Impact of the COVID-19 Pandemic Regulations on the Health Status and Medical Care of Children with Trisomy 21.

BACKGROUND: While children are considered at low risk for COVID-19, little is known about the impact of SARS-CoV-2 on paediatric risk patients like children with Trisomy 21 (T21). As these children often need regular therapy and various medical appointments, this study aimed to investigate the possible impact of the COVID-19 pandemic on children with T21. PATIENTS AND METHODS: Parents of children with T21 in the age of 0-12 years in Saxony-Anhalt were interviewed via phone in June 2021 regarding the health status and medical care of their children during the past 15 months of pandemic. RESULTS: 37 children with mean age of 6.1 years (min 0; max 12) were included in the study. The majority did not have any additional congenital anomalies. Surveyed parents hardly reported adverse changes of health status during the pandemic, but rather improvements, such as decreased number of respiratory infections and more time spend with their children. Outpatient appointments and therapy were cancelled or postponed at the onset of the pandemic, but parents reported low impact on their child's health and development. The main concern seemed to be lack of childcare during school and day-care closures and uncertainty concerning possible health impacts of an infection on their children. CONCLUSION: There was low impact of the COVID-19 pandemic on health and medical care of children with T21 in our study population. Further research is needed to help weigh the child's individual risk of infection against the need for medical treatment and therapy when dealing with paediatric risk patients.

Treatment of mid-trimester preterm premature rupture of membranes (PPROM) with multi-resistant bacteria-colonized anhydramnion with continuous amnioinfusion and meropenem: a case report and literature review.

PURPOSE: Treatment of mid-trimester classic preterm premature rupture of membranes (PPROM) with systemic antibiotics has limited success in the prevention of chorioamnionitis, funisitis and fetal inflammatory response syndrome because of very low transplacental passage. METHODS: Here we report a case of PPROM at 18 weeks gestation with anhydramnion colonized by multi-resistant Escherichia coli (E. coli). A catheter system was implanted at 23/2nd weeks gestation, enabling long-term continuous lavage of the amniotic cavity with Amnion Flush Solution (100 ml/h combined with intraamniotic meropenem application). RESULTS: The patient gave birth to a preterm male infant at 28/3rd without any signs of infection. In a follow-up examination at 24 months, there was no neurological disturbance or developmental delay. CONCLUSION: The classic PPROM with multi-resistant E. coli colonization could be treated with continuous amnioinfusion and meropenem.

Daily monitoring of vaginal interleukin 6 as a predictor of intraamniotic inflammation after preterm premature rupture of membranes - a new method of sampling studied in a prospective multicenter trial.

OBJECTIVES: (A) To introduce a new technique for vaginal fluid sampling (biocompatible synthetic fiber sponge) and (B) evaluate the collected vaginal fluid interleukine-6 (IL-6vag)-concentration as a new diagnostic tool for daily monitoring of intrauterine inflammation after preterm premature rupture of membranes (PPROM). Secondary objectives were to compare the potential to predict an intrauterine inflammation with established inflammation parameters (e.g., maternal white blood cell count). METHODS: This prospective clinical case-control diagnostic accuracy multicenter study was performed with women after PPROM (gestational age 24.0/7 - 34.0/7 weeks). Sampling of vaginal fluid was performed once daily. IL-6vag was determined by electrochemiluminescence-immunoassay-kit. Neonatal outcome and placental histology results were used to retrospectively allocate the cohort into two subgroups: 1) inflammation and 2) no inflammation (controls). RESULTS: A total of 37 cases were included in the final analysis. (A): Measurement of IL-6 was successful in 86% of 172 vaginal fluid samples. (B): Median concentration of IL-6vag in the last vaginal fluid sample before delivery was significantly higher within the inflammation group (17,085 pg/mL) compared to the controls (1,888 pg/mL; p=0.01). By Youden's index an optimal cut-off for prediction an intrauterine inflammation was: 6,417 pg/mL. Two days before delivery, in contrast to all other parameters IL-6vag remained the only parameter with a sufficient AUC of 0.877, p<0.001, 95%CI [0.670-1.000]. CONCLUSIONS: This study established a new technique for vaginal fluid sampling, which permits assessment of IL-6vag concentration noninvasively in clinical daily routine monitoring.

