Peritoneal dialysis and neurological outcome in infants and small children

Although improved outcomes for children on peritoneal dialysis (PD) have been seen in recent years, the youngest patients continue to demonstrate inferior growth, more frequent infections, more neurological sequelae, and higher mortality compared to older children. Also, maintain-ing normal intravascular volume status, especially in anuric patients, has proven difficult. This study was designed to treat and monitor these youngest PD patients, which are relatively many due to the high prevalence of congenital nephrotic syndrome of the Finnish type (CNF, NPHS1) in Finland, with a strict protocol, to evaluate the results and to improve metabolic balance, growth, and development. A retrospective analysis of 23 children under two years of age at onset of PD, treated between 1995 and 2000, was performed to obtain a control population for our prospective PD study. Respectively, 21 patients less than two years of age at the beginning of PD were enrolled in prospective studies between 2001 and 2005. Medication for uremia and nutrition were care-fully adjusted during PD. Laboratory parameters and intravascular volume status were regu-larly analyzed. Growth was analyzed and compared with midparental height. In a prospective neurological study, the risk factors for development and the neurological development was determined. Brain images were surveyed. Hearing was tested. In a retrospective neurological study, the data of six NPHS1 patients with a congruent neurological syndrome was analyzed. All these patients had a serious dyskinetic cerebral palsy-like syndrome with muscular dysto-nia and athetosis (MDA). They also had a hearing defect. Metabolic control was mainly good in both PD patient groups. Hospitalization time shortened clearly. The peritonitis rate diminished. Hypertension was a common problem. Left ventricular hypertrophy decreased during the prospective study period. None of the patients in either PD group had pulmonary edema or dialysis-related seizures. Growth was good and catch-up growth was documented in most patients in both patient groups during PD. Mortality was low (5% in prospective and 9% in retrospective PD patients). In the prospective PD patient group 11 patients (52%) had some risk factor for their neuro-development originating from the predialysis period. The neurological problems, detected be-fore PD, did not worsen during PD and none of the patients developed new neurological com-plications during PD. Brain infarcts were detected in four (19%) and other ischemic lesions in three patients (14%). At the end of this study, 29% of the prospectively followed patients had a major impairment of their neurodevelopment and 43% only minor impairment. In the NPHS1+MDA patients, no clear explanation for the neurological syndrome was found. The brain MRI showed increased signal intensity in the globus pallidus area. Kernic-terus was contemplated to be causative in the hypoproteinemic newborns but it could not be proven. Mortality was as high as 67%. Our results for young PD patients were promising. Metabolic control was acceptable and growth was good. However, the children were significantly smaller when compared to their midparental height. Although many patients were found to have neurological impairment at the end of our follow-up period, PD was a safe treatment whereby the neurodevelopment did not worsen during PD.

SOCIAL-DEVELOPMENT OF INFANTS OF MACACA-THIBETANA AT MOUNT-EMEI, CHINA

The development of infant Macaca thibetana was studied at Mount Emei, China, and compared to that of other macaque species. It was found that there are many common features in the process of infant socialization in species of the genus Macaca: mothers play an important and active role, other group members influence the infants' development to a greater or lesser extent and play is a major activity in the life of infants. Some differences were found to exist, however, between macaque species. These included differences in maternal care behaviour such as 'len', leaving time and weaning time. Paternal behaviours were also found to vary within and among species. Tibetan macaque males care for infants extensively, and they may use infants as an agonistic buffer. The natural and social environment may also influence differences between macaque species in infant development.

A Multicenter, Randomised Open Study of Early Corticosteroid Treatment (OSECT) in Preterm Infants With Respiratory Illness: Comparison of Early and Late Treatment and of Dexamethasone and Inhaled Budesonide

