Evidence for changing guidelines for routine screening for retinopathy of prematurity.

CONTEXT: Existing guidelines recommended by the Canadian Pediatric Society (CPS) and American Academy of Pediatrics (AAP) for routine screening for retinopathy of prematurity (ROP) remain controversial. OBJECTIVE: To determine whether current guidelines for routine screening for ROP should be changed. DESIGN: We examined data that were collected as part of a larger study of 14 neonatal intensive care units (NICUs) in Canada. We examined the effect of strategies using different birth weight (BW) and gestational age (GA) criteria for routine ROP screening, and performed a cost-effectiveness analysis. SETTING: The 14 NICUs (except one) are regional tertiary level referral centres serving geographic regions of Canada, and include approximately 60% of all tertiary-level NICU beds in Canada. PATIENTS: This large cohort included all 16 424 infants admitted to 14 Canadian NICUs from January 8, 1996, to October 31, 1997. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Treatment for ROP. RESULTS: The most cost-effective strategy was to routinely screen only infants having a BW of 1200 g or less. This included all infants treated for ROP (except 1 outlier at 32 weeks GA and 1785 g BW), at a marginal cost per additional person with improved vision of $513 081 for screening patients between 28 weeks GA and 1200 g BW, compared with$1 800 039 and $2 075 874 for using the current AAP and CPS guidelines, respectively (cryotherapy outcomes). Results for laser therapy were similar, but costs were slightly lower. This strategy reduced the number of infants screened under the current CPS guidelines by 46%. CONCLUSION: Screening only infants having a BW of 1200 g or less is the most cost-effective strategy for routine ROP screening

Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants.

BACKGROUND: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. METHOD: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. RESULTS: VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and ≥32 weeks, AUC 0.50-0.65; ≥1500 g and <32 weeks, AUC 0.60-0.62). CONCLUSION: There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking

Fetal, Infant and Maternal Outcomes among Women with Prolapsed Membranes Admitted before 29 Weeks Gestation

Few studies have examined fetal, infant and maternal mortality and morbidity among pregnant women at very early gestation with an open cervix and prolapsed membranes. We carried out a study describing the outcomes of women hospitalized with prolapsed membranes at 22-28 weeks' gestation.We prospectively recruited women with singleton pregnancies admitted at 22-28 weeks' gestation to tertiary hospitals of the Canadian Perinatal Network between 2005 and 2009. Time-to-delivery, perinatal death, neonatal intensive care unit (NICU) admission, severe neonatal morbidity and severe maternal morbidity were compared between women admitted at 22-25 vs. 26-28 weeks gestation. Logistic regression was used to estimate adjusted odds ratios (AOR) and 95% confidence intervals.129 women at 22-25 weeks gestation and 65 women at 26-28 weeks gestation were admitted to hospital and the median time-to-delivery was 4 days in both groups. Stillbirth rates were 12.4% vs 4.6% among women admitted at earlier vs later gestation (AOR 2.8, 95% CI 0.5-14.8), while perinatal death rates were 38.0% vs 6.1% (AOR 14.1, 95% CI 3.5-59.0), respectively. There were no significant differences in NICU admission and severe morbidity among live-born infants; 89.4% and 82.3% died or were admitted to NICU, (P value 0.18), and 53.9% vs 44.0% of NICU infants had severe neonatal morbidity (P value 0.28). Antibiotics, tocolysis and cerclage did not have a significant effect on perinatal death. Maternal death or severe maternal morbidity occurred in 8.5% and 6.2% of women admitted at 22-25 vs 26-28 weeks (AOR 1.2, 95% CI 0.4-4.2).Perinatal mortality among women with prolapsed membranes at very early gestation is high, although significantly lower among those admitted at a relatively later gestational age. Rates of adverse maternal outcomes are also high. This information can be used to counsel women with prolapsed membranes at 22 to 28 weeks gestation

Mortality and significant neurosensory impairment in preterm infants: an international comparison

Objective: To compare mortality and rates of significant neurosensory impairment (sNSI) at 18-36 months' corrected age in infants born extremely preterm across three international cohorts. Design: Retrospective analysis of prospectively collected neonatal and follow-up data. Setting: Three population-based observational cohort studies: the Australian and New Zealand Neonatal Network (ANZNN), the Canadian Neonatal and Follow-up Networks (CNN/CNFUN) and the French cohort Etude (Epidémiologique sur les Petits Ages Gestationnels: EPIPAGE-2). Patients: Extremely preterm neonates of &lt;28 weeks' gestation in year 2011. Main outcome measures: Primary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness. Results: Overall, 3055 infants (ANZNN n=960, CNN/CNFUN n=1019, EPIPAGE-2 n=1076) were included in the study. Primary composite outcome rates were 21.3%, 20.6% and 28.4%; mortality rates were 18.7%, 17.4% and 26.3%; and rates of sNSI among survivors were 4.3%, 5.3% and 3.3% for ANZNN, CNN/CNFUN and EPIPAGE-2, respectively. Adjusted for gestational age and multiple births, EPIPAGE-2 had higher odds of composite outcome compared with ANZNN (OR 1.71, 95% CI 1.38 to 2.13) and CNN/CNFUN (OR 1.72, 95% CI 1.39 to 2.12). EPIPAGE-2 did have a trend of lower odds of sNDI but far short of compensating for the significant increase in mortality odds. These differences may be related to variations in perinatal approach and practices (and not to differences in infants' baseline characteristics). Conclusions: Composite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.</p

