Correlation Between White Matter Injury Identified by Neonatal Diffusion Tensor Imaging and Neurodevelopmental Outcomes Following Term Neonatal Asphyxia and Therapeutic Hypothermia: An Exploratory Pilot Study.

AIM: Hypoxic-ischemic encephalopathy is associated with damage to deep gray matter; however, white matter involvement has become recognized. This study explored differences between patients and clinical controls on diffusion tensor imaging, and relationships between diffusion tensor imaging and neurodevelopmental outcomes. METHOD: Diffusion tensor imaging was obtained for 31 neonates after hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and 10 clinical controls. A subgroup of patients with hypoxic-ischemic encephalopathy (n = 14) had neurodevelopmental outcomes correlated with diffusion tensor imaging scalars. RESULTS: Group differences in diffusion tensor imaging scalars were observed in the putamen, anterior and posterior centrum semiovale, and the splenium of the corpus callosum. Differences in these regions of interest were correlated with neurodevelopmental outcomes between ages 20 and 32 months. CONCLUSION: Therapeutic hypothermia may not be a complete intervention for hypoxic-ischemic encephalopathy, as neonatal white matter changes may continue to be evident, but further research is warranted. Patterns of white matter change on neonatal diffusion tensor imaging correlated with neurodevelopmental outcomes in this exploratory pilot study.

Newborn care practices in rural Bangladesh: Implications for the adaptation of kangaroo mother care for community-based interventions.

Bangladesh has one of the world's highest rates of low birth weight along with prevalent traditional care practices that leave newborns highly vulnerable to hypothermia, infection, and early death. We conducted formative research to explore existing newborn care practices in rural Bangladesh with an emphasis on thermal protection, and to identify potential facilitators, barriers, and recommendations for the community level delivery of kangaroo mother care (CKMC). Forty in-depth interviews and 14 focus group discussions were conducted between September and December 2012. Participants included pregnant women and mothers, husbands, maternal and paternal grandmothers, traditional birth attendants, village doctors, traditional healers, pharmacy men, religious leaders, community leaders, and formal healthcare providers. Audio recordings were transcribed and translated into English, and the textual data were analyzed using the Framework Approach. We find that harmful newborn care practices, such as delayed wrapping and early initiation of bathing, are changing as more biomedical advice from formal healthcare providers is reaching the community through word-of-mouth and television campaigns. While the goal of CKMC was relatively easily understood and accepted by many of the participants, logistical and to a lesser extent ideological barriers exist that may keep the practice from being adopted easily. Women feel a sense of inevitable responsibility for household duties despite the desire to provide the best care for their new babies. Our findings showed that participants appreciated CKMC as an appropriate treatment method for ill babies, but were less accepting of it as a protective method of caring for seemingly healthy newborns during the first few days of life. Participants highlighted the necessity of receiving help from family members and witnessing other women performing CKMC with positive outcomes if they are to adopt the behavior themselves. Focusing intervention messages on building a supportive environment for CKMC practice will be critical for the intervention's success.

Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants.

OBJECTIVE: To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk. STUDY DESIGN: Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC). RESULTS: Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively (P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04. CONCLUSIONS: In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit.

Posthemorrhagic hydrocephalus in preterm neonates: socioeconomic characteristics in a single-institution experience.

UNLABELLED: Patients with posthemorrhagic hydrocephalus (PHH) from germinal matrix hemorrhage of prematurity often require numerous early interventions, as well as long-term follow-up care from pediatric neurosurgeons, which continues to place high demands on the existing workforce and pediatric health care system. There are established correlations between premature birth and low socioeconomic status. The aim of this study is to characterize the demographic profile and follow-up patterns in this subpopulation of surgically treated infants with PHH from prematurity. METHODS: A retrospective analysis of the electronic patient records for a single institution, from 2007 to 2010, was performed. All patients who underwent neurosurgical intervention for the treatment of PHH were selected for further analysis. Data elements available within the records included patient demographic features, inpatient treatments and procedures, inpatient mortality rates, length of stay, and postoperative follow-up at the institution. Socioeconomic status was assessed using the median household income for the patient's zip code, as reported in the United States Census for the year 2000. RESULTS: A total of 40 patients who underwent neurosurgical intervention for PHH at a single institution were identified. More patients were female (52.5%); the majority of patients were Black (57.5%). No patients were uninsured; most patients had public insurance (62.5%), and 65% were below the Maryland State median household income (USD 52,868). There were trends toward more frequent emergency room visits among those covered by public insurance and those below the state and national median house income, although differences were not statistically significant. CONCLUSIONS: Our data indicate that the majority of patients fall within lower household income brackets, are born into households earning less than the statewide median household income, and are covered by public insurance. In light of the socioeconomic profile of the patient population reported here, these data may prove to be useful in preventative strategies aimed toward prematurity, PHH, and the ongoing treatment of hydrocephalus by pediatric neurosurgeons and other pediatric subspecialists.

Outcomes of preterm infants: morbidity replaces mortality.

Over the last 50 years in the United States a rising preterm birth rate, a progressive decrease in preterm mortality, and a lowering of the limit of viability have made preterm birth a significant public health problem. Neuromaturation, the functional development of the central nervous system (CNS), is a dynamic process that promotes and shapes CNS structural development. This article reviews preterm outcomes, recognizing that multiple factors influence neuromaturation and lead to a range of neurodevelopmental disabilities, dysfunctions, and altered CNS processing. Ways to protect preterm infants and support their growth and development in and beyond intensive care are examined.

Isolated prenatal choroid plexus cysts do not affect child development.

OBJECTIVE: To examine the effect of isolated prenatal choroid plexus cysts (CPCs) on child cognitive, behavioral, motor, and autonomic development at 18 months of age. METHODS: A prospective design was implemented to identify CPC cases and controls in mid-pregnancy. Cases (n = 25) and controls (n = 45) participated in a follow-up visit when children were 18 months of age. Child mental and motor development was assessed using standard developmental assessments, socioemotional and behavioral functioning during testing was rated by examiners, and accelerometers provided measures of motor activity and energy expenditure. Cardiac patterns were collected using a three-lead electrocardiogram (ECG) and quantified as indicators of autonomic control of the heart, including vagal tone. RESULTS: No significant differences were found in any outcome measure between children with prenatal CPC detection and those without. CONCLUSION: Findings should provide reassurance to practitioners and parents that isolated CPCs in fetuses with normal karyotypes do not affect child development after birth.

An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products.

OBJECTIVE: To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants. STUDY DESIGN: Infants fed their own mothers' milk were randomized to 1 of 3 study groups. Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor human milk if no mother's milk was available. Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother's milk was available. Outcomes included duration of parenteral nutrition, morbidity, and growth. RESULTS: The 3 groups (total n = 207 infants) had similar baseline demographic variables, duration of parenteral nutrition, rates of late-onset sepsis, and growth. The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis (NEC; P = .02) and NEC requiring surgical intervention (P = .007). CONCLUSIONS: For extremely premature infants, an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother's milk-based diet that also includes bovine milk-based products.

Extrauterine neuromaturation of low risk preterm infants.

The objective of the study was to follow neuromaturation in preterm infants. From serial exams in 90 low risk very low birthweight infants, each infant's Maturity Scores (the sum of tone, reflex, and response items) were plotted against postmenstrual age (PMA) when examined. Each infant's estimated line of best fit provides two descriptors of that infant's neuromaturation: slope (Individual Maturity Slope) and y-value (Predicted Maturity Score at 32-wk PMA). We found that Maturity Scores increased with PMA; 96% had correlation coefficients >0.8. Mean Actual and Predicted Maturity Scores at 32-wk PMA were 60 and 58, respectively, in 65 infants. When stratified by gestational age, Mean Actual Maturity Score at 30-wk PMA were 50 whether infants were 1 or several weeks old when examined. Therefore, low risk preterm infants demonstrated individual variability in rate of neuromaturation. Tone, reflexes, and responses nonetheless emerged in a predictable pattern, whether neuromaturation was intrauterine or extrauterine. This unique tool that measures preterm neuromaturation requires expertise but no technology. It has an exciting potential for providing insight into how emerging central nervous system function and structure influence each other, as well as how the central nervous system recovers from injury.

Caffeine modulates TNF-alpha production by cord blood monocytes: the role of adenosine receptors.

Caffeine, a nonspecific adenosine receptor (AR) antagonist is widely used to treat apnea of prematurity. Because adenosine modulates multiple biologic processes including inflammation, we hypothesized that AR blockade by caffeine would increase cytokine release from neonatal monocytes. Using cord blood monocytes (CBM), we investigated 1) the changes in AR mRNA profile by real time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and protein expression (western blot) after in vitro culture, caffeine or lipopolysaccharide (LPS) exposure, and 2) the modulation of cytokine release and cyclic adenosine monophosphate (cAMP) production by enzyme-linked immunosorbent assay (ELISA) induced by caffeine and specific AR antagonists: DPCPX(A1R), ZM241385(A2aR), MRS1754(A2bR), and MRS1220(A3R). After 48 h in culture, A2aR and A2bR gene expression increased 1.9 (p = 0.04) and 2.5-fold (p = 0.003), respectively. A1R protein expression directly correlated with increasing LPS concentrations (p = 0.01), with minimal expression preexposure. Only caffeine (50 microM) and DPCPX (10 nM) decreased tumor necrosis factor-alpha (TNF-alpha) release from LPS activated-CBM by 20 and 25% (p = 0.01) and TNF-alpha gene expression by 30 and 50%, respectively, in conjunction with a > or =2-fold increase in cAMP (p < 0.05). AR blockade did not modulate other measured cytokines. The induction of A1R after LPS exposure suggests an important role of this receptor in the control of inflammation in neonates. Our findings also suggest that caffeine, via A1R blockade, increases cAMP production and inhibits pretranscriptional TNF-alpha production by CBM.