- Chorioamnionitis and Five-Year Neurodevelopmental Outcome in Preterm Infants. [JOURNAL ARTICLE]
- Neonatology 2016 Jun 29; 110(4):286-295.
Chorioamnionitis, a risk factor for preterm delivery, has been suggested to be associated with suboptimal neurological development in premature infants.To evaluate the association between chorioamnionitis and neurodevelopment in preterm infants at 5 years of age. Methods Very low birth weight and very low gestational age infants (n = 197) were recruited. Placental samples (n = 117) were evaluated for histological chorioamnionitis. Fetal histological chorioamnionitis was analyzed as a subgroup. The diagnosis of clinical chorioamnionitis was derived from medical records. Neurodevelopmental impairments were evaluated at 2 years of age, and cognitive development (n = 188) and neuropsychological performance (n = 193) were evaluated at 5 years of age.There were no associations between histological or clinical chorioamnionitis and neurodevelopmental impairments at 2 years of age. Clinical chorioamnionitis and fetal histological chorioamnionitis were not associated with cognitive development or neuropsychological performance, but histological chorioamnionitis was associated with poorer cognitive outcome (regression coefficient = -7.22, 95% CI: -14.31 to -0.13) and weaker memory and learning functions (regression coefficient = -1.29, 95% CI: -2.40 to -0.18) at 5 years of age.Our study findings do not support clinical chorioamnionitis having a major independent role in the pathogenesis of neurodevelopmental problems in very preterm infants. Histological chorioamnionitis was associated with slightly less optimal performance at 5 years of age, but further studies are needed to verify the clinical significance of these findings.
- A Prognostic Neonatal Neuroimaging Scale for Symptomatic Congenital Cytomegalovirus Infection. [JOURNAL ARTICLE]
- Neonatology 2016 Jun 24; 110(4):277-285.
Congenital cytomegalovirus (cCMV) can cause brain inflammation/destruction and teratogenic effects. The only validated neuroimaging prognostic categorization for symptomatic cCMV available is based on destructive lesions seen on computed tomography (CT).The aim of this study was to establish the predictive ability of a comprehensive neonatal neuroimaging scale in symptomatic cCMV.Twenty-six infants were studied by neonatal cranial ultrasound scans (US; n = 25), CT (n = 11) and magnetic resonance imaging (MRI; n = 9). A previously validated neuroimaging scale comprising calcifications, ventriculomegaly and atrophy was compared to a newly proposed system adding cerebral dysgenesis and white matter disease. The findings were graded from 0 to 3. Neurodevelopmental assessment included motor and cognitive functions, epilepsy, vision, hearing and behavioral disorders.Both scales showed a significant association with outcome (p < 0.005). Our scale was more accurate in predicting death or moderate-severe disability (area under the curve for scores ≥2, 0.88 ± 0.06 vs. 0.80 ± 0.08). All 5 infants with normal neuroimaging survived with intact neurological function. While our scale was highly associated with outcome in patients studied by MRI, it was unable to predict unfavorable outcomes in 2 patients with mildly abnormal US and/or CT.A comprehensive scale based on US and MRI predicts neurodevelopment in symptomatic cCMV. Significant destructive lesions are associated with a poor prognosis. While a strictly normal cranial US predicts a favorable outcome, in case of subtle US abnormalities, MRI is crucial for prognostication.
- Cooling Effect on Skin Microcirculation in Asphyxiated Newborn Infants with Increased C-Reactive Protein. [JOURNAL ARTICLE]
- Neonatology 2016 Jun 21; 110(4):270-276.
Therapeutic hypothermia is presumed to suppress inflammatory processes after perinatal asphyxia. In a previous study of neonatal hypoxic-ischemic encephalopathy (HIE) we found altered skin microcirculation in about a third of the infants after rewarming. We speculated whether this could be linked to increased inflammatory responses, such as high C-reactive protein (CRP). The present study further explored this question.The aim of this study was to explore the differences in skin microcirculation and its oxygen delivery ability during cooling and after rewarming in HIE infants with or without high CRP.A previously studied population of 28 HIE infants was divided into two subgroups depending on low or high CRP (repeated values above 30 mg/l for more than 24 h). The differences between the two groups regarding laser Doppler perfusion measurements (LDPMs), computer-assisted video microscopy and diffuse reflectance spectroscopies during cooling on days 1 and 3 and after rewarming on day 4 were assessed.After rewarming, infants with high CRP showed significantly higher skin LDPM perfusion, lower functional vessel density and larger heterogeneity of capillary flow velocities as compared to infants with low CRP, while no such differences were found during cooling.Skin microcirculatory responses differed significantly after rewarming, but not during cooling, between asphyxiated neonates with or without high CRP. We speculate whether cooling influences the inflammatory skin microcirculatory response and the ability of oxygen delivery to the cells. Further studies are needed to investigate this as well as its applicability to other vascular beds in the body.
- Neonatal Haemophagocytic Lymphohistiocytosis Associated with Maternal Adult-Onset Still's Disease. [JOURNAL ARTICLE]
- Neonatology 2016 Jun 16; 110(4):267-269.
