The use of biomarkers to stratify surgical care in women with ovarian cancer: Scientific Impact Paper No. 69 May 2022.

Biomarkers may offer unforeseen insights into clinical diagnosis, as well as the likely course and outcome of a condition. In this paper, the focus is on the use of biological molecules found in body fluids or tissues for diagnosis and prediction of outcome in ovarian cancer patients. In cancer care, biomarkers are being used to develop personalised treatment plans for patients based on the unique characteristics of their tumour. This tailoring of care can be used to pursue specific targets identified by biomarkers, or treat the patient according to specific tumour characteristics. Surgery is one of the core treatments for ovarian cancer, whether it is offered in primary surgery or following chemotherapy in delayed surgery. Biomarkers already exist to guide the treatment of tumours with chemotherapy, but very little research has determined the value of biomarkers in tailoring surgical care for ovarian cancer. Such research is required to identify new biomarkers and assess their effectiveness in a clinical setting as well as to help identify specific tumour types to guide surgery. Biomarkers could help to determine the success of removing the disease surgically, or help to identify tumour deposits that persist after chemotherapy. All of these aspects would improve current practice. This Scientific Impact Paper highlights research that may pave the way towards bespoke surgery according to the biological characteristics of a tumour and aid gynaecological oncologists to provide surgical treatment according to individual need, rather than a blanket approach for all.

Evaluating retinopathy of prematurity screening guidelines for 24- to 27-week gestational age infants.

OBJECTIVE: To determine whether current retinopathy of prematurity (ROP) screening guidelines adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants. STUDY DESIGN: Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants of 24 (0)/7 to 27 (6)/7 weeks gestational age (GA) with consent before delivery were enrolled in 2005 to 2009. Severe ROP (type 1 ROP or treatment with laser, cryotherapy or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed the then current AAP (American Academy of Pediatrics) screening recommendations, beginning by 31 to 33 weeks postmenstrual age (PMA). RESULT: One thousand three hundred and sixteen infants were enrolled in the trial. Nine hundred and ninety-seven of the 1121 who survived to first eye exam had final ROP outcome determined. One hundred and thirty-seven (14% of 997) met criteria for severe ROP and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe ROP. PMA at onset was 32.1 to 53.1 weeks. In this referral center cohort, 1.4% (14/997) developed severe ROP after discharge. CONCLUSION: Our contemporary data support the 2013 AAP screening guidelines for ROP for infants of 24 (0)/7 to 27 (6)/7 weeks GA. Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.

Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very low birth weight infants.

OBJECTIVE: Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500 g,VLBWs) with and without blood stream infection (BSI) during their birth hospitalization. STUDY DESIGN: Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4 and 6 months after birth with blood drawn 4 to 6 weeks after third dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with BW groups and other confounding factors identified in the primary study. RESULT: In all, 244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody 0.35 µg ml(-1). CONCLUSION: BSI was not associated with reduced odds of World Health Organization-defined protective PCV7 responses in VLBWs.

Efficacy of phototherapy devices and outcomes among extremely low birth weight infants: multi-center observational study.

OBJECTIVE: Evaluate the efficacy of phototherapy (PT) devices and the outcomes of extremely premature infants treated with those devices. STUDY DESIGN: This substudy of the National Institute of Child Health and Human Development Neonatal Research Network PT trial included 1404 infants treated with a single type of PT device during the first 24±12 h of treatment. The absolute (primary outcome) and relative decrease in total serum bilirubin (TSB) and other measures were evaluated. For infants treated with one PT type during the 2-week intervention period (n=1223), adjusted outcomes at discharge and 18 to 22 months corrected age were determined. RESULT: In the first 24 h, the adjusted absolute (mean (±s.d.)) and relative (%) decrease in TSB (mg dl(-1)) were: light-emitting diodes (LEDs) -2.2 (±3), -22%; Spotlights -1.7 (±2), -19%; Banks -1.3 (±3), -8%; Blankets -0.8 (±3), -1%; (P<0.0002). Some findings at 18 to 22 months differed between groups. CONCLUSION: LEDs achieved the greatest initial absolute reduction in TSB but were similar to Spots in the other performance measures. Long-term effects of PT devices in extremely premature infants deserve rigorous evaluation.

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants.

OBJECTIVES: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18-22 months corrected age in extremely low birth weight infants. METHOD: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 +/- 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18-22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. RESULTS: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. CONCLUSIONS: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18-22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.

Double wall versus single wall incubator for reducing heat loss in very low birth weight infants in incubators.

