Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Comparison of refugee patients with cystic fibrosis and their counterpart children from Turkey during the war.

Since the outbreak of the Syrian civil war in 2011, the population of Arab refugees in Turkey has rapidly increased. While cystic fibrosis (CF) is believed to be rare among Arabs, recent studies suggest it is underdiagnosed. This study aims to present the demographic, clinical, and genetic characteristics of CF patients among Arab refugees in Turkey. Additionally, a comparison is made between the findings in the National CF Registry 2021 in Turkey (NCFRT) and the refugee CF patient group. The study included refugee patients between the ages of 0 and 18 years who were diagnosed with CF and received ongoing care at pediatric pulmonology centers from March 2011 to March 2021. The study examined demographic information, age at diagnosis, age of diagnosis of patients through CF newborn screening (NBS), presenting symptoms, CF transmembrane conductance regulator (CFTR) mutation test results, sputum culture results, weight, height, and body mass index (BMI) z score. Their results were compared with the NCFRT results. The study included 14 pediatric pulmonology centers and 87 patients, consisting of 46 (52.9%) boys and 41 (47.1%) girls. All of the patients were Arab refugees, with 80 (92%) being Syrian. All the patients were diagnosed in Turkey. The median age at diagnosis of patients was 22.33 (interquartile range, 1-258) months. The median age of diagnosis of patients through NBS was 4.2 (interquartile range, 1-12) months. The median age of older patients, who were unable to be included in the NBS program, was 32.3 (interquartile range, 3-258) months. Parental consanguinity was observed in 52 (59.7%) patients. The mutation that was most frequently found was F508del, which accounted for 22.2% of the cases. It was present in 20 patients, constituting 32 out of the total 144 alleles. There was a large number of genetic variations. CFTR genotyping could not be conducted for 12 patients. These patients had high sweat tests, and their genetic mutations could not be determined due to a lack of data. Compared to NCFRT, refugee patients were diagnosed later, and long-term follow-up of refugee CF patients had significantly worse nutritional status and pseudomonas colonization.  Conclusion: Although refugee CF patients have equal access to NBS programs and CF medications as well as Turkish patients, the median age at diagnosis of patients, the median age of diagnosis of patients through NBS, their nutritional status, and Pseudomonas colonization were significantly worse than Turkish patients, which may be related to the difficulties of living in another country and poor living conditions. The high genetic heterogeneity and rare mutations detected in the refugee patient group compared to Turkish patients. Well-programmed NBS programs, thorough genetic studies, and the enhancement of living conditions for refugee patients in the countries they relocate to can have several advantages such as early detection and improved prognosis. What is Known: • Children who have chronic diseases are the group that is most affected by wars. • The outcome gets better with early diagnosis and treatment in patients with Cystic Fibrosis (CF). What is New: • Through the implementation of a newborn screening program, which has never been done in Syria previously, refugee patients, the majority of whom are Syrians were diagnosed with cystic fibrosis within a duration of 4 months. • Despite equal access to the newborn screening program and CF medications for both Turkish patients and refugee patients, the challenges of living in a foreign country have an impact on refugees.

Neutrophil lymphocyte ratio, mean platelet volume, and immunoreactive trypsinogen as early inflammatory biomarkers for cystic fibrosis in infancy: A retrospective cohort study.

