Neonatal Thyrotoxicosis in Infants of Mothers with Graves' Disease Treated for Radioiodine-Induced Hypothyroidism: A Literature Review.

Fetal and neonatal thyrotoxicosis occurs in up to 5% of pregnancies in mothers with Graves' disease (GD). This condition is caused by stimulating antibodies against the thyrotropin receptor (TRAbs) that cross the placenta and may stimulate the fetal thyroid, typically in the second half of pregnancy. GD is often treated with radioiodine, resulting in hypothyroidism in most patients, but TRAbs can persist for several years. Even if a pregnant mother is hypothyroid after radioiodine therapy or surgery, her TRAbs can still, although rarely, induce fetal hyperthyroidism. In this review, we first present two cases of neonatal hyperthyroidism in mothers with GD who became hypothyroid after prior radioiodine therapy, identified through a 10-year analysis of the National Perinatal System in Slovenia. Based on these cases, we provide an overview of existing data on this rare clinical condition in neonates. We also discuss the underlying mechanisms and clinical outcomes based on currently available data. In conclusion, our review highlights the importance of careful monitoring during pregnancy in all women with GD, even in those well managed after radioiodine therapy or surgery.

Association between colonization of the respiratory tract with Ureaplasma species and bronchopulmonary dysplasia in newborns with extremely low gestational age: a retrospective study.

AIM: To ascertain the incidence of respiratory tract colonization in extremely low gestational age newborns (ELGANs) with Ureaplasma parvum and Ureaplasma urealyticum and determine if there is a difference in the severity of bronchopulmonary dysplasia (BPD) between ELGANs with and without Ureaplasma species (spp) colonization. METHODS: We reviewed the medical records of ELGANs 23 0/7-27 6/7 weeks of gestation, tested for U. parvum and U. urealyticum in our Center from January 1, 2009 to December 31, 2019. Ureaplasma spp were identified with the Mycofast Screening Revolution assay based on liquid broth cultures or with polymerase chain reaction. RESULTS: This study enrolled 196 preterm newborns. Fifty (25.5%) newborns had Ureaplasma spp respiratory tract colonization, with U. parvum being the predominant species. The incidence rate of respiratory tract colonization with Ureaplasma spp slightly increased in the studied period. The incidence rate for 2019 was 16.2 per 100 infants. BPD severity significantly correlated with Ureaplasma spp colonization (P = 0.041). After controlling for other risk factors for BPD in a regression model, preterm infants colonized with Ureaplasma spp had 4.32 times (95% confidence interval, CI 1.20-15.49) higher odds for developing moderate-to-severe BPD. CONCLUSIONS: U. parvum and U. urealyticum could be associated with the development of BPD in ELGANs.

What Constitutes a "Good Death"?-A Representative Cross-Sectional Survey Among the General Public in Croatia.

Understanding the attitudes of a particular society on a "good death" is important when it comes to end-of-life decision-making and palliative care. In the Republic of Croatia no systematic research has been done on the attitudes of the general population about the concept of a "good death". This cross sectional survey was conducted on a three-stage random sample, stratified by regions, counties and locations within those counties (N = 1203) during November and December, 2019. ANOVA, to determine differences, factor analysis and multiple regression analysis were used. The most important characteristics of a good death outlined by the respondents were: the absence of pain, the presence and unencumberedness of family and loved ones, the importance of a sense of fulfilment and meaning in life in this regard, reconciliation with God, the presence of awareness and sobriety, and the possibility of treatment.

No increase in GFAP and S-100B in very preterm infants with mild periventricular leukomalacia or intraventricular hemorrhage: a pilot study.

