Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples.

BACKGROUND: Many drugs are used off-label or unlicensed in neonates. This does not mean they are used without evidence or knowledge. We aimed to apply and evaluate the Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies (GAPPS) scoring system for the level of evidence of two commonly used anti-epileptic drugs. METHODS: Midazolam and phenobarbital as anti-epileptics were evaluated with a systematic literature search on neonatal pharmacokinetic (PK) and/or pharmacodynamic [PD, (amplitude-integrated) electroencephalography effect] studies. With the GAPPS system, two evaluators graded the current level of evidence. Inter-rater agreement was assessed for dosing evidence score (DES), quality of evidence (QoE), and strength of recommendation (REC). RESULTS: Seventy-two studies were included. DES scores 4 and 9 were most frequently used for PK, and scores 0 and 1 for PD. Inter-rater agreements on DES, QoE, and REC ranged from moderate to very good. A final REC was provided for all PK studies, but only for 25% (midazolam) and 33% (phenobarbital) of PD studies. CONCLUSIONS: There is a reasonable level of evidence concerning midazolam and phenobarbital PK in neonates, although using a predefined target without integrated PK/PD evaluation. Further research is needed on midazolam use in term neonates with therapeutic hypothermia, and phenobarbital treatment in preterms. IMPACT: There is a reasonable level of evidence concerning pharmacotherapy of midazolam and phenobarbital in neonates. Most evidence is however based on PK studies, using a predefined target level or concentration range without integrated, combined PK/PD evaluation. Using the GAPPS system, final strength of recommendation could be provided for all PK studies, but only for 25% (midazolam) to 33% (phenobarbital) of PD studies. Due to the limited PK observations of midazolam in term neonates with therapeutic hypothermia, and of phenobarbital in preterm neonates these subgroups can be identified for further research.

Renal artery flow alterations in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: To compare kidney blood flow and kidney function tests in infants with hypoxic ischemic encephalopathy (HIE), and the effects of therapeutic hypothermia (TH) during the first 7 days of life. METHODS: Fifty-nine infants with HIE were prospectively evaluated. Infants with moderate-severe HIE who required TH were classified as group 1 (n = 36), infants with mild HIE were classified as group 2 (n = 23), and healthy infants were classified as group 3 (n = 60). Kidney function tests were evaluated on the sixth hour, third and seventh days of life in Group 1 and Group 2, and on the sixth hour and third day of life in group 3. Renal artery (RA) Doppler ultrasonography (dUS) was performed in all infants on the first, third, and seventh days of life. RESULTS: Systolic and end diastolic blood flow in RA tended to increase and RA resistive index (RI) tended to decrease with time in group 1 (p = 0.0001). While end diastolic blood flow rates in RA on the third day were similar in patients with severe HIE and mild HIE, it was lower in patients with mild-moderate-severe HIE than healthy newborns. On the seventh day, all three groups had similar values (p > 0.05). Serum blood urea nitrogen (BUN), creatinine, uric acid, and cystatin C levels gradually decreased and glomerular filtration rate (GFR) gradually increased during TH in group 1 (p = 0.0001). Serum creatinine levels gradually decreased while GFR gradually increased during the study period in group 2. CONCLUSIONS: Therapeutic hypothermia seems to help restore renal blood flow and kidney functions during the neonatal adaptive period with its neuroprotective properties.

Early postnatal metabolic profile in neonates with critical CHDs.

BACKGROUND: Cyanotic CHD is a life-threatening condition that presents with low oxygen saturation in the newborn period. Hypoxemia might cause alterations in the metabolic pathways. In the present study, we aimed to evaluate the early postnatal amino acid and carnitine/acylcarnitine profiles of newborn infants with cyanotic CHD. METHODS: A single centre case-control study was conducted. Twenty-seven patients with cyanotic CHD and 54 healthy newborn controls were enrolled. As part of the neonatal screening programme, results of amino acid and carnitine/acylcarnitine were recorded and compared between groups. RESULTS: Twenty-seven neonates with cyanotic CHD and 54 healthy newborns as controls were enrolled in the study. Cyanotic CHD neonates had higher levels of alanine, phenylalanine, leucine/isoleucine, citrulline, ornithine, C5, C5-OH; but lower levels of C3, C10, C12, C14, C14:1, C16, C16.1, C18, C5-DC, C6-DC, C16-OH, C16:1-OH when compared with the healthy controls. CONCLUSION: This study showed that there are differences between patients with cyanotic CHD and healthy controls in terms of postnatal amino acid and carnitine/acylcarnitine profiles.

