Roberta Pineda

Neonatal intensive care unit stress is associated with brain development in preterm infants

Although many perinatal factors have been linked to adverse neurodevelopmental outcomes in very premature infants, much of the variation in outcome remains unexplained. The impact on brain development of 1 potential factor, exposure to stressors in the neonatal intensive care unit, has not yet been studied in a systematic, prospective manner.

Alterations in Brain Structure and Neurodevelopmental Outcome in Preterm Infants Hospitalized in Different Neonatal Intensive Care Unit Environments

OBJECTIVE To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology, and brain structure at hospital discharge; and developmental outcomes at 2 years of age. STUDY DESIGN In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at 2 years of age (n = 86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were: (1) medical factors throughout the hospitalization; (2) neurobehavior; and (3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). RESULTS At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores (P = .02; β = -0.52 [CI -0.95, -0.10]). At age 2 years, infants from private rooms had lower language scores (P = .006; β = -8.3 [CI -14.2, -2.4]) and a trend toward lower motor scores (P = .02; β = -6.3 [CI -11.7, -0.99]), which persisted after adjustment for potential confounders. CONCLUSION These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.

Parental presence and holding in the neonatal intensive care unit and associations with early neurobehavior.

Objective:To investigate the effects of parental presence and infant holding in the neonatal intensive care unit (NICU) on neurobehavior at term equivalent.Study Design:Prospective cohort enrolled 81 infants born ⩽30 weeks gestation. Nurses tracked parent visitation, holding and skin-to-skin care throughout the NICU hospitalization. At term, the NICU Network Neurobehavioral Scale was administered. Associations between visitation, holding and early neurobehavior were determined using linear and logistic regression.Result:The mean hours per week of parent visitation was 21.33±20.88 (median=13.90; interquartile range 10.10 to 23.60). Infants were held an average of 2.29±1.47 days per week (median=2.00; interquartile range 1.20 to 3.10). Over the hospital stay, visitation hours decreased (P=0.01), while holding frequencies increased (P<0.001). More visitation was associated with better quality of movement (P=0.02), less arousal (P=0.01), less excitability (P=0.03), more lethargy (P=0.01) and more hypotonia (P<0.01). More holding was associated with improved quality of movement (P<0.01), less stress (P<0.01), less arousal (P=0.04) and less excitability (P<0.01).Conclusion:Infants of caregivers who were visited and held more often in the NICU had differences in early neurobehavior by term equivalent, which supports the need for and importance of early parenting in the NICU.

The single-patient room in the NICU: maternal and family effects.

Objective:To explore differences in maternal factors, including visitation and holding, among premature infants cared for in single-patient rooms (SPR) compared with open-bay in the neonatal intensive care unit (NICU).Study Design:A total of 81 premature infants were assigned to a bed space in either the open-bay area or in a SPR upon NICU admission, based on bed space and staffing availability in each area. Parent visitation and holding were tracked through term equivalent, and parents completed a comprehensive questionnaire at discharge to describe maternal health. Additional maternal and medical factors were collected from the medical record. Differences in outcome variables were investigated using linear regression.Result:No significant differences in gestational age at birth, initial medical severity, hours of intubation or other factors that could affect the outcome were observed across room type. Significantly more hours of visitation were observed in the first 2 weeks of life (P=0.02) and in weeks 3 and 4 (P=0.02) among infants in the SPR. More NICU stress was reported by mothers in the SPR after controlling for social support (P=0.04).Conclusion:Increased parent visitation is an important benefit of the SPR, however, mothers with infants in the SPR reported more stress.

Maternal obesity and increased risk for autism and developmental delay among very preterm infants

Objective:Thirty-five percent of women of child-bearing age are obese, and there is evidence that maternal obesity may increase the risk for adverse neurodevelopmental outcome. However, research regarding obesity and neurodevelopment among children born preterm is limited. This study aimed to determine associations between maternal obesity and neurodevelopment in very preterm children at age 2 years.Study Design:Maternal/infant dyads (n=62) born ⩽30 weeks gestation were enrolled in a prospective cohort study at a level-III neonatal intensive care unit. Mothers were classified as obese or non-obese based on pre-pregnancy body mass index. Infants underwent magnetic resonance imaging at term equivalent and developmental testing at age 2. Maternal obesity was investigated for associations with neurodevelopment.Result:Maternal obesity was associated with positive screen for autism (odds ratio=9.88, P=0.002) and lower composite language scores (β=−9.36, (confidence interval=−15.11, −3.61), P=0.002).Conclusion:Maternal obesity was associated with adverse neurodevelopmental outcome at age 2 in this cohort of very preterm children. This study requires replication, but may support targeted surveillance of infants born to women with maternal obesity.

Factors associated with feeding difficulties in the very preterm infant

To investigate early medical and family factors associated with later feeding risk in preterm infants.

