Long term outcome of babies with pulmonary hypertension

Neonatal pulmonary hypertension (PH) is associated with many severe congenital abnormalities (congenital diaphragmatic hernia) or acquired cardiorespiratory diseases such as pneumonia, meconium aspiration and bronchopulmonary dysplasia (BPD). If no cause is found it may be labelled idiopathic persistent pulmonary hypertension of the newborn. Although PH may result in life threatening hypoxia and circulatory failure, in the majority of cases, it resolves in the neonatal period following treatment of the underlying cause. However, in some cases, neonatal PH progresses into infancy and childhood where symptoms include failure to thrive and eventually right heart failure or death if left untreated. This chronic condition is termed pulmonary vascular hypertensive disease (PHVD). Although classification and diagnostic criteria have only recently been proposed for pediatric PHVD, little is known about the pathophysiology of chronic neonatal PH, or why pulmonary vascular resistance may remain elevated well beyond infancy. This review explores the many factors involved in chronic PH and what implications this may have on long term outcome when the disease progresses beyond the neonatal period.     

Initial health assessments for unaccompanied asylum-seeking children: advice and good practice

There were 3,762 unaccompanied asylum-seeking children (UASC) in the UK in 2021. UASC often have significant physical and mental health needs. They suffer from conditions linked to extreme poverty, such as malnutrition and tuberculosis. The proportion of UASC with complications related to their vision, dental health, skin, sleep, and mental health is high. They are also at increased risk of sexually transmitted diseases, including blood-borne infections. UASC become ‘looked after’ by their local authorities and therefore should have Initial Health Assessments (IHAs) in the same way as other children also in the care of their local authorities. IHAs are comprehensive and holistic health assessments, and as such are ideal for identifying previously unrecognized or unmet health needs of UASC and for providing clear health plans on how these health needs should be managed. This article will provide an overview of the national statistics and demographics of the UASC population, describe the demographics of the local UASC population within Birmingham and highlight their health needs, and then provide advice on how to conduct IHAs in the most effective and sensitive way for this particularly vulnerable group of children in care.     

Impact of neonatal nutrition on necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality in preterm infants. NEC is multifactorial and the result of a complex interaction of feeding, dysbiosis, and exaggerated inflammatory response. Feeding practices in the neonatal intensive care units (NICUs) can vary among institutions and have significant impact on the vulnerable gastointestinal tract of preterm infants. . These practices encompass factors such as the type of feeding and fortification, duration of feeding, and rate of advancement, among others. The purpose of this article is to review the data on some of the most common feeding practices in the NICU and their impact on the development of NEC in preterm infants. Data on the human milk bioactive component glycosaminoglycans, specifically hyaluronan, will also be discussed in the context of postnatal intestinal development and NEC prevention.     

Fluid management,electrolytes imbalance and renal management in neonates with neonatal encephalopathy treated with hypothermia

Kidney dysfunction and acute kidney injury (AKI) frequently accompanies neonatal encephalopathy and contributes to neonatal morbidity and mortality. While there are currently no proven therapies for the treatment of AKI, understanding the pathophysiology along with early recognition and treatment of alterations in fluid, electrolyte and metabolic homeostasis that accompany AKI offer opportunity to reduce associated morbidity. Promising new tests and technologies, including urine and serum biomarkers and renal near-infrared spectroscopy offer opportunities to improve diagnosis and monitoring of neonates at risk for kidney injury. Furthermore, recent advances in neonatal kidney supportive therapies such as hemofiltration and hemodialysis may further improve outcomes in this population. This chapter provides an overview of disorders of fluid balance, electrolyte homeostasis and kidney function associated with neonatal encephalopathy and therapeutic hypothermia. Recommendations for fluid and electrolyte management based upon published literature and authors’ opinions are provided.     

Management of seizures in neonates with neonatal encephalopathy treated with hypothermia

Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures – about half of neonates treated with therapeutic hypothermia for NE have EEG-confirmed seizures. These seizures are best identified with continuous EEG monitoring, as clinical diagnosis leads to under-diagnosis of subclinical seizures and over-treatment of events that are not seizures. High seizure burden, especially status epilepticus, is thought to augment brain injury. Treatment, therefore, is aimed at minimizing seizure burden. Phenobarbital remains the mainstay of treatment, as it is more effective than levetiracetam and easier to administer than fosphenytoin. Emerging evidence suggests that, for many neonates, it is safe to discontinue the phenobarbital after acute seizures resolve and prior to hospital discharge.     