Determining T and B Cell development by TREC/KREC analysis in primary immunodeficiency patients and healthy controls.

T cell receptor excision circles (TRECs) and kappa-deleting excision circles (KRECs) are DNA fragments potentially indicative of T and B cell development, respectively. Recent thymic emigrants (RTEs) are a subset of peripheral cells that may also represent thymic function. Here, we investigated TREC/KREC copy numbers by quantitative real-time PCR in the peripheral blood of patients with primary immunodeficiencies (PIDs, n = 145) and that of healthy controls (HCs, n = 86) and assessed the correlation between RTEs and TREC copy numbers. We found that TREC copy numbers were significantly lower in children and adults with PIDs (P < .0001 and P < .002, respectively) as compared with their respective age-matched HCs. A moderate correlation was observed between TREC copies and RTE numbers among children with PID (r = .5114, P < .01), whereas no significant correlation was detected between RTE values and TREC content in the HCs (r = .0205, P = .9208). Additionally, we determined TREC and KREC copy numbers in DNA isolated from the Guthrie cards of 200 newborns and showed that this method is applicable to DNA isolated from both peripheral blood samples and dried blood spots, with the two sample types showing comparable TREC and KREC values. We further showed that RTE values are not always reliable markers of T cell output. Although additional confirmatory studies with larger cohorts are needed, our results provide thresholds for TREC/KREC copy numbers for different age groups.

Does a prenatal diagnosis affect mortality and morbidity for neonatal arterial switch operation.

BACKGROUND: The effect of prenatal diagnosis on prognosis in patients with transposition of the great arteries is not clear. In this study, we compared the outcomes after arterial switch operation. METHODS: Outcome of 112 patients who had arterial switch operation in the neonatal period were analysed. The patients were divided into two groups: those who had prenatal diagnosis (Group 1; n = 34) and those who did not (Group 2; n = 78). The patients were also classified based on their diagnosis: simple transposition, transposition with ventricular septal defect and/or aortic arch hypoplasia, and Taussig-Bing anomaly. RESULTS: In Group 1, the C-section delivery rate was higher (82% vs. 44%; p = 0.004), and it was observed that patients in Group 1 were more often intubated upon admission to the neonatal ICU (38% vs. 9%; p = 0.005). No differences were found between the two groups in terms of operation time, cardiopulmonary bypass time, post-operative invasive respiratory support duration, or extracorporeal membrane oxygenation support. It was observed that those who had Taussig-Bing anomaly had a higher mortality. CONCLUSIONS: Timely treatment have a positive effect on neonatal mortality and morbidity. That's why all families with prenatal diagnosis of critical CHD should be recommended to have the delivery in a tertiary care hospital. Although it could not be demonstrated in this study, prenatal diagnosis has a potential to improve surgical results especially in countries or cities, which does not have enough resources for transfer and surgical units. Further efforts are needed to improve prenatal screening programmes.

Evaluation of neonatal acute kidney injury after critical congenital heart disease surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication of congenital heart diseases (CHDs) after cardiac surgery. This study aimed to define the frequency and critical course, risk factors and short-term outcomes of AKI in postoperative CHD neonates. METHODS: Postoperatively followed term CHD newborn infants were enrolled in the study. Infants with congenital anomalies of the urinary tract and other major congenital anomalies were excluded. Neonatal modified KDIGO criteria were used to assess AKI. RESULTS: A total of 199 postoperatively followed newborn infants were included in the study. Acute kidney injury was detected in 71 (35.6%) patients. Of these patients, 24 (33.8%) were in stage 1, 14 (19.7%) in stage 2, and 33 (46.5%) in stage 3. Acute kidney injury occurred within the first week (median 1 day [IQR 1-2 days]) of cardiac surgery in 93% of the patients. The duration of invasive respiratory support and extracorporeal membrane oxygenation (ECMO) and mortality were significantly higher in stage 3 patients. Higher vasoactive-inotropic score (OR, 1.02; 95% CI, 1.0-1.04; p = 0.008) and receiving ECMO (OR, 7.9; 95% CI, 2.6-24.4; p = 0.001) were associated with risk for the development of AKI. The mortality rate was 52.1% in the AKI (+) patients, and having AKI (OR 7.1; 95% CI, 3.5-14.18) was significantly associated with mortality. CONCLUSION: Acute kidney injury, a common early complication after critical neonatal CHD cardiac surgery, is associated with increased morbidity and mortality. Stage 3 AKI is associated with significantly higher mortality rates.

Negative Effects of Noise on NICU Graduates' Cochlear Functions.

AIM: To evaluate the adverse effects of noise on hearing. Methods: Thirty-two infants that had been admitted to neonatal intensive care unit (NICU) and 25 healthy controls were included in this study. Noise levels were recorded continously during the hospitalization period. Results: All healthy controls passed the hearing screening tests before discharge and on the sixth-month follow up. Hospitalized infants had lower "Distortion Product Auto Acoustic Emission Signal Noise Ratio" (DPOAE SNR) amplitudes (dB) at five frequencies (1001, 1501, 3003, 4004, 6006 Hz in both ears). DPOAE fail rates at 1001 Hz and 1501 Hz were higher than in hospitalized infants (81.8% and 50.0% vs 20.0% and 4.0%). Infants who failed the test at 1001 and 1501 Hz were exposed to noise above the recommended maximum level for longer periods of time. Conclusion: Hearing tests performed at sixth-months of life were adversely affected in NICU graduates.

Relationship between serum 25-hydroxy vitamin D levels and retinopathy of prematurity.

Aim To evaluate the relationship between serum 25-hydroxy vitamin D, 25 (OH) D, levels and retinopathy of prematurity. Methods and Results Serum 25 (OH) D levels were measured in 97 very low birth weight infants, prior to vitamin D supplementation. The development of retinopathy of prematurity and its treatment requirement were evaluated. At follow-up, retinopathy of prematurity developed in 71 (73.2%) infants. Serum 25 (OH) D levels were significantly lower in infants with retinopathy of prematurity than ones without retinopathy of prematurity ( P < 0.001). The infants who required treatment had lower 25 (OH) D levels compared with the infants who did not required treatment (7.1 ± 5.2 ng/ml vs. 11.9 ± 6.5 ng/ml; P = 0.003). Multivariate analysis showed that lower serum 25 (OH) D levels may be a risk factor for retinopathy of prematurity development [OR: 1.14, 95% CI (1.02-1.27), P = 0.02]. Conclusion Lower 25 (OH) D levels in the first days of life may be related to retinopathy of prematurity development and treatment requirement in premature infants.

Perfusion index assessment during transition period of newborns: an observational study.

BACKGROUND: Perfusion index (PI) is becoming a part of clinical practice in neonatology to monitor peripheral perfusion noninvasively. Hemodynamic and respiratory changes occur in newborns during the transition period after birth in which peripheral perfusion may be affected. Tachypnea is a frequent symptom during this period. While some tachypneic newborns get well in less than 6 h and diagnosed as "delayed transition", others get admitted to intensive care unit which transient tachypnea of newborn (TTN) being the most common diagnosis among them. We aimed to compare PI of neonates with TTN and delayed transition with controls, and assess its value on discrimination of delayed transition and TTN. METHODS: Neonates with gestational age between 37 and 40 weeks who were born with elective caesarian section were included. Eligible neonates were monitored with Masimo Set Radical7 pulse-oximeter (Masimo Corp., Irvine, CA, USA). Postductal PI, oxygen saturation and heart rate were manually recorded every 10 s for 3 min for two defined time periods as 10th minute and 1st hour. Axillary temperature were also recorded. Newborn infants were grouped as control, delayed transition, and TTN. RESULTS: Forty-nine tachypneic (TTN; 21, delayed transition; 28) and 30 healthy neonates completed the study. PI values were similar between three groups at both periods. There were no correlation between PI and respiratory rate, heart rate, and temperature. CONCLUSION: PI assessment in maternity unit does not discriminate TTN from delayed transitional period in newborns which may indicate that peripheral perfusion is not severely affected in either condition.

The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants.