BACKGROUND: Airway inflammation starts in early life in cystic fibrosis (CF) and limited, objective markers are available to help identify infants with increased inflammation. We aimed to investigate neutrophil, lymphocyte ratio (NLR), mean platelet volume (MPV) and immunoreactive trypsinogen (IRT) to be a possible inflammatory biomarker for CF in infancy. METHODS: This was a retrospective cohort study in three centers. Between January 2015 and December 2022, children with CF newborn screening (NBS) positivity and diagnosed as CF were included in the study. Correlation analysis were performed with NLR, MPV, IRT and follow-up parameters such as z-scores, modified Shwachman-Kulczycki score (mSKS) at the first, second, third and sixth ages and pulmonary function test (PFT) at the sixth age. RESULTS: A total of 92 children with CF included in the study and 47.8% of them were female. There were no correlations between NLR, MPV and weight and height z-scores for all ages (p > 0.05), a negative correlation was found between MPV and body mass indexes (BMI) z-score at the age of 6 (r = -0.443, p = 0.038). No correlation was found between NLR, MPV and PFT parameters and mSKS at all ages (p > 0.05). There was a negative correlation between first IRT and BMI z-score at 6 years of age (r = -0.381, p = 0.046) and negative correlations between second IRT and weight and BMI z-score at the age of 6 (r = -0.462, p = 0.010; r = -0.437, p = 0.016, respectively). CONCLUSION: Higher MPV and IRT levels during NBS period are associated with worse nutritional outcome which may reflect chronic inflammation. Children with higher MPV and IRT should be followed up closely in terms of chronic inflammation and nutritional status.

Childhood sarcoidosis in the middle Anatolia of Turkey.

OBJECTIVE: This retrospective study aimed to describe the clinical and radiological features, diagnostic methods, laboratory findings, organ involvement, and treatment strategies of 22 patients who followed up with late-onset childhood sarcoidosis and compare them with the literature. MATERIAL AND METHOD: This retrospective multicenter study reviewed the medical records of 22 children with sarcoidosis who applied to the Pediatric pulmonology department of Erciyes University Faculty of Medicine and Necmettin Erbakan Faculty of Medicine in 2012 and 2022. RESULTS: The mean age of the patients at the time of diagnosis was 13.1/year (interquartile range [IQR]1:6.3-[IQR]3:15.7). The most common first presenting symptom was cough 40.9% (n = 9), weight loss 31.8% (n = 7), and dyspnea 22.7% (n = 5). There were elevated levels of C-reactive protein (CRP; 59%), angiotensin-converting enzyme (ACE; 54.5%), erythrocyte sedimentation rate (ESR; 54.5%), and immunoglobulin G (IgG; 54.5%). Twenty patients (90%) received systemic steroid treatment. Eighteen (81.8%) of these patients responded positively to treatment. Two patients had a recurrence. CONCLUSION: The incidence of sarcoidosis in children in Turkey is currently unknown. However, a regional average of 2.2 cases per year has been documented for the first time. Contrary to previous studies, a significant prevalence of consanguineous marriage was observed in our study. While constitutional symptoms were most common in other studies, the cough was the most common symptom in our study. To our knowledge, this is one of the Turkish studies with the highest number of sarcoidosis in children and one of the few European studies on sarcoidosis in children.

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.

The Relationships between Prenatal Attachment, Basic Personality Traits, Styles of Coping with Stress, Depression, and Anxiety, and Marital Adjustment Among Women in the Third Trimester of Pregnancy.

OBJECTIVE: The importance of prenatal attachment, probably as the initial attachment of a pregnant woman to the fetus and which turn into the maternal-baby attachment after birth, for the well-being of the newborn and mother is well known. The aim of the present study was to explore the possible socio-demographic and clinical factors (personality features, styles used in coping with stress, depression, and situational anxiety levels, and marital adjustment) affecting maternal-fetal attachment. MATERIALS AND METHODS: Eighty women on their third trimesters of pregnancy were included in the study. After examination by a psychiatrist, a detailed socio-demographic form and scales including Prenatal Attachment Inventory, Basic Personality Traits Scale, Coping with Stress Attitudes Inventory, State-Trait Anxiety Inventory-1, Beck Depression Inventory (BDI), and Marital Adjustment Scale were applied. RESULTS: Educational level, marital adjustment, social support, and turning to religion as a coping mechanism with stress were found to be positively correlated with prenatal attachment scores. The duration of marriage and number of giving births and the avoidance/disengagement subscale of Coping with Stress Scale and BDI scores were negatively correlated with prenatal attachment scores. A BDI score of ≥17 (this score suggests moderate and/or severe symptoms of depression) was found to be an independent and a negative variable on prenatal attachment. CONCLUSION: We suggest that the detection of symptoms of depression and other factors that may affect prenatal attachment, may help shed light to the interventions to be performed to improve the quality of maternal-fetal attachment by society and governments.

