Histological chorioamnionitis is predicted by early infant C-reactive protein in preterm infants and correlates with neonatal outcomes.

AIM: Histological chorioamnionitis (HCA) is associated with preterm birth and adverse neonatal outcomes. We evaluated the rise in C-reactive protein (CRP) in preterm infants as a predictor of HCA severity and outcomes. METHODS: Consecutive preterm infants, born January 2009 to January 2014 in the National Maternity Hospital, Dublin, under 32 weeks' gestation or <1.5 kg birthweight, were included. Histological chorioamnionitis was staged as maternal inflammatory response, foetal inflammatory response and non-HCA. RESULTS: Preterm infants (n = 518) were included with a mean gestational age 28.5 ± 2.8 weeks, birthweight 1.1 ± 0.3 kg, and 53.5% were male. Histological chorioamnionitis was found in 25.4%. Histological chorioamnionitis was present in 93.7% when CRP > 5 mg/L, 65.2% when CRP 1-5 mg/L and in 19.4% when CRP < 1 mg/L. When both the immature to total neutrophil (IT) ratio was >0.2 and the CRP > 1 mg/L the positive predictive value and negative predictive value for HCA were 92.5% and 84.9%, respectively. Histological chorioamnionitis was associated with more resuscitation and respiratory distress syndrome (both P < .001). A CRP > 10 mg/L was associated with a foetal inflammatory response and increased early-onset sepsis. CONCLUSION: Higher early CRP was a surrogate predictor of HCA and correlated with the severity of HCA. Higher CRP and HCA were associated with adverse early outcomes.

Assessment of parental awareness of the shaken baby syndrome in Ireland.

UNLABELLED: Shaken baby syndrome (SBS) results in cerebral trauma. Creating awareness through education may improve parental response to a distressed infant. We aim to assess current parental understanding of SBS and identify knowledge gaps. A prospective assessment was carried out in two independent maternity hospitals (National Maternity Hospital (NMH) and Midland Regional Hospital (MRH)) over a 4-month period. Multi-dimensional questionnaires were distributed to parents (n = 233) and results were assessed anonymously. Statistical analysis was performed using SPSS21 software. Two hundred thirty-three participants were included: n = 114 (NMH), n = 119 (MRH). Fifty-four percent (n = 62, NMH) and 50 % (n = 60, MRH) had never heard of SBS. Of those who had, media was the commonest source: 94 % (47/50) NMH; 86 % (47/59) MRH. Less than 1 % of participants obtained information through a health care provider. Nearly all respondents wanted further information, regardless of whether they had prior knowledge (100 % (NMH); 99.2 % (MRH)). Participants wanted information delivered via a midwife (51 % (58/114) NMH; 45 % (54/119) MRH), with reading material (61 % (69/114) NMH; 59 % (70/119) MRH), during pre-natal period (50 % (57/114) NMH; 65 % (77/119) MRH). Importantly, parents of Irish origin were more likely to have heard of SBS compared to those of non-Irish origin (p = 0.026 (NMH), p = 0.020 (MRH)). CONCLUSION: Half of all participants had no prior knowledge of SBS, with majority expressing interest in learning more. Therefore, a national "Don't Shake" campaign is evolving. WHAT IS KNOWN: • Studies have shown that educating parents regarding shaken baby syndrome (SBS) may result in a more safe and appropriate response to infant crying [ 3 ]. • In Ireland, there is no such education provided to parents in maternity hospitals. What is New: • Just over half of our participants had not heard of SBS, and we have identified parental perceptions of SBS, and parents preferred method of anti-SBS education delivery. • This research will act as a launching platform for an anti-SBS campaign in Ireland.

Early electrographic seizures, brain injury, and neurodevelopmental risk in the very preterm infant.

