Vasoactive peptides as biomarkers for the prediction of retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major complication in preterm infants. We assessed if plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) serve as early markers for subsequent ROP development in preterm infants <32 weeks gestation. METHODS: Prospective, two-centre, observational cohort study. MR-proANP and CT-proET1 were measured on day seven of life. Associations with ROP ≥ stage II were investigated by univariable and multivariable logistic regression models. RESULTS: We included 224 infants born at median (IQR) 29.6 (27.1-30.8) weeks gestation and birth weight of 1160 (860-1435) g. Nineteen patients developed ROP ≥ stage II. MR-proANP and CT-proET1 levels were higher in these infants (median (IQR) 864 (659-1564) pmol/L and 348 (300-382) pmol/L, respectively) compared to infants without ROP (median (IQR) 299 (210-502) pmol/L and 196 (156-268) pmol/L, respectively; both P < 0.001). MR-proANP and CT-proET1 levels were significantly associated with ROP ≥ stage II in univariable logistic regression models and after adjusting for co-factors, including gestational age and birth weight z-score. CONCLUSIONS: MR-proANP and CT-proET1 measured on day seven of life are strongly associated with ROP ≥ stage II in very preterm infants and might improve early prediction of ROP in the future. IMPACT: Plasma levels of midregional pro-atrial natriuretic peptide and C-terminal pro-endothelin-1 measured on day seven of life in very preterm infants show a strong association with development of retinopathy of prematurity ≥ stage II. Both biomarkers have the potential to improve early prediction of retinopathy of prematurity. Vasoactive peptides might allow to reduce the proportion of screened infants substantially.

Volumetric Capnography at 36 Weeks Postmenstrual Age and Bronchopulmonary Dysplasia in Very Preterm Infants.

OBJECTIVES: To assess the feasibility of volumetric capnography in spontaneously breathing very preterm infants at 36 weeks postmenstrual age (PMA) and its association with clinical markers of lung disease including the duration of respiratory support and bronchopulmonary dysplasia (BPD). STUDY DESIGN: We obtained mainstream volumetric capnography measurements in 143 very preterm infants at 36 weeks PMA. BPD was categorized into no, mild, moderate, and severe according to the 2001 National Heart, Lung and Blood Institute workshop report. Normalized capnographic slopes of phase II (SnII) and phase III (SnIII) were calculated. We assessed the effect of BPD, duration of respiratory support, and duration of supplemental oxygen on capnographic slopes. RESULTS: SnIII was steeper in infants with moderate to severe BPD (76 ± 25/L) compared with mild (31 ± 20/L) or no BPD (26 ± 18/L) (P < .001). The association of SnIII with moderate to severe BPD persisted after adjusting for birth weight z-score, respiratory rate, and airway dead space to tidal volume ratio. The diagnostic usefulness of SnIII to discriminate between infants with and without moderate to severe BPD was high (area under the curve, 0.94; 95% CI, 0.89-0.99). CONCLUSIONS: Volumetric capnography is feasible in spontaneously breathing preterm infants at 36 weeks PMA and reflects the degree of lung disease. This promising bedside lung function technique may offer an objective, continuous physiological outcome measure for assessment of BPD severity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02083562.

Respiratory morbidity in preterm infants predicted by natriuretic peptide (MR-proANP) and endothelin-1 (CT-proET-1).

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major complication in preterm infants <32 weeks. We aimed to assess whether plasma levels of mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET-1) predict respiratory morbidity. METHODS: This was a prospective, two-center, observational cohort study. MR-proANP and CT-proET-1 were measured at day 7 (±2) of life. Associations with duration of supplemental oxygen and the composite outcome of moderate or severe BPD or death (BPD/death) were investigated. RESULTS: Two hundred and twenty-nine infants <32 weeks were included (median gestational age [GA] 29.6 weeks [interquartile range 29.0-30.7], median birth weight 1150 g [IQR 840-1410]). MR-proANP and CT-proET-1 were associated with the duration of supplemental oxygen in univariable analysis (both p < 0.001) but not after adjusting for co-factors. Infants with BPD/death showed higher plasma levels of MR-proANP (623.50 pmol/L [IQR 458.50-881.38] vs. 308.35 pmol/L [IQR 216.72-538.10]; p < 0.001) and CT-proET-1 (255.40 pmol/L [IQR 202.60-311.15] vs. 198.30 pmol/L [IQR 154.70-297.95]; p = 0.015) compared to infants without BPD/death. Levels of both biomarkers were significantly associated with BPD/death in univariable models but not after adjusting for co-factors. CONCLUSIONS: MR-proANP and CT-proET-1 are associated with the duration of supplemental oxygen and the composite outcome BPD/death, but their prognostic value does not complement that of clinical risk factors. IMPACT: Plasma levels of MR-proANP and CT-proET-1, measured on day 7 of life (±2 days) are associated in univariable analyses with duration of supplemental oxygen and the combined outcome of BPD or death in VLGA infants. Associations between both biomarkers and respiratory morbidity do not persist in multivariable models, in particular when gestational age is included. MR-proANP and CT-proET-1 have limited additional value to predict respiratory morbidity in VLGA infants compared to clinical parameters.