Comparison of Serum A Disintegrin and Metalloproteinase with Thrombospondin Motifs-19 Levels in Different Fertility Situations: Could It Be a Serum Marker of Ovarian Function and Oocyte Pool?

BACKGROUND/AIMS: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes take part in extracellular matrix (ECM) remodeling which has been shown to contribute to the ovulation and follicular functions. We aimed to compare serum levels of ADAMTS-19 in patients with different fertility situations. METHODS: A total of 86 women were enrolled to this cross sectional and case-control study. Four groups were constituted with respect to women's clinical and hormonal status: group 1, women with premature ovarian failure (POF; n = 21); group 2, women with natural menopause (n = 21); group 3, women with polycystic ovary syndrome (PCOS; n = 22); and group 4, healthy fertile controls. Serum ADAMTS-19 levels and individual characteristics were compared among groups. RESULTS: -ADAMTS-19 levels were found as 36.7 ± 10.2, 40.1 ± 12.6, 46.7 ± 16.1, and 51.0 ± 18.8 ng/mL in POF, fertile, natural menopause, and PCOS groups, respectively (p = 0.012). Especially, ADAMTS-19 levels in the PCOS group were significantly higher than the POF group, as found in dual comparisons (p = 0.010). CONCLUSIONS: ADAMTS-19 was found to be higher in PCOS patients than in POF patients. This work provides a novel vantage point for function of ECM within the ovary. ADAMTS-19 may have a potential for being an important marker of ovarian function and oocyte pool.

Is Striae Gravidarum related to Cesarean Scar and Peritoneal Adhesions?

OBJECTIVE: To evaluate the relationship between striae gravidarum (SG) score and abdominal scar characteristics together with intraperitoneal adhesion (IPA) grades of patients who were hospitalized for second cesarean delivery. METHODS: A total of 145 consecutive women undergoing scheduled cesarean section (CS) in a tertiary level maternity hospital between November 2013 and January 2014 were included in the study. All women had transverse suprapubic skin incision due to the previous CS and none of them had a history of vaginal delivery. Patients were classified according to the SG status, as women with no SG: Group-1(n=53), mild SG: Group-2(n=27) and severe SG: Group 3(n=65). Groups were compared between themselves with regard to various sociodemographic properties, cesarean scar characteristics and IPA scores. RESULTS: No significant difference in the length, width and color of the scar was detected among groups. While flat scar was the most prominent form of scar, the elevated scar was significantly more frequent in Group-1 compared to other groups (p=0.009). IPA grades were 0 or 1 in 77.3% of Group-1, 81.3% of Group-2 and 76% of Group-3. There was no significant difference in IPA scores between groups (p=0.884). After combining CS scar characteristics (flat, depressed and elevated) and SG status [SG (+) or SG (-)], we found no significant difference between the groups in terms of IPA severity. CONCLUSION: Striae gravidarum (SG) was found to be associated with scar characteristics, but not associated with the severity of intraperitoneal adhesion (IPA).

Prediction of the length of repeat post C-section hospital stay and comparison of perinatal outcomes in patients with ≥3 versus <3 previous C-section.

OBJECTIVE: To create a model for prediction of repeat post cesarean section (CS) length of hospital stay (LOHS) in patients undergoing repeat CS. Our other aim was to compare the perinatal outcomes in patients with ≥3 versus <3 previous CS procedures. METHODS: Individual characteristics, pre-, intra- and post-operative data of 186 pregnant women who had ≥3 previous CS were compared with 195 pregnant women with <3 previous CS. RESULTS: Regression analyses revealed that models can be used to predict the dependents "postpartum LOHS" and "needed units of erythrocyte suspension", both pre-operatively and intra-operatively. Patients with ≥3 previous CS procedures were older, delivered earlier and had lower Apgar 1 and Apgar 5 values than patients with <3 previous CS. The rate of elective CS operations was lower in patients with ≥3 previous CS. Pregnant women ≥3 previous CS had significantly more severe intraperitoneal adhesion (IPA) and higher rate of bladder injury. CONCLUSIONS: Prediction models can be conducted for LOHS and other perinatal and operative parameters in patients with previous CS. Pregnancy and repeat CS, even in patients with ≥3 previous CS procedures, are both safe conditions with optimal follow-up and management.