BACKGROUND: Previous studies of very preterm (VPT) infants have shown a wide range of seizure prevalence and association with intraventricular hemorrhage (IVH), white matter injury (WMI), and death. However, the impact of seizures on neurodevelopment is not well known. We hypothesized that seizures in the first 3 d after VPT birth would be associated with increased radiographic brain injury and later neurodevelopmental risk. METHODS: For 72 h after birth, 95 VPT infants underwent amplitude-integrated electroencephalogram monitoring. High and low seizure burdens were related to radiographic brain injury, death in the neonatal period, and children's Bayley III (Bayley Scales of Infant Development) performance at 2 y corrected age in a subgroup of 59 infants. RESULTS: The overall incidence of seizures in this sample was 48%. High seizure burden was associated with increased risk of IVH on day 1; IVH, WMI, and death on day 2; and high-grade IVH on day 3. The presence of seizures on any day was associated with decreased language performance at age 2, even after controlling for family social risk. CONCLUSION: Seizures during the first 3 d after birth are common and are associated with an increased risk of IVH, WMI, and death. They were also associated with poorer early language development.

Cerebral maturation on amplitude-integrated electroencephalography and perinatal exposures in preterm infants.

AIM: To determine the associations between perinatal exposures, cerebral maturation on amplitude-integrated encephalography (aEEG) and outcome. METHODS: During this prospective cohort study, 136 infants ≤30 weeks estimated gestational age received 4 h of aEEG at four time points (between the first 2 weeks of life and term-equivalent age) during hospitalisation. Perinatal factors were documented. Associations between perinatal exposures and Burdjalov-scores were investigated. Neurodevelopmental outcome was assessed at the age of two. RESULTS: Immature cyclicity on the initial aEEG recording was associated with higher CRIB score (p = 0.01), vaginal delivery (p = 0.02), male gender (p < 0.01) and death (p = 0.01). Perinatal factors associated with lower Burdjalov-scores included cerebral injury (p < 0.01), sepsis (p < 0.01), lower caffeine dose (p = 0.006), prolonged mechanical ventilation (p = 0.002) and death (p < 0.01). Burdjalov-scores at 30 (ß = 2.62, p < 0.01) and 34 weeks postmenstrual age (ß = 2.89, p = 0.05) predicted motor scores. CONCLUSION: aEEG measures of cyclicity and Burdjalov-scores in the first 6 weeks of life, with an emphasis on 30 and 34 weeks postmenstrual age, demonstrated associations with perinatal factors known to predict adverse neurodevelopmental outcome.

Patterns of altered neurobehavior in preterm infants within the neonatal intensive care unit.

OBJECTIVE: To investigate differences in neurobehavior between preterm infants at term and full-term infants, changes in neurobehavior between 34 weeks postmenstrual age (PMA) and term equivalent in the preterm infant, and the relationship of neurobehavior to perinatal exposures. STUDY DESIGN: In this prospective cohort study, 75 infants were tested at 34 weeks PMA and again at term using the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Infants underwent magnetic resonance imaging at term equivalent. Regression was used to investigate differences in the scale's domains of function across time and in relation to perinatal exposures. RESULTS: At term equivalent, preterm infants exhibited altered behavior compared with full-term infants, with poorer orientation (P < .001), lower tolerance of handling (P < .001), lower self-regulation (P < .001), poorer reflexes (P < .001), more stress (P < .001), hypertonicity (P < .001), hypotonia (P < .001), and more excitability (P = .007). Preterm infants from 34 weeks PMA to term equivalent, demonstrated changes in motor functions with declining quality of movement (P = .006), increasing hypertonia (P < .001), decreasing hypotonia (P = .001), and changes in behavior with increasing arousal (P < .001), increasing excitability (P < .001), and decreasing lethargy (P < .001). Cerebral injury was associated with more excitability (P = .002). However, no associations were detected between any of the perinatal exposures and developmental change from 34 weeks PMA to term equivalent. CONCLUSION: Preterm infants have altered neurobehavior in a broad number of domains at term equivalent. Cerebral injury alters neurobehavior but does not appear to impair early neurobehavioral changes. Important neurobehavioral changes occur before term, and this provides an opportunity for interventions in the neonatal intensive care unit.

An unusual case of a giant fetal facial tumour and review of the literature.

