Pharmacokinetics of melatonin in preterm infants

Aims - Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials. Methods - Melatonin was administered to 18 preterm infants in doses ranging from 0.04–0.6 μg kg−1 over 0.5–6 h. Pharmacokinetic profiles were analyzed individually and by population methods. Results - Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1 μg kg−1 h−1 for 2 h showed a median half-life of 15.82 h and median maximum plasma concentration of 203.3 pg ml−1. On population pharmacokinetics, clearance was 0.045 l h−1, volume of distribution 1.098 l and elimination half-life 16.91 h with gender (P = 0.047) and race (P < 0.0001) as significant covariates. Conclusions - A 2 h infusion of 0.1 μg kg−1 h−1 increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants.

Improving the care of preterm infants: before, during, and after, stabilisation in the delivery room

Introduction Up to 10% of infants require stabilisation during transition to extrauterine life. Enhanced monitoring of cardiorespiratory parameters during this time may improve stabilisation outcomes. In addition, technology may facilitate improved preparation for delivery room stabilisation as well as NICU procedures, through educational techniques. Aim To improve infant care 1) before birth via improved training, 2) during stabilisation via enhanced physiological monitoring and improved practice, and 3) after delivery, in the neonatal intensive care unit (NICU), via improved procedural care. Methods A multifaceted approach was utilised including; a combination of questionnaire based surveys, mannequin-based investigations, prospective observational investigations, and a randomised controlled trial involving preterm infants less than 32 weeks in the delivery room. Forms of technology utilised included; different types of mannequins including a CO2 producing mannequin, qualitative end tidal CO2 (EtCO2) detectors, a bespoke quantitative EtCO2 detector, and annotated videos of infant stabilisation as well as NICU procedures Results Manual ventilation improved with the use of EtCO2 detection, and was positively assessed by trainees. Quantitative EtCO2 detection in the delivery room is feasible, EtCO2 increased over the first 4 minutes of life in preterm infants, and EtCO2 was higher in preterm infants who were intubated. Current methods of heart rate assessment were found to be unreliable. Electrocardiography (ECG) application warrants further evaluation. Perfusion index (PI) monitoring utilised in the delivery room was feasible. Video recording technology was utilised in several ways. This technology has many potential benefits, including debriefing and coaching in procedural healthcare, and warrants further evaluation. Parents would welcome the introduction of webcams in the NICU. Conclusions I have evaluated new methods of improving infant care before, during, and after stabilisation in the DR. Specifically, I have developed novel educational tools to facilitate training, and evaluated EtCO2, PI, and ECG during infant stabilisation. I have identified barriers in using webcams in the NICU, to now be addressed prior to webcam implementation.

Oxygen targeting in preterm infants using the Masimo SET Radical pulse oximeter

BACKGROUND: A pretrial clinical improvement project for the BOOST-II UK trial of oxygen saturation targeting revealed an artefact affecting saturation profiles obtained from the Masimo Set Radical pulse oximeter.

METHODS: Saturation was recorded every 10 s for up to 2 weeks in 176 oxygen dependent preterm infants in 35 UK and Irish neonatal units between August 2006 and April 2009 using Masimo SET Radical pulse oximeters. Frequency distributions of % time at each saturation were plotted. An artefact affecting the saturation distribution was found to be attributable to the oximeter's internal calibration algorithm. Revised software was installed and saturation distributions obtained were compared with four other current oximeters in paired studies.

RESULTS: There was a reduction in saturation values of 87-90%. Values above 87% were elevated by up to 2%, giving a relative excess of higher values. The software revision eliminated this, improving the distribution of saturation values. In paired comparisons with four current commercially available oximeters, Masimo oximeters with the revised software returned similar saturation distributions.

CONCLUSIONS: A characteristic of the software algorithm reduces the frequency of saturations of 87-90% and increases the frequency of higher values returned by the Masimo SET Radical pulse oximeter. This effect, which remains within the recommended standards for accuracy, is removed by installing revised software (board firmware V4.8 or higher). Because this observation is likely to influence oxygen targeting, it should be considered in the analysis of the oxygen trial results to maximise their generalisability.

The Effects of Non-Nutritive Sucking and Pre-Feeding Oral Stimulation on Time to Achieve Independent Oral Feeding for Preterm Infants

Background: The survival rates of preterm infants has increased over the last years, but oral feeding difficulties are the most common problems encountered by them Objectives: This study aimed at comparing the effects of non-nutritive sucking (NNS) and pre-feeding oral stimulation on feeding skills, length of hospital stay and weight gain of 26-32 weeks gestational age preterm infants in NICU, to determine the more effective intervention. Patients and Methods: Thirty-two preterm infants were assigned randomly into three groups. One intervention group received pre-feeding oral stimulation program and the other received non-nutritive sucking stimulation, while the control group received a sham intervention. Gestational age of infants was calculated during 1, 4 and 8 oral feeding and discharge time from NICU. The infants’ weights were measured weekly from birth and at discharge time. Results: Mean gestational age on 8 time oral feeding per day, in 3 groups was not significant (P = 0.282). Although NNS and pre-feeding oral stimulation groups has fulfilled this criterion 7.55 and 6.07 days sooner than the control group, respectively (a result which is of great clinical and economic importance), but the difference did not reach statistical significance. Weight gaining at discharge time in NNS group was significantly higher than control and pre-feeding oral stimulation groups (P < 0.05). Conclusions: This study revealed that pre-feeding oral stimulation and NNS programs both were effective on oral feeding skills and weight gaining of the immature newborns. Yet, it seems that NNS program was more effective than pre-feeding oral stimulation on weight gaining.

Comparison of Complications and Efficacy of NIPPV and Nasal CPAP in Preterm Infants With RDS

Background: Respiratory distress syndrome (RDS) is one of the most common diseases in neonates admitted to NICU. For this important cause of morbidity and mortality in preterm neonates, several treatment methods have been used. To date, non-invasive methods are preferred due to fewer complications. Objectives: Herein, two non-invasive methods of ventilation support are compared: NCPAP vs. NIPPV. Patients and Methods: This is a randomized clinical trial. Premature neonates with less than 34 weeks gestation, suffering from RDS entered the study, including 151 newborns admitted to Vali-Asr NICU during 2012-2013. Most of these patients received surfactant as early rescue via INSURE method and then randomly divided into two NCPAP (73 neonates) and NIPPV (78 neonates) groups. Both early and late complications are compared including extubation failure, hospital length of stay, GI perforation, apnea, intraventricular hemorrhage (IVH) and mortality rate. Results: The need for re-intubation was 6% in NIPPV vs. 17.6% in NCPAP group, which was statistically significant (P = 0.031). The length of hospital stay was 23.92 ± 13.5 vs. 32.61 ± 21.07 days in NIPPV and NCPAP groups, respectively (P = 0.002). Chronic lung disease (CLD) was reported to be 4% in NCPAP and 0% in NIPPV groups (P = 0.035). The most common complication occurred in both groups was traumatization of nasal skin and mucosa, all of which fully recovered. Gastrointestinal perforation was not reported in either group. Conclusions: This study reveals the hospital length of stay, re-intubation and BPD rates are significantly declined in neonates receiving NIPPV as the treatment for RDS.

Changes in the prevalence of breast feeding in preterm infants discharged from neonatal units : a register study over 10 years

Objective: There are indications that the prevalence of exclusively breastfed preterm infants is decreasing in Sweden. The objective was to investigate trends in exclusive breast feeding at discharge from Swedish neonatal units and associated factors in preterm infants. Design, setting and participants: This is a register study with data from the Swedish Neonatal Quality Register. Data from 29 445 preterm infants (gestational age (GA) <37 weeks) who were born during the period 2004–2013 were retrieved. Data included maternal, perinatal and neonatal characteristics. Data were analysed for the whole population as well as for 3 GA groups. Results: From 2004 to 2013, the prevalence of exclusive breast feeding decreased, in extremely preterm (GA 22–27 weeks) from 55% to 16%, in very preterm (GA 28–31 weeks) from 41% to 34% and in moderately preterm infants (GA 32–36 weeks) from 64% to 49%. The decline was statistically significant (p<0.001) in all 3 GA groups. This decline remained significant when adjustments were made for factors negatively associated with exclusive breast feeding and which became more prevalent during the study period, that is, small for GA (all groups) and maternal mental illness (very preterm and moderately preterm infants). Conclusions: In the past 10 years, Sweden has experienced a lower rate of exclusive breast feeding in preterm infants, especially in extremely preterm infants. The factors analysed in this study explain only a small proportion of this decline. The decline in exclusive breast feeding at discharge from neonatal units raises concern and present challenges to the units to support and promote breast feeding.

Prediction of Length of Hospital Stay in Preterm Infants - A Case-Based Reasoning View

The length of stay of preterm infants in a neonatology service has become an issue of a growing concern, namely considering, on the one hand, the mothers and infants health conditions and, on the other hand, the scarce healthcare facilities own resources. Thus, a pro-active strategy for problem solving has to be put in place, either to improve the quality-of-service provided or to reduce the inherent financial costs. Therefore, this work will focus on the development of a diagnosis decision support system in terms of a formal agenda built on a Logic Programming approach to knowledge representation and reasoning, complemented with a case-based problem solving methodology to computing, that caters for the handling of incomplete, unknown, or even contradictory in-formation. The proposed model has been quite accurate in predicting the length of stay (overall accuracy of 84.9%) and by reducing the computational time with values around 21.3%.

Motor development curve from 0 to 12 months in infants born preterm

Aim: To trace a reference curve for motor development from birth up to 12 months of corrected chronological age in infants born preterm and low birth weight. Methods: This is a cross-sectional study with a sample of 308 preterm infants (53% boys) weighing < 2500 g at birth. The Alberta Infant Motor Scale (AIMS) was used for motor development assessment. Results: Comparing the motor performance of preterm infants with infants from a standardized sample on the AIMS, it was found that, except for the age group of the newborn, preterm infants showed lower motor development scores in comparison with the AIMS normative sample in all age groups between 1 and 12 months. The curve of motor development showed a continuous increase in the number of motor skills of preterm infants during their first 12 months of age. However, the average of motor acquisitions of preterm infants showed a nonlinear pattern with a standard indicator of stabilization between 8 and 10 months of age. Conclusion: Preterm infants, 1-12 months of age, showed motor development AIMS scores lower than the standards established in the normative sample. The findings may contribute as norm-reference for assessing the motor development of preterm infants in follow-up programmes in developing countries.

Immunoglobulins in saliva of preterm and full-term infants. A longitudinal study from 0-18 months of age

The aim of this longitudinal study was to determine salivary levels of total IgA, IgG and IgM in 84 preterm and 214 full-term infants, from birth to 18 months of age. Unstimulated whole saliva was collected from each infant at birth, and subsequently at 3-monthly intervals. Immunoglobulin levels were estimated using an ELISA technique. At birth, IgA was detected in 147/214 (69%) full-term infants but only 47/84 (56%) preterm infants (P

Prediction of hyperglycemia in preterm newborn infants

Many conditions are associated with hyperglycemia in preterm neonates because they are very susceptible to changes in carbohydrate homeostasis. The purpose of this study was to evaluate the occurrence of hyperglycemia in preterm infants undergoing glucose infusion during the first week of life, and to enumerate the main variables predictive of hyperglycemia. This prospective study (during 1994) included 40 preterm neonates (gestational age <37 weeks); 511 determinations of glycemic status were made in these infants (average 12.8/infant), classified by gestational age, birth weight, glucose infusion rate and clinical status at the time of determination (based on clinical and laboratory parameters). The clinical status was classified as stable or unstable, as an indication of the stability or instability of the mechanisms governing glucose homeostasis at the time of determination of blood glucose; 59 episodes of hyperglycemia (11.5%) were identified. A case-control study was used (case = hyperglycemia; control = normoglycemia) to derive a model for predicting glycemia. The risk factors considered were gestational age (<=31 vs. >31 weeks), birth weight (<=1500 vs. >1500 g), glucose infusion rate (<=6 vs. >6 mg/kg/min) and clinical status (stable vs. unstable). Multivariate analysis by logistic regression gave the following mathematical model for predicting the probability of hyperglycemia: 1/exp{-3.1437 + 0.5819(GA) + 0.9234(GIR) + 1.0978(Clinical status)} The main predictive variables in our study, in increasing order of importance, were gestational age, glucose infusion rate and, the clinical status (stable or unstable) of the preterm newborn infant. The probability of hyperglycemia ranged from 4.1% to 36.9%.

Relationship between plasma creatinine concentration and glomerular filtration in preterm newborn infants

Fluid management and dosage regimens of drugs in preterm infants should be based on the glomerular filtration rate. The current methods to determine glomerular flitration rate are invasive, time-consuming, and expensive. In contrast, creatinine clearance can be easy obtained and quickly determined. The purpose of this study was to compare plasma creatinine on the third and seventh day of life in preterm newborn infants, to evaluate the influence of maternal creatinine, and to demonstrate creatinine clearance can be used as a reliable indicator of glomerular filtration rate. We developed a prospective study (1994) including 40 preterm newborns (gestational age < 37 weeks), average = 34 weeks; birth weight (average) = 1840 g, in the first week of life. Inclusion criteria consisted of: absence of renal and urinary tract anomalies; O2 saturation 3 92%; adequate urine output (>1ml/kg/hr); normal blood pressure; absence of infections and no sympathomimetic amines in use. A blood sample was collected to determine plasma creatinine (enzymatic method) on the third and seventh day of life and creatinine clearance (CrCl) was obtained using the following equation: , k = 0.33 in preterm infant All plasma creatinine determinations showed normal values [third day: 0.78 mg/dl ± 0.24 (mean ± SD)and seventh day: 0.67 mg/dl ± 0.31 - (p>0.05)]. Also all creatinine clearance at third and seventh day of life were normal [third day: 19.5 ml/min ± 5.2 (mean ± SD) and seventh day: 23.8 ml/min ± 7.3 - (p>0,05)]. All preterm infants developed adequate renal function for their respective gestational age. In summary, our results indicate that, for clinical practice, the creatinine clearance, using newborn length, can be used to estimate glomerular filtration rate in preterm newborn infants.