AIM: To determine the serum levels of glial fibrillary acidic protein (GFAP) and S-100B in very preterm infants with and without periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH). METHODS: The study enrolled preterm infants born between 23 and 32 weeks of gestation admitted to the Neonatal Intensive Care Unit, University Medical Center Ljubljana. PVL and IVH were determined with cranial ultrasound. Peripheral blood was collected in the first 24 hours after delivery and once between days 4 to 7. GFAP and S-100B concentrations were measured in serum samples. Infants with PVL or IVH were compared with infants without PVL or IVH. RESULTS: Of 40 patients (mean gestational age 29.4 weeks), 7 had IVH and/or PVL. S-100B was detectable in peripheral blood in all patients at every measurement. In the group with IVH or PVL, the median S-100B at the first sampling was 0.43 (IQR 0.29-0.60) ng/mL, and 0.40 (IQR 0.33-1.01) ng/mL at the second sampling. In the group without PVL or IVH, it was 0.40 (IQR 0.29-0.6) ng/mL at the first sampling and 0.43 (IQR 0.34-0.62) ng/mL at the second sampling. The median GFAP was 0 regardless of the group and sampling time. The groups did not significantly differ in serum GFAP or S-100B levels. CONCLUSION: Peripheral blood levels of GFAP and S-100B were not significantly increased in very preterm infants that developed PVL or IVH. The predictive value of GFAP and S-100B as biomarkers of neonatal brain injury should be further explored in a larger cohort of neonates with more extensive IVH or PVL.

Serum hepcidin and ferritin as markers of iron deficiency in premature infants born at less than 32 weeks of gestation: prospective observational study.

BACKGROUND: Preterm infants born at less than 32 weeks of gestation are at higher risk of low total iron stores (iron deficiency). Serum ferritin is used as a valid total iron stores and iron deficiency biomarker, usually as a combination of ferritin and red blood cell counts. METHODS: Serum hepcidin and ferritin values and red blood cell counts were obtained from 37 of 40 included premature infants born at less than 32 weeks of gestation at risk of iron deficiency. The first sample was obtained in the first week of life, and the second at transfer from the Neonatal intensive care unit to the maternity ward, when serum ferritin level below 25 µg/L has been defined as very low total iron stores (iron deficiency). RESULTS: Ferritin median levels decreased from a median value of 152 µg/L at the first measurement to 54 µg/L at the second measurement. Hepcidin median levels also decreased from 30.1 µg/L to 2.1 µg/L. We found a positive and statistically significant correlation between levels of ferritin and hepcidin at both measurements (r = 0.57; p < 0.001 and r = 0.72; p < 0.001, respectively). Compared to serum hepcidin, ferritin at the first measurement has not statistically significant higher power in predicting children with iron deficiency before discharge from the hospital. CONCLUSIONS: We found a correlation between ferritin and hepcidin levels. Nevertheless, hepcidin does not have a worse power in predicting children with iron deficiency compared to ferritin.

Prolonged hospitalization is a risk factor for delirium onset: one-day prevalence study in Slovenian INTENSIVE CARE UNITS.

Delirium is a clinical syndrome often underestimated in the intensive care units (ICU). The aim of this study was to determine the prevalence and factors that influence the onset of delirium. A questionnaire was sent to intensivists in Slovenian ICUs, who estimated the prevalence of delirious patients. The questionnaire consisted of demographic data, type of ICU, diagnosis, reason for admission to the ICU, type of anesthesia and surgery, clinical condition, type of supportive therapy, presence of delirium, data on discharge, transfers between departments or patient outcome on day 30. Patient consciousness was assessed by the Richmond Agitation-Sedation Scale (RASS) and the presence of delirium by the validated delirium-screening Confusion Assessment Method for the ICU (CAM-ICU). Replies received from intensivists included data on 103 patients. According to RASS ≥-3, the prevalence of delirium was 9.5% (7 out of 74 patients). There was no difference in the prevalence of delirium between surgical and medical ICU patients (p=0.388). Delirious patients had longer hospital stay (p=0.002) and ICU stay (p=0.032) compared to patients without delirium. All delirious patients survived until day 30, whereas 19 patients without delirium died (p=0.092). Logistic regression analysis dismissed any association of delirium with patient mortality (p=0.998). Age, gender, anesthesia, mechanical ventilation, and type of surgical procedure could not be evaluated as risk factors for delirium. In Slovenian ICUs, a lower proportion of delirium was observed, as reported from similar studies. Risk factors such as gender, age, mechanical ventilation, sedation, anesthesia, or department could not predict delirium. However, prolonged hospitalization of ICU patients could predict the onset of delirium, but the presence of delirium did not increase patient mortality.

Notes on the Development of the Slovenian Ethical Recommendations for Decision-Making on Treatment and Palliative Care of Patients at the End of Life in Intensive Care Medicine.