A pilot randomized trial of high-dose caffeine therapy in preterm infants

Background:Standard-dose caffeine improves white matter microstructural development assessed by diffusion magnetic resonance imaging (MRI). We hypothesized that early high-dose caffeine would result in further improvement in white matter microstructural development.Methods:Seventy-four preterm infants (≤30 wk gestational age) were randomly assigned to either a high (80 mg/kg i.v.) or standard (20 mg/kg i.v.) loading dose of caffeine citrate in the first 24 h of life. MRI and neurobehavioral testing were undertaken at term equivalent age. Infants returned at 2 y of age for developmental testing.Results:Clinical characteristics were similar between groups, with the exception of higher maternal age in the high-dose caffeine group. There was an increased incidence of cerebellar hemorrhage in infants randomized to high-dose caffeine (36 vs. 10%, P = 0.03). Infants in the high-dose caffeine group also demonstrated more hypertonicity (P = 0.02) and more deviant neurologic signs (P = 0.04) at term equivalent age. Diffusion measures at term equivalent age and developmental outcomes at 2 y of age did not differ between groups.Conclusion:Preterm infants randomized to early high-dose caffeine had a higher incidence of cerebellar injury with subsequent alterations in early motor performance. The results of this pilot trial discourage a larger randomized controlled trial.

The effects of alternative positioning on preterm infants in the neonatal intensive care unit: a randomized clinical trial.

There is a paucity of studies that have investigated the developmental benefits of positioning in the neonatal intensive care unit. The purpose of this study was to investigate the effects of a new, alternative positioning device compared to traditional positioning methods used with preterm infants. In this randomized, blinded clinical trial, one hundred preterm infants (born ≤ 32 weeks gestation) from a level III neonatal intensive care unit in the United States were enrolled at birth. Participants were randomized to be positioned in the alternative positioning device or to traditional positioning methods for their length of stay in the neonatal intensive care unit. Infants were assessed using the NICU Network Neurobehavioral Scale between 35-40 weeks postmenstrual age. Clinical and feeding outcomes were also captured. Linear and logistic regressions were used to investigate differences in neurobehavioral outcome, feeding performance, and medical outcomes. Infants in the alternative positioning arm of the study demonstrated less asymmetry of reflex and motor responses on the NICU Network Neurobehavioral Scale (p=0.04; adjusted mean difference=0.90, 95% CI 0.05-1.75) than those positioned using traditional positioning methods. No other significant differences were observed. Reduction in asymmetry among preterm infants is an important benefit of alternative positioning, as symmetrical movement and responses are crucial for early development. However, it will be important to follow this sample of preterm infants to determine the effects of early positioning on neurodevelopmental outcome in childhood.

Enhancing sensory experiences for very preterm infants in the NICU: an integrative review

Objective:Very preterm infants hospitalized in the neonatal intensive care unit (NICU) experience alterations in sensory experiences. Defining types, timing and frequency of sensory-based interventions that optimize outcomes can inform environmental modifications. The objective of this study was to conduct an integrative review on sensory-based interventions used with very preterm infants in the NICU to improve infant and parent outcomes.Study Design:The data sources include MEDLINE, CINAHL, Cochrane Library and Google Scholar. Studies were identified that used sensory-based interventions in the NICU with preterm infants born ⩽32 weeks gestation, were published in a peer-reviewed journal between 1995 and 2015, and measured outcomes related to infant and parent outcomes. Studies were extracted from electronic databases and hand-searched from identified reference lists.Results:Eighty-eight articles were identified (31 tactile, 12 auditory, 3 visual, 2 kinesthetic, 2 gustatory/olfactory and 37 multimodal). There was evidence to support the use of kangaroo care, music and language exposure, and multimodal interventions starting at 25 to 28 weeks postmenstrual age. These interventions were related to better infant development and lower maternal stress, but not all findings were consistent. Limitations included lack of consistent outcome measures, study quality and gaps in the literature.Conclusions:Most research identified interventions that were done for short periods of time. It is unclear what the potential is for improving outcomes if positive sensory exposures occur consistently throughout NICU hospitalization. Until more research defines appropriate sensory-based interventions to use with infants born very preterm in the NICU, information from this review can be combined with expert opinion and parent/family values to determine best practice.

Brain Injury and Development in Preterm Infants Exposed to Fentanyl

Background: Fentanyl is commonly used in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. Objective: To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants. Methods: Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤30 weeks gestational age (mean gestational age 26.9 ± 1.8 weeks) who underwent magnetic resonance imaging at term equivalent age. Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. Results: Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 µg/kg, interquartile range 1-441 µg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (odds ratio 2.1, 95% confidence interval 1.1-4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates, including the presence of cerebellar hemorrhage (r = 0.461, P = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. Conclusions: Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly used analgesic agents in preterm infants.