[Herpes Simplex Virus Infection in Two Premature Infants - Diagnostic and Therapeutic Management]. / Infektion durch Herpes simplex Virus bei zwei unreifen Frühgeborenen ­ Diagnostisches und therapeutisches Management.

Herpes simplex virus type 1 or 2 (HSV 1/2)-related infections in neonates are rare but associated with high morbidity and mortality, especially if specific treatment is delayed. Due to immaturity of the immunological system, premature infants are particularly at risk. In addition, symptoms of neonatal HSV infections may imitate prematurity-related problems, such as sepsis. So, a thorough patient's history and appropriate diagnostic measures are important to confirm the diagnosis. We present 2 premature infants with systemic HSV infections and discuss diagnostic and therapeutic management. Both were treated with intravenous acyclovir followed by enteral aciclovir suppressive therapy.

Correction to: Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation.

Following publication of the original article [1], the authors flagged that the article had published with an error in 'Table 1'.

Receptor for advanced glycation end-products modulates lung development and lung sensitivity to hyperoxic injury in newborn mice.

The receptor for advanced glycation end-products is mainly expressed in type I alveolar epithelial cells but its importance in lung development and response to neonatal hyperoxia is unclear. Therefore, our study aimed at the analysis of young wildtype and RAGE knockout mice which grew up under normoxic or hyperoxic air conditions for the first 14 days followed by a longer period of normoxic conditions. Lung histology, expression of lung-specific proteins, and respiratory mechanics were analyzed when the mice reached an age of 2 or 4 months. These analyses indicated less but larger and thicker alveoli in RAGE knockout mice, reverse differences in the mRNA and protein amount of pro-surfactant proteins (pro-SP-B, pro-SP-C) and aquaporin-5, and differences in the amount of elastin and CREB, a pro-survival transcription factor, as well as higher lung compliance. Despite this potential disadvantages, RAGE knockout lungs showed less long-term damages mediated by neonatal hyperoxia. In detail, the hyperoxia-mediated reduction in alveoli, enlargement of airspaces, fragmentation of elastic fibers, and increased lung compliance combined with reduced peak airflows was less pronounced in RAGE knockout mice. In conclusion, RAGE supports the alveolarization but makes the lung more susceptible to hyperoxic injury shortly after birth. Blocking RAGE function could still be a helpful tool in reducing hyperoxia-mediated lung pathologies during alveolarization.

Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation.

BACKGROUND: Preterm newborns typically require supplemental oxygen but hyperoxic conditions also damage the premature lung. Oxygen-induced lung damages are mainly studied in newborn mouse models using oxygen concentrations above 75% and looking at short-term effects. Therefore, we aimed at the investigation of long-term effects and their dependency on different oxygen concentrations. METHODS: Newborn mice were exposed to moderate vs. severe hyperoxic air conditions (50 vs. 75% O2) for 14 days followed by a longer period of normoxic conditions. Lung-related parameters were collected at an age of 60 or 120 days. RESULTS: Severe hyperoxia caused lower alveolar density, enlargement of parenchymal air spaces and fragmented elastic fibers as well as higher lung compliance with peak airflow limitations and higher sensitivity to ventilation-mediated damages in later life. However, these long-term lung structural and functional changes did not restrict the voluntary physical activity. Also, they were not accompanied by ongoing inflammatory processes, increased formation of reactive oxygen species (ROS) or altered expressions of antioxidant enzymes (superoxide dismutases, catalase) and lung elasticity-relevant proteins (elastin, pro-surfactant proteins) in adulthood. In contrast to severe hyperoxia, moderate hyperoxia was less lung damaging but also not free of long-term effects (higher lung compliance without peak airflow limitations, increased ROS formation). CONCLUSIONS: Severe but not moderate neonatal hyperoxia causes emphysematous lungs without persisting oxidative stress and inflammation in adulthood. As the existing fragmentation of the elastic fibers seems to play a pivotal role, it indicates the usefulness of elastin-protecting compounds in the reduction of long-term oxygen-related lung damages.

Long tail balloon as a new approach for fetoscopic tracheal occlusion for a treatment of severe congenital diaphragmatic hernia.

