Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial.

Our aim was to assess the efficacy and safety of intravenous (i.v.) paracetamol vs. i.v. ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. This is a multicenter randomized controlled study. Infants with a gestational age of 25+0-31+6 weeks were randomized to receive i.v. paracetamol (15 mg/kg/6 h for 3 days) or i.v. ibuprofen (10-5-5 mg/kg/day). The primary outcome was the closure rate of hsPDA after the first treatment course with paracetamol or ibuprofen. Secondary outcomes included the constriction rate of hsPDA, the re-opening rate, and the need for surgical closure. Fifty-two and 49 infants received paracetamol or ibuprofen, respectively. Paracetamol was less effective in closing hsPDA than ibuprofen (52 vs. 78%; P = 0.026), but the constriction rate of the ductus was similar (81 vs. 90%; P = 0.202), as confirmed by logistic regression analysis. The re-opening rate, the need for surgical closure, and the occurrence of adverse effects were also similar.Conclusions: Intravenous paracetamol was less effective in closing hsPDA than ibuprofen, but due to a similar constriction effect, its use was associated with the same hsPDA outcome. These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.Trial registration: Clinicaltrials.gov : NCT02422966, Date of registration: 04/09/2015; EudraCT no: 2013-003883-30. What is Known: • The successful closure of patent ductus arteriosus with oral paracetamol has been recently reported in several preterm infants, but only one randomized controlled study investigated the efficacy of intravenous paracetamol. What is New: • Intravenous paracetamol is less effective in closing hsPDA than ibuprofen, but have a similar constriction effect. • These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.

Neonatal lung ultrasonography score after surfactant in preterm infants: A prospective observational study.

OBJECTIVE: To assess changes in neonatal lung ultrasonography score (nLUS) after surfactant administration in preterm infants with respiratory distress syndrome (RDS). WORKING HYPOTHESIS: The reduction of nLUS score before (nLUSpre), 2 hours (nLUS2h), and 12 hours (nLUS12h) after surfactant administration to identify patients who will not need a second treatment. STUDY DESIGN AND SETTING: Prospective observational study in the tertiary neonatal intensive care unit. PATIENTS SELECTION: Forty-six preterm neonates with RDS of 32 weeks median gestational age (IQR 30-33) and mean birth weight of 1650 ± 715 g. METHODOLOGY: Lung ultrasonography was performed before, 2 hours, and 12 hours after surfactant administration in preterm infants with RDS needing surfactant treatment. Resulting nLUS was analyzed. RESULTS: The Wilcoxon signed-rank test demonstrated an nLUS lowering after 2 hours (P < .001) and 12 hours (P < .001) from surfactant administration. Sixteen newborns required surfactant retreatment with median gestational age of 32 weeks (IQR 29-33) and mean birth weight of 1519 ± 506 g.The receiver operating characteristic analysis for the nLUS2h yielded an area under the curve of 0.80 (95% confidence interval, 0.76-0.85; P < .001). A nLUS2h ≥7 showed a sensitivity of 94% and a specificity of 60% for needing a second treatment with surfactant. CONCLUSIONS: In preterm infants with RDS requiring surfactant treatment, nLUS evaluated 2 hours after surfactant administration can be used to identify patients who will not need a second treatment.

Neonatal transient pseudohypoparathyroidism: could it be included among inactivating parathyroid hormone (PTH)/PTH-related protein signalling disorders?

We report a case of transient pseudohypoparathyroidism in a full-term newborn that presented at 20 hours of life with hypocalcemic seizures, hyperphosphatemia and raised parathormone levels. The diagnosis of pseudohypoparathyroidism was made according to biochemical investigations. The infant was treated with calcium supplementation and vitamin D analog therapy, and he remained stable and symptom-free with normal serum biochemistries during follow-up. We suggest that transient pseudohypoparathyroidism of the newborn (ntPHP) might be included among inactivating parathyroid hormone (PTH)/PTH-related protein signaling disorders as defined by the classification schema recently proposed by the European Pseudohypoparathyroidism Network. To the best of our knowledge, this is the first report in which the new classification has been applied to a case of ntPHP.

A modified physiologic test for bronchopulmonary dysplasia: a clinical tool for weaning from CPAP and/or oxygen-therapy the premature babies?

