Does noninvasive electrical stimulation of acupuncture points reduce heelstick pain in neonates?

AIM: Noninvasive electrical stimulation at acupuncture points (NESAP) for analgesia is used in children, but has not been widely studied in neonates. The purpose of this study was to determine whether NESAP alone or in combination with sucrose relieved heelstick pain in neonates. METHODS: Term neonates (n = 162) receiving routine heelsticks for newborn screening were enrolled following parental consent. All infants received facilitated tucking and non-nutritive sucking. Neonates were randomised to standard care, sucrose, NESAP or sucrose plus NESAP. NESAP (3.5 mA, 10 Hz) or sham was administered over four acupuncture points. The Premature Infant Pain Profile (PIPP), heart rate variability (HRV) and salivary cortisol were used to measure heelstick pain. RESULTS: PIPP scores among all four treatment groups increased during heelstick, F (9,119) = 1.95, p = 0.05 and NESAP therapy had no significant effect on PIPP scores. However, PIPP scores from baseline to heelstick increased the most in the two groups not receiving sucrose (p < 0.01). Mean PIPP scores remained below five during the heelstick in all four groups, indicating minimal or no pain. Differences in HRV and salivary cortisol among groups were insignificant. CONCLUSION: NESAP at 3.5 mA, 10 Hz is not effective in relieving pain during heelsticks in neonates.

Time trends and payer differences in lengths of initial hospitalization for preterm infants, Arkansas, 2004 to 2010.

OBJECTIVE: The objective of this study was to examine the time trend in length of stay (LOS) and explore potential differences in neonatal LOS by insurance type for preterm infants in Arkansas between 2004 and 2010. STUDY DESIGN: There were 18,712 preterm infants included in our analyses. Accelerated failure time models were used to model neonatal LOS as a function of insurance type and discharge year while adjusting for key maternal and infant characteristics, and complication/anomaly indicators. RESULTS: Before adjusting for the complication/anomaly indicators, the LOS for preterm infants delivered to mothers in the Medicaid group was 3.2% shorter than those in the private payer group. Furthermore, each subsequent year was associated with a 1.6% increase in the expected LOS. However, after accounting for complications and anomalies, insurance coverage differences in neonatal LOS were not statistically significant while the trend in LOS persisted at a 0.59% increase for each succeeding year. CONCLUSION: All of the apparent differences in LOS by insurance type and more than half of the apparent increase in LOS over time are accounted for by higher rates of complications among privately insured preterm infants and increasing rates of complications for all surviving preterm infants between 2004 and 2010.

Reducing Iatrogenic Blood Losses in Premature Infants.

OBJECTIVE: Iatrogenic blood losses from repetitive laboratory testing are a leading cause of anemia of prematurity and blood transfusions. We used an implementation science approach to decrease iatrogenic blood losses during the first 3 postnatal weeks among very low birth weight infants. METHODS: We performed qualitative interviews of key stakeholders to assess implementation determinants (ie, barriers and facilitators to reducing iatrogenic blood losses), guided by the Consolidated Framework for Implementation Research. Next, we selected implementation strategies matched to these implementation determinants to de-implement excess laboratory tests. The number of laboratory tests, amount of blood taken (ml/kg), and laboratory charges were compared before and after implementation using quasi-Poisson and multi-variable regression models. RESULTS: Qualitative interviews with 14 clinicians revealed implementation-related themes, including provider-specific factors, recurring orders, awareness of blood loss and cost, and balance between over- and under-testing. Implementation strategies deployed included resident education, revised order sets, blood loss and cost awareness, audit and feedback, and the documentation of blood out. There were 184 and 170 infants in the pre- and postimplementation cohorts, respectively. There was an 18.5% reduction in laboratory tests (median 54 [36 - 80] versus 44 [29 - 74], P = .01) in the first 3 postnatal weeks, a 17% decrease in blood taken (mean 18.1 [16.4 - 20.1] versus 15 [13.4 - 16.8], P = .01), and an overall reduction of $290 328 in laboratory charges. No difference was noted in the number of blood transfusions. Postimplementation interviews showed no adverse events attributable to implementation strategies. CONCLUSIONS: An implementation science approach combining qualitative and quantitative methods reduced laboratory tests, blood loss, and charges.

Anxiety, Depression, and Behavioral and/or Conduct Disorder in Adolescence Among Former Preterm and Term Infants of Different Race and Ethnicities.