Severe congenital diaphragmatic hernia (CDH) remains a significant challenge for neonatal specialists. In order to reduce complications during extraction of the surgical balloon after fetoscopic tracheal occlusion (FETO) CDH, we have developed a FETO with a 'long tail balloon' of 2.5 mL volume. Here we describe two successful uses of the device with observed/expected total fetal lung volume (o/e TFLV) of 15% and with o/e TFLV of 24% and 'liver up'. The o/e TFLV increased to 134% in first case and to 47% in second fetus. The balloon was successfully extracted at 34 weeks' gestation by pulling the long tail suture during second fetoscopy. In the second case the fetus pulled out the balloon from trachea itself by traction onto the balloon's long tail. Both neonates were operated on for their CDH with a good outcome. This work showed the feasibility of this long tail balloon for FETO to reduce the technical difficulty of the balloon extraction and the possibility that fetuses are able to extract the balloon by itself by pulling the balloons' long tail. Further development of long tail balloon for FETO could facilitate its extraction thereby reducing neonatal complications.

Treatment of Preterm Premature Rupture of Membranes with Oligo-/Anhydramnion Colonized by Multiresistant Bacteria with Continuous Amnioinfusion and Antibiotic Administrations through a Subcutaneously Implanted Intrauterine Port System: A Case Report.

Bacterial infection is one of the main causes of preterm premature rupture of membranes (PPROM) leading to preterm delivery, pulmonary hypoplasia, sepsis and joint deformities. Expectant management, broad-spectrum antibiotics and antenatal corticosteroids are routinely used in this condition with very limited success to prevent bacteremia, chorioamnionitis, funisitis and intra-amniotic infection syndrome. Here, we report a case in which we attempted to treat PPROM at 26+3 weeks of gestation with anhydramnion colonized by multiresistant Klebsiella. A perinatal port system was implanted subcutaneously at 28+0 weeks of gestation, enabling long-term continuous lavage of the amniotic cavity with a hypotonic aqueous composition similar to human amniotic fluid combined with intra-amniotic antibiotic application. The patient gave birth to a preterm female infant at 31+1 weeks without any signs of infection. The girl was discharged with a weight of 2,730 g in very good condition. In the follow-up examinations at 5 months and 1 year of age, there was no apparent neurological disturbance, developmental delay or Klebsiella colonization.

Doppler Sonography of Blood Flow Velocity in the Vertebral Arteries of Preterm and Term Neonates.

OBJECTIVES: This study aimed to evaluate normal blood flow in the vertebral arteries and the basilar artery of preterm and term neonates by Doppler sonography. METHODS: Blood flow in both vertebral arteries and the basilar artery was examined in 102 neonates between the biological ages of 28 and 41 weeks. Fifty-one boys and 51 girls underwent Doppler sonography. Measurements were usually undertaken at 6 days old. Systolic and diastolic flow velocities, including the resistive index, were measured and analyzed, taking into consideration biological age, weight, and sex. Anatomic aberrations of the vertebral arteries were recorded. RESULTS: Mean blood flow values ± SD in the basilar artery were 35.2 ± 7.4 cm/s (systolic velocity) and 10.9 ± 3.5 cm/s (diastolic velocity). Mean blood flow values in the right vertebral artery were 26.8 ± 9.3 cm/s (systolic velocity) and 8.0 ± 3.7 cm/s (diastolic velocity). Mean blood flow values in the left vertebral artery were 28.6 ± 8.3 cm/s (systolic velocity) and 8.7 ± 3.3 cm/s (diastolic velocity). Systolic and diastolic blood flow in both vertebral arteries was significantly higher from 38 to 41 weeks compared with 28 to 32 and 33 to 37 weeks (P < .05). Regression analysis of systolic and diastolic blood flow velocities in the vertebral arteries versus biological age yielded significant results (P < .05). CONCLUSIONS: Sonography is an excellent tool for examining blood flow in the basilar and vertebral arteries of premature and term neonates. Mean systolic and diastolic blood flow velocities in the vertebral arteries increase significantly with age.

Extensive hypertrophic scarring after toxic epidermal necrolysis in a child.

Stevens-Johnson syndrome and toxic epidermal necrolysis are some of the most serious, usually drug-induced, skin reactions. We report a case of severe toxic epidermal necrolysis in a child, which in addition to ophthalmic sequelae, caused extensive hypertrophic scarring of the skin. Such a course is uncommon and has rarely been described in the literature.

Similar adverse outcome rates with high or low oxygen saturation targets in an area with low background mortality.