A comparison of strategies for managing the umbilical cord at birth in preterm infants

Objective: to evaluate the rates of practice, and the associations between different cord management strategies at birth (delayed cord clamping [DCC], umbilical cord milking [UCM], and early cord clamping [ECC]) and mortality or major morbidity, rates of blood transfusion, and peak serum bilirubin in a large national cohort of very preterm infants. Study design: we retrospectively studied preterm infants &lt;33 weeks of gestation admitted to the Canadian Neonatal Network between January 2015 and December 2017. Patients who received ECC (&lt;30 seconds), UCM, or DCC (≥30 seconds) were compared. Multiple generalized linear/quantile logistic regression models were used. Results: of 12 749 admitted infants, 9729 were included; 4916 (50.5%) received ECC, 394 (4.1%) UCM, and 4419 (45.4%) DCC. After adjustment for potential confounders identified between groups in univariate analyses, the odds of mortality or major morbidity were higher in the ECC group when compared with UCM group (aOR, 1.18; 95% CI, 1.03-1.35). Mortality and intraventricular hemorrhage were associated with ECC as compared with DCC (aOR, 1.6 [95% CI, 1.22-2.1] and aOR, 1.29 [95% CI, 1.19-1.41], respectively). The odds of severe intraventricular hemorrhage were higher with UCM compared with DCC (aOR, 1.38; 95% CI, 1.05-1.81). Rates of blood transfusion were higher with ECC compared with UCM and DCC (aOR, 1.67 [95% CI, 1.31-2.14] and aOR, 1.68 [95% CI, 1.35-2.09], respectively), although peak serum bilirubin levels were not significantly different. Conclusions: both DCC and UCM were associated with better short-term outcomes than ECC; however, the odds of severe intraventricular hemorrhage were higher with UCM compared with DCC.</p

Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants

Abstract Background Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. Method Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. Results VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81–0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and ≥32 weeks, AUC 0.50–0.65; ≥1500 g and <32 weeks, AUC 0.60–0.62). Conclusion There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking

Intermediate vs. high oxygen saturation targets in preterm infants: a national cohort study

Introduction: optimal oxygen saturation targets remain unknown for extremely preterm infants. Methods: cohort analysis of eligible preterm infants born &lt; 29 weeks gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88 93%) or high (90 95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices. Results: there were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72). Conclusion: for neonates &lt; 29 weeks gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target.</p

Association of 24-Hour in-house neonatologist coverage with outcomes of extremely preterm infants

Objective: this study aimed to assess if 24-hour in-house neonatologist (NN) coverage is associated with delivery room (DR) resuscitation/stabilization and outcomes among inborn infants &lt;29 weeks' gestational age (GA).Study design: survey-linked cohort study of 2,476 inborn infants of 23 to 28 weeks' gestation, admitted between 2014 and 2015 to Canadian Neonatal Network Level-3 neonatal intensive care units (NICUs) with a maternity unit. Exposures were classified using survey responses based on the most senior provider offering 24-hour in-house coverage: NN, fellow, and no NN/fellow. Primary outcome was death and/or major morbidity (bronchopulmonary dysplasia, severe neurological injury, late-onset sepsis, necrotizing enterocolitis, and retinopathy of prematurity). Multivariable logistic regression analysis was used to assess the association between exposures and outcomes and adjust for confounders.Results: among the 28 participating NICUs, most senior providers ensuring 24-hour in-house coverage were NN (32%, 9/28), fellows (39%, 11/28), and no NN/fellow (29%, 8/28). No NN/fellow coverage and 24-hour fellow coverage were associated with higher odds of infants receiving DR chest compressions/epinephrine compared with 24-hour NN coverage (adjusted odds ratio [aOR] = 4.72, 95% confidence interval [CI]: 2.12-10.6 and aOR = 3.33, 95% CI: 1.44-7.70, respectively). Rates of mortality/major morbidity did not differ significantly among the three groups: NN, 63% (249/395 infants); fellow, 64% (1092/1700 infants); no NN/fellow, 70% (266/381 infants).Conclusion: 24-hour in-house NN coverage was associated with lower rates of DR chest compressions/epinephrine. There was no difference in neonatal outcomes based on type of coverage; however, further studies are needed as ecological fallacy cannot be ruled out.Key points: lower rates of DR cardiopulmonary resuscitation with 24h in-house NN coverage. · The type of 24h in-house coverage was not associated with mortality and/or major morbidity.. · High-volume centers more often have 24h in-house neonatal fellow coverage.</p

Association of Weight Changes by Three Days after Birth and Mortality and/or Severe Neurological Injury in Preterm Infants < 29 Weeks Gestational Age: A Multicenter Cohort Study

Objective: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants <29 weeks gestational age (GA). Study design: This multicenter retrospective cohort study employed data from the Canadian Neonatal Network database. The primary outcome was a composite of mortality and/or severe neurological injury. Multivariable quadratic and linear regression models which adjusted for potential confounders were built. Results: A total of 9275 preterm infants (median GA 26, IQR 25, 28 weeks) were included. The optimal weight change range at day three, after adjustment for potential confounders for the primary outcomes, was −15 to −8.9%. Conclusions: There is a ‘U’-shaped relationship between weight change from birth to day three and mortality and/or severe neurological injury. Interventional studies, which target weight loss within the range found in this study and evaluate the impact on neonatal outcomes, are needed to corroborate our findings