BACKGROUND: Studies have shown improved survival of newborn infants maintained in the thermoneutral range. The concept of an incubator with additional insulation, a double plexiglass wall, is appealing for very low birth weight infants as it may help to provide a thermoneutral environment. OBJECTIVES: To assess the effects of double walled incubator versus a single wall incubator on insensible water loss, rate of oxygen consumption, episodes of hypothermia, time to regain birth weight, duration of hospitalization and infant mortality in premature infants. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - 2006), EMBASE, previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants in all published languages, and CINAHL (1982 - 2006). SELECTION CRITERIA: Only studies using random or quasi-random methods of allocation were considered for this review. Eligible studies assessed at least one of the outcome variables identified as important to this topic. DATA COLLECTION AND ANALYSIS: Independent data extraction and quality assessment of included trials was conducted by the review authors. Data were analyzed using generic inverse variance methodology and weighted mean difference (WMD). Results are presented with 95% confidence intervals. Meta-analysis was undertaken using a fixed effect model. MAIN RESULTS: Three studies met the criteria. Four other studies were excluded, as they did not compare double versus single wall incubators (details of the studies are given in the included and excluded studies section). Double wall incubators have the advantage of decreasing heat loss, decreasing heat production and decreasing radiant heat loss when compared to single wall incubators. There is also the advantage of reduced oxygen consumption. A minimal increase in conductive heat loss was noted when compared to single wall incubators. All of these effects are small and do not support the proposition that double wall incubators have a beneficial effect on long term outcomes including mortality or the duration of hospitalization. AUTHORS' CONCLUSIONS: Although it appears that caring for extremely small infants in double wall incubators may theoretically result in shorter hospitalization and may have metabolic advantages, this review was unable to find any data in the literature to support or refute this hypothesis. The studies do not provide any evidence that the small decrease in heat loss improves clinical outcome. Therefore, the available data is insufficient to directly guide clinical practice.

Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum.

BACKGROUND: Controversy exists over whether or not Ureaplasma urealyticum colonization or infection of the respiratory tract contributes to the severity of chronic lung disease (CLD), a major cause of morbidity and mortality in preterm infants. OBJECTIVES: To evaluate the efficacy and safety of prophylactic or therapeutic erythromycin in preventing chronic lung disease in intubated preterm infants with unknown U. urealyticum status or proven positivity. SEARCH STRATEGY: Searches were done of MEDLINE (1966-June 9, 2003), EMBASE (1980-May 5, 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), previous reviews including cross-references, and abstracts of conference proceedings (Pediatric Academic Societies 2000-2003, American Thoracic Society 2001-2003). There were no language restrictions. Expert informants were contacted. SELECTION CRITERIA: Randomized or quasi-randomized studies comparing either prophylactic or therapeutic administration of oral or intravenous erythromycin (regardless of dose and duration) versus no treatment or placebo among intubated preterm infants <37 weeks and <2500 grams with either unknown U. urealyticum status or proven positivity by culture or polymerase chain reaction. DATA COLLECTION AND ANALYSIS: Data were extracted by all of the authors independently and differences were resolved by consensus. Treatment effects for categorical outcomes were expressed as relative risk, with 95% confidence intervals. MAIN RESULTS: Two small controlled studies, both involving intubated babies <30 weeks gestation, were eligible for inclusion. Lyon 1998 tested prophylactic erythromycin in babies whose U. urealyticum status was unknown at the time of initiation of treatment. Jonsson 1998 tested erythromycin in babies known to be culture positive for U. urealyticum. Neither trial showed a statistically significant effect of erythromycin on CLD, death or the combined outcome CLD or death. Because the two studies differed importantly in their design, the results were not combined in meta-analyses. No adverse effects of a 7-10 day course of erythromycin were reported in either study. REVIEWER'S CONCLUSIONS: Current evidence does not demonstrate a reduction in CLD/death when intubated preterm infants are treated with erythromycin prophylactically before U. urealyticum culture/PCR results are known or when Ureaplasma colonized, intubated preterm infants are treated with erythromycin. However, a true benefit could easily have been missed with the small sample sizes in the two eligible studies. The studies were greatly underpowered to detect uncommon adverse effects such as pyloric stenosis. Additional controlled trials are required to determine whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated preterm infants.

Do urinary levels of vascular endothelial growth factor predict proliferative retinopathy?

