Quantifying the Impact of Common Feeding Interventions on Nutritive Sucking Performance Using a Commercially Available Smart Bottle.

An estimated 25% to 40% of infants experience difficulties with learning to breast- or bottle-feed. Yet, guidelines and evidence-based support for common feeding practices are limited. The objective of this case report was to quantify the impact of feeding interventions on nutritive sucking performance after discharge in an outpatient setting. This observational case series involved 2 infants. To determine the impact of cumulative interventions, pre- and postintervention effect sizes were calculated. Sucking performance metrics of interest included nipple movement peak sucking amplitude, duration, frequency, and smoothness. Interventions included positional changes and changes in nipple flow rate, among others. For both infants, cumulative interventions had the greatest impact on suck frequency; postintervention, infants were able to increase their rate of nutritive sucking per burst. Other aspects of sucking performance were differentially impacted for each baby. Researchers agree that neonatal and infant feeding has been understudied and that the evidence for common interventions needs to be strengthened. We have demonstrated the implementation of readily available technology that can be used to quantify the direct impact of any intervention on actual sucking performance. In doing so, we can individualize care to support skill development and improve outcomes for infants at risk for ongoing feeding challenges.

Thyroid gland volumes in premature infants using serial ultrasounds.

BACKGROUND: There is a gap in knowledge about the postnatal growth of thyroid gland in preterm infants. OBJECTIVE: To determine postnatal growth of thyroid gland in preterm infants. METHODS: Thyroid gland volume was calculated in 57 prospectively enrolled preterm infants by measuring serial longitudinal, antero-posterior, and transverse dimensions of thyroid gland with ultrasound. Data were analyzed by using the Wilcoxon and independent t test. RESULTS: There was a significant correlation between thyroid volume (TV) and birthweight (BW) (p = 0.01), and between TV and gestational age (p = 0.02). However, unexpectedly, 12 infants had a decrease in TV between the first and second ultrasounds. Infants with late onset bacterial sepsis had lower TVs on their second ultrasounds than infants without sepsis. CONCLUSIONS: Thyroid ultrasound in preterm infants provides noninvasive and quick approach to determine TV and morphology. TV in preterm infants correlates positively with BW and gestational age. However, postnatal growth of thyroid gland is variable and may seemingly be affected by postnatal factors.

Progression of Gastric Acid Production in Preterm Neonates: Utilization of In-vitro Method.

Background: Limited studies are done regarding ability to produce gastric acid in preterm infants and most studies used in vivo method of assessing gastric pH. Objectives: To assess the feasibility of using an in vitro method of measuring gastric pH in babies ≤ 28 weeks gestational age (GA) and determine whether changes in gastric pH differ with gestational age, mode of delivery, and use of antenatal steroids. Design/Methods: Prospective study that enrolled extremely low birth weight (ELBW) babies. Gastric aspirate collected before feeding. In vitro testing of gastric aspirates for pH were done on days of life 1, 3, 5, 7, 14, and 28 by using pH electrode. The pH was measured on each sample in triplicate, mean calculated and used for data analysis. Stastical methods included descriptive statistics, t-tests and repeated measures ANOVA. Results: 29 subjects ≤ 28 weeks or birth weight ≤ 1,000 g were enrolled. No significant change was noted in pH measurements over time. Antenatal steroids and mode of delivery did not affect gastric acid pH. Conclusion: The in vitro method for gastric pH measurements is non-invasive and affords more frequent testing. It would be useful in studying various conditions that may affect gastric pH.

Expedient treatment of a collodion baby.

Only ~270 cases of collodion babies have been reported in the literature since 1892. As the name suggests, the term "collodion baby" refers to a phenotype that can be characterized by a yellow, shiny, tight parchment-like membrane stretched over the skin. Although the collodion membrane is only an evanescent condition of the newborn, neonatal complications can occur in 45% of all collodion babies, leading to a mortality rate of ~11% in the first few weeks of life. Most children born as collodion babies will spontaneously desquamate within 2 weeks, but may be as long as 3 months. Eventually, these children develop signs of one of several types of ichthyosis, which gives the skin the appearance of "fish scales." We report a unique case of a Caucasian male that was born as a Collodion baby at the University of Kentucky Children's Hospital in Lexington, Kentucky. Although the impairment of the skin barrier function put the patient at risk for a number of complications, he improved significantly after being treated with emollients and antibiotics. In contrast to previous findings, we found that skin emollients were beneficial and did not increase the risk of infection.

Brain-derived neurotrophic factor in infants <32 weeks gestational age: correlation with antenatal factors and postnatal outcomes.

Neurotrophins (NTs) play important roles in brain growth and development. Cord blood (CB) brain-derived neurotrophic factor (BDNF) concentrations increase with gestational age but data regarding postnatal changes are limited. We measured BDNF concentrations after birth in 33 preterm infants <32-wk gestation. Serum was collected at birth (CB), at day 2, between day 6 and 10 (D6), at day 30 (D30), and at day 60 (D60). BDNF concentrations fell on D2 (p = 0.03), recovered by D6 (p = 0.10), and continued to rise thereafter at D30 (p = 0.06) and D60 (p = 0.01) compared with CB. CB BDNF concentrations positively correlated with duration of rupture of membranes (r = 0.43, p = 0.04). Antenatal steroids (ANS, p = 0.02), postnatal steroids (PNS, p = 0.04), and retinopathy of prematurity (ROP, p = 0.02) were identified as significant factors in multivariate analyses. The median (25-75th interquartile range) CB BDNF concentrations were higher in infants who received a complete course ANS compared with those who received a partial course [1461 (553-2064) versus 281 (171-536) pg/mL, p = 0.04]. BDNF concentrations negatively correlated with the use of PNS at D30 (r = -0.53, p = 0.002) and at D60 (r = -0.55, p = 0.009). PNS use was associated with reduced concentrations of BDNF at D30 [733 (101-1983) versus 2224 (1677- 4400) pg/mL, p = 0.004] and at D60 [1149 (288-2270) versus 2560 (1337-5166) pg/mL, p = 0.01]. BDNF concentrations on D60 in infants who developed ROP (n = 16) were lower than those who did not develop ROP (n = 7) [1417 (553-2540) versus 3593 (2620-7433) pg/mL, respectively, p = 0.005]. Our data suggests that BDNF concentrations rise beyond the first week of age. BDNF concentrations correlate with factors that influence neurodevelopment outcomes.

Neurobehavior of preterm infants at 36 weeks postconception as a function of morphine analgesia.

This study evaluated early neurobehavioral outcomes in ventilated preterm infants randomized to receive morphine analgesia or placebo in the Neurological Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial. Eight hundred and ninety-eight infants between 23 and 32 weeks of gestation were randomized to receive preemptive morphine analgesia (morphine) or placebo. Infants also received additional analgesia (AA) with open-label morphine. The Neurobehavioral Assessment of the Preterm Infant (NAPI) was used to evaluate 572 of 793 survivors (72.1%) at 36 weeks of postconceptual age. The Neonatal Medical Index (NMI) was used to evaluate the severity of medical complications. Regression analyses were used to determine the effect of covariates. Infants were equally distributed in morphine and placebo groups with similar neonatal and demographic characteristics. Infants assessed with the NAPI were more likely to have sepsis ( P = 0.03), bronchopulmonary dysplasia ( P = 0.02), and longer length of stay ( P = 0.008). Infants randomized to the morphine group had higher NMI scores (odds ratio [OR]; 95% confidence interval [CI]: 1.75; 1.23 to 2.50; P = 0.002). Use of AA was associated with higher NMI scores (OR; 95% CI: 4.5; 2.9 to 5.9; P < 0.001). Of the NAPI subscales, the (mean +/- standard deviation [SD]) popliteal angle cluster scores were significantly higher in the morphine group compared with placebo (51.2 +/- 33.2 versus 45.0 +/- 33.5; P = 0.03). AA use was associated with lower (mean +/- SD) MOTOR scores in the morphine group (48.2 +/- 16.1 versus 52.7 +/- 19.1; P = 0.03) and with lower POPLITEAL ANGLE cluster scores in both the morphine group (41.5 +/- 34.0 versus 59.5 +/- 30.1; P < 0.0001) and the placebo group (40.8 +/- 36.8 versus 49.4 +/- 28.0; P = 0.004). No differences were noted in the other NAPI subscales cluster scores in either subgroup. We conclude that morphine analgesia may result in subtle neurobehavioral differences in premature infants.

An unusual case of severe therapy-resistant hypertension in a newborn.

Hypertension can occur in up to 2% of neonates, and the spectrum of potential causes is broad. Prompt and thorough evaluation with a main focus on kidney disease is key for appropriate therapy. Here we describe a 2-day-old neonate with feeding intolerance and elevated blood pressure readings. Within 24 hours after birth, the infant's blood pressure increased significantly, with sustained mean arterial pressure >85. Renal Doppler ultrasound showed decreased venous blood flow in the right kidney with an abnormal Doppler wave form suggestive of unilateral renal venous thrombosis. Despite aggressive antihypertensive therapy including hydralazine and enalaprilat, hypertension remained sustained. On day-of-life 4, the infant developed clinical signs of hypertensive encephalopathy and significant cardiac dysfunction. A renal angiography showed complete, likely thrombotic occlusion of the right renal artery. Renal MAG3 imaging showed minimal function of the affected kidney, and a nephrectomy secondary to medically uncontrollable hypertension and worsening cardiac dysfunction was performed. The child is developing normally in all aspects on follow-up evaluations at 6 months and 1 year of age. Reevaluation of the working diagnosis in neonates with hypertension can be necessary to optimize the outcome. The overall prognosis can be excellent even in newborns with profound cardiac and neurologic involvement.