OBJECTIVES: To describe the process of development of "Slovenian Ethical Recommendations for Decision-Making on Treatment and Palliative Care of Patients at the End of Life in Intensive Care Medicine" and its final outcomes. DATA SOURCES: Personal experience and reflection, complemented by published data. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Narrative, experiential reflection, literature review. CONCLUSIONS: Slovenian ethical recommendations bring a small piece to a long tradition of ethical practice in a small European country. Despite the availability of informative international guiding documents on the issue, there are several specific good reasons for a small country or a region to develop its own unique guidelines (i.e., lack of local directives and legislation, unique cultural and political situation, need for development of professional expertise and terminology, and to educate healthcare providers). The authors strongly believe that our recommendations positively impact practice and will support best possible integrated palliative and end-of-life quality care with the ICU.

Passive therapeutic hypothermia during ambulance and helicopter secondary neonatal transport in neonates with hypoxic brain injury: a 10-year retrospective survey.

BACKGROUND: Therapeutic hypothermia is a method of treatment in newborns with hypoxic ischemic encephalopathy. Hypothermia should be initiated no later than 6 h after birth. The purpose of this study was to evaluate the quality of the passive therapeutic cooling during neonatal transport. PURPOSE: The study aims to evaluate the efficiency of our transport in maintenance of target body temperature during transport. METHODS: We conducted a 10-year retrospective study in neonates, transported by helicopter or ambulance, who received therapeutic passive-induced hypothermia during transport to the Department of Pediatric Surgery and Intensive Therapy at the University Medical Centre Ljubljana between September 1, 2006, and December 31, 2016. RESULTS: Out of 68 transported newborns, 57 met the criteria for therapeutic induced hypothermia. Eight out of 51 (15.7%) were within therapeutic temperature zone before start of transport while 30 out of 57 (52.6%) were within therapeutic temperature zone at the end of transport. There was a negative correlation between the duration of transport and temperature at the admission (ρ = - 0.306; p = 0.026). A positive correlation was found between the body temperature before and at the end of transport (ρ = 0.410; p = 0,003). A positive correlation between axillary and rectal temperature on admission was found (ρ = 0,832; p < 0,0005). The type of transport, meteorological season, or gender differences did not affect any of measured parameters. Newborns who received chest compression had lower temperature. CONCLUSION: Therapeutic temperature zone during transport was achieved in 52.6% of transported neonates. Axillary temperature positively correlated with rectal temperature on admission.

Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics.

BACKGROUND: Twenty-five percent to 50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. METHODS: Two hundred ninety seven children ≤6 years of age, admitted to hospital in Slovenia, October 2011 to October 2012, with AGE, and 88 ≤6 years old healthy children were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. RESULTS: At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing, and a potential viral pathogen was detected in 17 additional samples (5.8%). CONCLUSIONS: Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens.

Mediastinal teratoma with hydrops fetalis in a newborn and development of chronic respiratory insufficiency.

BACKGROUND: Mediastinal fetal teratoma can be detected as a mass in the chest during a routine prenatal ultra-sound screening. Because of the pressure on mediastinal structures it can be the cause of non-immune hydrops fetalis and polyhydramnion. The development of hydrops fetalis leads to fetal death or premature delivery in most reported cases. Early surgical removal is important, but, the result of treatment depends on the stage of development of mediastinal organs and complications in the postoperative period. CASE REPORT: A 31-year-old gravida carrying twins, with spontaneous membrane rupture at 32 weeks gestation underwent urgent caesarean section after antenatal ultrasound revealed severe polyhydramnion and hydrops fetalis in geminus A. The child was intubated immediately after birth due to severe respiratory distress. Ultrasound and X-ray revealed a tumour mass in the right hemithorax. Tumour resection was performed at the age of 7 days. Histology examination revealed an encapsulated immature teratoma. The postoperative course was complicated with respiratory insufficiency which turned into chronic at the age of eight months. CONCLUSION: This is the fifth reported child with fetal mediastinal teratoma and severe hydrops fetalis that survived the neonatal period. Additional diagnostic search revealed abnormal course of both pulmonary arteries, which was probably one of the main causes of respiratory insufficiency.

Low CD8 T cells in neonates and infants prior to surgery, and health-care-associated infections: prospective observational study.

BACKGROUND: Major surgery suppresses the cell-mediated immune response in children and adults. Data on preoperative and postoperative T-cell counts in pediatric surgical patients and their relationship to health-care-associated infection (HAI) are not yet known. METHODS: A prospective observational study was carried out in a level III multidisciplinary neonatal and pediatric intensive care unit. Before and after, and in the first 3 days after surgery, lymphocyte subsets in peripheral blood were measured in 28 neonates and infants on flow cytometry. HAI were classified according to CDC/NHSN criteria. RESULTS: Six out of 28 neonates and infants (21.4%) developed HAI (group I-HAI), while 22 out of 28 (78.6%) remained infection free (group II-non-HAI). In group I with HAI, the preoperative median cytotoxic T-lymphocyte (CD8-T-cell) level was found to be below normal, and remained very low throughout the study period. In addition, the median and interquartile CD8 T-cell range (358 cells/µL; 304-424 cells/µL) were twice as low compared to group II without HAI (822 cells/µL; 522-933 cells/µL; P = 0.013). No differences were found between the two groups with regard to patient demographics and clinical data. CONCLUSION: Neonates and infants who underwent a major surgical procedure and who had a very low preoperative CD8 T-cell level, developed HAI postoperatively.

Prolonged prostaglandin E1 therapy in a neonate with pulmonary atresia and ventricular septal defect and the development of antral foveolar hyperplasia and hypertrophic pyloric stenosis.

Prostaglandin E1 (alprostadil) is widely used for maintaining the patency of ductus arteriosus in ductus-dependent congenital heart defects in neonates to improve oxygenation. Among more common side effects are fever, rash, apnoea, diarrhoea, jitteriness, and flushing. More severe side effects are brown fat necrosis, cortical hyperostosis, and gastric outlet obstruction, most commonly the result of antral foveolar hyperplasia or hypertrophic pyloric stenosis. We report on an infant with a ductus-dependent congenital heart defect who developed symptoms and sonographic evidence of focal foveolar hyperplasia and hypertrophic pyloric stenosis after prolonged treatment with prostaglandin E1. Gastrointestinal symptoms persisted after corrective cardiac surgery, and pyloromyotomy was required. Study of the case and of available literature showed an association between the total dose of prostaglandin E1 administered and duration of treatment and the development of gastric outlet obstruction. We conclude that if patients are treated with a prostaglandin E1 infusion, careful monitoring for symptoms and signs of gastric outlet obstruction is required.

Detection of human coronaviruses in simultaneously collected stool samples and nasopharyngeal swabs from hospitalized children with acute gastroenteritis.

BACKGROUND: Human coronaviruses (HCoVs) are a well-known cause of respiratory infections but their role in gastrointestinal infections is unclear. The objective of our study was to assess the significance of HCoVs in the etiology of acute gastroenteritis (AGE) in children <6 years of age. METHODS: Stool samples and nasopharyngeal (NP) swabs collected from 260 children hospitalized for AGE (160 also had respiratory symptoms) and 157 otherwise healthy control children admitted for elective surgery were tested for the presence of four HCoVs using real time RT-PCR. Registered at ClinicalTrials.gov (reg. NCT00987519). RESULTS: HCoVs were more frequent in patients with AGE than in controls (23/260, 8.8% versus 4/151, 2.6%; odds ratio, OR 3.3; 95% confidence interval, CI 1.3-10.0; P = 0.01). Three of four HCoV-positive members in the control group, asymptomatic when sampled, recalled gastrointestinal or respiratory symptoms within the previous 14 days. In patients with AGE, HCoVs were present in NP samples more often than in stools (22/256, 8.6%, versus 6/260, 2.3%; P = 0.0004). In 5/6 children with HCoVs detected in stools, the viruses were also detected in NP swabs. Patients had a significantly higher probability of HCoV detection in stool (OR 4; 95% CI 1.4-15.3; P = 0.006) and also in stool and/or NP (OR 3.3, 95% CI 1.3-10.0; P = 0.01) than healthy controls. All four HCoVs species were detected in stool and NP samples. CONCLUSIONS: Although HCoVs were more frequently detected in patients with AGE than in the control group, high prevalence of HCoVs in NP swabs compounded by their low occurrence in stool samples and detection of other viruses in stool samples, indicate that HCoVs probably play only a minor role in causing gastrointestinal illness in children <6 years old.

High-dose methylprednisolone in a pregnant woman with Crohn's disease and adrenal suppression in her newborn.

BACKGROUND: The synthetic corticosteroid methylprednisolone is used for the treatment of acute exacerbations of Crohn's disease, also in pregnancy. Its use is considered to be less harmful than the effect of active disease on the fetus. Adrenal suppression in a fetus due to administration of methylprednisolone has hitherto been rarely published. OBJECTIVE: To present a case of neonatal adrenal suppression due to the use of high-dose methylprednisolone in late pregnancy of a woman with Crohn's disease. METHODS AND RESULTS: Clinical signs of adrenal suppression were observed in the newborn 3 h after birth. After hydrocortisone supplementation and intensive therapy the baby recovered completely. CONCLUSIONS: Life-threatening adrenal suppression, requiring hydrocortisone supplementation and intensive therapy, was observed and successfully treated in a newborn, whose mother had received high-dose methylprednisolone in late pregnancy.

Methylprednisolone, cortisol and the cell-mediated immune response in children after ventricular septal defect repair.

BACKGROUND: This study evaluated the effects of methylprednisolone on cortisol and cell-mediated immune response (T-lymphocytes and HLA-DR+ monocytes) in peripheral blood after open-heart surgery with cardiopulmonary bypass (CPB) for ventricular septal defect. METHODS: A prospective observational study was carried out in a tertiary multidisciplinary neonatal and paediatric intensive care unit. Ten children under 2 years of age received methylprednisolone succinate (30 mg/kg body weight) in CPB priming solutions before the CPB system was connected to the patient during surgery. Before and immediately after and at 24 and 96 h after the operation, T-lymphocytes and HLA-DR+ monocytes were measured by flow cytometry, and methylprednisolone, methylprednisolone succinate and cortisol in blood plasma were assayed by liquid chromatography-mass spectrometry. RESULTS: The children were divided into groups with normal cardiac index (CI) and low CI. No significant differences in methylprednisolone and cortisol concentrations before and after surgery were found between the two groups. The normal CI group exhibited more than a three-fold decrease in T-lymphocytes 24 h after surgery and a two-fold decrease in HLA-DR+ monocyte fluorescence immediately after surgery. CONCLUSIONS: Children with normal and low CI were differentiated by T-lymphocytes and HLA-DR+ monocytes. Since no differences in methylprednisolone exposure and cortisol plasma levels between the low-CI and normal-CI groups were found, it can be concluded that factors other than methylprednisolone must contribute to differences in the cell-mediated response.

Interleukin-10, T-lymphocytes, and cardiac output in children after ventricular septal defect repair: a pilot study.

OBJECTIVE: To evaluate the acute inflammatory response and cardiac output in children after surgery for ventricular septal defect. DESIGN AND SETTING: Prospective, observational study in a level III multidisciplinary neonatal and pediatric intensive care unit. PATIENTS: Ten children undergoing open-heart surgery for ventricular septal defect. INTERVENTIONS: All children received methylprednisolone (30 mg/kg) in cardiopulmonary bypass (CPB) prime. MEASUREMENTS AND RESULTS: Before and after cardiopulmonary bypass, plasma interleukin-10 and tumor necrosis factor alpha were measured by enzyme-linked immunosorbent assay, and lymphocyte subsets in peripheral blood by flow cytometry. Relative values (post-/pre-CPB) of interleukin-10 and tumor necrosis factor alpha were calculated. The cardiac index (CI) was measured continuously beat-to-beat by a pulse contour analysis (PiCCO). Children above the cutoff value (median cardiac index value 3.0 l min(-1) m(-2)) were designated as the normal CI group and those below this value as the low CI group. In the normal CI group the relative values of interleukin-10 remained almost seven times higher than pre-CPB values at 24 h while in the low CI group they decreased almost to pre-CPB values. Furthermore, the normal CI group, but not the low CI group, exhibited more than threefold decrease in T-lymphocytes (lymphocyte T-cells, T-helper cells, and cytotoxic T-cells) 24 h after CPB. CONCLUSIONS: Children operated on for ventricular septal defect developed either a normal or low CI. The higher relative values of interleukin-10 and lower counts of lymphocyte T-cells, T-helper and cytotoxic T-cells differentiated the normal CI group from the low CI group at 24 h after cardiopulmonary bypass.