PURPOSE: Vascular endothelial growth factor (VEGF) is elevated in the vitreous of patients with proliferative retinopathies (PR). Angiogenic factors like VEGF are elevated in the urine of subjects with cancers, including those distant from the genitourinary tract. We hypothesized that local increases in VEGF in the vitreous would be reflected in the urine of subjects with PR. METHODS: Urine samples were collected from adults with absent, mild, or severe (requiring laser photocoagulation) PR. VEGF was measured by enzyme linked immunosorbent assay. RESULTS: Of 42 subjects, 16 had no PR and 26 had PR (8 mild, 18 severe). Thirty subjects had diabetes mellitus; 24 of these had PR. Subjects with PR were older than controls. Subjects with PR tended to have higher urinary VEGF (median 123 pg/ml Cr, range 3--1738) than controls without PR (median 93 pg/ml Cr, range 2--200) (p = 0.08). None of 16 controls, but 11/15 subjects with PR had >200 mg VEGF/mg Cr (p = 0.003), yielding high specificity (100%), but poor sensitivity (42%) of elevated urinary VEGF for PR. Urinary VEGF was also modestly correlated with urinary protein excretion (r(2 ) = 0.23). Correction of VEGF values for urinary protein abrogated any correlation with PR. CONCLUSIONS: Urinary levels of VEGF are associated with PR, but this relationship may be caused by concurrent renal diseases that result in proteinuria and/or renal VEGF production. The insensitivity of the association may preclude its use in screening to avoid eye examinations.

Early light reduction for preventing retinopathy of prematurity in very low birth weight infants.

BACKGROUND: Retinopathy of prematurity (ROP) causes vision loss in many premature infants each year, despite the advances being made in treatment. In the search for ways to prevent the disease altogether, the exposure of the retina to bright ambient light following premature birth has been a natural hypothesis, since the premature infant normally would be in the dark in-utero environment. Several controlled studies have now addressed this theory. OBJECTIVES: To answer the question: "Among very low birth weight infants, what is the effect of reducing early environmental light exposure on the incidence of any "Acute ROP", or "Poor ROP Outcomes"? SEARCH STRATEGY: Searches were made of the Cochrane Neonatal Group Register of Controlled Trials, Medline, EMBASE, the Cochrane Library, previous reviews including cross references, abstracts, conference and symposia proceedings, and expert informants. The search terms used were [retrolental fibroplasia or retinopathy of prematurity] and [light or light/ae or lighting or lighting/ae or light/tu or lighting/st]. This search was updated as of November 2000. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that reduced light exposure to premature infants within the first 7 days following birth were considered for this review. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes including any Acute ROP and Poor ROP Outcome were excerpted by both reviewers independently and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Data from four recent randomized trials, and one much older quasi-randomized trial failed to show any reduction in Acute ROP, or Poor ROP Outcome with the reduction of ambient light to premature infants' retinas. The number of infants studied to date allows 95% confidence that IF there were a true difference being missed, it would be smaller than 7 percentage points on a background of 54% of all infants under 2 kg developing ROP. REVIEWER'S CONCLUSIONS: Decreasing retinal ambient light exposure in premature infants is very unlikely to reduce the incidence of ROP.

D-Penicillamine for preventing retinopathy of prematurity in preterm infants.

BACKGROUND: Retinopathy of prematurity remains a common problem. A low rate of this disorder was unexpectedly observed among infants treated with intravenous d-penicillamine to prevent hyperbilirubinemia. This observation led to the investigation of its use to prevent retinopathy of prematurity. OBJECTIVES: To answer the question: Among very low birth weight infants, what is the effect of prophylactic administration of d-penicillamine on the incidence of acute ROP or severe ROP, and side effects including death? SEARCH STRATEGY: Searches were made of multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. The search was updated to November 2000. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that administered d-penicillamine to infants less than 2000g birth weight within the day following birth were considered relevant to this review. Additional case series were examined for potential side effects. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes were excerpted by 3 reviewers independently, and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Two randomized trials on the effects on ROP were identified. When combined, they showed a significantly lower incidence of acute ROP in the treated infants, relative risk of 0.09, 95% CI [0.01,0.71]. Severe stages of ROP could not be analyzed. There was no effect on death rates, relative risk 0.99 95% CI [0.70,1.39]. No side effects were reported, and follow up at one year revealed no significant differences in spasticity or developmental delay, although there were more rehospitalizations among the controls. In other reports of using d-penicillamine in over 140 infants for hyperbilirubinemia, skin rashes were reported in 2 infants and one had vomiting that may have been related. REVIEWER'S CONCLUSIONS: D-penicillamine is unlikely to affect survival, and may reduce the incidence of acute ROP among survivors. Studies to date justify further investigation of this drug in a broader population; careful attention to possible side effects is needed.

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial.