Background: Randomized controlled trials have indicated reduced mortality rates in very preterm infants assigned to high compared to low oxygen saturation (SpO2) target levels, accompanied by higher rates of retinopathy of prematurity and bronchopulmonary dysplasia. However, the benefit-to-harm ratio may depend on the local background mortality risk. We therefore aimed to quantify the risk-benefit ratios of different SpO2 target ranges in 10 tertiary newborn intensive care units (NICUs) in East Germany. Methods: In a retrospective multicenter study, 1,399 infants born between 2008 and 2012 at a gestational age between 24 0/7 and 27 6/7 weeks and with a birthweight below 1,250 g were grouped according to the hospital's target SpO2 range [high oxygen saturation group (HOSG) above 90%], low oxygen saturation group (LOSG) below 90%] and the compliance of units with their target SpO2 range. The association between neonatal morbidities, neurodevelopmental outcomes, selected treatment strategies, and target SpO2 ranges was calculated using chi-squared and Mann Whitney U tests. Results: Nine of the ten participating NICUs met their SpO2 target ranges. Five units were considered as HOSG, and five units were considered as LOSG. Necrotizing enterocolitis and intraventricular hemorrhage grade ≥ 2 occurred significantly more frequently in the HOSG than in the LOSG (8.4% vs. 5.1%, p = 0.02; and 26.6% vs. 17.7%, p < 0.001). No significant differences in the mortality rate and the rate of retinopathy of prematurity were found. Conclusion: In our patient population, a lower SpO2 target range was not associated with increased safety risks in extremely preterm infants. We cannot be sure that our outcome differences are associated with differences in oxygen saturations due to the retrospective study design and the differences in site practices.

T cell repertoire breadth is associated with the number of acute respiratory infections in the LoewenKIDS birth cohort.

We set out to gain insight into peripheral blood B and T cell repertoires from 120 infants of the LoewenKIDS birth cohort to investigate potential determinants of early life respiratory infections. Low antigen-dependent somatic hypermutation of B cell repertoires, as well as low T and B cell repertoire clonality, high diversity, and high richness especially in public T cell clonotypes reflected the immunological naivety at 12 months of age when high thymic and bone marrow output are associated with relatively few prior antigen encounters. Infants with inadequately low T cell repertoire diversity or high clonality showed higher numbers of acute respiratory infections over the first 4 years of life. No correlation of T or B cell repertoire metrics with other parameters such as sex, birth mode, older siblings, pets, the onset of daycare, or duration of breast feeding was noted. Together, this study supports that-regardless of T cell functionality-the breadth of the T cell repertoire is associated with the number of acute respiratory infections in the first 4 years of life. Moreover, this study provides a valuable resource of millions of T and B cell receptor sequences from infants with available metadata for researchers in the field.

Case report: Otitis media with subsequent mastoiditis and cerebral herniation in a patient with Arnold chiari malformation.

We present the case of a 13-year-old boy who unexpectedly needed to be resuscitated at home after an assumed uncomplicated otitis media. Imaging at our clinic showed mastoiditis and a cystoid mass in the left cerebellopontine angle compressing the brainstem, as well as an Arnold-Chiari-Malformation. Both the laboratory examination of cerebrospinal fluid (CSF) and surgical biopsy with pathological evaluation of the mastoid supported the inflammatory etiology of the mass. Microbiologically, Streptococcus intermedius was detected in the blood culture and CSF. Due to brain death, which most likely already existed preclinically, the organs were released for donation during the course. Our case demonstrates a very rare lethal complication of acute otitis media on the basis of a cerebral malformation and emphasizes the need to stay alert when patients complain of symptoms after assumed resolution.

Monitoring Antibiotic Consumption in Pediatrics. How Close to Reality Are Days of Therapy and Recommended Daily Dose Methods?

BACKGROUND: Hospitals are advised to monitor antibiotic use. Several approximation methods do exist to perform this task. Adult cohorts can easily be monitored using the defined daily dose method, or its German adaption recommended daily doses (RDD) method, that seems inapplicable in pediatric cohorts due to body weight variations. Guidelines recommend the days of therapy (DOT) method in pediatrics. Still, there is a need for more detailed analysis regarding the performance of both methods. METHODS: Based on data from 4½ years of our fully computerized patient care data managing system in a combined neonatal and pediatric intensive care unit, we compare the results for DOT and RDD per 100 patient days with exact measurement of antibiotic consumption (individual daily dose per 100 patient days) as internal reference. RESULTS: The DOT method reflected antibiotic consumption in our cohort on the level of total consumption, subgroups, and agents with almost always high accuracy (correlation with individual daily dose between 0.73 and 1.00). The RDD method showed poor correlation on the level of total consumption (r = 0.21) and fluctuating results on more detailed levels (correlation, 0.01-0.94). A detailed analysis of body weight distribution and ordered packaging sizes of single agents revealed that RDD seems to work well when only one package size of the agent was ordered in our pharmacy. CONCLUSION: The DOT method is superior to RDD for monitoring antibiotic drug consumption in pediatric cohorts. RDD seems to work satisfactory well for selected antibiotic agents that are administered with little variation in packaging size.

Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Pediatric ICU Admissions After Adolescent Suicide Attempts During the Pandemic.

BACKGROUND AND OBJECTIVES: The worldwide severe acute respiratory syndrome coronavirus 2 pandemic challenges adolescents' mental health. In this study, we aim to compare the number of pediatric ICU (PICU) admissions after suicide attempts during the first German lockdown and one year later during a second, prolonged lockdown with prepandemic years. METHODS: A retrospective multicenter study was conducted among 27 German PICUs. Cases <18 years admitted to the PICU because of accidents or injuries between March 16 and May 31 of 2017 to 2021 were identified based on International Classification of Diseases, 10th Revision codes (German modification) and patient data entered into a database. This study is a subset analysis on suicide attempts in adolescents aged 12 to 17.9 years. The Federal Statistics Office was queried for data on fatal suicides, which were available only for 2020 in adolescents aged 10 to 17.9 years. RESULTS: Total admissions and suicide attempts declined during the first lockdown in 2020 (standardized morbidity ratio 0.74 (95% confidence interval; 0.58-0.92) and 0.69 (0.43-1.04), respectively) and increased in 2021 (standardized morbidity ratio 2.14 [1.86-2.45] and 2.84 [2.29-3.49], respectively). Fatal suicide rates remained stable between 2017 to 2019 and 2020 (1.57 vs 1.48 per 100 000 adolescent years) with monthly numbers showing no clear trend during the course of 2020. CONCLUSIONS: This study shows a strong increase in serious suicide attempts among adolescents during the course of the pandemic in Germany. More research is needed to understand the relation between pandemic prevention measures and suicidal ideation to help implement mental health support for adolescents.

Impact of the First COVID Lockdown on Accident- and Injury-Related Pediatric Intensive Care Admissions in Germany-A Multicenter Study.

Children's and adolescents' lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017-2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85-1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93-1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57-1.02 and 0.26 (0.05-0.75)), whereas household and leisure accidents increased (1.33 (1.06-1.66) and 1.34 (1.06-1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38-1.16) and 2.09 (1.19-3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42-1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51-3.02)), but decreased in adolescent girls (0.56 (0.32-0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation.

Co-Culture of Peripheral Blood Mononuclear Cells and Endothelial Colony Forming Cells from Cord Blood of Preterm Born Babies.

Umbilical cord blood of neonates is a precious source for many fields of research because of distinct unique features combined with easy accessibility at the time of birth. The number of applications are vast with an emphasis in the field of stem cell therapy and regenerative medicine since cord blood contains relatively large numbers of pluripotent cells. This chapter provides a protocol for developing an autologous co-culture of endothelial-like cells and peripheral blood mononuclear cells from umbilical cord blood of premature born babies and describes an experimental setting to investigate inflammatory processes that are a cornerstone of pathophysiology in the developing organs of preterm born babies.

Critical illness polyneuropathy: a rare but serious adverse event in pediatric oncology.

Critical illness polyneuropathy (CIP) may aggravate sepsis and multiorgan dysfunction in pediatric oncology patients characterized by quadriparesis and difficult weaning from mechanical ventilation. Here, we report on an adolescent patient with acute lymphoblastic T-cell leukemia who developed critical illness neuropathy after an episode of sepsis with need for mechanical ventilation and intravenous catecholamines. Differential diagnoses like vincristine-induced polyneuropathy, anterior lumbosacral radiculopathy (ALR), Guillain-Barré syndrome, and chronic inflammatory demyelinating polyneuropathy - all occurring in pediatric patients with acute leukemia - are discussed.