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis.

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION: In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN: • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW: • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed.

Bronchopulmonary dysplasia: a predictive scoring system for very low birth weight infants. A diagnostic accuracy study with prospective data collection.

Our aim was to develop and validate a predictive risk score for bronchopulmonary dysplasia (BPD), according to two clinically used definitions: 1. Need for supplementary oxygen during ≥ 28 cumulative days, BPD28, 2. Need for supplementary oxygen at 36 weeks postmenstrual age (PMA), BPD36. Logistic regression was performed in a national cohort (infants born in Switzerland with a birth weight < 1501 g and/or between 23 0/7 and 31 6/7 weeks PMA in 2009 and 2010), to identify predictors of BPD. We built the score as the sum of predicting factors, weighted according to their ORs, and analysed its discriminative properties by calculating the area under the ROC (receiver operating characteristic) curves (AUCs). This score was then applied to the Swiss national cohort from the years 2014-2015 to perform external validation. The incidence of BPD28 was 21.6% in the derivation cohort (n = 1488) and 25.2% in the validation cohort (n = 2006). The corresponding numbers for BPD36 were 11.3% and 11.1%, respectively. We identified gestational age, birth weight, antenatal corticosteroids, surfactant administration, proven infection, patent ductus arteriosus and duration of mechanical ventilation as independent predictors of BPD28. The AUCs of the BPD risk scores in the derivation cohort were 0.90 and 0.89 for the BPD28 and BPD36 definitions, respectively. The corresponding AUCs in the validation cohort were 0.92 and 0.88, respectively.Conclusion: This score allows for predicting the risk of a very low birth weight infant to develop BPD early in life and may be a useful tool in clinical practice and neonatal research. What is Known: • Many studies have proposed scoring systems to predict bronchopulmonary dysplasia (BPD). • Such a risk prediction may be important to identify high-risk patients for counselling parents, research purposes and to identify candidates for specific treatment. What is New: • A predictive risk score for BPD was developed and validated in a large national multicentre cohort and its performance assessed by two indices of accuracy. • The developed scoring system allows to predict the risk of BPD development early but also at any day of life with high validity.

High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity.

OBJECTIVE: Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA. STUDY DESIGN: Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI. RESULTS: In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI. CONCLUSION: HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.

Prediction of ROP Treatment and Evaluation of Screening Criteria in VLBW Infants-a Population Based Analysis.

BACKGROUND: The incidence of retinopathy of prematurity (ROP) and ROP screening criteria differ between countries. We assessed whether ROP screening could be reduced based on the local ROP incidence. METHODS: Observational cohort study of infants born in Switzerland between 2006 and 2015 <32 0/7 weeks. Chronological and postmenstrual ages at ROP treatment were analyzed. A model to identify ROP treatment on patients born between 2006 and 2012 (training set) was developed and tested on patients born between 2013 and 2015 (validation set). RESULTS: Of 7817 live-born infants, 1098 died within the first 5 weeks of life. The remaining 6719 infants were included into analysis. All patients requiring ROP treatment would have been identified if screening had been performed before reaching 60 days of life or 37 3/7 weeks postmenstrual age, whichever came first. The training and validation sets included 4522 and 2197 preterm infants encompassing 56 and 20 patients receiving ROP treatment, respectively. All patients would have required screening to reach 100% sensitivity. To reach a sensitivity of 95.0% and a specificity of 87.6%, we predicted a reduction in 13.2% of patients requiring screening (c-statistic = 0.916). CONCLUSIONS: A substantial reduction of infants requiring screening seems possible, but necessitates prospective testing of new screening criteria.

Impact of Fetal Weight Estimation on the Prediction of Neonatal Morbidity and Mortality at the Limit of Viability.