PURPOSE: To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION: Cryotherapy for ROP. MAIN OUTCOME MEASURES: Cycloplegic Refraction METHODS: The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS: At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS: In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapy's preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.

Severity of neonatal retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. METHODS: Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). RESULTS: Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. CONCLUSION: Severity of neonatal ROP seems to be a marker for functional disability at age 5. 5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Using cluster analysis of alcohol use disorders to investigate 'diagnostic orphans': subjects with alcohol dependence symptoms but no diagnosis.

The purpose of this paper is to examine the characteristics of community subjects with one or two alcohol dependence symptoms who did not satisfy the criteria for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol dependence or abuse (sub-diagnostic group or diagnostic orphans). Variables not included in the DSM-IV alcohol abuse and dependence criteria are used to compare the different alcohol statuses. The results indicate that the sub-diagnostic group 'diagnostic orphans' formed a cluster distinct from that of the non-problem drinkers group, and appeared to be closer to those with alcohol abuse than to those with alcohol dependence. The diagnosis of DSM-IV alcohol dependence (with three, four, or five or more symptoms) appeared to be its own entity. The findings lend credence to the requirement of three symptoms (in any 12 months) for the diagnosis of alcohol dependence in DSM-IV. However, those with one or two symptoms of alcohol dependence should be considered along with alcohol abuse as an entity in future DSM classifications.

Substance dependence and other psychiatric disorders among drug dependent subjects: race and gender correlates.

Persons in drug treatment with drug dependence were interviewed with the NIMH Diagnostic Interview Schedule to ascertain DSM-III-R disorders. Lifetime prevalence rates were 64% for alcohol dependence, 44% for antisocial personality disorder (ASPD), 39% for phobic disorders, 24% for major depression, 12% for dysthymia, 10% for generalized anxiety disorder, 3% for panic disorder, 3% for mania, 3% for obsessive compulsive disorder, 2% for bulimia, 1% for schizophrenia, and 1% for anorexia. When stratified by race and age, significant main effects were seen, but there were no significant interactions except in "any non-substance disorder" and in the mean number of non-substance use disorders. Caucasians had a higher mean number of drug dependence disorders and higher overall rates of "any other" disorder than African-Americans, and Caucasians and males had higher mean numbers of non-substance use disorders than African-Americans and females, respectively. This was related to rates of alcohol, cannabis, and hallucinogen dependence, and ASPD rates that were higher among men than women and higher among Caucasian respondents than African-American for alcohol, cannabis, hallucinogen, opiate and sedative dependence, major depression, dysthymia, and generalized anxiety disorder. In contrast, women had higher rates than men of amphetamine dependence, phobic disorder, major depression, dysthymia, panic disorder, obsessive compulsive disorder, and mania. African-Americans had higher rates than Caucasians of amphetamine, cocaine, and phencyclidine dependence, but for no comorbid disorders were the rates higher among African-Americans than Caucasians. The differences according to gender in rates of disorders among substance dependent persons are consistent with the results of general population surveys, but the differences in rates according to race are in contrast to these same community surveys. Limitations in the utility of the concept of race as a valid category diminish the generalizability of the findings; however, one possible explanation is differential treatment seeking in African-American and Caucasian populations that would result in the differences seen.

Psychiatric disorders among drug dependent subjects: are they primary or secondary?

The relationship between substance use disorders and comorbid psychiatric conditions was investigated among 425 persons in drug treatment who met DSM-III-R criteria for drug dependence. Using the NIMH Diagnostic Interview Schedule to ascertain DSM-III-R psychiatric disorders among these drug dependent subjects, lifetime prevalence rates were 64% for alcohol abuse/dependence, 44% for antisocial personality disorder, 39% for phobic disorders, 24% for major depression, 12% for dysthymia, and 10% for generalized anxiety disorder. We found that antisocial personality disorder and phobias generally had onsets prior to the onset of drug dependence (that is, they were primary disorders). The majority of drug dependent persons with generalized anxiety disorder reported an onset after the onset of drug dependence (that is, they had secondary generalized anxiety). Alcohol dependence, depression, and dysthymia were divided nearly evenly between earlier (primary disorder) and later (secondary disorder). These results are consistent with the body of literature indicating the importance of antisocial syndromes in the etiology of substance abuse and the literature indicating the complex, varying nature of the relationship of psychiatric disorders to substance dependence. Finally, a precise nomenclature for "age of onset," "primary," and "secondary" was developed for this study that is critical to understanding these issues and is recommended for other studies.