Influenza infections in the 2014-2015 season and pregnancy outcomes.

INTRODUCTION: The most recent influenza season saw a prominent infectious burden over a period of six months in the Turkish capital, reminding observers of the pandemic in 2009 year. The aim of the present study was to investigate the consequences of seasonal outbreaks in pregnant women during the 2014-2015 influenza season. METHODOLOGY: Forty-seven pregnant female patients with symptoms of influenza-like illness who were admitted to tertiary perinatal care center in Ankara, Tukrey, between October 2014 and May 2015 were included in this case-control study. The subtype determination of influenza was performed with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing. Clinical observations and pregnancy outcomes were compared with respect to subtypes. RESULTS: Classifications were available for 35 patients, of whom 12 were determined to have influenza A infection, while 10 had influenza B infection. The remaining 13 patients were influenza-negative. Eight of the 22 (36.4%) influenza-positive patients delivered their babies in the preterm period (< 37 weeks). The corresponding rate was 8.3% (1/12) in the influenza-negative group. This difference was not statistically significant (p = 0.077). CONCLUSIONS: Preterm deliveries in pregnant women did not differ significantly among influenza-postive and influenza-negative pregnant women in non-vaccinated study population. Further studies with larger sample sizes may provide more supporting results.

Maternal venous SHARP1 levels in preeclampsia.

AIM: Owing to its mysterious etiology, pathogenesis of preeclampsia (PE) remains controversial. Here we aimed to compare the levels of an angiogenesis marker, split and hairy related protein-1 (SHARP1), in PE vs. normal pregnancy. METHODS: Thirty-one patients with early-onset PE (EOPE), 26 patients with late-onset PE (LOPE), and 33 patients as a control group were recruited for this study in a tertiary referral center in Ankara, Turkey. Maternal venous SHARP1 levels and individual characteristics of the three groups were compared. RESULTS: Age and body mass indices were similar among the three groups. SHARP1 levels in patients with PE (27.7±13.2 ng/mL) were significantly lower than in the control group (34.7±17 ng/mL) (P=0.006). Additionally, SHARP1 levels were significantly different among patients in EOPE, LOPE, and control groups (P=0.022). Birth weights and Apgar scores in patients in EOPE group were significantly lower than the other two groups and showed a gradual increase from the EOPE group to the LOPE and the control group. Binary logistic regression method demonstrated that maternal venous SHARP1 level was a risk factor for PE. CONCLUSIONS: Maternal venous SHARP1 levels in PE are lower than a normal pregnancy. Its clinical applicability and role as a candidate for making sense of the distinctive pathogenesis of the EOPE and LOPE remain to be elucidated.

The association between placenta previa and leukocyte and platelet indices - a case control study.