AIM: To compare early (15 days) steroid therapy and dexamethasone with inhaled budesonide in very preterm infants at risk of developing chronic lung disease. METHODS: Five hundred seventy infants from 47 neonatal intensive care units were enrolled. Criteria for enrollment included gestational age 30%. Infants were randomly allocated to 1 of 4 treatment groups in a factorial design: early (15 days) dexamethasone, and delayed selective budesonide. Dexamethasone was given in a tapering course beginning with 0.50 mg/kg/day in 2 divided doses for 3 days reducing by half until 12 days of therapy had elapsed. Budesonide was administered by metered dose inhaler and a spacing chamber in a dose of 400 microg/kg twice daily for 12 days. Delayed selective treatment was started if infants needed mechanical ventilation and >30% oxygen for >15 days. The factorial design allowed 2 major comparisons: early versus late treatment and systemic dexamethasone versus inhaled budesonide. The primary outcome was death or oxygen dependency at 36 weeks and analysis was on an intention-to-treat basis. Secondary outcome measures included death or major cerebral abnormality, duration of oxygen treatment, and complications of prematurity. Adverse effects were also monitored daily. RESULTS: There were no significant differences among the groups for the primary outcome. Early steroid treatment was associated with a lower primary outcome rate (odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.61,1.18) but even after adjustment for confounding variables the difference remained nonsignificant. Dexamethasone-treated infants also had a lower primary outcome rate (OR: 0.86; 95% CI: 0.62,1.20) but again this difference remained not significant after adjustment. For death before discharge, dexamethasone and early treatment had worse outcomes than budesonide and delayed selective treatment (OR: 1.42; 95% CI: 0.93,2.16; OR: 1.51; 95% CI: 0.99,2.30 after adjustment, respectively) with the results not quite reaching significance. Duration of supplementary oxygen was shorter in the early dexamethasone group (median: 31 days vs 40-44 days). Early dexamethasone was also associated with increased weight loss during the first 12 days of treatment (52 g vs 3 g) compared with early budesonide, but over 30 days there was no difference. In the early dexamethasone group, there was a reduced incidence of persistent ductus arteriosus (34% vs 52%-59%) and an increased risk of hyperglycemia (55% vs 29%-34%) compared with the other 3 groups. Dexamethasone was associated with an increased risk of hypertension and gastrointestinal problems compared with budesonide but only the former attained significance. CONCLUSIONS: Infants given early treatment and dexamethasone therapy had improved survival without chronic lung disease at 36 weeks compared with those given delayed selective treatment and inhaled budesonide, respectively, but results for survival to discharge were in the opposite direction; however, none of these findings attained statistical significance. Early dexamethasone treatment reduced the risk of persistent ductus arteriosus. Inhaled budesonide may be safer than dexamethasone, but there is no clear evidence that it is more or less effective

Utilization of analgesics, sedatives, and pain scores in infants with a prolonged hospitlaization: A prospective descriptive cohort study

Aim
Describe the utilization of analgesic and sedative medications and documentation of pain scores in a cohort of critically ill infants in a neonatal intensive care unit.

Method
A prospective, longitudinal, cohort study of infants with a predicted length of stay =28 days. Dosages and routes of administration of analgesic and sedative medications and documentation of pain scores were collected on a daily basis.

Results
55 infants were enrolled into the study. Oral sucrose was administered to all 55 infants, 51 infants (93%) were administered enteral acetaminophen and 50 (91%) infants were administered morphine during their hospitalization. Sedatives were administered to 42 infants (76%); 36 (65%) were administered chloral hydrate and 32 (58%) were administered intravenous midazolam. With the exception of the first week of admission, when there was highest utilization of opioids and lower use of sucrose, acetaminophen and sedatives, the pattern of administration of analgesic and sedative agents remained relatively constant throughout the hospitalization. Pain scores were documented for 36 (65%) infants during their hospitalisation, however for these 36 infants, pain scores were infrequently recorded.

Conclusion
There was substantial and varied analgesic and sedative use in this cohort of infants, yet infrequent documentation of pain assessment scores. These practices highlight important clinical implications for sick infants requiring careful consideration of pain and distress management.

In Vivo Age Dependency of Unfractionated Heparin in Infants and Children

Introduction
Unfractionated Heparin (UFH) is used widely in paediatrics. Paediatric specific recommendations for UFH therapy are few, with the majority of recommendations being extrapolated from adult practice. In vitro studies have shown that this practice may be suboptimal. This study aimed to improve the understanding of the impact of age upon UFH response in vivo.

Materials and Methods
This prospective, observational study, conducted in the Paediatric Intensive Care Unit (PICU), included: patients 16 years or younger; treated with UFH of at least 10 U/Kg/hr. Laboratory analysis included: Antithrombin, APTT, Anti-Xa, Anti-IIa and thrombin generation expressed as the Endogenous Thrombin Potential. Results were grouped according to patient age (i.e. < 1, 1-5, 6-10 and 11-16 years).

Results
85 patients received an equivalent mean UFH dose with a median duration of 3 days. Antithrombin levels were decreased compared to age-related norms in children up to 11 years of age. APTT results were comparable across the age-groups. The Anti-Xa results using two different assays showed a trend for lower values in younger children. All children less than one year old recorded Anti-Xa values outside the therapeutic range for heparin therapy, for both assays. There was a trend for decreased Anti-IIa activity in younger children. Endogenous Thrombin Potential showed a significant trend for increased inhibition in older children. In vitro Antithrombin supplementation did not change the Anti-Xa or thrombin generation.

