Course of Stress during the Neonatal Intensive Care Unit Stay in Preterm Infants

Introduction: Understanding the course of stress during the neonatal intensive care unit stay may provide targets for interventions. Our aim was to describe the course of stress in preterm infants during the first 28 days of life, the influence of gestational age, and associations with clinical characteristics. Methods: In a single centre prospective cohort study, we included infants with a gestational age <30 weeks and/or birth weight <1,000 g. We measured stress over the first 28 days using the Neonatal Infant Stressor Scale (NISS). We plotted daily NISS total and subcategory scores by gestational age. The subcategories were (1) nursing, (2) skin-breaking, (3) monitoring and imaging, and (4) medical morbidity-related scores. We assessed associations of cumulative NISS scores over the first 7, 14, and 28 days with clinical characteristics using regression analyses. Results: We included 45 infants, with a median gestational age of 27 weeks. The mean daily NISS score was 66.5 (SD 8.7), with highest scores in the first 7 days of life. Scores decreased the slowest for the lowest gestational ages, in particular for nursing scores, rather than skin-breaking, monitoring and imaging, and medical morbidity-related scores. Adjusted for gestational age, infants with lower Apgar scores, sepsis, intraventricular haemorrhages, and on mechanical ventilation had significantly higher cumulative NISS scores at 7, 14, and 28 days. Conclusion: NISS scores varied greatly within infants and over time, with the highest mean scores in the first week after birth. The course of declining NISS scores in the first 28 days depended on gestational age at birth

Differential Placental DNA Methylation of NR3C1 in Extremely Preterm Infants With Poorer Neurological Functioning

Background: Understanding underlying mechanisms of neurodevelopmental impairment following preterm birth may enhance opportunities for targeted interventions. We aimed to assess whether placental DNA methylation of selected genes affected early neurological functioning in preterm infants. Methods: We included 43 infants, with gestational age <30 weeks and/or birth weight <1,000 g and placental samples at birth. We selected genes based on their associations with several prenatal conditions that may be related to poor neurodevelopmental outcomes. We determined DNA methylation using pyrosequencing, and neurological functioning at 3 months post-term using Prechtl's General Movement Assessment, including the Motor Optimality Score-Revised (MOS-R). Results: Twenty-four infants had atypical MOS-R, 19 infants had near-optimal MOS-R. We identified differences in average methylation of NR3C1 (encoding for the glucocorticoid receptor) [3.3% (95%-CI: 2.4%-3.9%) for near-optimal vs. 2.3% (95%-CI: 1.7%-3.0%), p = 0.008 for atypical], and at three of the five individual CpG-sites. For EPO, SLC6A3, TLR4, VEGFA, LEP and HSD11B2 we found no differences between the groups. Conclusion: Hypomethylation of NR3C1 in placental tissue is associated with poorer neurological functioning at 3 months post-term in extremely preterm infants. Alleviating stress during pregnancy and its impact on preterm infants and their neurodevelopmental outcomes should be further investigated

Maternal Anxiety, Infant Stress, and the Role of Live-Performed Music Therapy during NICU Stay in The Netherlands

Having an infant in the neonatal intensive care unit (NICU) elicits maternal anxiety, which may hamper parent−child bonding. We performed a prospective cohort study to describe anxiety in mothers of infants born before 30 weeks of gestation during NICU stay in The Netherlands, and investigated the influence of infant stress and gestational age. Second, we performed a randomized-controlled live-performed music therapy trial (LPMT trial) to investigate whether music therapy applied to the infant alleviated maternal anxiety. The relation between infant stress, gestational age, and maternal anxiety was measured in 45 mother−infant dyads, using the Neonatal Infant Stressor Scale and the State-Trait Anxiety Inventory (STAI). The effect of LPMT on anxiety was assessed in 21 mothers whose infants were assigned to either LPMT (n = 12) or waitlist (n = 9). Mothers completed the STAI before and after this period. Maternal anxiety decreased over time in all mothers, and was strongly related with infant stress (r = 0.706, p < 0.001), but not with gestational age. Anxiety scores decreased by 12% after LMPT, and increased by 1% after a waitlist period (p = 0.30). Our results indicate that LPMT in the weeks after birth may accelerate the reduction of maternal anxiety. Further research should focus on the effects on mother−child bonding