OBJECTIVES: Despite medical advances, rising awareness, and satisfactory care facilities, placenta previa (PP) remains a challenging clinical entity due to the risk of excessive obstetric hemorrhage. Etiological concerns gave way to life-saving concerns about the prediction of maternal outcomes due to hemorrhage. Our study aimed to detect an early predictive marker of placenta previa. MATERIAL AND METHODS: Ninety-three pregnant patients diagnosed with PP and 247 controls were recruited for this retro-spective study. Platelet and leukocyte indices were compared between the two groups. RESULTS: The groups were similar with regard to age distribution (31.2 ± 5.1 years [mean ± SD] in the PP group and 31.7 ± 4.2 years in controls), body mass index (BMI) (27.7 ± 3.6 kg/m2 in the PP group and 27.4 ± 4.6 kg/m2 in controls), and most characteristics of the obstetric history. Total leukocyte count, neutrophil count, and neutrophil-to-lymphocyte ratio were significantly higher in the PP group. Mean platelet volume (MPV) and large platelet cell ratio (P-LCR) values were significantly lower in the PP group as compared to controls, with regard to third trimester values. However, patients who were diagnosed postnatally with placenta percreta had lower MPV and P-LCR values than other patients with PP. There were no statistically significant differences between the two groups as far as first trimester values were concerned. CONCLUSIONS: Platelet and leukocyte indices in the third trimester of pregnancy may be valuable predictors of placenta previa and placenta percreta. More comprehensive studies are needed to address this issue.

An Unusual Origin of Fetal Lymphangioma Filling Right Axilla.

Fetal lymphangioma is a hamartomatous congenital anomaly of the lymphatic system, which is embracing the fetal skin (sometimes mucous membranes) and the subcutaneous tissue. The general consensus is that it occurs as a result of failure in lymphatic drainage. A 36-year-old pregnant woman was referred to our perinatology clinic at 22 weeks' gestation, because of a fetal right-sided axillary mass revealed by ultrasonography. The mass measuring 5x7x7cm in three dimensions had a multilocular structure without colour Doppler flow and well-circumscribed borders. Amniocentesis revealed a normal constitutional karyotyping. Lymphangioma was considered as prediagnosis. A healthy female baby weighing 3470 grams was delivered at term. Neonatal examination and the postnatal MRI confirmed the diagnosis. The baby is still on follow-up with the medical treatment of Sirolimus an anti-proliferative drug, and the mass got smaller significantly in 8 months after delivery.

Is it possible to prevent striae gravidarum?

BACKGROUND: Striae gravidarum (SG), commonly called stretch marks, is an important cosmetic problem which is not treatable, although preventive measures might be effective. The aim of this study was to determine individual risk factors causing SG and the degree to which preventive measures could be effective. METHODS: This prospective observational study included 211 singleton primiparous pregnant women who were hospitalized for birth and who did not have systemic diseases or other risk factors, like drug use or polyhydramnios. Patients were examined and divided into two groups with respect to whether or not they had striae. Individual features were compared between the two groups. RESULTS: While 159 patients (75.4%) had SG, 52 (24.6%) did not. Patients with striae had a significantly lower mean age and higher mean preconceptional body mass indices than ones without striae (p < 0.001 and p = 0.001, respectively). Family history (p = 0.002), having a male baby (p = 0.042), and lower educational level (p = 0.033) were also statistically significant in predicting striae. Use of preventive oil or drugs, smoking status, skin type, water intake, and level of financial income did not significantly predict SG. CONCLUSION: Informing women preconceptionally on the importance of modifiable risk factors, such as body weight and maternal age before pregnancy, can be useful, considering that stretch marks are carried for a lifetime and there is no conclusive treatment.

Are progranulin levels associated with polycystic ovary syndrome and its possible metabolic effects in adolescents and young women?

PURPOSE: Polycystic ovary syndrome (PCOS) is an important disease that may alter metabolic balances of the whole body. Progranulin is a growth factor which is related to epithelial, neuronal growth and oogenesis. Here, we aimed to investigate the diagnostic value of the levels of Progranulin in the clinical setting of PCOS, and its metabolic effects. METHODS: Forty-one adolescents and young women with PCOS and 39 age and body mass index matched adolescents and young women as a control group who attended to the youth center of a tertiary referral center were included in this cross-sectional case-control study. Progranulin levels, indices of insulin sensitivity, lipidemic markers, metabolic syndrome (MetS) criteria were compared between the groups. RESULTS: Progranulin levels in patients with PCOS (7.48 ± 1.93 ng/mL) were significantly higher than in the control group (6.25 ± 1.98 ng/mL) (p = 0.006). Luteinizing hormone (LH) levels, LH/Follicle stimulating hormone (FSH) ratios, free testosterone, dehydroepiandrosterone sulfate (DHEAS), C-reactive protein (CRP) levels in patients with PCOS were significantly higher than in the control group (p < 0.05, for all). The MetS was present in 8 (19.5 %) of the patients in the study group and in 1 (2.3 %) of the patients in the control group (p = 0.029). There was significant inverse correlation between high-density lipoprotein cholesterol (HDL-C) and progranulin levels of patients diagnosed with PCOS (p = 0.008). CONCLUSIONS: Progranulin may be a novel biomarker for cardiovascular risk in patients with PCOS, thus these cases should be directed to close follow-up for possible cardiovascular diseases. Future larger studies should focus on this entity.