Conclusions
This study confirms that, in vivo, for the same dose of UFH, the anti Xa and anti IIa effect, as well as the inhibition of endogenous thrombin potential is age dependent and that these differences are not purely AT dependent. The implication is that the anticoagulant and antithrombotic effect of a given dose of UFH differs with age. Clinical outcome studies to determine the optimal dosing for each age group are warranted.

Abbreviations
UFH, Unfractionated Heparin; ETP, Endogenous Thrombin Potential; AT, Antithrombin; APTT, Activated Partial Thromboplastin Time

Developmental care for high-risk newborns:Emerging science, clinical application, and continuity from newborn intensive care unit to community

Neonatology has optimized medical outcomes for high-risk newborns yet neurodevelopmental outcomes continue to be a concern. Basic science, clinical research, and environmental design perspectives have shown the impact of the caregiving environment on the developing brain and the role of professional caregivers in providing supportive intervention to both infants and their families. This recognition has prompted a focus on early developmentally supportive care (DSC) for high-risk newborns both in the hospital and in community follow up. DSC has emerged as a recognized standard of care in most neonatal intensive care units. Still, many questions remain and much integrative research is needed.

Experiences of fathering a baby admitted to neonatal intensive care: A critical gender analysis

More fathers than ever before attend at the birth of their child and, internationally, there is a palpable pressure on maternity and neonatal services to include and engage with fathers. It is, thus, more important than ever to understand how fathers experience reproductive and neonatal health services and to understand how fathers can be successfully accommodated in these environments alongside their partners. In this paper we advance a theoretical framework for re-thinking fatherhood and health services approaches to fatherhood based on Critical Studies of Men and Masculinities (CSM). We illustrate the importance of this feminist-informed theoretical approach to understanding the gendered experiences of fathers in a Neonatal Intensive Care Unit (NICU) setting. Using a longitudinal follow-up research design, with two data collection points, a total of 39 in-depth semi-structured interviews was conducted with 21 fathers of infants admitted to NICU between August 2008 and December 2009. The findings demonstrate: (i) ways in which men are forging new gendered identities around the birth of their baby but, over time, acknowledge women as the primary caregivers; (ii) how social class is a key determinant of men’s ability to enact hegemonic forms of ‘involved fatherhood’ in the NICU, and; (iii) how men also encounter resistance from their partners and health professionals in challenging a gender order which associates women with the competent care of infants. An understanding of these gendered experiences operating at both individual and structural levels is critical to leading change for the inclusion of fathers as equal parents in healthcare settings. © 2012 Elsevier Ltd. All rights reserved.

Regional Follow up of Late Preterm Neonatal Intensive Care Graduates: Methodological Considerations.

The aim is to guide researchers who are contemplating embarking on research by discussing the methodological challenges encountered in a retrospective follow-up study of three-year-old, late preterm infants (LPIs) who received neonatal intensive care (NIC) in Northern Ireland in 2006. The importance of effective research examining the longer term outcomes of infants admitted to NIC has received increasing recognition. Follow-up cohort and longitudinal studies have grown in number globally, yet the research methodology relating to follow up of NIC graduates is unclear. This paper highlights the methodological challenges of conducting retrospective follow-up research, from the initial planning stages through to the collection of data from the children, including identification of infants from a retrospective database, ethical issues, child-safety concerns and recruitment challenges. This paper creates an awareness of potential issues that may arise in follow-up research with NIC graduates. The paper also offers practical and effective examples of dealing with these issues, helping to ensure the smooth running of an ethical, professionally conducted, methodologically sound and clinically relevant follow-up study.

Electroencephalographic Activity in Response to Procedural Pain in Preterm Infants Born at 28 and 33 Weeks Gestational Age

OBJECTIVES:: Preterm infants undergo frequent painful procedures in the neonatal intensive care unit. Electroencephalography (EEG) changes in reaction to invasive procedures have been reported in preterm and full-term neonates. Frontal EEG asymmetry as an index of emotion during tactile stimulation shows inconsistent findings in full-term infants, and has not been examined in the context of pain in preterm infants. Our aim was to examine whether heel lance for blood collection induces changes in right-left frontal asymmetry, suggesting negative emotional response, in preterm neonates at different gestational age (GA) at birth and different duration of stay in the neonatal intensive care unit. MATERIALS AND METHODS:: Three groups of preterm infants were compared: set 1: group 1 (n=24), born and tested at 28 weeks GA; group 2 (n=22), born at 28 weeks GA and tested at 33 weeks; set 2: group 3 (n=25), born and tested at 33 weeks GA. EEG power was calculated for 30-second artifact-free periods, in standard frequency bandwidths, in 3 phases (baseline, up to 5 min after heel lance, 10 min after heel lance). RESULTS:: No significant differences were found in right-left frontal asymmetry, or in ipsilateral or contralateral somatosensory response, across phases. In contrast, the Behavioral Indicators of Infant Pain scores changed across phase (P

Neonatal pain in relation to postnatal growth in infants born very preterm

Procedural pain is associated with poorer neurodevelopment in infants born very preterm (= 32 weeks gestational age), however, the etiology is unclear. Animal studies have demonstrated that early environmental stress leads to slower postnatal growth; however, it is unknown whether neonatal pain-related stress affects postnatal growth in infants born very preterm. The aim of this study was to examine whether greater neonatal pain (number of skin-breaking procedures adjusted for medical confounders) is related to decreased postnatal growth (weight and head circumference [HC] percentiles) early in life and at term-equivalent age in infants born very preterm. Participants were n=78 preterm infants born = 32 weeks gestational age, followed prospectively since birth. Infants were weighed and HC measured at birth, early in life (median: 32 weeks [interquartile range 30.7-33.6]) and at term-equivalent age (40 weeks [interquartile range 38.6-42.6]). Weight and HC percentiles were computed from sex-specific British Columbia population-based data. Greater neonatal pain predicted lower body weight (Wald ?(2)=7.36, P=0.01) and HC (Wald ?(2)=4.36, P=0.04) percentiles at 32 weeks postconceptional age, after adjusting for birth weight percentile and postnatal risk factors of illness severity, duration of mechanical ventilation, infection, and morphine and corticosteroid exposure. However, later neonatal infection predicted lower weight percentile at term (Wald ?(2)=5.09, P=0.02). Infants born very preterm undergo repetitive procedural pain during a period of physiological immaturity that appears to impact postnatal growth, and may activate a downstream cascade of stress signaling that affects later growth in the neonatal intensive care unit.

School entry age outcomes for infants with birth weight ≤ 800 grams

To evaluate the mortality and long-term morbidity rates of extremely low birth weight (ELBW) infants admitted to neonatal intensive care units (NICUs).

Cortisol, behavior, and heart rate reactivity to immunization pain at 4 months corrected age in infants born very preterm

Pain response may be altered in infants born very preterm owing to repeated exposure to procedures in the neonatal intensive care unit. Findings have been inconsistent in studies of behavioral and cardiac responses to brief pain in preterm versus full-term infants following neonatal intensive care unit discharge. To our knowledge, cortisol reactivity to pain has not been compared in preterm and full-term infants. We examined pain reactivity to immunization in preterm and full-term infants.

Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants

Procedural pain in the neonatal intensive care unit triggers a cascade of physiological, behavioral and hormonal disruptions which may contribute to altered neurodevelopment in infants born very preterm, who undergo prolonged hospitalization at a time of physiological immaturity and rapid brain development. The aim of this study was to examine relationships between cumulative procedural pain (number of skin-breaking procedures from birth to term, adjusted for early illness severity and overall intravenous morphine exposure), and later cognitive, motor abilities and behavior in very preterm infants at 8 and 18 months corrected chronological age (CCA), and further, to evaluate the extent to which parenting factors modulate these relationships over time. Participants were N=211 infants (n=137 born preterm 32 weeks gestational age [GA] and n=74 full-term controls) followed prospectively since birth. Infants with significant neonatal brain injury (periventricular leucomalacia, grade 3 or 4 intraventricular hemorrhage) and/or major sensori-neural impairments, were excluded. Poorer cognition and motor function were associated with higher number of skin-breaking procedures, independent of early illness severity, overall intravenous morphine, and exposure to postnatal steroids. The number of skin-breaking procedures as a marker of neonatal pain was closely related to days on mechanical ventilation. In general, greater overall exposure to intravenous morphine was associated with poorer motor development at 8 months, but not at 18 months CCA, however, specific protocols for morphine administration were not evaluated. Lower parenting stress modulated effects of neonatal pain, only on cognitive outcome at 18 months.

Biobehavioural reactivity to pain in preterm infants:a marker of neuromotor development

In this preliminary study, it was examined whether capacity to react to external stress (acute pain) during neonatal intensive care predicts later neuromotor development at 4 and 8 months corrected chronological age (CCA) in high-risk preterm infants. Behavioural and cardiac reactivity to blood collection at 32 weeks postconceptional age (PCA) were recorded in addition to developmental outcomes at 4 and 8 months CCA in 35 preterm infants (17 males, 18 females) born