OBJECTIVE: To compare parental reports of recent diagnoses of anxiety, depression, and/or behavioral/conduct disorder among former preterm (PT) and term adolescents by race/ethnicity and evaluate receipt of mental healthcare within the past year among those adolescents with any of these conditions. STUDY DESIGN: A total of 20,871 Non-Hispanic white (NHW), Non-Hispanic black (NHB), and Hispanic adolescents were evaluated using data from the 2017/2018 National Survey of Children's Health. PT birth and race/ethnicity disparity in the diagnosis of these emotional/behavioral problems and receipt of mental healthcare among adolescents with any of these diagnoses were analyzed using logistic regression. RESULTS: The unadjusted prevalence (95% CI) of these diagnoses was significantly higher among former PT (0.19 [0.17-0.22]) compared to term (0.15 [0.14-0.16]) adolescents. Despite having higher rates of adverse socioeconomic measures, former PT and term NHBs and Hispanics had lower unadjusted prevalence of these diagnoses in comparison to NHWs. After adjusting for differences in demographic, clinical, and socioeconomic characteristics, NHBs (0.47 [0.36-0.64]) and Hispanics (0.40 [0.30-0.54]) remain at lower odds of the composite measure of the emotional and/or behavioral problems compared to NHWs, while PT birth did not have a significant impact on this outcome measure. Only 53% of adolescents with these diagnoses received recent mental healthcare. No significant differences in the adjusted odds of receipt of mental healthcare were noted across the groups based on PT birth or race/ethnicity. CONCLUSIONS: In contrast to PT birth, race/ethnicity had a significant impact on the adjusted odds of emotional/behavioral disorders during adolescence. Among adolescents with these diagnoses, PT birth and race/ethnicity did not significantly influence the adjusted odds of receipt of mental healthcare.

Telehealth innovations in health education and training.

Telehealth applications are increasingly important in many areas of health education and training. In addition, they will play a vital role in biomedical research and research training by facilitating remote collaborations and providing access to expensive/remote instrumentation. In order to fulfill their true potential to leverage education, training, and research activities, innovations in telehealth applications should be fostered across a range of technology fronts, including online, on-demand computational models for simulation; simplified interfaces for software and hardware; software frameworks for simulations; portable telepresence systems; artificial intelligence applications to be applied when simulated human patients are not options; and the development of more simulator applications. This article presents the results of discussion on potential areas of future development, barries to overcome, and suggestions to translate the promise of telehealth applications into a transformed environment of training, education, and research in the health sciences.

Reducing Infant Mortality Using Telemedicine and Implementation Science.

Optimal perinatal regionalization is a proven evidence-based strategy to lower infant mortality. Telemedicine can engage community stakeholders, providers, and patients to facilitate optimal perinatal regionalization leading to lower infant mortality. Rural community caregivers and administrators can participate in forming optimal perinatal guidelines without leaving their community. The visual picture created by telemedicine facilitates better transport decisions; ensuring infants who are transferred to larger centers truly need it while supporting smaller nurseries by providing better consultation services and back transport of patients when appropriate. Telemedicine can also provide educational opportunities to community practices, leading to better evidence-based care.

Ketamine analgesia for inflammatory pain in neonatal rats: a factorial randomized trial examining long-term effects.

