Clinical Application of Postmortem Magnetic Resonance Imaging in Neonates.

BACKGROUND: Recent reports advocate the use of MRI either as a substitute for postmortem examinations or for a more targeted autopsy. METHODS: A full-body postmortem MRI (pMRI) of infants was performed as early as possible after death, and findings were compared to clinical premortem diagnoses. RESULTS: Thirty-one infants were scanned during the study period. Median gestation at birth was 34 weeks (ranges: 24-43). In 3 (10%) cases, no new findings were detected. In 2 (6%), new minor findings not related to the cause of death were detected, and in 17 (55%), new minor findings related to the cause of death were detected. New major findings related to the cause of death were detected in 4 (13%) cases, and new major findings not related to the cause of death were detected in 5 (16%) cases. In 3 (10%), findings thought to alter the perceived cause of death were detected. Overall, in 23 (74%) cases, pMRI findings reinforced the clinical premortem diagnoses. CONCLUSIONS: pMRI is a culturally accepted alternative when autopsy is not performed and can either reinforce, refute, or add to premortem clinical diagnoses.

Diagnostic accuracy of interleukin-6 for early-onset sepsis in preterm neonates.

Background: Early-onset sepsis (EOS) is a leading cause of morbidity and mortality among neonates. Yet, accurate diagnosis remains a major challenge in clinical routine.Objective: The aim of this study was to evaluate the diagnostic accuracy of Interleukin-6 (IL-6) in combination with other objective perinatal data for early-onset sepsis (EOS) in preterm neonates.Methods: We conducted a retrospective nested case-control study with preterm neonates with a birth weight < 2000 g born in our NICU between January 2007 and June 2016. Differences of IL-6 levels and other perinatal clinical and laboratory data between neonates with and without EOS were statistically analyzed.Results: Sixty-seven preterm infants with and 115 neonates without EOS were included in this study. Specificity and sensitivity for IL-6 were 72.8% and 75.0%, respectively, with an area under the curve of 0.804 at a cut-off point of 40 ng/l. Depending on the statistical method applied, combining IL-6 with a second perinatal factor led either to an increase of specificity (82.4-100%) or sensitivity (75.0-92.2%).Conclusion: The combination of IL-6 with other perinatal factors can significantly increase specificity and sensitivity in the diagnosis of EOS. However, overall diagnostic accuracy cannot be notably improved as there is a tradeoff between sensitivity and specificity. Although these findings do not necessarily apply in clinical routine, they can be of substantial value in the assistance of individual decision making.

Evaluating the effect of care around labor and delivery practices on early neonatal mortality in the Global Network's Maternal and Newborn Health Registry.

BACKGROUND: Neonatal deaths in first 28-days of life represent 47% of all deaths under the age of five years globally and are a focus of the United Nation's (UN's) Sustainable Development Goals. Pregnant women are delivering in facilities but that does not indicate quality of care during delivery and the postpartum period. The World Health Organization's Essential Newborn Care (ENC) package reduces neonatal mortality, but lacks a simple and valid composite index that measures its effectiveness. METHODS: Data on 5 intra-partum and 3 post-partum practices (indicators) recommended as part of ENC, routinely collected in NICHD's Global Network's (GN) Maternal Newborn Health Registry (MNHR) between 2010 and 2013, were included. We evaluated if all 8 practices (Care around Delivery - CAD), combined as an index was associated with reduced early neonatal mortality rates (days 0-6 of life). RESULTS: A total of 150,848 live births were included in the analysis. The individual indicators varied across sites. All components were present in 19.9% births (range 0.4 to 31% across sites). Present indicators (8 components) were associated with reduced early neonatal mortality [adjusted RR (95% CI):0.81 (0.77, 0.85); p < 0.0001]. Despite an overall association between CAD and early neonatal mortality (RR < 1.0 for all early mortality): delivery by skilled birth attendant; presence of fetal heart and delayed bathing were associated with increased early neonatal mortality. CONCLUSIONS: Present indicators (8 practices) of CAD were associated with a 19% reduction in the risk of neonatal death in the diverse health facilities where delivery occurred within the GN MNHR. These indicators could be monitored to identify facilities that need to improve compliance with ENC practices to reduce preventable neonatal deaths. Three of the 8 indicators were associated with increased neonatal mortality, due to baby being sick at birth. Although promising, this composite index needs refinement before use to monitor facility-based quality of care in association with early neonatal mortality. Trial registration The identifier of the Maternal Newborn Health Registry at ClinicalTrials.gov is NCT01073475.

Lost in Transition: Is Early Respiratory Support in Newborn Infants the Best Option?