The Association between N-terminal Pro-Brain Natriuretic Peptide Levels in the Umbilical Vein and Amniotic Fluid Volume Abnormalities.

Purpose The amniotic fluid volume (AFV) is known as a predictor for the wellness of a fetus. We aimed to investigate whether N-terminal pro-brain natriuretic peptide (NTproBNP) levels reflect AFV abnormalities in otherwise normal fetuses. Methods We recruited 24 women with isolated oligohydramnios, 23 women with isolated polyhydramnios, and 36 women with normal AFV at a tertiary referral center. NT-proBNP levels in umbilical venous samples and the individual characteristics of the three groups were compared. One-way ANOVA and Kruskal-Wallis analysis of variance were used for multi-group comparisons of continuous variables. When a significant difference was detected, the Scheffe test was performed as a post-hoc analysis. Proportions were compared using the Chi-square (χ2) test. Results Maternal age, body mass indices, weight gained in pregnancy and NT-proBNP levels were similar among the three groups. Apgar scores at 1 and 5 minutes significantly correlated with NT-proBNP levels in all newborns (Spearman's r = 0.23; p = 0.03 and Spearman's r = 0.24; p = 0.02, respectively). The umbilical venous NT-proBNP levels did not differ between newborns who needed mechanical ventilation and those who didn't (p = 0.595). Conclusions NT-proBNP is a biomolecule that may provide insights into the pathogenesis of fetal circulatory problems and subsequent renal failure. Further investigations are warranted.

The Association between N-terminal Pro-Brain Natriuretic Peptide Levels in the Umbilical Vein and Amniotic Fluid Volume Abnormalities / Associação entre níveis de peptídeo natriurético prócerebral N-terminal na veia umbilical e as anormalidades do volume de líquido amniótico

Abstract Purpose The amniotic fluid volume (AFV) is known as a predictor for the wellness of a fetus. We aimed to investigate whether N-terminal pro-brain natriuretic peptide (NTproBNP) levels reflect AFV abnormalities in otherwise normal fetuses. Methods We recruited 24 women with isolated oligohydramnios, 23 women with isolated polyhydramnios, and 36 women with normal AFV at a tertiary referral center. NT-proBNP levels in umbilical venous samples and the individual characteristics of the three groups were compared. One-way ANOVA and Kruskal-Wallis analysis of variance were used for multi-group comparisons of continuous variables. When a significant difference was detected, the Scheffe test was performed as a post-hoc analysis. Proportions were compared using the Chi-square (2) test. Results Maternal age, body mass indices, weight gained in pregnancy and NT-proBNP levels were similar among the three groups. Apgar scores at 1 and 5 minutes significantly correlated with NT-proBNP levels in all newborns (Spearman's r = 0.23 ; p = 0.03 and Spearman's r = 0.24; p = 0.02, respectively). The umbilical venous NTproBNP levels did not differ between newborns who needed mechanical ventilation and those who didn't (p = 0.595). Conclusions NT-proBNP is a biomolecule that may provide insights into the pathogenesis of fetal circulatory problems and subsequent renal failure. Further investigations are warranted.