We present the case of a pregnant 32-year-old woman who presented with a giant fetal facial tumour at 22 weeks. The mass, initially 4 × 3.5 × 3 cm in size, was largely cystic with a small solid component. It subsequently increased to 9 × 9 × 10 cm. Significant compression effects on the fetal orbit, temple and infratemporal fossa, with potential compression of the optic nerve, were noted on ultrasound and MRI. The cyst required drainage twice in the pregnancy: firstly to reduce the compression effects and secondly to facilitate caesarean delivery. Postnatally, the baby had significant compression and displacement of the craniofacial skeleton from the mass effect. Postnatal histology revealed a diagnosis of a teratoma. This case highlights the complexities and challenges surrounding the diagnosis and management of a giant fetal facial tumour.

Melatonin Alters Innate Immune Function in Infants with Neonatal Encephalopathy.

INTRODUCTION: Melatonin has been suggested an adjunctive therapy in neonatal encephalopathy (NE). Melatonin reduces oxidative stress and neutrophil activation; however, the immunological effects in NE have not been studied. METHODS: Infants with NE and neonatal controls were prospectively recruited. Whole blood was sampled in the first week of life. Following endotoxin and or melatonin treatment, diurnal variation was measured by RT PCR for circadian rhythm genes (brain and Muscle Arnt-Like protein [BMAL1], circadian locomotor output cycles kaput [CLOCK], Nuclear Receptor Subfamily 1 Group D Member 2 [REV Erß], and cryptochrome circadian clock [CRY]). Neutrophil and monocyte cell surface markers of activation CD11b, reactive oxygen intermediates (ROIs), and Toll-like receptor (TLR)-4 were also examined by flow cytometry in matching samples. RESULTS: Serum and RNA samples from forty infants were included (controls n = 20; NE n = 20) over the first week of life. Melatonin reduced neutrophil CD11b and TLR-4 expression in response to LPS in infants with NE compared to controls. There were no differences in ROIs. BMAL1 and CLOCK baseline gene expression levels were similar. BMAL1 was significantly decreased with LPS stimulation in NE. There was no significant diurnal variation in melatonin, neutrophil, and monocyte function or circadian genes. CONCLUSIONS: Melatonin alters immune function ex vivo in infants with NE. Infants with NE have altered immune circadian responses following LPS stimulation, which have potential for modulation.

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

OBJECTIVE: 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. METHODS: In this prospective cohort study of infants born at <30 weeks gestation, nurses were trained in recording procedures and cares. These recordings were used to derive Neonatal Infant Stressor Scale scores, which were employed to measure exposure to stressors. Magnetic resonance imaging (brain metrics, diffusion, and functional magnetic resonance imaging) and neurobehavioral examinations at term equivalent postmenstrual age were used to assess cerebral structure and function. Simple and partial correlations corrected for confounders, including immaturity and severity of illness, were used to explore these relations. RESULTS: Exposure to stressors was highly variable, both between infants and throughout a single infant's hospital course. Exposure to a greater number of stressors was associated with decreased frontal and parietal brain width, altered diffusion measures and functional connectivity in the temporal lobes, and abnormalities in motor behavior on neurobehavioral examination. INTERPRETATION: Exposure to stressors in the Neonatal Intensive Care Unit is associated with regional alterations in brain structure and function. Further research into interventions that may decrease or mitigate exposure to stressors in the neonatal intensive care unit is warranted.

Altered Cytokine Endotoxin Responses in Neonatal Encephalopathy Predict MRI Outcomes.