Proposing a care practice bundle for neonatal encephalopathy during therapeutic hypothermia

Neonates with neonatal encephalopathy (NE) often present with multi-organ dysfunction that requires multidisciplinary specialized management. Care of the neonate with NE is thus complex with interaction between the brain and various organ systems. Illness severity during the first days of birth, and not only during the initial hypoxia-ischemia event, is a significant predictor of adverse outcomes in neonates with NE treated with therapeutic hypothermia (TH). We thus propose a care practice bundle dedicated to support the injured neonatal brain that is based on the current best evidence for each organ system. The impact of using such bundle on outcomes in NE remains to be demonstrated.     

Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet

PurposeThe modified Atkins diet (MAD) is a less restrictive treatment option than the ketogenic diet (KD) for intractable epilepsy and some metabolic conditions. Prolonged KD treatment may decrease bone mineralization and affect linear growth; however, long-term studies of MAD treatment are lacking. This study was designed to assess growth, body composition, and bone mass in children on MAD treatment for 24 months.MethodsThirty-eight patients, mean age (SD) 6.1 years (4.8 years), 21 girls, with intractable epilepsy (n = 22), glucose transporter type 1 deficiency syndrome (n = 7), or pyruvate dehydrogenase complex deficiency (n = 9) were included. Body weight, height, body mass index (BMI), bone mass, and laboratory tests (calcium, phosphorus, magnesium, alkaline phosphatase, cholesterol, 25-hydroxyvitamin D, insulin-like growth factor-I and insulin-like growth factor binding protein 3) were assessed at baseline and after 24 months of MAD treatment.ResultsApproximately 50% of the patients responded with more than 50% seizure reduction. Weight and height standard deviation score (SDS) were stable over 24 months, whereas median (minimum – maximum) BMI SDS increased from 0.2 (−3.3 to 4.5) to 0.7 (−0.9 to 2.6), p < 0.005. No effects were observed for bone mass (total body, lumbar spine and hip) or fat mass.ConclusionsThe MAD was efficient in reducing seizures, and no negative effect was observed on longitudinal growth or bone mass after MAD treatment for 24 months.     

Optimizing hemodynamic care in neonatal encephalopathy

Hemodynamic impairment occurs in up to 80% of infants with neonatal encephalopathy (NE). Not all infants benefit from therapeutic hypothermia (HT); there are some indications that the trajectory of brain injury might be modified by neurologic monitoring and early management over the first 72-h period. It is also possible that optimizing hemodynamic management may further improve outomes. The coupling between cerebral blood flow and cerebral metabolism is disrupted in NE, increasing the vulnerability of the newborn brain to secondary injury. Hemodynamic monitoring is usually limited to blood pressure and functional echocardiographic measurements, which may not accurately reflect brain perfusion. This review explores the evidence base for hemodynamic assessment and management of infants with NE while undergoing HT. We discuss the literature behind a systematic approach to a baby with NE with the aim to define best therapies to optimize brain perfusion and reduce secondary injury.     

Evaluation for the etiology of neonatal encephalopathy and the diagnosis of FIRS

A common disorder managed in the neonatal intensive care unit (NICU) is neonatal encephalopathy (NE). There are multiple causes of NE, including hypoxic-ischemic encephalopathy (HIE) and the fetal inflammatory response syndrome (FIRS). It is important to ascertain the specific cause of NE in an affected child, as it may affect the clinical management and will assist in prognostication. This paper discusses the background of inflammatory damage to the fetal brain, the history of FIRS as a clinical diagnosis, the characteristics of infants with FIRS, and methods to evaluate the etiology of NE.     

Ethics of care for the micropreemies. Just because we can,should we?

Debates about treatment for the tiniest premature babies focus on three different approaches – universal non-resuscitation, selective resuscitation, and universal resuscitation. Doctors, hospitals, and professional societies differ on which approach is preferable. The debate is evolving as studies show that survival rates for babies born at 22 and 23 weeks of gestation are steadily improving at centers that offer active treatment to these babies. Still, many centers do not offer such treatment or, if they do, actively discourage it. The doctors and centers that discourage treatment have concerns about the chances for survival, neurodevelopmental impairment among survivors, and cost. Centers that offer and encourage treatment cite evidence that many babies born at 22 weeks can survive, that most survivors have good neurodevelopmental outcomes, and that NICU care for tiny babies is cost-effective compared to many common and uncontroversial treatments. The debate touches on many fundamental ethical issues that have been present in neonatology since its inception as a medical specialty.     

Early prediction of unilateral cerebral palsy in infants with asymmetric perinatal brain injury – Model development and internal validation

BackgroundEarly diagnosis of unilateral cerebral palsy is important after asymmetric perinatal brain injury (APBI). Our objective is to estimate the risk of unilateral cerebral palsy (UCP) in infants with APBI during the first months of life using neuroimaging and clinical assessment.Patients and methodsPrognostic multivariable prediction modeling study including 52 infants (27 males), median gestational age 39.3 weeks with APBI from Sweden (n = 33) and the Netherlands (n = 19). Inclusion criteria: (1) neonatal MRI within one month after term equivalent age (TEA), (2) Hand Assessment for Infants (HAI) between 3.5 and 4.5 months of (corrected) age. UCP was diagnosed ≥24 months of age. Firth regression with cross-validation was used to construct and internally validate the model to estimate the risk for UCP based on the predictors corticospinal tract (CST) and basal ganglia/thalamus (BGT) involvement, contralesional HAI Each hand sum score (EaHS), gestational age and sex.ResultsUCP was diagnosed in 18 infants (35%). Infants who developed UCP more often had involvement of the CST and BGT on neonatal MRI and had lower contralesional HAI EaHS compared to those who did not develop UCP. The final model showed excellent accuracy for UCP prediction between 3.5 and 4.5 months (area under the curve, AUC = 0.980; 95% CI 0.95–1.00).ConclusionsCombining neonatal MRI, the HAI, gestational age and sex accurately identify the prognostic risk of UCP at 3.5–4.5 months in infants with APBI.     

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action

Although low- and middle-income countries (LMICs) shoulder 90 % of the neonatal encephalopathy (NE) burden, there is very little evidence base for prevention or management of this condition in these settings. A variety of antenatal factors including socio-economic deprivation, undernutrition and sub optimal antenatal and intrapartum care increase the risk of NE, although little is known about the underlying mechanisms. Implementing interventions based on the evidence from high-income countries to LMICs, may cause more harm than benefit as shown by the increased mortality and lack of neuroprotection with cooling therapy in the hypothermia for moderate or severe NE in low and middle-income countries (HELIX) trial. Pooled data from pilot trials suggest that erythropoietin monotherapy reduces death and disability in LMICs, but this needs further evaluation in clinical trials. Careful attention to supportive care, including avoiding hyperoxia, hypocarbia, hypoglycemia, and hyperthermia, are likely to improve outcomes until specific neuroprotective or neurorestorative therapies available.     

Probiotics and novel probiotic delivery systems

Necrotizing enterocolitis (NEC) is an infectious and inflammatory intestinal disease that is the most common surgical emergency in the premature patient population. Although the etiology of the disease is multifactorial, intestinal dysbiosis is a hallmark of this disease. Based on this, probiotics may play a therapeutic role in NEC by introducing beneficial bacteria with immunomodulating, antimicrobial, and anti-inflammatory functions into the gastrointestinal tract. Currently, there is no Food and Drug Administration (FDA)-approved probiotic for the prevention and treatment of NEC. All probiotic clinical studies to date have administered the bacteria in their planktonic (free-living) state. This review will discuss established probiotic delivery systems including planktonic probiotics, prebiotics, and synbiotics, as well as novel probiotic delivery systems such as biofilm-based and designer probiotics. We will also shed light on whether or not probiotic efficacy is influenced by administration with breast milk. Finally, we will consider the challenges associated with developing an FDA-approved probiotic for NEC.     