OBJECTIVE: To test the efficacy of probiotic and prebiotic, alone or combined (synbiotic), on the prevention of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. STUDY DESIGN: A prospective, randomized, controlled trial was conducted at 5 neonatal intensive care units in Turkey. VLBW infants (n = 400) were assigned to a control group and 3 study groups that were given probiotic (Bifidobacterium lactis), prebiotic (inulin), or synbiotic (Bifidobacterium lactis plus inulin) added to breastmilk or formula for a maximum of 8 weeks before discharge or death. The primary outcome was NEC (Bell stage ≥2). RESULTS: The rate of NEC was lower in probiotic (2.0%) and synbiotic (4.0%) groups compared with prebiotic (12.0%) and placebo (18.0%) groups (P < .001). The times to reach full enteral feeding were faster (P < .001), the rates of clinical nosocomial sepsis were lower (P = .004), stays in the neonatal intensive care unit were shorter, (P = .002), and mortality rates were lower (P = .003) for infants receiving probiotics, prebiotics, or synbiotic than controls. The use of antenatal steroid (OR 0.5, 95% CI 0.3-0.9) and postnatal probiotic (alone or in synbiotic) (OR 0.5, 95% CI 0.2-0.8) decreased the risk of NEC, and maternal antibiotic exposure increased this risk (OR 1.9, 95% CI 1.1-3.6). CONCLUSIONS: In VLBW infants, probiotic (Bifidobacterium lactis) and synbiotic (Bifidobacterium lactis plus inulin) but not prebiotic (inulin) alone decrease NEC.

Is higher 25-hydroxyvitamin D level preventive for respiratory distress syndrome in preterm infants?

OBJECTIVE: The objective of this study was to investigate the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) levels and respiratory distress syndrome (RDS) development in preterm infants. STUDY DESIGN: Between January 2012 and January 2013, 81 preterm infants, gestational age below 32 weeks, were prospectively enrolled into the study. Cord bloods of these newborns were tested for 25(OH)D levels. Low level was defined as ≤ 15 ng/mL (Group 1) and normal level as > 15 ng/mL (Group 2). Patients in Group 1 were also divided further into two subgroups as severe deficiency (Group 1a, ≤ 5 ng/mL) and mild deficiency (Group 1b, 5-15 ng/mL). RESULTS: In this study, 57 infants had low 25(OH)D levels (Group 1, median 8.0 ng/mL [interquartile range, IQR, 5-10]; Group 2, median 21 ng/mL [IQR, 19-24.7]). RDS rate was significantly higher in Group 1a (n = 18, 32.7%) and Group 1b (n = 34, 61.8%) compared with Group 2 (n = 3, 5.4%) (p = 0.001). There were no difference of having RDS between Group 1a (94.7%) and Group1b (89.5) (p = 0.512). Multivariate analysis showed that higher 25(OH)D level can be preventive for the development of RDS (odds ratio, 0.6; 95% confidence interval (0.5-0.8); p = 0.001). CONCLUSION: Lower cord blood 25(OH)D levels might be associated with increased risk of RDS in preterm infants with very low birth weight.

Effect of therapeutic hypothermia on C-reactive protein levels in patients with perinatal asphyxia.

OBJECTIVE: To determine the changes in serum C-reactive protein (CRP) levels during therapeutic hypothermia. STUDY DESIGN: Between January 2011 and June 2013, 133 hypoxic-ischemic encephalopathy patients being followed up in the neonatal intensive care unit of Dr. Sami Ulus Maternity and Children's Hospital are prospectively evaluated. Group 1; patients that received therapeutic hypothermia (n = 74) and group 2; patients that did not required therapeutic hypothermia (n = 59). All the patients underwent serial complete blood cell count and CRP assessments; blood cultures were obtained from all the cases at the time of admission and when CRP levels were elevated. RESULTS: Positive blood cultures were encountered in five cases (6.7%) in group 1 while no blood culture-proven septicemia was encountered in group 2. The CRP levels elevated gradually reaching a peak level on the 4th day and then decreased during the therapeutic hypothermia in patients with no blood culture-proven septicemia in group 1. The CRP levels showed statistically significant changes reaching a peak level on the 7th day in patients with blood culture-proven septicemia in group 2. Also, the CRP levels showed no alteration with time in group 2. CONCLUSION: Therapeutic hypothermia itself might be associated with CRP elevation rather than an actual infection.

Regression of symptomatic multiple cardiac rhabdomyomas associated with tuberous sclerosis complex in a newborn receiving everolimus.