Background: Neonatal encephalopathy (NE) is associated with adverse neurodevelopmental outcome and is linked with systemic inflammation. Pro-inflammatory and anti-inflammatory cytokines are known to play a role in the pathology of NE by activating innate immune cells. Methods: Eighty-seven infants were enrolled including 53 infants with NE of whom 52 received therapeutic hypothermia (TH) and 34 term infant healthy controls (TC). Whole blood sampling was performed in the first 4 days of life, and a 14-spot ELISA Multiplex Cytokine Array was carried out on baseline samples or after stimulation with lipopolysaccharide (LPS) as an additional inflammatory stimulus. The cytokine medians were examined for differences between infants with NE and healthy TC; and then short-term outcomes of Sarnat stage, seizures, and MRI brain were examined within the NE group. The potential of LPS stimulation to predict abnormal MRI was explored using receiver operating characteristic (ROC) curves. Results: At baseline, infants with NE had significantly higher levels of erythropoietin (Epo), interleukin (IL)-6, and IL-1ra and significantly lower vascular endothelial growth factor (VEGF) than had controls. All cytokines were increased after LPS stimulation in infants with NE with an excessive Epo and IL-1ra response than in controls. Infants with NE had lower IL-8, IL-2, IL-6, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), VEGF, and interferon (IFN)-γ than controls had following LPS. GM-CSF and IFN-γ, IL-1ß, IL-1ra, and VEGF were higher on days 1-2 in NE infants with abnormal neuroimaging. GM-CSF, IFN-γ, and TNF-α levels with LPS stimulation were different upon stimulation between normal and abnormal neuroimaging. TNF-α is the only strong cytokine predictor both pre- and post-LPS stimulation of abnormal brain imaging. Conclusions: Altered cytokine responses are found in infants with NE vs. controls, and more significant differences are unmasked by the additional stimulus of LPS, which potentially improves the predictive power of these cytokines for the detection of abnormal MRIs. Infants with NE undergoing TH demonstrate both trained immunity and tolerance, and understanding these responses will facilitate adjunctive immunomodulatory treatments.

Dysregulated Monocyte and Neutrophil Functional Phenotype in Infants With Neonatal Encephalopathy Requiring Therapeutic Hypothermia.

Neonatal encephalopathy (NE) is a significant cause of morbidity and mortality. Persistent inflammation and activation of leukocytes mediate brain injury in NE. The standard of care for NE, therapeutic hypothermia (TH), does not improve outcomes in nearly half of moderate to severe cases, resulting in the need for new adjuvant therapies, and immunomodulation holds promise. Our objective was to explore systemic leukocyte phenotype in infants with NE and healthy controls in response to lipopolysaccharide (LPS). Twenty-four infants with NE (NE II-20; NE III = 4) requiring TH and 17 term neonatal controls were enrolled, and blood samples were analyzed between days 1 and 4 of life at a mean (SD) timepoint of 2.1 (± 0.81) days of postnatal life at the time of the routine phlebotomy. Leukocyte cell surface expression levels of Toll-like receptor 4, NADPH oxidase (NOX2), CD11b, mitochondrial mass, and mitochondrial superoxide production were measured by flow cytometry. Gene expression of TRIF (TIR domain-containing adapter-inducing interferon-ß), MyD88 and IRAK4 was measured by reverse transcription-polymerase chain reaction. Infants with NE had significantly lower expression of neutrophil CD11b and NOX2 with LPS stimulation compared to healthy term controls. Mitochondrial mass in neutrophils and monocytes was significantly increased in NE infants with LPS compared to controls, potentially indicating a dysregulated metabolism. Infants with NE had significantly lower IRAK4 at baseline than controls. NE infants display a dysregulated inflammatory response compared to healthy infants, with LPS hyporesponsiveness to CD11b and NOX2 and decreased IRAK4 gene expression. This dysregulated immune profile may indicate an adaptable response to limit hyperinflammation.

Easily missed, potentially fatal complication in an extremely preterm infant.

A baby girl was delivered by emergency caesarean section at 23+6 weeks gestation weighing 440 g. Apgar scores were 1, 3 and 4 at 1, 5 and 10 min, respectively. She was intubated and transferred to the neonatal intensive care unit. Umbilical arterial and venous lines and an orogastric tube (OGT) were inserted. On day 4 of life the OGT appeared to be outside of the gastrointestinal tract on X-ray. Feeds were held and contrast oesophagography confirmed suspicion of an oesophageal perforation. She was treated with intravenous metronidazole, gentamycin and amoxicillin and placed nil by mouth for 10 days. Resolution of the perforation was confirmed on repeat contrast study (day 10) and feeds were restarted with no further complications.