Emotional and neuroendocrine regulation in very preterm and full-term infants at six months of age

Emotional and neuroendocrine regulation have been shown to be associated. However, results are inconsistent. This paper explores the functioning and relationships between these two systems in 54 healthy preterm and 25 full-term born infants at six months of age. Results showed significant differences between very preterm and full-term children in emotional intensity and regulation, as well as in neuroendocrine regulation. No evidence of an association between neuroendocrine and emotional regulations was found. Results suggest a possible delay in the maturation of the neuroendocrine system as well as in emotional regulation in very preterm infants.

Influence of nutrition on urinary oxalate and calcium in preterm and term infants.

Few data for normal urinary oxalate (Ox) and calcium (Ca) excretion related both to gestational age and nutritional factors have been reported in preterm or term infants. We therefore determined the molar Ox and Ca to creatinine (Cr) ratios in spot urines from 64 preterm and 37 term infants aged 1-60 days, either fed formula or human milk (HM). Only vitamin D was supplemented; renal or metabolic diseases were excluded. Urinary Ox/Cr ratio was higher in preterm than in term infants, both when formula fed (1st month 253 vs. 180 mmol/mol and 2nd month 306 vs. 212 mmol/mol; P&lt;0.05) or HM fed (206 vs. 169 mmol/ mol and 283* vs. 232 mmol/mol; *P&lt;0.05). Ox/Cr was also higher in formula- than HM-fed preterm infants. The ratio increased during the first 2 months of life irrespective of nutrition. Urinary Ca/Cr ratio was comparable in all groups during the 1st month of life, except for a lower (P &lt; 0.05) value in term infants fed HM (0.10 mol/mol). It increased in all groups during the 2nd month of life, being highest in HM-fed preterm infants (1.86 mol/mol). In conclusion, urinary Ox and Ca excretion is influenced by both gestational age and nutrient intake in preterm and term infants.

Interrater reliability of Alberta Infant Motor Scale in term and preterm born infants between 10 to 16 months age from Talca province - Chile

Purpose: To examine the ‘interrater reliability’ of the Alberta Infant Motor Scale (AIMS) in term and preterm born infants between 10 to 16 months age from Talca province, Maule Region - Chile. Subjects: 115 infants between 10 to 16 months age were incorporated to the study; 95 term born infants were attended in the local Health Centre in Talca City, and 20 preterm infants belonged to the Premature Infants Follow-Up Programme of Talca Regional Hospital. Methods: The motor behaviour of each infant was recorded and later it was assessed by two trained assessors using AIMS. It was obtained the total AIMS’ score and also from prone, supine, seated, and stand subscales. For ‘interrater reliability’ analysis it was used the Intraclass Coefficient of Correlation (ICC), the Standard Error of Measurement (SEM) and 95% limits of agreement. Results: The obtained ICC for the total scores AIMS were major than 0.94 (p<0.0002) for term and preterm born infants. The SEM of total scores was less than 3.1 points, higher than what was found in other similar studies. The 95% limits of agreement were +5.3 to -4.1 points and +7.7 to – 3.9 points in term and preterm born, respectively, revealing ‘interrater agreement’. Conclusion: The AIMS showed adequate ‘interrater reliable’ levels when was applied in Chilean term and preterm born from 10 to 16 month’s age.

Growth of preterm low birth weight infants until 24 months corrected age: effect of maternal hypertension

Objective: To evaluate the growth pattern of low birth weight preterm infants born to hypertensive mothers, the occurrence of growth disorders, and risk factors for inadequate growth at 24 months of corrected age (CA).Methods: Cohort study of preterm low birth weight infants followed until 24 months CA, in a university hospital between January 2009 and December 2010. Inclusion criteria: gestational age < 37 weeks and birth weight of 1,500-2,499g. Exclusion criteria: multiple pregnancies, major congenital anomalies, and loss to follow up in the 2nd year of life. The following were evaluated: weight, length, and BMI. Outcomes: growth failure and risk of overweight at 0, 12, and 24 months CA. Student's t-test, Repeated measures ANOVA (RM-ANOVA), and multiple logistic regression were used.Results: A total of 80 preterm low birth weight infants born to hypertensive mothers and 101 born to normotensive mothers were studied. There was a higher risk of overweight in children of hypertensive mothers at 24 months; however, maternal hypertension was not a risk factor for inadequate growth. Logistic regression showed that being born small for gestational age and inadequate growth in the first 12 months of life were associated with poorer growth at 24 months.Conclusion: Preterm low birth weight born infants to hypertensive mothers have an increased risk of overweight at 24 months CA. Being born small for gestational age and inadequate growth in the 1st year of life are risk factors for growth disorders at 24 months CA. (C) 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.