BACKGROUND: Neonatal rats exposed to repetitive inflammatory pain have altered behaviors in young adulthood, partly ameliorated by Ketamine analgesia. We examined the relationships between protein expression, neuronal survival and plasticity in the neonatal rat brain, and correlated these changes with adult cognitive behavior. METHODS: Using Western immunoblot techniques, homogenates of cortical tissue were analyzed from neonatal rats 18-20 hours following repeated exposure to 4% formalin injections (F, N = 9), Ketamine (K, 2.5 mg/kg x 2, N = 9), Ketamine prior to formalin (KF, N = 9), or undisturbed controls (C, N = 9). Brain tissues from another cohort of rat pups (F = 11, K = 12, KF = 10, C = 15) were used for cellular staining with Fos immunohistochemistry or FluoroJade-B (FJB), followed by cell counting in eleven cortical and three hippocampal areas. Long-term cognitive testing using a delayed non-match to sample (DNMS) paradigm in the 8-arm radial maze was performed in adult rats receiving the same treatments (F = 20, K = 24, KF = 21, C = 27) in the neonatal period. RESULTS: Greater cell death occurred in F vs. C, K, KF in parietal and retrosplenial areas, vs. K, KF in piriform, temporal, and occipital areas, vs. C, K in frontal and hindlimb areas. In retrosplenial cortex, less Fos expression occurred in F vs. C, KF. Cell death correlated inversely with Fos expression in piriform, retrosplenial, and occipital areas, but only in F. Cortical expression of glial fibrillary acidic protein (GFAP) was elevated in F, K and KF vs. C. No significant differences occurred in Caspase-3, Bax, and Bcl-2 expression between groups, but cellular changes in cortical areas were significantly correlated with protein expression patterns. Cluster analysis of the frequencies and durations of behaviors grouped them as exploratory, learning, preparatory, consumptive, and foraging behaviors. Neonatal inflammatory pain exposure reduced exploratory behaviors in adult males, learning and preparatory behaviors in females, whereas Ketamine ameliorated these long-term effects. CONCLUSION: Neuroprotective effects of Ketamine attenuate the impaired cognitive behaviors resulting from pain-induced cell death in the cortical and hippocampal fields of neonatal rats. This cell death was not dependent on the apoptosis associated proteins, but was correlated with glial activation.

Systemic Absorption of Cyclopentolate and Adverse Events After Retinopathy of Prematurity Exams.

PURPOSE: Preterm infants undergoing Retinopathy of Prematurity Eye Exams (ROPEE) may experience adverse events, possibly from systemic absorption of cyclopentolate. The purpose of this study was to analyze the association between adverse events and drug levels found in neonates undergoing ROPEE. MATERIALS AND METHODS: 25 infants were randomized into two groups during routine ROP screening: 5 infants for blood collection before mydriatic drops and 20 for blood collection 1 h after eye drops. Blood was collected onto dried blood spot cards, extracted, and analyzed for cyclopentolate and phenylephrine using liquid chromatography and mass spectrometry. Relationships between drug levels and adverse events were assessed. RESULTS: Cyclopentolate (range 6-53 ng/ml) was observed in 15 of 18 infants, while phenylephrine was not detected. Levels of cyclopentolate were significantly higher in infants who were on oxygen (p = 0.01). There was a significant association between cyclopentolate levels and gastric residuals in tube-fed infants not receiving oxygen (p = 0.01). CONCLUSIONS: Cyclopentolate levels varied among preterm infants after ROPEE. Cyclopentolate was positively associated with increased gastric residuals. Underlying medical conditions requiring oxygen administration may affect absorption and metabolism of cyclopentolate. There is a need to predict infants at risk for high blood levels of cyclopentolate in order to prevent or treat adverse events after ROPEE.

Effect of inborn versus outborn delivery on clinical outcomes in ventilated preterm neonates: secondary results from the NEOPAIN trial.

OBJECTIVE: The objective of this study was to evaluate the effect of birth center (inborn versus outborn) on morbidity and mortality for preterm neonates (23 to 32 weeks) using data collected prospectively within a uniform protocol. STUDY DESIGN: Secondary analyses of data from the NEurologic Outcomes and Pre-emptive Analgesia In Neonates (NEOPAIN) trial (n=898) were performed to evaluate the effect of inborn versus outborn delivery on neonatal outcomes, including the occurrence of severe intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), chronic lung disease (CLD), and mortality. RESULTS: Outborn babies were more likely to have severe IVH (p=0.0005); this increased risk persisted after controlling for severity of illness. When adjustments for antenatal steroids were added, the effect of birth center was no longer significant. Neither the occurrences of PVL or CLD nor mortality were significantly different between the inborn and outborn infants. CONCLUSION: Outborn babies are more likely to have severe IVH than inborn babies, perhaps because their mothers are less likely to receive antenatal steroids. Improvements in antenatal steroid administration to high-risk women may substantially reduce neonatal morbidity.

Prolonged morphine exposure in utero causes fetal and placental vasoconstriction: a case report.

Vasoconstriction was observed in the fetal middle cerebral and umbilical arteries by Doppler assessment at 27 weeks gestation in a patient requiring continuous morphine infusion for pain control. Fetal heart tracings were also concerning. Fetal status improved after a change to fentanyl infusion, a shorter acting opioid. Caution is recommended when long-term chronic narcotic infusion is used in pregnancy.

Pain management in newborns.

As a standard of care for preterm/term newborns effective pain management may improve their clinical and neurodevelopmental outcomes. Neonatal pain is assessed using context-specific, validated, and objective pain methods, despite the limitations of currently available tools. Therapeutic approaches reducing invasive procedures and using pharmacologic, behavioral, or environmental measures are used to manage neonatal pain. Nonpharmacologic approaches like kangaroo care, facilitated tucking, non-nutritive sucking, sucrose, and others can be used for procedural pain or adjunctive therapy. Local/topical anesthetics, opioids, NSAIDs/acetaminophen and other sedative/anesthetic agents can be incorporated into NICU protocols for managing moderate/severe pain or distress in all newborns.

Safety of Noninvasive Electrical Stimulation of Acupuncture Points During a Routine Neonatal Heel Stick.

BACKGROUND: Hospitalized infants may undergo frequent painful procedures with inadequate pain relief. Alternative pain relief interventions are needed. OBJECTIVE: The aim of this research was to determine the safety of noninvasive electrical stimulation of acupuncture points (NESAP) in neonates who were receiving routine heel sticks. DESIGN: This was a descriptive study performed to assess the safety of using a transcutaneous electrical nerve stimulation (TENS) unit to deliver NESAP to neonates. SETTING/SUBJECTS: The subjects were healthy newborn infants<3 days old before hospital discharge. INTERVENTION: The intervention was NESAP delivered via a TENS unit, administered before, during, and after heel stick. The electrodes of the TENS unit were applied at four acupuncture points. Settings were gradually increased: 6 infants received 1.0 mA, 2 Hz; the second 6 infants received 2.0 mA, 10 Hz; and the last 18 infants received 3.5 mA, 10 Hz. MAIN OUTCOME MEASURES: THREE MAIN MEASURES WERE USED: (1) skin assessment (2) vital signs; (3) pain scores using the Premature Infant Pain Profile (PIPP). RESULTS: There were no significant changes in vital signs during and after NESAP. There were no changes in PIPP scores in the first 12 infants after initiation of NESAP. A slight but nonsignificant increase in PIPP scores (from 2.65 to 3.5 on a scale of 0-18) occurred in the last 18 infants. There were no adverse events during or after NESAP. CONCLUSIONS: NESAP is safe for infants with low settings on a TENS unit.

Improving perinatal regionalization for preterm deliveries in a Medicaid covered population: initial impact of the Arkansas ANGELS intervention.

OBJECTIVE: To examine the factors associated with delivery of preterm infants at neonatal intensive care unit (NICU) hospitals in Arkansas during the period 2001-2006, with a focus on the impact of a Medicaid supported intervention, Antenatal and Neonatal Guidelines, Education, and Learning System (ANGELS), that expanded the consulting capacity of the academic medical center's maternal fetal medicine practice. DATA SOURCES: A dataset of linked Medicaid claims and birth certificates for the time period by clustering Medicaid claims by pregnancy episode. Pregnancy episodes were linked to residential county-level demographic and medical resource characteristics. Deliveries occurring before 35 weeks gestation (n=5,150) were used for analysis. STUDY DESIGN: Logistic regression analysis was used to examine time trends and individual, county, and intervention characteristics associated with delivery at hospitals with NICU, and delivery at the academic medical center. PRINCIPAL FINDINGS: Perceived risk, age, education, and prenatal care characteristics of women affected the likelihood of use of the NICU. The perceived availability of local expertise was associated with a lower likelihood that preterm infants would deliver at the NICU. ANGELS did not increase the overall use of NICU, but it did shift some deliveries to the academic setting. CONCLUSION: Perinatal regionalization is the consequence of a complex set of provider and patient decisions, and it is difficult to alter with a voluntary program.

Late preterm infants: birth outcomes and health care utilization in the first year.

OBJECTIVE: To distinguish the effects of late preterm birth from the complications associated with the causes of delivery timing, this study used propensity score-matching methods on a statewide database that contains information on both mothers and infants. METHODS: Data for this study came from Arkansas Medicaid claims data linked to state birth certificate data for the years 2001 through 2005. We excluded all multiple births, infants with birth defects, and infants at <33 weeks of gestation. Late preterm infants (LPIs) (34 to 36 weeks of gestation) were matched with term infants (37-42 weeks of gestation) according to propensity scores, on the basis of infant, maternal, and clinical characteristics. RESULTS: A total of 5188 LPIs were matched successfully with 15303 term infants. LPIs had increased odds of poor outcomes during their birth hospitalization, including a need for mechanical ventilation (adjusted odds ratio [aOR]: 1.31 [95% confidence interval [CI]: 1.01-1.68]), respiratory distress syndrome (aOR: 2.84 [95% CI: 2.33-3.45]), and hypoglycemia (aOR: 1.60 [95% CI: 1.26-2.03]). Outpatient and inpatient Medicaid expenditures in the first year were both modestly higher (outpatient, adjusted marginal effect: $108 [95% CI: $58-$158]; inpatient, $597 [95% CI: $528-$666]) for LPIs. CONCLUSIONS: LPIs are at increased risk of poor health-related outcomes during their birth hospitalization and of increased health care utilization during their first year.

Ketamine reduces the cell death following inflammatory pain in newborn rat brain.

Premature infants experience untreated repetitive pain that may alter their brain development. Effects of ketamine and repetitive pain on cellular death and subsequent behavior were studied in neonatal rats. Rat pups were randomized to undisturbed controls (C), 4% formalin injection (F), ketamine alone (K, 5 mg/kg) or formalin plus ketamine (KF) and were assessed for neuroactivation with Fos protein, cellular death with FluoroJade-B, cognition with the radial arm maze, and pain thresholds with the hot-plate. Greater Fos expression and cell death occurred in F vs. C groups in defined brain areas at 1 and 4 h in F compared with other groups. Cell death was accentuated 3.3-fold in cortical areas and 1.6-fold in subcortical areas in the F compared with the C group following repetitive pain and sacrifice 18-20 h later. These effects were ameliorated by ketamine. Compared with the F group, all other groups demonstrated greater exploratory and rearing behaviors and decreased time for bait consumption at 1-h and 3-h intervals. Significantly greater thermal pain latencies occurred in the KF and F groups. Repetitive neonatal pain accentuates neuronal excitation and cell death in developmentally regulated cortical and subcortical areas, which decreases the acquisition of visual-spatial clues, short-term and long-term memory, and increases pain latencies. Ketamine analgesia mitigates most of these effects.

Morphine, hypotension, and adverse outcomes among preterm neonates: who's to blame? Secondary results from the NEOPAIN trial.

OBJECTIVES: Hypotension occurs commonly among preterm neonates, but its cause and consequences remain unclear. Secondary data analyses from the NEOPAIN trial identified the clinical factors associated with hypotension and examined the contributions of morphine treatment or hypotension to severe intraventricular hemorrhage (IVH) (grades 3 and 4), any IVH (grades 1-4), or death. METHODS: In the NEOPAIN trial, 898 ventilated neonates between 23 and 32 weeks of gestation were enrolled, with equal numbers randomized to receive masked morphine or placebo infusions. Additional doses of open-label morphine were administered as necessary by medical staff members. IVH was diagnosed with centralized readings of early and late cranial ultrasonograms. Hypotension was assessed before study drug infusion, during the loading dose, and at 24 and 72 hours during study drug infusion. Logistic regression analyses with stepdown elimination identified the predictor factors associated with the hypotension, severe IVH, any IVH, or death outcomes at each time point. RESULTS: Hypotension was associated with 23 to 26 weeks of gestation, morphine infusions, severity of illness, additional morphine doses, and prior hypotension. Severe IVH was associated with shorter gestation, higher Clinical Risk Index for Babies scores, no prenatal steroids, pulmonary hemorrhage, hypotension before the loading dose, and morphine doses before intubation and at 25 to 72 hours. Neonatal deaths were associated with 23 to 26 weeks of gestation, higher Clinical Risk Index for Babies scores, pulmonary hemorrhage, patent ductus arteriosus, thrombocytopenia, and hypotension before the loading dose. Morphine infusions were not a significant factor in logistic models for severe IVH, any IVH, or death. CONCLUSIONS: Preemptive morphine infusions, additional morphine, and lower gestational age were associated with hypotension among preterm neonates. Severe IVH, any IVH, and death were associated with preexisting hypotension, but morphine therapy did not contribute to these outcomes. Morphine infusions, although they cause hypotension, can be used safely for most preterm neonates but should be used cautiously for 23- to 26-week neonates and those with preexisting hypotension.