UNLABELLED: Cardiac rhabdomyoma is the most common primary cardiac tumor, is considered to be a hamartoma of developing cardiac myocytes. Cardiac rhabdomyoma is associated with tuberous sclerosis complex (TSC) in 50-86% of cases. Mutations in TSC-1/TSC-2 genes result in increased mammalian target of rapamycin (mTOR) pathway activation responsible for the hamartomatous lesions of tuberous sclerosis complex. Therapy with mTOR inhibitors is currently under investigation as a treatment option for tumors associated with TSC. In this report we present a case with multiple symptomatic rhabdomyomas associated with tuberous sclerosis complex, deemed to be ineligible for surgical removal, treated with everolimus (mTOR inhibitor). CONCLUSION: As we observed in our patient, in cases with inoperable symptomatic rhabdomyomas associated with TSC, everolimus, an mTOR inhibitor, may be the treatment of choice, which should be confirmed with additional studies.

Analysis of serum γ-glutamyl transferase levels in neonatal intensive care unit patients.

OBJECTIVES: Gamma-glutamyl transferase (GGT) is commonly measured in newborn infants as a sensitive liver function test; however, reference ranges are mostly based on early studies, including relatively small number of patients. The aim of this study was to emphasise recently changed GGT values because of changed newborns profile admitted to neonatal intensive care units (NICUs) and establish new cross-sectional reference ranges for the serum GGT levels in a cohort of neonates between 26 and 42 weeks' gestational age in 1 centre. METHODS: From January 1, 2010 to December 31, 2012, liver function tests including serum GGT measurements were performed in 705 newborns who were admitted to NICUs because of different aetiologies at Gazi University School of Medicine Hospital, Ankara, Turkey. Infants with Apgar score <8 at the fifth minute, any metabolic or liver disease, cholestasis, congenital infection, culture-proven sepsis, elevated serum aminotransferases, and who were treated with phenobarbital were excluded. Clinical and laboratory data of 583 neonates were analysed retrospectively. GGT was measured by enzymatic method using the Abbott Architect C16000 autoanalyser. Mean, 2.5th, and 97.5th percentiles were used to express the reference range data. RESULTS: Four hundred sixty-one GGT values of 200 preterm infants and 501 GGT values of 383 term infants during the first 28 days after birth were analysed. Serum GGT levels of preterm infants in the first 7 days and between 8 and 28 days after delivery were (mean±standard deviation; 141.81±88.56 U/L and 131.17±85.53 U/L) similar to term infants (139.90±86.46 U/L and 144.56±86.51 U/L), respectively (P=0.649 and P=0.087). Serum GGT levels were found to be significantly higher in male infants (no need of query) (145.98±93.68 U/L) than female infants (132.18±78.97 U/L) (P=0.035), and infants born vaginally (152.24±90.71 U/L) also had higher serum GGT activity than those born by caesarean section (135.38±85.37 U/L) (P=0.005). CONCLUSIONS: A new reference range for serum GGT levels that is higher than previous reference values can identify neonates with truly abnormal results and prevent unnecessary interventions.

Perfusion index variability in preterm infants treated with two different natural surfactants for respiratory distress syndrome.

OBJECTIVE: The objective of this study was to compare the perfusion index (PI) variability in premature infants with respiratory distress syndrome (RDS) following administration of two different natural surfactant preparations. STUDY DESIGN: This was a prospective study on 92 preterm infants with RDS. Patients were randomized into two groups. Group 1 (n = 46) received beractant; Group 2 (n = 46) received poractant alfa. Oxygen saturation, PI, and heart rate were measured by Masimo Rainbow SET Radical-7 pulse oximeter (Masimo Corp., Irvine, CA) before and after surfactant. The effects of the two treatment regimens on PI and oxygenation were compared. RESULTS: Repeated doses were more needed in beractant group (p = 0.04). Median oxygenation index (OI) before surfactant were similar, but improvement in OI was more prominent at 6th hour of surfactant in Group 2 (p = 0.001). Both groups had similar preductal PI values before surfactant. PI was higher at 6th hour of surfactant in Group 2 (p = 0.001). Pulmonary hemorrhage, intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, and mortality were more frequent in infants whose PI values lower than 0.7 within the first 5 days of life (p = 0.001). CONCLUSION: Poractant alfa resulted in more prominent improvement in PI and OI. Low PI values measured at early postnatal period may predict poor clinical outcome in preterm infants with RDS.

Surfactant for acute respiratory distress syndrome caused by near drowning in a newborn.