INTRODUCTION: To determine the accuracy of estimated fetal weight (EFW) at the limit of viability in a delivery room setting and its impact on the prediction of neonatal outcome. MATERIAL AND METHODS: In this retrospective, single-center cohort study we included patients with preterm birth between 230/7 and 260/7 weeks of gestation. Neonates were divided into 3 groups according to birth weight at delivery (accuracy index 90-110%, <90%, >110%). Neonatal outcome for each group was categorized into survival with and without impairment and death, with a follow-up period of 6 weeks. RESULTS: Eighty-seven newborns were included, with 62.1% accurately estimated. Gestational age at birth, fetal sex, maternal body mass index, and time interval between birth and ultrasound affected the accuracy of EFW. Chances of survival were significantly higher in the underestimated group for birth weight at delivery compared with estimated weight (p < 0.001), with risk of death being significantly lower (p < 0.001). The reverse was true for overestimated infants, for both risk of death and chances of survival. At 6 weeks' follow-up, there were significantly more deceased overestimated infants (p = 0.041). DISCUSSION: Our study shows that inaccuracy of EFW at the limit of viability occurs frequently in a delivery room setting with a potential impact on neonatal outcome.

Less invasive ventilation in extremely low birth weight infants from 1997 to 2011: survey versus evidence.

Evidence for target values of arterial oxygen saturation (SaO2), CO2, and pH has changed substantially over the last 20 years. A representative survey concerning treatment strategies in extremely low-birth-weight infants (ELBW) was sent to all German neonatal intensive care units (NICUs) treating ELBW infants in 1997. A follow-up survey was conducted in 2011 and sent to all NICUs in Germany, Austria, and Switzerland. During the observation period, NICUs targeting SaO2 of 80, 85, and 90 % have increased, while units aiming for 94 and 96 % decreased (all p < 0.001). Similarly, NICUs aiming for pH 7.25 or lower increased, while 7.35 or higher decreased (both p < 0.001). Furthermore, more units targeted a CO2 of 50 mmHg (7.3 kPa) or higher (p < 0.001), while fewer targeted 40 or 35 mmHg (p < 0.001). Non-invasive ventilation (NIV) was used in 80.2 % of NICUs in 2011. The most frequently used ventilation modes were synchronized intermittent mandatory ventilation (SIMV) (67.5 %) and intermittent positive pressure ventilation (IPPV) (59.7 %) in 1997 and SIMV (77.2 %) and synchronized intermittent positive pressure ventilation (SIPPV) (26.8 %) in 2011. NICUs reporting frequent or always use of IPPV decreased to 11.0 % (p < 0.001). SIMV (77.2 %) and SIPPV (26.8 %) did not change from 1997 to 2011, while high-frequency oscillation (HFO) increased from 9.1 to 19.7 % (p = 0.018). Differences between countries, level of care, and size of the NICU were minimal. CONCLUSIONS: Target values for SaO2 decreased, while CO2 and pH increased significantly during the observation period. Current values largely reflect available evidence at time of the surveys. WHAT IS KNOWN: • Evidence concerning target values of oxygen saturation, CO 2 , and pH in extremely low-birth-weight infants has grown substantially. • It is not known to which extent this knowledge is transferred into clinical practice and if treatment strategies have changed. WHAT IS NEW: • Target values for oxygen saturation in ELBW infants decreased between 1997 and 2011 while target values for CO 2 and pH increased. • Similar treatment strategies existed in different countries, hospitals of different size, or university versus nonuniversity hospitals in 2011.

Physiological parameters after nonpharmacological analgesia in preterm infants: a randomized trial.

AIM: To compare the influence of three different nonpharmacological interventions on cortical activation, heart rate and peripheral oxygen saturation (SaO2 ) after heelstick in preterm infants. METHODS: Twenty five preterm infants between 24 0/7 and 32 0/7 weeks of gestational age were randomized to either oral sucrose (S), facilitated tucking (FT) or a combination of the two interventions (SFT) prior to five heelsticks each within the first 14 days of life. SaO2 , heart rate and oxygenation of the somatosensory cortex, measured by near infrared spectroscopy (NIRS), were analysed. RESULTS: Hundred and twenty five heelsticks were performed. The heart rate increased significantly after heelstick in all three intervention groups (p < 0.004 in all groups). The increase was higher in the FT group compared with the other groups (S: p = 0.007; SFT: p = 0.004). There was no difference among the two groups receiving sucrose (S and SFT; p = 0.87). SaO2 did not change significantly after heelstick in all intervention groups. Near infrared spectroscopy measurements did not show a significant change in the curve but patients in the FT group showed a trend towards higher average oxygenation of the contralateral somatosensory cortex. CONCLUSION: Oral sucrose seems to be more effective in reducing reaction to pain than FT. Application of both interventions did not show an additive effect.