A homozygous variant in growth and differentiation factor 2(GDF2)may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant inGDF2(c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for theGDF2variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant inGDF2with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis

Early stress during NICU stay and parent-reported health-related quality of life after extremely preterm birth: an exploratory study with possible targets for early intervention

IntroductionThe association between neonatal intensive care unit (NICU) related stress in preterm infants and their health-related quality of life (HRQoL) in the first year following preterm birth remains unexplored. Understanding this association is crucial for enhancing preventive and supportive measures for infants and parents within and beyond the NICU.MethodsFrom a single center observational cohort study, we included infants with gestational ages below 30 weeks and/or birth weights under 1,000 grams. HRQoL was quantified using the Infant Quality of Life Instrument (IQI) at 3-, 6-, 9- and 12-months corrected age, covering seven domains. NICU stress was quantified using the Neonatal Infant Stressor Scale (NISS) for the first week of life. We performed Spearman's correlation analyses to test this association.ResultsOf the 45 included infants, the IQI was completed for 27 (60%) at 3, 15 (33%) at 6, 14 (31%) at 9 and 15 (33%) at 12 months. The HRQoL sum scores were related to neonatal stress at 9 and 12 months (ρ = 0.643 and 0.591, p = 0.013 and p = 0.019, respectively) but not at 3 and 6 months (ρ = −0.001 and −0.077 respectively, p &gt; 0.05). Higher NICU stress tended to be associated with more respiratory and mood problems throughout the first year.DiscussionFrom a parental perspective on infant HRQoL, extremely preterm infants with higher stress exposure show more problems in the second half-year of life, mainly breathing and possibly mood-related problems. This knowledge may help improve our neonatal care, both during NICU stay and in follow-up clinics, by implementing targeted interventions

Functional outcome at school age of preterm-born children treated with low-dose dexamethasone in infancy

BACKGROUND: Surviving preterm born children, postnatally exposed to high doses of dexamethasone, show an increased risk of neurodevelopmental impairments. Regarding treatment with low doses of dexamethasone, no data exist on outcomes at school age. AIM: To assess the functional outcome at school age of preterm-born children treated with low-dose dexamethasone. STUDY DESIGN: In this cohort study, twenty-seven very preterm-born infants treated with dexamethasone from eight days after birth, underwent neuropsychological assessments at age 6-13 years. Their scores were compared with those of the norm population, and scores on total IQ and motor functioning also with those of a preterm reference group, using one-sample-chi-square and student's t-tests. RESULTS: Compared with the norm population, performance of dexamethasone-treated children was poorer, particularly in the motor domain (mean z-score - 1.81). Dexamethasone-treated children also had lower scores on IQ (-0.29 to -1.12), verbal memory (-0.41 to -0.56), attention (-0.90 to -1.28), and word generation (-0.75). Their parents reported behavioral problems more often. Compared with preterm peers, motor skills remained poor, but total IQs were similar. Adjustment for bronchopulmonary dysplasia did not change our results, because all surviving children had bronchopulmonary dysplasia. CONCLUSIONS: At school age, the prevalence of adverse motor, cognitive, and behavioral outcomes of preterm-born children treated with low-dose dexamethasone is increased. This could be the consequence of either dexamethasone or BPD

Hepatosplenic Cat-Scratch Disease in Children and the Positive Contribution of F-18-FDG Imaging

Two patients were referred to our hospital because of suspected malignancy. In patient 1, a 4-year-old boy, a F-18-FDG PET scan showed an enlarged liver with multiple FDG-positive nodular lesions. In patient 2, a 16-year-old boy, a FDG PET-(low-dose) CT showed an enlarged liver and spleen with multiple nodular lesions and a solitary hypodense nodule adjacent to the pancreatic head. The lesions were thought to originate from infectious disease or lymphoma. Polymeric chain reaction (PCR) on a liver biopsy was positive for Bartonella henselae. Both patients were treated with antibiotics and recovered completely

Supplementary Material for: Course of Stress during the Neonatal Intensive Care Unit Stay in Preterm Infants

Introduction: Understanding the course of stress during the neonatal intensive care unit stay may provide targets for interventions. Our aim was to describe the course of stress in preterm infants during the first 28 days of life, the influence of gestational age, and associations with clinical characteristics. Methods: In a single centre prospective cohort study, we included infants with a gestational ag