BACKGROUND: Late preterm and term newborns with respiratory distress are increasingly treated with non-invasive ventilation (NIV) including nasal high-flow or continuous positive airway pressure. For infants with mild distress, NIV may be unnecessary. OBJECTIVES: We speculated that treatment with supplemental oxygen (SO) prior to NIV could help clinicians select infants for NIV treatment, and examined this hypothesis using data from a recently completed trial. METHOD: Post hoc analysis of data from a subset of infants enrolled in the HUNTER trial. Infants born at ≥36 weeks' gestation were categorized by whether they were receiving SO prior to randomization. The 2 groups were compared for illness severity (indicated by treatment failure at 72 h, mechanical ventilation, need for up-transfer, SO requirement post-randomization, and length of time receiving respiratory support), use of selected medical interventions (antibiotics, intravenous fluids), and breastfeeding at discharge. RESULTS: Analysis included 380 infants. Infants not receiving SO had less severe illness; lower rates of treatment failure (7.3 vs. 17.2%), mechanical ventilation (0.6 vs. 5.9%), need for transfer (6.8 vs. 13.8%), and more often did not receive any SO post-randomization (75.1 vs. 3.0%). Most infants in both groups received intravenous fluids (93 and 98%) and antibiotics (81 and 93%); the rate of full breastfeeding was low in both groups (51 and 45%). CONCLUSIONS: Late preterm and term newborn infants without SO requirement at the time of commencing NIV for respiratory distress are at lower risk of requiring treatment escalation. Close observation of these infants (watch and wait strategy) may avoid unnecessary treatment.

Prediction of Neurodevelopmental Impairment in Congenital Cytomegalovirus Infection by Early Postnatal Magnetic Resonance Imaging.

INTRODUCTION: Congenital cytomegalovirus infection (CCMVI) may result in neurodevelopmental impairments (NDIs) such as hearing loss, developmental delay, epilepsy, and cerebral palsy. We aimed to investigate the potential for brain magnetic resonance imaging (MRI) to predict NDI in patients with CCMVI. METHODS: We studied infants with CCMVI who were referred to our hospital from April 2010 to October 2018 and underwent a brain MRI within 3 months since birth. We screened for 6 classic presentations of CCMVI including ventriculomegaly, periventricular cysts, hippocampal dysplasia, cerebellar hypoplasia, migration disorders, and white matter abnormalities. Images were interpreted by a blinded pediatric radiologist. NDI was defined as having a developmental quotient <80, hearing dysfunction, blindness, or epilepsy requiring anti-epileptic drugs at approximately 18 months of corrected age. RESULTS: The study involved 42 infants with CCMVI (median gestational age 38 weeks, birthweight 2,516 g). At least one abnormal finding was detected in 28 (67%) infants. Abnormal findings consisted of 3 cerebellar hypoplasia (7%), 7 migration disorders (17%), 26 white matter abnormalities (62%), 12 periventricular cysts (28%), 1 hippocampal dysplasia (2%), and 20 ventriculomegaly (48%). Abnormal findings were significantly more prevalent in infants with clinical symptoms (21/24, 91%) than in those without (7/19, 37%, p < 0.01). For NDI prediction, having ≥2 of ventriculomegaly, periventricular cysts, and white matter abnormality produced the highest Youden index values (0.78). CONCLUSION: Infants with CCMVI with at least 2 of the abovementioned specific brain image abnormalities may be at high risk of developing NDI.

The Physiological Variation in Plasma Presepsin Levels During the Early Neonatal Period.

Neonatal sepsis continues to be a global problem with significant morbidity and mortality, because of the difficulty in predicting its onset with clinical symptoms alone. Thus, the presence of biomarkers is useful for the diagnosis of neonatal sepsis. Presepsin is a 13-kDa truncated form of soluble CD14 that is produced through proteolytic cleavage on activated monocytes. Presepsin, consisting of 64 amino acid residues, has been proposed as a reliable biomarker for the early diagnosis of sepsis in neonates. However, some biomarkers for the diagnosis of sepsis are elevated during the early neonatal period due to physiological variation, whereas such variation in presepsin levels is uncertain. The objective of this study is to investigate the physiological variation in plasma presepsin levels during the early neonatal period. This prospective study included 30 full-term healthy neonates, including 15 neonates delivered by cesarean section. Plasma presepsin levels were examined at birth and on the first day and the fifth day of life in neonates, and the levels on the 5th day of life were lower than those at any other points (P < 0.001). Moreover, there was no significant difference of plasma presepsin levels between neonates delivered vaginally and by cesarean section. The physiological variation in plasma presepsin levels was observed during the early neonatal period. Attention needs to be paid when measuring plasma presespsin levels for the screening of sepsis during the early neonatal period.