BACKGROUND: A physiologic test for estimating BPD rate has been developed by Walsh and collaborators. Actually there are not standard criteria for weaning from CPAP and/or oxygen therapy the premature babies. Aim of this study was to verify if a physiologic test, modified respect to that developed by Walsh and collaborators for estimating BPD rate, can be used as a clinical tool for weaning the premature babies from CPAP and/or oxygen therapy. METHODS: Neonates with BW 500-1250 g and GA ≤ 32 weeks, receiving FiO2 ≤ 0.30 by hood or CPAP, were prospectively studied at 28 days of life and at 36 weeks of postmestrual age. The test was performed in 3 steps: baseline, challenge (FiO2 and CPAP reduction to room air) and post test (room air). Monitoring of transcutaneous CO2 was added to SpO2 and the newborns passing the test were left in room air. RESULTS: Six of 23 tested babies (26%) passed the challenge at 28 days of life, 4 of 10 tested babies (40%) passed the challenge at 36 weeks. Median values of SpO2 were significantly higher in the neonates passing the test, respect to the failing patients. At the same time median values of TcPCO2 were significantly higher in the latter babies. CONCLUSION: TcPCO2 monitoring appeared to be a new useful parameter for failure prediction of weaning. The test represented a clinical guide because the newborns passing it were left in room air.

Continuous glucose monitoring (CGM) in very low birth weight newborns needing parenteral nutrition: validation and glycemic percentiles.

BACKGROUND: Continuous glucose monitoring using subcutaneous sensors is useful in the management of glucose control in neonatal intensive care. We evaluated feasibility and reliability of a continuous glucose monitoring system in a population of very low birth weight neonates needing parenteral nutrition. Moreover, we presented percentiles of glycemia of the studied population. METHODS: Very low birth weight neonates were enrolled within 24 h from birth. An ENLITE sensor connected to a continuous glucose monitoring system was inserted and maintained for at least 72 h. Data obtained with the continuous glucose monitoring system and with a glucometer were compared. Calibration was performed every 12 h. RESULTS: Twenty-three patients (9 males) were included. Median gestational age was 28 weeks (range 23-30) and median birth weight was 860 g (range 500-1092). A total of 299 paired glucose values were obtained. Modified Clarke Error Grid criteria for clinical significance were met. 74 and 33 episodes of hypoglycemia and hyperglycemia were detected, respectively. 31,329 values of glycemia were analyzed and the percentiles calculated. CONCLUSIONS: This continuous glucose monitoring system is safe and accurate. It allows increasing the detection of hypo- and hyper-glycaemia episodes and it could be routinely used in the management of glucose infusion in very low birth weight neonates under total parenteral nutrition.

Lung ultrasonography score versus chest X-ray score to predict surfactant administration in newborns with respiratory distress syndrome.

OBJECTIVES: We aim to verify the diagnostic accuracy of a lung ultrasonography (LUS) score to early predict the need for surfactant therapy in newborns with respiratory distress syndrome (RDS), and to compare it with a chest X-ray score. METHODS: In this prospective diagnostic accuracy study we included all newborns admitted for respiratory distress and initially treated with nasal CPAP. LUS was performed within 2 h from nasal CPAP positioning and in any case before surfactant administration. A chest X-ray was also performed. A LUS score and an X-ray score were used and compared. Ability of the scores to predict surfactant administration was evaluated through ROC analysis. RESULTS: In our population of 56 newborns with mean gestational age of 31 weeks (SD 3) and mean birth weight of 1442 g (SD 520), LUS score showed higher AUC than X-ray score in early recognition of infants with respiratory distress syndrome requiring surfactant treatment (0.94; 95%CI, 0.89-0.98; P < 0.001 vs 0.80; 95%CI, 0.74-0.86; P < 0.001). It showed also higher sensitivity (86% vs 82%), higher specificity (88% vs 76%), better positive (83% vs 69%), and negative (91% vs 87%) predictive values. CONCLUSIONS: LUS is a non-invasive, bedside and reproducible method that could improve the management of neonatal respiratory distress. It is accurate and reliable to early identify patients who will need treatment with surfactant allowing both an early treatment and a reduction of radiation exposure.

Semipermeable membranes and hypernatremic dehydration in preterms. A randomized-controlled trial.

BACKGROUND: Hypernatremic dehydration is a complication of preterm infants with reportedly high morbility. In preterm infants, this happens due to a combination of low fluid intake, transepidermal water loss (TEWL), and immaturity of kidney function. Semipermeable membranes are self-adhesive membranes that can be applied as an artificial skin to reduce TEWL. AIMS: To test the hypothesis that early application of a semipermeable membrane (Tegaderm™) in preterm infants ≤30 weeks could result in a significant reduction of hypernatremia (serum Na > 145 mEq/l) during the first 15 days of life. STUDY DESIGN: Randomized controlled trial (UMIN000010515). SUBJECTS: 164 consecutive newborns with gestational age ≤ 30 weeks, absence of congenital skin defects, and duration of admission ≥ 15 days. Patients were randomized to receive semipermeable membrane (n = 82) or no membrane (n = 82) for the first 15 days of life. OUTCOME MEASURES: The primary endpoint of the study was the incidence reduction of hypernatremia (Na > 145 mEq/l). Secondary endpoints included: postnatal weight loss (WL) and time to birth weight (BW) recovery. RESULTS: Incidence of hypernatremia in the control and semipermeable membrane group was 59.7% and 41.6%, respectively (p = 0.030). Postnatal WL was larger in the control group (13.9 ±â€¯5.6% vs 11.1 ±â€¯3.4%, p = 0.005) and occurred later than the semipermeable membrane group (5.4 ±â€¯2.3 vs 4.5 ±â€¯1.4 days, p = 0.005). Time to BW recovery was also longer for control group (13.5 ±â€¯4.3 vs 11.9 ±â€¯3.2 days, p = 0.016). CONCLUSIONS: Early application of skin semipermeable membrane to ≤30 week preterm is associated with decreased incidence of hypernatremia, decreased %WL, and earlier BW recovery. No complications were observed with membrane application.

The Long-Term Efficacy of a Galactagogue Containing Sylimarin-Phosphatidylserine and Galega on Milk Production of Mothers of Preterm Infants.

AIMS: To investigate the efficacy of a galactagogue, containing Sylimarin-phosphatidylserine (SILITIDIL) and galega consumed in the first month after delivery by mothers of preterm infants, in maintaining milk production during the first 3-6 months after delivery. MATERIALS AND METHODS: Mothers of infants born at gestational age (GA) between 27 and 32 weeks, enrolled in our previous prospective, double-blind, randomized trial and randomly allocated to receive either the galactagogue (GG) or a placebo (PG), were asked about their milk production at 3 and 6 months after delivery. RESULTS: Of the 100 mothers involved in this study, 45 of GG and 44 of PG responded comprehensively to the questions asked. At the third month after delivery, exclusive human milk administration was reported by 22 mothers of GG and 12 mothers of PG (p < 0.05), whereas 29 mothers of GG and 18 mothers of PG were able to administer >50% of the amount of milk assumed. At the sixth month of life, only eight infants received exclusive human milk (six and two of GG and PG, respectively), and the data are not sufficient for a meaningful clinical evaluation. CONCLUSIONS: It is assumed that a galactagogue during the first month after delivery improves human milk administration to preterm neonates after discharge and for the first 3 months of life.

Continuous glucose monitoring in preterm infants: evaluation by a modified Clarke error grid.

BACKGROUND: Continuous glucose monitoring using subcutaneous sensors has been validated in adults and children with diabetes, and was found to be useful in the management of glucose control. We aimed to assess feasibility and reliability of a new continuous glucose monitoring system (CGMS) in a population of preterm neonates using a Clarke error grid (CEG) specifically modified for preterm infants. METHODS: Preterm infants were recruited within 24 h from delivery. A subcutaneous sensor connected to a CGMS was inserted and maintained for 6 days. Data collected from CGMS were compared with data obtained using a glucometer. Management of the infants followed standard protocols and was not influenced by CGMS readings. RESULTS: Twenty patients (9 males) were included. Median (range) gestational age was 32 weeks (27-36) and median (range) birth weight was 1350 g (860-3360). Average CGMS recording time was 137 h, for a total of 449 paired glucose levels. CEG and modified CEG criteria for clinical significance were met. CONCLUSION: CGMS is a safe and clinically adequate method to estimate glucose levels in preterm infants. As the glucose level can be evaluated in real time, this CGMS could be useful to reduce the number of heel sticks, to observe glycaemic trends and to promptly detect episodes of both hypo- and hyper-glycaemia.

Proactive enteral nutrition in moderately preterm small for gestational age infants: a randomized clinical trial.

OBJECTIVE: To investigate the efficacy of a proactive feeding regimen (PFR) in reducing hospital length of stay in a population of moderately preterm small for gestational age (SGA) infants. STUDY DESIGN: SGA infants (z-score <-1.28) of gestational age (GA) 32-36 weeks and birth weight (BW) >1499 g were allocated at random to receive either a PFR, starting with 100 mL/kg/day and gradually increasing to 200 mL/kg/day by day 4, or a standard feeding regimen, starting with 60 mL/kg/day and gradually increasing to 170 mL/kg/day by day 9. All infants received human milk. RESULTS: A total of 72 infants were randomized to the 2 groups, 36 to the PFR group (mean GA, 35.1 ± 0.7 weeks; mean BW, 1761 ± 177 g) and 36 to the standard feeding regimen group (mean GA, 35.5 ± 1.2 weeks; mean BW, 1754 ± 212 g). Infants in the PFR group were discharged significantly earlier (mean, 9.8 ± 3.1 days vs 11.9 ± 4.7 days; P = .029). The need for intravenous fluids (2.8% vs 33.3%; P = .0013) and the incidence of hypoglycemia (0 vs 33.3%; P = .00016) were significantly lower in the PFR group. Feeding intolerance and fecal calprotectin levels did not differ between the 2 groups. CONCLUSION: A PFR in moderately preterm SGA infants is well tolerated and significantly reduces both the length of stay and the risk of neonatal hypoglycemia.

Feasibility of transferring intensive cared preterm infants from incubator to open crib at 1600 grams.

BACKGROUND: Ability to maintain a normal body temperature in an open crib is an important physiologic competency generally requested to discharge preterm infants from the hospital. The aim of this study is to assess the feasibility of an early weaning protocol from incubator in preterm newborns in a Neonatal Intensive Care Unit. METHODS: 101 infants with birth weight < 1600 g were included in this feasibility study. We compared 80 newborns successfully transferred from an incubator to open crib at 1600 g with 21 infants transferred at weight ≥ 1700 g. The primary outcome was to evaluate feasibility of the protocol and the reasons for the eventual delay. Secondary outcomes were the identification of factors that would increase the likelihood of early weaning, the impact of an earlier weaning on discharge timing, and the incidence of adverse outcomes. Newborns in the study period were then compared with an historical control group with similar characteristics. RESULTS: Early weaning was achieved in 79.2% of infants without significant adverse effects on temperature stability or weight gain. Delayed weaning was mainly due to the need of respiratory support. Gestational age affected the likelihood of early weaning (OR 1.7282 95% CI: 1.3071 - 2.2850). In the multivariate linear regression, early weaning reduced length of stay (LOS) by 25.8 days (p < 0.0001). CONCLUSIONS: Preterm infants can be weaned successfully from an incubator to an open crib at weight as low as 1600 grams without significant adverse effect. Early weaning significantly reduces LOS in preterm newborns.

Italian guidelines for management and treatment of hyperbilirubinaemia of newborn infants ≥ 35 weeks' gestational age.

Hyperbilirubinaemia is one of the most frequent problems in otherwise healthy newborn infants. Early discharge of the healthy newborn infants, particularly those in whom breastfeeding is not fully established, may be associated with delayed diagnosis of significant hyperbilirubinaemia that has the potential for causing severe neurological impairments. We present the shared Italian guidelines for management and treatment of jaundice established by the Task Force on Hyperbilirubinaemia of the Italian Society of Neonatology.The overall aim of the present guidelines is to provide an useful tool for neonatologists and family paediatricians for managing hyperbilirubinaemia.

BiliCheck vs JM-103 in identifying neonates not at risk of hyperbilirubinaemia.

BACKGROUND: Transcutaneous bilirubinometry is widely used to predict hyperbilirubinemia by using several devices. The aim of this study was to compare the predictive ability of BiliCheck vs JM-103 in identifying neonates not at risk of significant hyperbilirubinemia, putting the data obtained with the two instruments on our transcutaneous bilirubin nomogram built with the BiliCheck. METHODS: Transcutaneous bilirubin (TcB) measurement was performed when jaundice appeared in newborn babies and/or just before discharge from the hospital. It was performed at the forehead with the two instruments within 5 minutes by two experienced neonatologists, each one blind to the value obtained by the other. Blood samples were drawn to obtain total serum bilirubin (TSB) levels soon after TcB measurements. RESULTS: A total of 627 paired-sample measurements were obtained from 298 newborn babies. Out of the total population studied, 16 newborn babies (5.4%) showed significant hyperbilirubinemia defined as TSB value >17 mg/dL, or as need for phototherapy treatment according to the AAP guidelines. TcB measurements showed false negative results in the first 60 hours of life using both devices. After the 60th hour of life, TcB measurements using both devices successfully predicted newborn babies not at risk of significant hyperbilirubinemia, being the JM-103 more reliable than BC because of fewer false positive results. CONCLUSIONS: Our study shows that both BC and JM-103 can exclude subsequent significant hyperbilirubinemia when the measurements are performed after the 60th hour of life. Nevertheless, the transcutaneous pre-discharge screening should be considered only as the first step, and it has to be followed by a follow-up through the first days after discharge.

How to feed small for gestational age newborns.

Feeding small for gestational age (SGA) newborns is extremely challenging and the neonatologist should be brave and cautious at the same time. Although these babies have a high risk of milk intolerance and necrotising enterocolitis, enteral feeding guidelines are not well established and practice varies widely among different neonatal units. Currently available studies on this topic include extremely and very low birth weight neonates, but are not focused specifically on small for gestational age infants. This review analyzes papers focused on feeding interventions in order to provide the best available evidences about the optimum timing for introduction of enteral feeding, how fast feed volume can be advanced, which milk and which feeding method is more appropriate in SGA infants.

Transcutaneous bilirubin measurement: comparison of Respironics BiliCheck and JM-103 in a normal newborn population.

OBJECTIVES: To compare the accuracy of BiliCheck™ (Respironics, Marietta, GA) and Konica-Minolta Air Shield JM-103 (Drager Medical Inc, Telford, PA) to evaluate total serum bilirubin (TSB). METHODS: Prospective blinded study comparing two diagnostic devices in 630 neonates requiring TSB measurement. RESULTS: Linear regression analysis showed a good correlation between BiliCheck™ and TSB (r=0.8212) as well as between JM-103 and TSB (r=0.8686). BiliCheck shows a tendency to underestimate TSB. The mean difference in TSB-TcB was -1.4 mg/dL for BC (-4.7/+1.8 mg/dL) and 0.3 mg/dL for JM-103 (-2.6/+3.2mg/dL). ROC analysis for TSB≥ 12 mg/dL showed area under the curve for BiliCheck™ significantly lower than those for JM-103 (p<0.0001). JM-103 resulted less time expensive than BiliCheck. CONCLUSIONS: In spite of similar diagnostic accuracy JM-103 could be preferred for some practical advantages, but its suitability in performing universal screening for severe hyperbilirubinemia deserves further investigations.

Development and validation of serum bilirubin nomogram to predict the absence of risk for severe hyperbilirubinaemia before discharge: a prospective, multicenter study.

BACKGROUND: Early discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB) nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before discharge. METHODS: A percentile-based hour-specific nomogram for TSB values was performed using TSB data of 1708 healthy full term neonates. The nomogram's predictive ability was then prospectively assessed in five different first level neonatal units, using a single TSB value determined before discharge. RESULTS: The 75 th percentile of hour specific TSB nomogram allows to predict newborn babies without significant hyperbilirubinemia only after the first 72 hours of life. In the first 48 hours of life the observation of false negative results did not permit a safe discharge from the hospital. CONCLUSION: The hour-specific TSB nomogram is able to predict all neonates without risk of non physiologic hyperbilirubinemia only after 48 to 72 hours of life. The combination of TSB determination and risk factors for hyperbilirubinemia could facilitate a safe discharge from the hospital and a targeted intervention and follow-up.

Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: a prospective, observational, multicenter study.

BACKGROUND: Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia. AIMS: To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia. STUDY DESIGN: prospective, observational, multicenter. SUBJECTS: 2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy. METHODS: All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin >17 mg/dL or need for phototherapy. RESULTS: Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age. CONCLUSIONS: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48 h of life ahead.