Increase of caffeine and decrease of corticosteroids for extremely low-birthweight infants with respiratory failure from 1997 to 2011.

AIM: To compare treatment strategies for respiratory failure in extremely low-birthweight (ELBW) infants in Germany in 1997 to Germany, Austria and Switzerland in 2011. METHODS: A detailed questionnaire about treatment strategies for ELBW infants was sent to all German centres treating ELBW infants in 1997. A follow-up survey was conducted in 2011 in Germany, Austria and Switzerland. RESULTS: In 1997 and 2011, 63.6% and 66.2% of the hospitals responded. In 2011, the response rate was higher in Switzerland than in Germany, and in university hospitals versus nonuniversity hospitals. Treatment strategies did not differ between university and nonuniversity hospitals as well as NICUs of different sizes in 2011. Differences between Germany, Austria and Switzerland were minimal. Administration of caffeine increased significantly, whereas theophylline and doxapram declined (all p < 0.001). While the use of dexamethasone decreased and the use of hydrocortisone increased, the overall use of corticosteroids declined (all p < 0.001). Between 1997 and 2011, therapy with inhalations and mucolytics decreased (both p < 0.001), whereas the use application of diuretics did not change significantly. In mechanically ventilated infants, the application of muscle relaxants and sedation declined significantly (p = 0.009 and p < 0.001), whereas analgesia use did not change. CONCLUSION: Treatment strategies for respiratory failure in ELBW infants have changed significantly between 1997 and 2011.

Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review.

OBJECTIVES: The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome. DATA SOURCES: PubMed was searched using the terms toxic epidermal necrolysis, Stevens-Johnson syndrome, drug toxicity, drug interaction, and skin diseases. DATA SYNTHESIS: Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute inflammatory skin reactions. The onset is usually triggered by infections of the upper respiratory tract or by preceding medication, among which nonsteroidal anti-inflammatory agents, antibiotics, and anticonvulsants are the most common triggers. Initially the diseases present with unspecific symptoms, followed by more or less extensive blistering and shedding of the skin. Complete death of the epidermis leads to sloughing similar to that seen in large burns. Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. Stevens-Johnson syndrome affects <10%, whereas involvement of 10%-30% of body surface area is called Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Besides the skin, mucous membranes such as oral, genital, anal, nasal, and conjunctival mucosa are frequently involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Toxic epidermal necrolysis is associated with a significant mortality of 30%-50% and long-term sequelae. Treatment includes early admission to a burn unit, where treatment with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. CONCLUSION: Profound knowledge of exfoliative skin diseases is needed to improve therapy and outcome of these life-threatening illnesses.

Association between perinatal interventional activity and 2-year outcome of Swiss extremely preterm born infants: a population-based cohort study.

OBJECTIVES: To investigate if centre-specific levels of perinatal interventional activity were associated with neonatal and neurodevelopmental outcome at 2 years of age in two separately analysed cohorts of infants: cohort A born at 22-25 and cohort B born at 26-27 gestational weeks, respectively. DESIGN: Geographically defined, retrospective cohort study. SETTING: All nine level III perinatal centres (neonatal intensive care units and affiliated obstetrical services) in Switzerland. PATIENTS: All live-born infants in Switzerland in 2006-2013 below 28 gestational weeks, excluding infants with major congenital malformation. OUTCOME MEASURES: Outcomes at 2 years corrected for prematurity were mortality, survival with any major neonatal morbidity and with severe-to-moderate neurodevelopmental impairment (NDI). RESULTS: Cohort A associated birth in a centre with high perinatal activity with low mortality adjusted OR (aOR 0.22; 95% CI 0.16 to 0.32), while no association was observed with survival with major morbidity (aOR 0.74; 95% CI 0.46 to 1.19) and with NDI (aOR 0.97; 95% CI 0.46 to 2.02). Median age at death (8 vs 4 days) and length of stay (100 vs 73 days) were higher in high than in low activity centres. The results for cohort B mirrored those for cohort A. CONCLUSIONS: Centres with high perinatal activity in Switzerland have a significantly lower risk for mortality while having comparable outcomes among survivors. This confirms the results of other studies but in a geographically defined area applying a more restrictive approach to initiation of perinatal intensive care than previous studies. The study adds that infants up to 28 weeks benefited from a higher perinatal activity and why further research is required to better estimate the added burden on children who ultimately do not survive.

Do late preterm twins face an increased neonatal morbidity compared with singletons?