Neonatal haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially lethal condition. We recently encountered a preterm infant who developed severe HLH associated with maternal adult-onset Still's disease, which to our knowledge has not been previously reported. The infant presented with fever, generalised lymphadenopathy, transient erythematous skin rash, hepatosplenomegaly, ascites, pancytopenia, marked hyperferritinaemia, and hypofibrinogenaemia, which were features similar to maternal presentation during late pregnancy. Whole gene exome sequencing screening for familial HLH (PRF1, STX11, STXBP2, and MUNC13D genes) was negative. We postulated that factors such as auto-antibodies, antigens, or inflammatory mediators transmitted vertically from the mother could have triggered the intense inflammation in the infant. The infant responded promptly to dexamethasone, etoposide, and cyclosporin A, without the need for bone marrow transplantation. Neonatologists should be alerted to the rare diagnosis of HLH in the presence of active maternal diseases, including infection or autoimmune conditions, especially in association with fever, cytopenia, and hepatosplenomegaly.
- Pain-Related Reactions among Premature Infants with Gestational Age Less than 26 Weeks: An Observational Cohort Study. [JOURNAL ARTICLE]
- Neonatology 2016 Jun 14; 110(4):261-266.
There is insufficient information regarding acute pain reactions among premature infants with a gestational age of less than 26 weeks and no appropriate scale for pain measurement in this age group. We hypothesized that these infants present specific reactions to a standardized pain stimulus within the first 3 days of life.Mixed-methods, prospective, open-label, single-arm, observational study. Routine capillary or peripheral blood takes were filmed. The model consisting of a baseline, a preparatory, an interventional and a return-to-baseline phase was filmed. After a pilot evaluation, experienced medical and nursing neonatal intensive care unit (NICU) staff analysed the videos.Twenty infants with gestational ages ranging from 22 weeks and 3 days to 26 weeks (mean 24 weeks) were recruited. Nineteen infants showed pain reactions, with a mean latency of 8.3 s (range 2-30). The majority presented eye movements, changes of the breath pattern and a slight increase in the mean SpO2 value. A high degree of interrater and intrarater reliability was found.Premature infants with a gestational age of up to 26 weeks can present a variety of discrete reactions as response to a pain stimulus within the first 72 h of life. Experienced NICU staff can perform a valid and reliable evaluation of these reactions.
- Novel Echocardiography Methods in the Functional Assessment of the Newborn Heart. [JOURNAL ARTICLE]
- Neonatology 2016 Jun 10; 110(4):248-260.
Echocardiography in the neonatal intensive care unit has led to improvements in our ability to assess the neonatal heart in health and disease. Advances in neonatal cardiac imaging have provided the capability to obtain quantitative information that often supersedes the qualitative information provided by conventional methods. Novel quantitative measures of function include the assessment of the velocity of muscle tissue movement during systole and diastole using tissue Doppler velocity imaging, and evaluation of deformation and rotational characteristics of the myocardium utilizing speckle tracking echocardiography or tissue Doppler-derived strain imaging. A comprehensive understanding of these novel functional modalities, their predictive value, and limitations can greatly assist in managing both the normal and maladaptive responses in the newborn period. This article discusses the novel and emerging methods for assessment of left and right heart function in the neonatal population.
- Physical Activity and Gastric Residuals as Biomarkers for Region-Specific NEC Lesions in Preterm Neonates. [JOURNAL ARTICLE]
- Neonatology 2016 Jun 7; 110(4):241-247.
Necrotizing enterocolitis (NEC) is a serious feeding-related inflammatory gut disease with high mortality. Early clinical markers of NEC are of great importance for optimizing preventive interventions.Using preterm pigs as models, we hypothesized that an early postnatal onset of NEC can be predicted by decreased physical activity during the first few days after birth.Cesarean-delivered preterm pigs were fed parenteral nutrition and increasing amounts of formula for 5 days after birth (n = 120). Their physical activity was quantified by a continuous camera surveillance system and they were evaluated twice daily for clinical signs of apathy, discoloration, respiratory distress, abdominal distension and diarrhea. The volume of gastric residuals and the presence of macroscopic NEC-like lesions in the stomach, intestine and colon were recorded at euthanasia on day 5.Half of the pigs (48%) showed clear NEC-like lesions on day 5, and these individuals had more adverse clinical symptoms from day 3 but decreased physical activity already from day 2 relative to the unaffected pigs (both p < 0.05). Only animals with NEC lesions in the small intestine had lower physical activity on days 2 and 3, and the increased volume of gastric residuals was specifically related to colon lesions (both p < 0.05).Decreased physical activity precedes the clinical symptoms of NEC in the small intestine of preterm pigs, and increased gastric residuals predict NEC lesions in the colon. Physical activity and gastric residuals may function as clinical biomarkers for region-specific NEC lesions in preterm neonates.
- Sharing Progress in Neonatal (SPIN) Lung and Brain. [Journal Article]
- Neonatology 2016; 109(4):322-4.
- Stem Cells for Neonatal Brain Disorders. [Journal Article]
- Neonatology 2016; 109(4):377-83.
Despite recent advances in neonatal intensive care medicine, neonatal brain injury resulting from intraventricular hemorrhage or hypoxic-ischemic encephalopathy remains a major cause of neonatal mortality and neurologic morbidities in survivors. Several studies have indicated that stem cell therapy is a promising novel therapy for neonatal brain injury resulting from these disorders. This review summarizes recent advances in stem cell research for treating neonatal brain injury due to intraventricular hemorrhage or hypoxic-ischemic encephalopathy with a particular focus on preclinical data, covering important issues for clinical translation such as optimal cell type, route, dose and timing of stem cell therapy, and translation of these preclinical results into a clinical trial.
- Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology. [Journal Article]
- Neonatology 2016; 109(4):369-76.
Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85-89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally.