Childhood interstitial lung disease in Turkey: first data from the national registry.

The childhood interstitial lung diseases (chILD) Turkey registry (chILD-TR) was established in November 2021 to increase awareness of disease, and in collaboration with the centers to improve the diagnostic and treatment standards. Here, the first results of the chILD registry system were presented. In this prospective cohort study, data were collected using a data-entry software system. The demographic characteristics, clinical, laboratory, radiologic findings, diagnoses, and treatment characteristics of the patients were evaluated. Clinical characteristics were compared between two main chILD groups ((A) diffuse parenchymal lung diseases (DPLD) disorders manifesting primarily in infancy [group1] and (B) DPLD disorders occurring at all ages [group 2]). There were 416 patients registered from 19 centers. Forty-six patients were excluded due to missing information. The median age of diagnosis of the patients was 6.05 (1.3-11.6) years. Across the study population (n = 370), 81 (21.8%) were in group 1, and 289 (78.1%) were in group 2. The median weight z-score was significantly lower in group 1 (- 2.0 [- 3.36 to - 0.81]) than in group 2 (- 0.80 [- 1.7 to 0.20]) (p < 0.001). When we compared the groups according to chest CT findings, ground-glass opacities were significantly more common in group 1, and nodular opacities, bronchiectasis, mosaic perfusion, and mediastinal lymphadenopathy were significantly more common in group 2. Out of the overall study population, 67.8% were undergoing some form of treatment. The use of oral steroids was significantly higher in group 2 than in group 1 (40.6% vs. 23.3%, respectively; p = 0.040).   Conclusion: This study showed that national registry allowed to obtain information about the frequency, types, and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. What is Known: • Childhood interstitial lung diseases comprise many diverse entities which are challenging to diagnose and manage. What is New: • This study showed that national registry allowed to obtain information about the frequency, types and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. Also, our findings reveal that nutrition should be considered in all patients with chILD, especially in A-DPLD disorders manifesting primarily in infancy.

Amnioinfusion vs. standard management for the second trimester PPROM: a systematic review and meta-analysis of observational studies and RCTs.

OBJECTIVE: This meta-analysis aims to review the effect of serial transabdominal amnioinfusion (TAI) on short-term and long-term perinatal outcomes in mid-trimester preterm premature rupture of membranes (PPROM). METHODS: Literature searches of PubMed, Web of Sciences, Scopus, and Cochrane Library were performed from their inception to April 2022. Studies comparing conventional treatment with serial TAI in women with proven PPROM at less than 26 + 0 weeks of gestation with oligohydramnios were included. Studies that included oligohydramnios due to other reasons such as fetal growth retardation or renal anomalies were excluded. Risk of bias in observational studies was assessed using the tool of the Cochrane Review group identified as risk of bias in non-randomized studies - of interventions. The risk of bias assessments for RCTs were performed according to the Cochrane risk-of-bias tool for randomized trials. An I2 score was used to assess the heterogeneity of included studies. The analyses were performed by using random-effect model, and the results were expressed as relative risk (RR) or mean difference with 95% confidence intervals (CIs). RESULTS: Overall, eight relevant studies including five observational studies (n = 252; 130 women allocated to the intervention) and three RCTs (n = 183; 93 women allocated to the intervention) were eligible. The pooled latency period was 21.9 days (95% CI, 13.1-30.8) and 5.8 days (95% CI, -11.6-23.2) longer in the TAI group in the observational studies and RCTs, respectively. The perinatal mortality rate reduced in the intervention group when tested in observational studies (RR 0.68; 95% CI, 0.51-0.92), but not in RCTs (RR 0.79; 95% CI, 0.56-1.13). The rate of long-term healthy survival was higher in the children whose mothers were treated with the TAI (35.7%) than those were treated with the standard management (28.6%) (RR 1.30, 95% CI 0.47-3.60, "best case scenario"). CONCLUSIONS: The efficacy of serial TA on early PPROM associated morbidity and mortality is not attested. Additional randomized control trials with adequate power are needed.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

BACKGROUND: We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV1) decline and LT candidates without rapid FEV1 decline in the last year to identify a preventable cause in patients with such rapid FEV1 decline. METHODS: All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV1 below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV1 decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. RESULTS: Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV1 in 2017 in Group 1 and between FEV1 values in 2017 and 2018 in Group 2. CONCLUSIONS: There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

Diffuse alveolar haemorrhage in children: an international multicentre study.

Background: Paediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome. Methods: A retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years. Results: Data of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0-12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function. Conclusions: Paediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.

Perceived Need for Mental Health Services Among Healthcare Workers During the Coronavirus Disease-19 Pandemic in Turkey: A Multicenter Cross-sectional Study

Background: The coronavirus disease-2019 pandemic has contributed to work-related psychosocial risks in healthcare workers. Aims: To evaluate the perceived need for mental health services and related factors in Turkish healthcare workers practicing in pandemic hospitals. Study Design: Cross-sectional study. Methods: Data were collected from face-to-face interviews with healthcare workers at 19 pandemic hospitals in 13 provinces between September and November 2021. The study survey included the evaluation of the perceived need for and utilization of mental health services in the previous year, as well as sociodemographic, health-related, and work-related characteristics, the General Health Questionnaire-12, the World Health Organization Quality of Life-BREF (WHOQoL-BREF) questionnaire, and the Fear of coronavirus disease-2019 scale (FCV-19S). Results: Of 1,556 participants, 522 (33.5%) reported a perceived need for mental health services, but only 133 (8.5%) reported receiving these services. Multiple logistic regression analysis of the perceived need for mental health services revealed significant relationships with lower age, female sex, being a current smoker, having a chronic disease, having a mental disorder, coronavirus disease-2019 contact within the last three months in settings other than the home or workplace, a positive coronavirus disease-2019 vaccination history, being a physician, being a non-physician healthcare professional, and coronavirus disease-2019 contact within the last three months at work. After adjustment for these characteristics, higher General Health Questionnaire-12 and FCV-19S scores and lower WHOQoL-BREF domain scores were related to the perceived need for mental health services in logistic regression analyses. Conclusion: The findings indicate a substantial need for mental health services amongst Turkish healthcare workers during the pandemic and outline participants' characteristics regarding high-priority groups for the intervention. Future research may focus on developing actions and evaluating their efficiency.

The associations between the clinical course of children with tracheostomy and their mothers' depression, burnout, burden, and self-esteem.

AIMS AND OBJECTIVES: The aim of this study was to evaluate the clinical features of children with tracheostomy and the predictors of psychological status of their primary caregivers in order to determine the associations between the children's clinical course with their caregivers' psychological status. BACKGROUND: The caregivers of children with tracheostomy are responsible for providing basic tracheostomy care at home. All these responsibilities may be associated with significant changes in family members' lifestyles, daily routines and family dynamics. DESIGN: This study is a cross sectional study. METHODS: Data of the family's socioeconomic status and clinical status of children with tracheostomy were noted in four paediatric pulmonology centers. The Beck Depression Inventory, Maslach Burnout Inventory, Zarit Caregiver Burden Scale, and Rosenberg Self-esteem Scale were used for psychological measurements of the caregivers. The STROBE checklist was used for this study. RESULTS: Eighty-five children and their primary caregivers were enrolled in the study. The children's median age was 4.1 years. Thirty-eight of them were dependent on home ventilators. Twenty-one had bacterial colonisation. All children's primary caregivers were their mothers. Beck Depression Inventory scores of mothers of children with colonisation were higher. Number of hospitalizations in previous 6 months was related to mothers' emotional exhaustion and depersonalization scores. Duration of children's hospitalizations in previous 6 months was positively correlated to mothers' emotional exhaustion, depersonalization, and Beck Depression Inventory scores. CONCLUSIONS: Mothers of children with tracheostomy may experience psychological conditions, such as high levels of depression, burnout, burden and low levels of self-esteem. Frequent and long-term hospitalizations of children correlated with mother's depression and burnout. Therefore, primary caregivers should be evaluated and supported psychologically. RELEVANCE TO CLINICAL PRACTICE: Preventing mothers of children with tracheostomy from experiencing psychological conditions such as depression, burnout, burden and low self-esteem can also increase the quality of care for children.

A homozygous missense variant in the WRN gene segregating in a family with progressive pulmonary failure with recurrent spontaneous pneumothorax and interstitial lung disease.

Interstitial lung disease (ILD) is a condition affecting the lung parenchyma by inflammation and fibrosis and can be caused by various exposures, connective tissue diseases (CTD), and genetic disorders. In this report, a family with five patients having progressive respiratory failure that begins with coughing in adolescence, followed by dyspnea and recurrent spontaneous pneumothorax, and death in early adulthood is presented. The patients were diagnosed to have ILD through clinical and radiological evaluations. Molecular genetic analyses of the family provided two homozygous rare variants in the WRN and SFXN5 genes, co-segregating with the phenotype. The network analyses pointed out that the variant in the WRN, rather than that in the SFXN5 gene, could be the main factor in the existence of the ILD phenotype, putatively through the altered DNA repair and telomere maintenance pathways. In silico analyses suggested that the variant could affect the exonuclease activity or the stability of the WRN protein. Moreover, the adolescent-onset pulmonary phenotype described in the case has not been reported in Werner Syndrome, the only disease known to be associated with biallelic WRN pathogenic variants. Thus, the present phenotype could be either a very atypical presentation of Werner syndrome or a new clinical entity associated with the WRN gene.

Evaluation of specificity and sensitivity of IRT/IRT protocol in the cystic fibrosis newborn screening program: 6-year experience of three tertiary centers.

We aimed to evaluate cutoff values of immunoreactive trypsinogen (IRT)/IRT and determine relationship between IRT values and clinical characteristics of children with cystic fibrosis (CF). This study is cross-sectional study. Data of children with positive newborn screening (NBS) between 2015 and 2021 were evaluated in three pediatric pulmonology centers. Age at admission, sex, gestational age, presence of history of meconium ileus, parental consanguinity, sibling with CF, and doll-like face appearance, first and second IRT values, sweat chloride test, fecal elastase, fecal fat, biochemistry results, and age at CF diagnosis were recorded. Sensitivity and specificity of IRT cutoff values were evaluated. Of 815 children with positive NBS, 58 (7.1%) children were diagnosed with CF. Median values of first and second IRT were 157.2 (103.7-247.6) and 113.0 (84.0-201.5) µg/L. IRT values used in current protocol, sensitivity was determined as 96.6%, specificity as 17.2% for first IRT, and 96.6% sensitivity, 20.5% specificity for second IRT. Positive predictive value (PPV) was determined as 7.1%. When cutoff value for first IRT was estimated as 116.7 µg/L, sensitivity was 69.0% and specificity was 69.6%, and when cutoff value was set to 88.7 µg/L for second IRT, sensitivity was 69.0% and specificity was 69.0%. Area under curve was 0.757 for first and 0.763 for second IRT (p < 0.001, p < 0.001, respectively). PPV was calculated as 4.3%.    Conclusion: Although sensitivity of CF NBS is high in our country, its PPV is significantly lower than expected from CF NBS programs. False-positive NBS results could have been overcome by revising NBS strategy. What is Known: • Although immunoreactive trypsinogen elevation is a sensitive test used in cystic fibrosis newborn screening, its specificity is low. • In countries although different algorithms are used, all strategies begin with the measurement of immunoreactive trypsinogen in dried blood spots. What is New: • In our study, it was shown that use of the IRT/IRT protocol for cystic fibrosis newborn screening is not sufficient for the cut-off values determined by the high number of patients. • Newborn screening strategy should be reviewed to reduce false positive newborn screening results.

Pulmonary Embolism in Childhood: A Multicenter Experience from Turkey

Background: Pulmonary embolism is a clinical condition caused by the obstruction of the pulmonary artery and its branches with endogenous, exogenous embolism, or local thrombus formation. It is a rare but potentially life-threatening event in the pediatric population. Pediatric pulmonary embolism has many unknown characteristics. Aims: To evaluate clinical features, genetic and acquired risk factors, diagnostic imaging, and treatment strategies with long-term results in children with pulmonary embolism. Study Design: A retrospective multicenter clinical trial. Methods: Patients aged 0-18 years who were diagnosed with pulmonary embolism with computed tomography pulmonary angiography (CTPA) findings (intraluminal filling defect in the lobar or main pulmonary artery) in 3 university hospitals between 2006 and 2021 were included in the study. A form was created for data standardization, and variables were collected retrospectively through medical record review. In addition to the features given above, we also evaluated in situ pulmonary artery thrombosis (ISPAT) and patients' Wells scores. Follow-up CTPA results were evaluated for patient response to treatment. Complete recovery means that there were no lesions, incomplete recovery if there was still embolism, and no response if there was no change. Results: Twenty-four patients (female:13, male:11) were included in the study. The mean age was 13.5 years. All patients but one had at least one or more genetic or acquired risk factors. Factor V Leiden mutation (16.6%) was the most common genetic risk factor. Six of 16 patients with Doppler ultrasonography were diagnosed with ISPAT because there was no sign of thromboembolic thrombosis. Nine (41.6%) patients had a Wells score of >4 (pulmonary embolism clinically strong), and 15 (58.4%) patients scored <4 (pulmonary embolism clinically likely weak), indicating that an alternative diagnosis was more likely than pulmonary embolism (sensitivity %37.5). The mean follow-up period was 23 (±17) months. Complete and incomplete recovery was observed in 15 (62.5%) and 7 (29.1%) patients, respectively, among the patients who underwent follow-up evaluation. No response was obtained in 2 patients (8.3%) who died. Conclusion: The Wells scoring system seems insufficient to diagnose pulmonary embolism in children and should be improved by adding new parameters. ISPAT may be more common in children with congenital heart disease and systemic disease.

Psychological status of mothers of children with cystic fibrosis and primary ciliary dyskinesia.

OBJECTIVES: We aimed to investigate depression, burnout, attitude, and burden of caregivers of children with cystic fibrosis (CF), and especially caregivers of children with primary ciliary dyskinesia (PCD) due to limited number of studies on this topic, and to compare them according to their children's clinical status. METHODS: Clinical features and demographic data of children and their families were asked from caregivers in four pediatric pulmonology centers. Beck Depression Inventory, Maslach Burnout Inventory, Zarit Caregiver Burden Scale, and Parental Attitude Research Instrument were administered to caregivers in both groups. Results were compared between the two groups. RESULTS: In total, 131 children with CF and 39 with PCD and their caregivers were involved in the study. All primary caregivers were mothers in both groups. Depression, burnout, and burden scores of mothers of children with CF were significantly higher than mothers of children with PCD (p = 0.017, p = 0.024, p = 0.038, respectively). Burnout was higher in both CF and PCD groups with low family income (p = 0.022, p = 0.034). Number of hospital visits in the previous 6 months was correlated with burnout in both CF and PCD groups (r = 0.207, p = 0.034; r = 0.352, p = 0.044). CONCLUSIONS: Although mothers with children with CF have higher levels of depression, burnout, burden, and negative attitudes toward children than mothers with children with PCD, these are also significantly high in mothers with children with PCD. Psychological problems of mothers of children with CF and PCD may increase with frequent hospital visits, hospitalizations, low family income, number of children, and chronic disease in another child.

Caspase-1 and interleukin-18 in children with post infectious bronchiolitis obliterans: a case-control study.

The exact immunological mechanisms of post infectious bronchiolitis obliterans (PIBO) in childhood are not fully known. It has been shown that the inflammasome and IL-18 pathway play important roles in the pathogenesis of lung fibrosis. We aimed to investigate the role of caspase-1, IL-18, and IL-18 components in PIBO. From January to May 2020, children with PIBO, children with history of influenza infection without PIBO, and healthy children were asked to participate in the study in three pediatric pulmonology centers. Serum caspase-1, IL-18, IL-18BP, IL-18R, and INF-γ levels were measured by ELISA and compared between the 3 groups. There were 21 children in the PIBO group, 16 children in the influenza group, and 39 children in the healthy control group. No differences in terms of age and gender between the 3 groups were found. IL-18 and IL-18BP levels were higher in the healthy control group (p = 0.018, p = 0.005, respectively). IL-18R was higher in the PIBO group (p = 0.001) and caspase-1 was higher in the PIBO and influenza group than the healthy control group (p = 0.002). IFN-γ levels did not differ between the 3 groups. IL-18BP/IL-18 was higher in the influenza group than the PIBO group and the healthy control group (p = 0.003). CONCLUSIONS: Caspase-1 level was increased in patients with PIBO which suggests that inflammasome activation may have a role in fibrosis; however, IL-18 level was found to be low. Mediators other than IL-18 may be involved in the inflammatory pathway in PIBO. Further immunological studies investigating inflammasome pathway are needed for PIBO with chronic inflammation. WHAT IS KNOWN: • Post infectious bronchiolitis obliterans (PIBO) is a rare, severe chronic lung disease during childhood which is associated with inflammation and fibrosis which lead to partial or complete luminal obstruction especially in small airways. • The exact immunological mechanisms of PIBO in childhood are not fully known. WHAT IS NEW: • Inflammasome activation persists even years after acute infection and may play a role in fibrosis in PIBO. • Mediators other than IL-18 may be involved in these inflammatory pathway.

ERS International Virtual Congress 2021: Highlights from the Turkish Thoracic Society Early Career Members.

This review aimed to highlight some important points derived from the presentations of the European Respiratory Society 2021 Virtual International Congress by a committee formed by the Early Career Task Group of the Turkish Thoracic Society. We summarized a wide range of topics including current developments of respiratory diseases and provided an overview of important and striking topics of the congress. Our primary motivation was to give some up-to-date information and new developments discussed during congress especially for the pulmonologists who did not have a chance to follow the congress. This review also committed an opportunity to get an overview of the newest data in the diverse fields of respiratory medicine such as post-coronavirus disease 2019, some new interventional and technologic developments related to respiratory health, and new treatment strategies.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.

Placental deficiency during maternal SARS-CoV-2 infection.

INTRODUCTION: Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures. METHODS: This is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth. RESULTS: The concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein. DISCUSSION: The maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.

Thoracic Air Leak Syndrome, Pulmonary Aspergillosis, and COVID-19 Pneumonia After Allogeneic Stem Cell Transplantation in a Child With Myelodysplastic Syndrome.

Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed.

Clinical findings of patients with cystic fibrosis according to newborn screening results.

BACKGROUND: Cystic fibrosis (CF) is a lethal recessive genetic disease caused by loss of function associated with mutations in the CF trans-membrane conductance regulator. It is highly prevalent (approximately 1 in 3,500) in Caucasians. The aim of this study was to compare demographic and clinical features, diagnostic tests, treatments, and complications of patients with CF whose newborn screening (NBS) with twice-repeated immune reactive trypsinogen testing was positive, normal, and not performed. METHODS: In this study, 359 of all 1,488 CF patients recorded in the CF Registry of Turkey in 2018, who had been born through the process of NBS, were evaluated. Demographic and clinical features were compared in patients diagnosed with positive NBS (Group 1), normal (Group 2), or without NBS (Group 3). RESULTS: In Group 1, there were 299 patients, in Group 2, there were 40 patients, and in Group 3, there were 20 patients. Among all patients, the median age at diagnosis was 0.17 years. The median age at diagnosis was higher in Groups 2 and 3 than in Group 1 (P = 0.001). Fecal elastase results were higher in Group 2 (P = 0.033). The weight z-score was lower and chronic Staphylococcus aureus infection was more common in Group 3 (P = 0.017, P = 0.004, respectively). CONCLUSIONS: Frequency of growth retardation and chronic S. aureus infection can be reduced with an early diagnosis using NBS. In the presence of clinical suspicion in patients with normal NBS, further analyses such as genetic testing should be performed, especially to prevent missing patients with severe mutations.

Maternal Stress and Neonatal Nutrition during the COVID-19 Era.

Objective: COVID-19 pandemic has put a tremendous amount of stress on people, which can negatively affect nursing. Previous studies showed that perceived stress and cortisol levels in the postpartum period correlate with the LATCH scores, which is a simple tool to assess the pattern of nursing. Likewise, greater prenatal anxiety was associated with a shorter breastfeeding duration. We aimed to evaluate whether pregnant women were under extra stress due to the COVID-19 pandemic and if this stress affected their breastfeeding patterns and anthropometric measures of the neonates. Methods: Pregnant women giving birth to healthy neonates were included. Coronavirus Anxiety Scale (CAS) and Beck Anxiety Inventory (BAI) were used to assess the anxiety levels of the mothers, and LATCH breastfeeding assessment tool was used to assess the nursing. The results of these scales and anthropometric measures of the neonates were recorded. Results: Only one mother showed coronavirus-specific anxiety. Therefore, further analysis was done based on the Beck Anxiety (BA) levels of the mothers. CAS and BA scores were positively correlated (p<0.001, r=0.444), indicating that coronavirus-specific anxiety increased with increasing general anxiety. None of the variables changed depending on the anxiety levels of the mothers, except for the % weight gain at day five (p=0.020, r=-0.248). Even though anxiety seemed to show a small effect on weight loss during the first neonatal days, percent weight gain results did not seem to correlate with the anxiety levels in later stages (first month of life). Furthermore, LATCH scores of the infants on day one were positively correlated with BA scores of the mothers (p=0.045, r=0.175). Conclusion: COVID-19 seemed to have no additional effect on the stress levels of the mothers. The more the mothers have anxiety, the more they may stress about the well-being of their infants, which can improve their nursing pattern.

The Genetic Analysis of Cystic Fibrosis Patients With Seven Novel Mutations in the CFTR Gene in the Central Anatolian Region of Turkey.

BACKGROUND: Cystic fibrosis, a pulmonary disease which is an autosomal recessive, inherited, multisystemic genetic disease commonly seen in the Caucasian race, is the most frequent cause of mortality and morbidity. So far, more than 2000 disease-causing gene variants have been found and this number has been increasing with the studies conducted. Although there is not yet enough data that include the Turkish population, the recent increase of studies is noteworthy. AIMS: To discover the genetic variation in patients diagnosed with cystic fibrosis in the Central Anatolian region. STUDY DESIGN: Cross-sectional study. METHODS: The study was carried out in the Central Anatolian region in 3 pediatric pulmonology departments (Kayseri, Konya, and Ankara) in Turkey between July 2014 and December 2017. The Sanger and Next Generation Sequence analyses were used for exon and exon-intron boundaries in the cystic fibrosis transmembrane conductance regulatory (CFTR) gene, and in selected patients, mutation analysis was performed using the Multiplex Ligation-dependent Probe Amplification technique for large deletions and duplications. RESULTS: CFTR gene analysis was performed for 316 patients and 215 of them were genetically diagnosed with cystic fibrosis. Sixtythree different variants were defined in these patients and 7 of these were large deletions/duplications detected with the MLPA method. The most frequent variants were F508del (29.6%), G85E (8.2%), N1303K (8.2%), Y515* (7.5%), and G542* (3.4%). CONCLUSION: Using sequencing and Multiplex Ligation-dependent Probe Amplification methods, the identification of seven new mutations that were not previously reported in the literature contributes to a better understanding of the heterogeneous nature of CFTR mutations in the Turkish population. When no mutations are detected (pathogenic/probably pathogenic) in clinically compatible cases, Multiplex Ligationdependent Probe Amplification analysis contributes significantly to the diagnosis.

Positive Direct Antiglobulin Test: Is It a Risk Factor for Significant Hyperbilirubinemia in Neonates with ABO Incompatibility?

OBJECTIVE: ABO blood group (ABO) incompatibility is a common cause of neonatal indirect hyperbilirubinemia. The direct antiglobulin test (DAT) can identify infants developing hemolytic disease. This study aims to evaluate the significance of DAT positivity among neonates with ABO incompatibility. STUDY DESIGN: This retrospective study included 820 neonates with blood group A or B who were born to blood group O mothers. The study group consisted of neonates (n = 79) who had positive DAT, and the control group consisted of infants (n = 741) who had negative DAT. Demographic and clinical data of the neonates regarding jaundice were collected and compared statistically. RESULTS: The bilirubin level at 24 hours of life (study group: 8 ± 2.6 mg/dL, control group: 6 ± 2.2 mg/dL, p < 0.001) and the highest bilirubin level (study group: 12.7 ± 3.6 mg/dL, control group: 10.4 ± 4.2 mg/dL, p < 0.001) were higher in infants with positive DAT. A total of 37 (46.8%) infants in the study group and 83 (11.2%) infants in the control group received phototherapy (PT) in the nursery (p < 0.001). In neonates with positive DAT, direct bilirubin level, duration of hospitalization, and PT in the nursery were higher (p = 0.002, <0.001, and <0.001, respectively), whereas hemoglobin level was lower (p < 0.001). CONCLUSION: In neonates with ABO incompatibility, a positive DAT is a risk factor for developing significant hyperbilirubinemia. Close follow-up of newborn infants with ABO incompatibility is crucial for early detection and treatment of neonatal jaundice to avoid early and late complications. KEY POINTS: · The clinical spectrum of ABO incompatibility varies widely.. · The ABO incompatibility with positive DAT are at greater risk for high bilirubin levels.. · Infants with blood group incompatibilities must be monitored closely..