OBJECTIVE: Late preterm infants (born between 34 0/7 and 36 6/7 weeks of gestation) have been shown to have a higher morbidity and mortality than term infants. Furthermore, twins, both term and preterm, have a higher neonatal morbidity than singletons. The aim of our study was to examine if late preterm twins consequently have twice the neonatal morbidity when both risk factors prematurity and multiple pregnancy are present. STUDY DESIGN: A retrospective single-centre study was conducted to compare neonatal outcome of late preterm singletons and late preterm twins born between 34 0/7 and 36 6/7 weeks of gestation as well as term twins with a gestational age from 37 0/7 to 41 6/7 weeks. Primary outcome was length of hospitalisation. Secondary outcome was neonatal morbidity. RESULTS: A total of 845 infants were included. Late preterm twins (n = 243) were hospitalised significantly longer than term twins (n = 107) (13.5 ± 8.0 vs 6.29 ± 2.0 days, p <0.001) and late preterm singletons (n = 495) (13.5 ± 8.0 vs 12.6 ± 8.6 days, p = 0.011). Hyperbilirubinaemia occurred significantly more often in late preterm singletons than in late preterm twins (49.7 vs 29.2%; p<0.001). Otherwise, no significant differences were detected regarding neonatal morbidities or mortality of late preterm singletons and late preterm twins. Late preterm twins had a significantly higher incidence of most morbidities than term twins. CONCLUSION: Late preterm twins are hospitalised significantly longer than similar-aged singletons, but have otherwise similar neonatal morbidities. Hyperbilirubinaemia is less frequent in late preterm twins than late preterm singletons.

Incidence of retinopathy of prematurity (ROP) and ROP treatment in Switzerland 2006-2015: a population-based analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a severe complication of preterm birth and can lead to severe visual impairment or even blindness if untreated. The incidence of ROP requiring treatment is increasing in some developed countries in conjunction with higher survival rates at the lower end of gestational age (GA). MATERIAL AND METHODS: The incidence of ROP and severe ROP (sROP) requiring treatment in Switzerland was analysed using the SwissNeoNet registry. We conducted a retrospective cohort analysis of very preterm infants with a GA below 32 weeks who were born between 2006 and 2015 in Switzerland. Patient characteristics were stratified according to GA. RESULTS: 9.3% and 1.8% of very preterm infants in Switzerland developed ROP of any stage and sROP, respectively. The incidence of ROP treatment was 1.2%. Patients with 24 and 25 weeks GA had the highest proportion of ROP treatment at 14.5% and 7.3%, respectively, whereas the proportion of treated infants at or above a GA of 29 weeks was 0.06%. Similarly, the risk of sROP declined strongly with increasing GA. During the observation period of 10 years, the incidence of ROP treatment ranged between 0.8% and 2.0%. Incidences of sROP or ROP treatment did not increase over time. CONCLUSION: The incidence of ROP treatment in Switzerland is low and was stable over the analysed period. The low incidence of sROP in patients with a GA of 29 weeks or more leaves room for a redefinition of ROP screening criteria.

Oral sucrose and "facilitated tucking" for repeated pain relief in preterms: a randomized controlled trial.

OBJECTIVES: To test the comparative effectiveness of 2 nonpharmacologic pain-relieving interventions administered alone or in combination across time for repeated heel sticks in preterm infants. METHODS: A multicenter randomized controlled trial in 3 NICUs in Switzerland compared the effectiveness of oral sucrose, facilitated tucking (FT), and a combination of both interventions in preterm infants between 24 and 32 weeks of gestation. Data were collected during the first 14 days of their NICU stay. Three phases (baseline, heel stick, recovery) of 5 heel stick procedures were videotaped for each infant. Four independent experienced nurses blinded to the heel stick phase rated 1055 video sequences presented in random order by using the Bernese Pain Scale for Neonates, a validated pain tool. RESULTS: Seventy-one infants were included in the study. Interrater reliability was high for the total Bernese Pain Scale for Neonates score (Cronbach's α: 0.90-0.95). FT alone was significantly less effective in relieving repeated procedural pain (P < .002) than sucrose (0.2 mL/kg). FT in combination with sucrose seemed to have added value in the recovery phase with lower pain scores (P = .003) compared with both the single-treatment groups. There were no significant differences in pain responses across gestational ages. CONCLUSIONS: Sucrose with and without FT had pain-relieving effects even in preterm infants of <32 weeks of gestation having repeated pain exposures. These interventions remained effective during repeated heel sticks across time. FT was not as effective and cannot be recommended as a nonpharmacologic pain relief intervention for repeated pain exposure.