Neonatal research and the validity of informed consent obtained in the perinatal period.

BACKGROUND: Consent for participation in clinical research is considered valid if it is informed, understood, and voluntary. In the case of minors, parents give permission for their child to participate in research studies after being presented with all information needed to make an informed decision. Although informed consent is a vital component of clinical research, there is little information evaluating its validity in neonatal intensive-care populations. The objective of this project was to determine the validity of informed consent obtained from parents of infants enrolled in the multicenter randomized research study, neurologic outcomes and pre-emptive analgesia in the neonate (NEOPAIN). DESIGN/METHODS: Parents of infants who survived to discharge and had signed consent for their newborn to participate in the NEOPAIN study at the University of Kentucky were asked 20 open-ended questions to determine their level of understanding about the NEOPAIN study. The NEOPAIN consent form, which had been approved by the University of Kentucky Medical Institutional Review Board (IRB), was used to formulate these questions. Questions addressed the timing of consent, parental understanding of the purpose, benefits, and risks of the study, the voluntary nature of the project, and their willingness to enroll in future studies if the opportunity presented. Answers were scored on a Likert scale, with 1 for no understanding and 5 for complete understanding. RESULTS: Five of 64 parents (7.8%) had no recollection of the NEOPAIN study or of signing consent. Of those who remembered the study, only 67.8% understood the purpose of the study, with a higher proportion of the mothers than fathers knowing the purpose of the study (73.3% vs 57.1%), (p=0.029). Of those who understood the purpose of the study 95% were able to verbalize the benefits, but only 5% understood any potential risks. No parents reported feeling pressured or coerced to sign consent for the project and all parents reported they would enroll their child in additional studies if asked. CONCLUSIONS: Valid consent in the antenatal/perinatal population is difficult, if not impossible, to obtain. To maximize validity of consent in the antenatal/perinatal population every effort should be made to include mothers in the consent process. Additional attention during the consent process should be given to possible risks of the study.

Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.

BACKGROUND: Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates. METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat. FINDINGS: Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024). INTERPRETATION: Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

Changes in neurotrophin levels in umbilical cord blood from infants with different gestational ages and clinical conditions.

Apoptotic neuronal loss may be responsible for altered brain development associated with prematurity and perinatal insults. Neurotrophins play crucial roles in protecting neurons from entering or progressing along an apoptotic pathway. The present study examined levels of neurotrophins in human umbilical cord blood from infants at different gestational ages and clinical conditions. We collected 60 samples of cord blood and categorized them accordingly into three gestational age groups: group A (24-28 wk), group B (29-35 wk), and group C (>/=36 wk). Neurotrophin levels were determined by using brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) ELISA. Clinical data were obtained by medical chart analysis. The BDNF levels were 884 +/- 386, 1421 +/- 616, and 2190 +/- 356 pg/mL in group A, group B, and group C, respectively. Significant differences were found between groups A and B (p = 0.038), groups A and C (p = 0.0001), and groups B and C (p = 0.001). Infants with severe intraventricular hemorrhage had significantly lower cord blood BDNF levels (925 +/- 513 pg/mL) compared with their normal counterparts (1650 +/- 674 pg/mL; p = 0.021). NT3 levels did not show significant change either across gestational ages or with the presence of intraventricular hemorrhage. Cord blood levels of BDNF may reflect the degree of neural maturity in premature infants. Interestingly, when a complete course of antenatal steroids was given, BDNF and NT3 cord blood levels were higher than when no steroid was given. Increased neurotrophins levels may also mediate improved neurodevelopmental outcome in infants who received antenatal steroids.

Hydromorphone transfer into breast milk after intranasal administration.

STUDY OBJECTIVES: To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model. DESIGN: Single-dose, pharmacokinetic study. SETTING: University clinical research unit. PATIENTS: Eight lactating, nonsmoking, healthy women aged 24-32 years. INTERVENTION: Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk. MEASUREMENTS AND MAIN RESULTS: Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk. CONCLUSION: Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.

OxyContin and neonatal abstinence syndrome.

Opioids are a commonly abused class of drugs. OxyContin abuse, a long-acting oxycodone derivative, has been increasingly identified as a potent narcotic resulting in drug dependence, overdose and even death. Use during pregnancy may result in withdrawal symptoms in the neonate. However, detection of the drug and its metabolites needs special methods in order to initiate appropriate therapy.