BACKGROUND: Near drowning is the term for survival after suffocation caused by submersion in water or another fluid. Pulmonary insufficiency may develop insidiously or suddenly because of near drowning. AIM: We want to present a newborn case of acute respiratory distress syndrome caused by near drowning. CASE: A 26-day-old boy was brought to the emergency department because of severe respiratory distress. Two hours before admission, the baby suddenly slipped out his mother's hands and fell in the bathtub full of water while bathing. After initial resuscitation, he was transferred to the neonatal intensive care unit for mechanical ventilation. PaO2/FIO2 ratio was 97, with SaO2 of 84%. Bilateral heterogeneous densities were seen on his chest x-ray film. The baby was considered to have acute respiratory distress syndrome. Antibiotics were given to prevent infection. Because conventional therapy failed to improve oxygenation, a single dose of surfactant was tested via an intubation cannula. Four hours later, poractant alfa (Curosurf) administered repeatedly at the same dosage because of hypoxemia (PaO2/FIO2 ratio, 124; SaO2, 88%). Oxygen saturation was increased to more than 90% in 24 hours, which was maintained for 3 days when we were able to wean him from mechanical ventilation. After 7 days, the x-ray film showed considerable clearing of shadows. He was discharged home on the 15th day after full recovery. CONCLUSIONS: This case report describes a rapid and persistent improvement after 2 doses of surfactant in acute respiratory distress syndrome with severe oxygenation failure caused by near drowning in a newborn.

The effects of phototherapy on eosinophil and eosinophilic cationic protein in newborns with hyperbilirubinemia.

Newborns with jaundice requiring or not requiring phototherapy (PT) are at greater risk of developing asthma later in life. In this study, we investigated the effect of PT treatment on eosinophil and eosinophilic cationic protein (ECP) levels in newborns with severe hyperbilirubinemia. Thirty newborns diagnosed with severe hyperbilirubinemia and exposed to light-emitting diode (LED) PT were enrolled into the study. Total serum bilirubin (TSB) levels, complete blood count and serum ECP concentrations were measured before and after PT. TSB and hemoglobin (Hb) counts were lower after PT (p = 0.001). There was no difference between leukocyte, lymphocyte, neutrophil and platelet count before and after PT. Eosinophil levels were increased after PT, although not significantly. ECP levels were higher after PT (p = 0.006). It may be speculated that newborns treated with LED PT, increased ECP might play a role in developing allergic diseases later in life.

ITGB4-Related pyloric atresia without epidermolysis in two siblings.

Pyloric atresia is a rare gastrointestinal anomaly with an incidence of 1/100,000 in live births. It is usually seen as an isolated condition or in combination with other congenital or hereditary anomalies. Autosomal recessive inherited either fatal or non-fatal variants of pyloric atresia with epidermolysis bullosa are known due to mutations in ITGA6, ITGB4, and PLEC genes. ITGB4 gene mutation was recently identified in 5 siblings in 2 families associated with familial isolated pyloric atresia. Herein, we present two siblings who had pyloric atresia together with a homozygous variant in the ITGB4 gene and without epidermolysis bullosa. The development of isolated familial pyloric atresia without epidermolysis bullosa may occur due to homozygous variants of the ITGB4 gene. Detection of more variants in this gene may help to establish a genotype-phenotype correlation and may suggest the ITGB4 gene in patients who have pyloric atresia without epidermolysis bullosa.

Parents in Neonatal Pain Management-An International Survey of Parent-Delivered Interventions and Parental Pain Assessment.

BACKGROUND: While parent-delivered pain management has been demonstrated to effectively reduce neonatal procedural pain responses, little is known about to what extent it is utilized. Our aim was to explore the utilization of parents in neonatal pain management and investigate whether local guidelines promote parent-delivered interventions. METHODS: A web-based survey was distributed to neonatal units worldwide. RESULTS: The majority of the 303 responding neonatal intensive care units (NICUs) from 44 countries were situated in high-income countries from Europe and Central Asia. Of the responding units, 67% had local guidelines about neonatal pain management, and of these, 40% answered that parental involvement was recommended, 27% answered that the role of parents in pain management was mentioned as optional, and 32% responded that it was not mentioned in the guidelines. According to the free-text responses, parent-delivered interventions of skin-to-skin contact, breastfeeding, and parental live singing were the most frequently performed in the NICUs. Of the responding units, 65% answered that parents performed some form of pain management regularly or always. CONCLUSIONS: There appears to be some practice uptake of parent-delivered pain management to reduce neonatal pain in high-income countries. Additional incorporation of these interventions into NICU pain guidelines is needed, as well as a better understanding of the use of parent-delivered pain management in low- and middle-income countries.