Neonatal Leukemoid Reaction with Fetal Inflammatory Response Syndrome Is Associated with Elevated Serum Granulocyte Colony Stimulating Factor and Interleukin-6.

Leukemoid reaction (LR) is a reactive disease that exhibits abnormal blood values similar to leukemia, but not due to leukemia. One report showed that neonatal LR (NLR) was associated with elevated serum granulocyte colony stimulating factor (G-CSF) in only 30% of the study neonates. NLR is not always associated with the elevation of serum G-CSF. NLR was defined as a white blood cell count of ≥ 40 × 103/µL and/or blast cell concentration of > 2%. We have focused on NLR with fetal inflammatory response syndrome (FIRS), defined as a fetal systemic inflammatory reaction triggered by intrauterine infection. FIRS was diagnosed based on a cord serum interleukin-6 (IL-6) concentration ≥ 17.5 pg/mL and histopathological chorioamnionitis. Because NLR is highly associated with FIRS, we have hypothesized that NLR is associated with the elevation of both G-CSF and IL-6. This is the first report to measure multiple cytokines in NLR at the same time. The study comprised 19 preterm infants with FIRS: 8 with NLR (study group) and 11 without NLR (control group). Serum G-CSF and IL-6 concentrations were significantly higher in the study group than the control group. There was a positive correlation between G-CSF and IL-6 levels in the study group but not in the control group. These results suggest that elevated serum G-CSF and IL-6 may underlie NLR. Thus, G-CSF and IL-6 concentrations may be predictive of the onset of NLR. Measuring these cytokines is useful for judging the prognosis of preterm infants and for their post-natal clinical management.

A Study on the differences in Blood Pictures of Premature Babies and Term Babies

The author has studied on the differences in blood pictures, especially the differences of blood pictures in capillary blood and venous blood, in 25 premature babies and 50 term babies from birth to 7 days of age sequentially during the period of 6 monts from April 1980 to Sept. 1980. The results are summarized as follws; 1. As comparing blood pictures with term babies, premature babies showed somewhat lower values in erythrocyte, hemoglobin, hematocrit. MCV, MCH, leucocyte and platelet but somewhat higher values in reticulocyte and MCHC. 2. As comparing blood pictures with the venous blood, the capillary blood showed significantly higher values in erythrocyte, hemoglobin and hematocrit during the neonatal period in both premature babies and term babies, but showed somewhat lower values in MCV, MCH, MCHC, and platelet. 3. According to the time of clamping the umbilical cord after birth, there were significant differences of blood pictures between early and late clamping of the umbilical cord. 4. The highest mean erythrocyte counts in both term babies and premaature babies were 5,896,000/cub.mm and 5,542,000/cub.mm at 3-6 hours after birth. Those values were gradually decreased to 5,104,000/cub.mm and 4,753,000/cub.mm on the 6th-7the day of life. 5. The highest average hemoglobin levels in both term babies and premature babies were 21.1gm/dl and 19.5gm/dl at 3-6 hours after birth. Those values were gradually decreased to 18.1gm/dl and 17.1gm/dl on the 6th-7th day of life. 6. The mean values of hematocrit in both term babies and premature babies were higest, 64.5% and 59.9% at 3-6 hours after birth. Those values were gradually decreased to 54.8% and 50.2% on the 6th-7the of life. 7. The average total serum protein levels in both term babies and premature babies were 5.76gm/dl and 5.22gm/dl at birth. Those values were increased to 6.45gm/dl and 5.74gm/dl at 3- hours after birth. 8. The average MCV in both term babies and premature babies showed highest values, 114.2fl and 110.1fl at birth. Those values were gradually decreased to 107.0fl and 103.4fl on the 6th-7th day of life. 9. The average MCH in both term babies and premature babies showed highest values, 36.8pg and 35.3pg at birth. Those values were gradually decreased to 107.0fl and 103.4fl on the 6th-7th day of life. 10. The average MCHC in both term babies and premature babies showed constant levels, 31.3-32.0% and 32.2-33.1% from birth to 7the day of life. 11. The average platelet counts in both term babies and premature babies were 243,000/cub.mm and 229,000/cub.mm during the first 4 days of life. Those values were gradually increased to 283,000/cub.mm and 253,000/cub.mm on the 6th-7the day of life. 12. The highest reticulocyte counts in both term babies and premature babies were 3.1% and 3.6% at the age of 3-6 hours. Those values were rapidly dropped down from 4th day to 7th day of life, decreasing from 1.7% and 1.9% to 1.0% and 1.3%. 13. The highest llecucyte counts in both term babies and premature babies were 25,794/cub.mm and 23,363/cub.mm at the age of 3-6 hours. Both values were gradually decreased to 13,213/cub.mm and 11,870/cub.mm on the 6th-7th day of life.