Mineral and bone physiology in the foetus,preterm and full-term neonates

Mother is the major source of minerals in foetal life with placenta actively transporting against a concentration and electrochemical gradient. The foetal serum mineral concentration is thereby higher as compared to maternal values, which possibly help in its rapid accretion in developing bones and for counteracting postnatal fall in calcium levels at birth. Parathyroid hormone related peptide (PTHrP) and parathyroid hormone (PTH) play a major role in mineral physiology during foetal life with hormones like calcitriol, calcitonin, FGF-23 and sex steroids having minimal role. PTHrP and PTH also play a major role in endochondral bone formation and mineralization of skeleton. At the birth, as the cord is clamped, there is loss of active transport of minerals through placenta and the neonate has to rely on enteral intake of minerals to meet the demands of growing bones and metabolisms. The calcium levels fall after birth, reaching a nadir at 24–48 h and gradually rise to adult values over several days, probably resulting from a fall in PTHrP levels and hyporesponsiveness of parathyroid glands. As PTH and calcitriol levels increase postnatally, there is a rise in calcium levels with maturation in functioning of kidneys and intestines. However, there may be significant delay in intestinal maturation in preterm infants along with an increased demand for mineral accretion, which predispose them to osteopenia of prematurity.     

Social determinants of health as drivers of inequities in pediatric injury

A child's social determinants of health (SDH), including their neighborhood environment, insurance status, race and ethnicity, English language proficiency and geographic location, all significantly impact their risk of injury and outcomes after injury. Children from socioeconomically disadvantaged neighborhoods experience overall higher rates of injury and different types of injuries, including higher rates of motor vehicle-, firearm-, and violence-related injuries. Similarly, children with public insurance or no insurance, as a proxy for lower socioeconomic status, experience higher rates of injuries including firearm-related injuries and non-accidental trauma, with overall worse outcomes. Race and associated racism also impact a child's risk of injury and care received after injury. Black children, Hispanic children, and those from other minority groups disproportionately experience socioeconomic disadvantage with sequelae of injury risk as described above. Even after controlling for socioeconomic status, there are still notable disparities with further evidence of racial inequities and bias in pediatric trauma care after injury. Finally, where a child lives geographically also significantly impacts their risk of injury and available care after injury, with differences based on whether a child lives in a rural or urban area and the degree of state laws regarding injury prevention. There are clear inequities based on a child's SDH, most predominantly in a child's risk of injury and the types of injuries they experience. These injuries are preventable and the SDH provide potential upstream targets in injury prevention efforts.     

Breastmilk feeding for mothers and infants with opioid exposure: What is best?

With rare exception, breastfeeding is the optimal way to feed infants, and has special benefits for women and infants with perinatal opioid exposure. Infants breastfed and/or fed their mother's own breastmilk experience less severe opioid withdrawal symptoms, have shorter hospital stays, and are less likely to be treated with medication for withdrawal. The specific impact of mothers' milk feeding on opioid withdrawal may be related to the act of breastfeeding and associated skin-to-skin contact, qualities of breastmilk, healthier microbiome, small amounts of opioid drug in breastmilk, or a combination of these. Women with opioid use disorder face significant breastfeeding obstacles, including psychosocial, behavioral, concomitant medications, and tobacco use and thus may require high levels of support to achieve their breastfeeding goals. They often don't receive information to make informed infant feeding decisions. Hospital practices such as prenatal education, rooming-in and having a policy that minimizes barriers to breastfeeding are associated with increased breastfeeding rates.     

Adverse events related to ibuprofen treatment for patent ductus arteriosus in premature neonates

ObjectiveOur study aimed to review adverse drug reactions (ADRs) associated with ibuprofen treatment of patent ductus arteriosus (PDA) in premature neonates.MethodWe retrospectively evaluated electronic patient records from neonates treated with ibuprofen for PDA during 5 years in a French neonatal intensive care unit. Full chart review and targeted triggers were used to detect ADRs. The causality between suspected ADRs and medication was evaluated using the WHO causality assessment method by pharmacovigilance experts. Categorical variables were compared using chi-square tests or Fisher's test. Quantitative variables were compared using the Student t test. We explored the risk factors associated with ADR using univariate model analysis.ResultOf 227 infants with a mean gestational age (GA) of 27 weeks (24–33), 12 (5%) developed intestinal perforation and seven, necrotizing enterocolitis (3%). The perforation occurred less frequently in infants older than 27 weeks GA (OR = 0.14; 95% CI = 0.03–0.66, P = 0.01). Other observed ADRs were acute renal failure (25 infants, 11%) and thrombocytopenia (five infants, 2%).ConclusionGastrointestinal complications observed in infants treated with ibuprofen for PDA including gastrointestinal perforations occur in less mature infants. Active chart review of the patient's medical file with a trigger tool should be evaluated for routine ADR monitoring.     

Evaluation of health-related quality of life in childhood cancer survivors

BackgroundConsidering the high survival rates of childhood cancers and their stable incidence, concepts such as quality of life (QOL) and health-related quality of life (HRQOL) are impactful issues that have consistently retained their importance worldwide.ObjectiveThis study aimed to evaluate HRQOL at least 5 years after treatment in childhood cancer survivors (CCSs) with the hypothesis that their QOL could be adversely affected later in their lives. Additionally, we sought to assess the parents of pediatric CCSs with respect to HRQOL.Patients and MethodsWe evaluated CCSs aged 8–18 years and compared the results with healthy controls (matched for age and sex). The parents of the pediatric CCSs and control groups were also analyzed. A total of 174 cases (patients and controls) and 168 parents (of patients and controls) were included in the study. HRQOL was evaluated by applying the Pediatric Quality of Life Inventory (PedsQL).ResultsThe mean HRQOL scores of CCSs were significantly lower than those of the controls (p= 0.04). No differences were found between the parents of these groups. The physical and social functionality scores of CCSs were significantly lower when compared to healthy controls (p = 0.02 and p<0.01, respectively). In addition, according to cancer type, the HRQOL scores of those with solid tumors were found to be significantly lower than those with hematological cancers (p=0.02).(p = 0.02)ConclusionThis study shows that HRQOL is lower in CCSs compared to healthy controls. The most important differences in HRQOL among CCSs were found in the physical and social subdimensions compared to the controls. In this regard, it appears to be vital to provide mental support to CCSs after cancer treatment. These findings also indicate the need for health-focused social policies that can increase HRQOL in CCSs.     

Cerebral palsy among children of immigrants in Denmark and the role of socioeconomic status

BackgroundChildren of immigrants in Denmark have excess risk for some of the most well-established risk factors for cerebral palsy (CP).ObjectivesTo study differences in risk of CP between children of immigrants and children of Danish-born mothers, and explore whether socioeconomic status drives any potential association.MethodsA register-based cohort study including 1,274,616 children born in Denmark between 1981 and 2007. Of these, 2807 had a validated CP diagnosis in the Danish CP Register. We estimated the risk of CP as odds ratios (OR) using logistic regression and assessed mediation through socioeconomic status using natural effect models.ResultsIn children of Danish-born mothers, 2.2/1000 had CP overall and the prevalence was similar for children of immigrants. However, children of immigrants had lower risk of unilateral spastic CP than children of Danish native-born mothers; OR = 0.59 (95% CI:0.38–0.91) for Western and OR = 0.79 (95% CI:0.61–1.03) for Non-Western immigrants. By contrast, the risk of bilateral spastic CP was higher in children of Non-Western immigrants (OR = 1.27 (95% CI:1.05–1.53)), especially from Turkey and Pakistan compared with children of Danish native-born mothers. The mediation analysis revealed an indirect effect (through maternal educational level and household income) with an OR of 1.06 (95% CI:0.99–1.14) for children of Non-Western immigrants.ConclusionsWhile children of immigrants had lower risk of unilateral spastic CP than children of Danish-born mothers, the risk of bilateral spastic CP was increased in children of Non-Western immigrants. Socioeconomic status did not appear to be a significant contributor to the increased risk of bilateral spastic CP.     

Promoting secure attachment

Attachment is an infant's inherent drive to seek comfort from their caregiver, particularly at times of perceived threat. A child can show a number of attachment patterns, with a secure attachment pattern linked to improved long term outcomes, such as healthy social and emotional development. A range of parenting interventions have been developed aiming to increase secure attachment. To understand what interventions are being used and the evidence base behind these a national survey of UK services was conducted to find about how attachment problems are assessed and treated. We identified the ten most commonly used interventions in UK practice. We then conducted two systematic reviews. One searched for all randomised controlled trial (RCT) evidence for any attachment parenting intervention. The second review searched for all available research focused on the ten interventions identified from the survey. For the first review, a meta-analysis showed parenting interventions are effective at increasing secure attachment in children. The second review found that the most commonly used interventions in UK services have a limited evidence base whereas the interventions with the most evidence are not as widely used. It is important to improve the integration of research and practice to develop the best care.