Early light reduction for preventing retinopathy of prematurity in very low birth weight infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To answer the question: "Among very low birth weight infants, what is the effect of reducing early environmental light exposure on the incidence of any "Acute ROP", or "Poor ROP Outcomes"? SEARCH STRATEGY: Searches were made of the Cochrane Neonatal Group Register of Controlled Trials, Medline, EMBASE, the Cochrane Library, previous reviews including cross references, abstracts, conference and symposia proceedings, and expert informants. The search terms used were [retrolental fibroplasia or retinopathy of prematurity] and [light or light/ae or lighting or lighting/ae or light/tu or lighting/st]. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that reduced light exposure to premature infants within the first 7 days following birth were considered for this review. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes including any Acute ROP and Poor ROP Outcome were excerpted by both reviewers independently and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Data from four recent randomized trials, and one much older quasi-randomized trial failed to show any reduction in Acute ROP, or Poor ROP Outcome with the reduction of light to premature infants' retinas. The number of infants studied to date allows 95% confidence that IF there were a true difference being missed, it would be smaller than 7 percentage points on a background of 54% of all infants under 2 kg developing ROP. REVIEWER'S CONCLUSIONS: Decreasing retinal light exposure in premature infants is very unlikely to reduce the incidence of ROP.

D-Penicillamine for preventing retinopathy of prematurity in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To answer the question: Among very low birth weight infants, what is the effect of prophylactic administration of d-penicillamine on the incidence of acute ROP or severe ROP, and side effects including death? SEARCH STRATEGY: Searches were made of multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials that administered d-penicillamine to infants less than 2000g birth weight within the day following birth were considered relevant to this review. Additional case series were examined for potential side effects. DATA COLLECTION AND ANALYSIS: Data on clinical outcomes were excerpted by 3 reviewers independently, and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: Two randomized trials on the effects on ROP were identified. When combined, they showed a significantly lower incidence of acute ROP in the treated infants, relative risk of 0.09, 95% CI [0.01,0.71]. Severe stages of ROP could not be analyzed. There was no effect on death rates, relative risk 0.99 95% CI [0.70,1.39]. No side effects were reported, and follow up at one year revealed no significant differences in spasticity or developmental delay, although there were more rehospitalizations among the controls. In other reports of using d-penicillamine in over 140 infants for hyperbilirubinemia, skin rashes were reported in 2 infants and one had vomiting that may have been related. REVIEWER'S CONCLUSIONS: D-penicillamine is unlikely to affect survival, and may reduce the incidence of acute ROP among survivors. Studies to date justify further investigation of this drug in a broader population; careful attention to possible side effects is needed.

Peripheral retinal ablation for threshold retinopathy of prematurity in preterm infants.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: In premature infants with threshold retinopathy of prematurity (ROP) does peripheral retinal ablation, by any means, reduce the incidence of adverse ophthalmic outcome? SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included a search of the Cochrane Neonatal Group Register of Clinical Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts from pediatric and ophthalmologic meetings, letters and expert informants. Search terms included "Retinopathy of Prematurity" [MeSH Terms], "Retrolental Fibroplasia" [All Fields] and "Lightcoagulation" [All Fields] or "Cryosurgery" [All Fields]. In addition, a personal bibliographic database was used as a cross-reference. SELECTION CRITERIA: All trials in human premature infants with threshold ROP utilizing random or quasi random allocation to either peripheral retinal ablation of the avascular retina, by any means, or concurrent control group with independent outcome assessment were initially selected for review. Following methodologic review, only studies using random allocation were selected for data extraction. DATA COLLECTION AND ANALYSIS: Relevance and validity were assessed by the two authors and consensus reached. Each author extracted clinical outcomes from valid reports independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Two randomised trials were identified. Data from these studies show that peripheral retinal ablation reduces the risk of (1) early unfavorable retinal structure from 47. 9% to 28.1% (absolute risk reduction 19.8% [95% CI 27.9 - 11.8%]), (2) unfavorable retinal structure in early childhood from 44.3% to 26.3% (absolute risk reduction 18% [95% CI 27.0 - 9.1%]) and (3) unfavorable visual acuity in early childhood from 63% to 50.6% (absolute risk reduction 12.2% [95% CI 21.2 - 3.1]). In addition, visual fields in sighted eyes were slightly smaller in the treated (51.3 degrees +/- 11.8 degrees ) group as compared to the control (58.2 degrees +/- 14.5 degrees ) group. REVIEWER'S CONCLUSIONS: Peripheral retinal ablation reduces the incidence of adverse ophthalmic outcome in premature infants with threshold ROP. In sighted eyes, peripheral retinal ablation may reduce the size of the visual field. At this stage, long term outcomes remain unknown.