that further trials involving a no prophylaxis group are not warranted.23:86–91.g. and efficacy against both GON and CON into consideration. but povidone-iodine is increasingly used elsewhere. systemic antibiotics are recommended for the newborn. both erythromycin and povidone-iodine are more effective than silver nitrate in the prevention of CON.79:262–6. it is apparent that all prophylactic agents have clinically significant failure rates. Taylor-Robinson D. GA: US Department of Health and Human Services. the evidence supports the universal use of eye prophylaxis.org In settings where the prevalence of maternal gonorrheal or chlamydial infection at birth is high. is inexpensive.86.42 While it may seem reasonable based on the clinical evidence to offer parents an informed choice regarding prophylaxis. Is Crede ´ ’s prophylaxis for ophthalmia neonatorum still valid? Bull World Health Organ 2001. however. Presently. Journal of Midwifery & Women’s Health  www. Schneider G. 2188 newborns). Further research to evaluate the safety. and drug-resistance is not a concern. When there is known maternal gonorrheal infection at the time of birth. Universal prophylaxis will not prevent all cases of ON. erythromycin is primarily the prophylaxis of choice in North America. which are also key considerations in reevaluating the utility of neonatal eye prophylaxis.54:5–22. the state in which they practice).and newborn. Schaller UC. Interpretation of the findings would be strengthened if swabs to detect chlamydia and gonorrhea are collected in labor. 325 .06. and particularly where health care resources are limited.jmwh. efficacy. is used for other ocular purposes. While there is not sufficient evidence to detect statistically significant differences in the efficacy of various agents in the prevention of GON. 2008. Although more accurate estimations of effect size (particularly of erythromycin and povidone-iodine) would be helpful in considering the utility of universal prophylaxis in low-risk settings. Estimates of failure rates are likely inaccurate. CONCLUSION The evidence from randomized and quasirandomized trials regarding the efficacy of prophylactic agents used to prevent GON and CON is not of high quality.

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