Treatment outside the Recommended Guidelines for Retinopathy of Prematurity (ROP): Prevalence, Characteristics, and Issues

International audienceThis study aims to assess the prevalence and characteristics of preterm infants with retinopathy of prematurity (ROP) treated outside the recommended guidelines. In this retrospective monocentric cohort, we included all premature children treated in our department for ROP by laser photoablation or anti-VEGF intravitreal injection. The main outcome was treatment of both eyes for ROP less severe than pre-threshold type 1, treated outside ETROP guidelines. A total of 114 children received treatment for ROP in our department, among whom 32 (28.1%) children received treatment for indications outside the ETROP guidelines for both eyes. The indications outside the guidelines were persistent stage 2 or 3 ROP that showed no evidence of regression after 41 weeks of corrected gestational age (11 children; 34.4%), pre-plus stage (11; 34.4%), difficulties in disease staging (7; 21.9%), type 2 ROP with plus disease (2; 6.2%), and treatment due to logistical difficulties (1; 3.1%; hospitalized in neonatal units hundreds of miles away from our department, with no fundus examination possible in the neonatal unit). To resume, in our cohort, 28.1% of children received treatment for ROP less severe than pre-threshold type 1 both eyes. The main indications for off-label treatment were the persistence of active ROP during follow-up and the presence of pre-plus-stage disease. Our data suggest the need to update ROP treatment criteria to reflect real-life practices. Additional studies are required in order to evaluate the long-term benefits and side effects of treatments outside the recommended indications, and to establish revised treatment guidelines

Treatment Failure of Nosocomial Pertussis Infection in a Very-Low-Birth-Weight Neonate

We describe a case of nosocomial maternal transmission of Bordetella pertussis to a very-low-birth-weight (VLBW) neonate in whom treatment was unsuccessful. This case underscores the need for rapid and sensitive PCR diagnosis in VLBW neonates and in parents with clinical signs of pertussis and suggests that standard treatment may not be appropriate for VLBW neonates

Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach

<div><p>Objective</p><p>Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker.</p><p>Design</p><p>Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%).</p><p>Setting</p><p>Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France.</p><p>Patients</p><p>Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth.</p><p>Intervention</p><p>Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day.</p><p>Main outcome measures</p><p>Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation.</p><p>Results</p><p>Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30), the MED was 2.5mg/kg/day with an estimated mean <i>posterior</i> probability of success of 97.7% (95% credibility interval: 90.3–99.7%). The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24).</p><p>Conclusions</p><p>Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ among neonates. Both gestational and postnatal ages account for these differences but their differential impact on omeprazole doses remains to be determined.</p></div

Staging and distribution of NEC (according to Bell, modified by Walsh).

<p>Staging and distribution of NEC (according to Bell, modified by Walsh).</p

Evolution of NEC in the studied population.

<p>Evolution of NEC in the studied population.</p

Sequential estimation of posterior probabilities of success after the inclusion of each group of three patients in the group of neonates born at less than 32 weeks of gestational age.

<p>Sequential estimation of posterior probabilities of success after the inclusion of each group of three patients in the group of neonates born at less than 32 weeks of gestational age.</p

Efficacy parameters at baseline and 72 (±12) hours after omeprazole initiation.

<p>Efficacy parameters at baseline and 72 (±12) hours after omeprazole initiation.</p

CRP and comparison between groups with and without stricture.

<p>CRP and comparison between groups with and without stricture.</p

Treatment of strictures after contrast study (NEC cases treated medically during the acute phase).

<p>Treatment of strictures after contrast study (NEC cases treated medically during the acute phase).</p