Resumo Objetivo Investigar se os níveis de peptídeo natriurético pró-cerebral N-terminal (NTproBNP) refletem anormalidades no volume de líquido amniótico (VLA) em fetos normais. Métodos Reunimos 24 mulheres com oligoidrâmnios isolados, 23 com poli-hidrâmnios isolados, e 36 com VLA normal em um centro de referência. Comparamos os níveis de NT-proBNP em amostras venosas umbilicais e características individuais em três grupos. Usamos análise de variância simples (One-way ANOVA) e a análise de variação Kruskal-Wallis para comparação de variáveis contínuas em múltiplos grupos. Quando identificada uma diferença significativa, o teste de Scheffe foi aplicado como uma análise post-hoc. Comparamos proporções usando o teste Qui-quadrado (2). Resultados Idade fértil, índice de massa corporal, ganho de peso na gestação e níveis de NT-proBNP foram similares nos três grupos. Apgar em 1 e 5 minutos correlacionaram significativamente com os níveis de NT-proBNP em todos os recém-nascidos (Spearman's r = 0,23; p = 0,03 e Spearman's r = 0,24; p = 0,02, respectivamente). Os níves de NT-proBNP venoso umbilical não se distinguiram entre os recém-nascidos que precisaram de ventilação mecânica e aqueles que não precisaram (p = 0,595). Conclusões NT-proBNP é um candidato biomolecular que pode contribuir na patogênese de problemas circulatórios fetais e subsequente insuficiência renal. São necessárias futuras investigações.

A novel mutated sequence in the T-box transcription factor-5 (TBX-5) gene (c.241A>T) in Holt-Oram syndrome.

We report a case of a 31-year-old pregnant woman who was admitted to our perinatology outpatient clinic because of a fetal ventricular septal defect and limb reduction in the upper extremities of fetus revealed by ultrasonographic investigation diagnosed in the 16(th) week of gestation. First child of the family was diagnosed with Holt-Oram syndrome who had atrial septal defect and upper limb anomalies, whereas the father was documented to have arrhythmia and shortening of upper limbs. The pregnancy was terminated in the 16(th) week of gestation with the consent of the family. We performed mutation analysis in T-box transcription factor-5 (TBX5) gene coding exons, including exon/intron boundaries from peripheral blood or skin fibroblasts. The sequence analysis revealed c.241 adenine (A)>thymine (T) [p. arginine (Arg) 81 Tryptophan (Trp)] alteration in exon-3 of the TBX5 gene in affected family members and fetus. This is a novel mutation causing Holt-Oram syndrome.

Decreased placental and maternal serum TRAIL-R2 levels are associated with placenta accreta.

OBJECTIVES: TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) is produced both by decidual and trophoblast cells during pregnancy and known to participate in apoptosis. In this study, we aimed to determine and to compare maternal serum and placental TRAIL-R2 levels in patients with placenta accreta, non-adherent placenta previa and in healthy pregnancies. We also aimed to analyze the association of placenta accreta with the occurrence of previous C-sections. STUDY DESIGN: A total of 82 pregnant women were enrolled in this case-control study (27 placenta accreta patients, 26 non-adherent placenta previa patients and 29 age-, and BMI-matched healthy, uncomplicated pregnant controls). TRAIL-R2 levels were studied in both maternal serum and placental tissue homogenates. Determining the best predictor(s) which discriminate placenta accreta was analyzed by multiple logistic regression analyses. Adjusted odds ratios and 95% confidence intervals were also calculated. RESULTS: Both placental and serum TRAIL-R2 levels were significantly lower in placenta accreta group (median 34.82 pg/mg and 19.85 pg/mL, respectively) when compared with both non-adherent placenta previa (median 39.24 pg/mg and 25.99 pg/mL, respectively) and the control groups (median 41.62 pg/mg and 25.87 pg/mL, respectively) (p < 0.05). Placental TRAIL-R2 levels and previous cesarean section were found to be significantly associated with placenta accreta (OR: 0.934 95% CI 0.883-0.987, p = 0.016 and OR:7.725 95% CI: 2.717-21.965, p < 0.001, respectively). Placental and serum TRAIL-R2 levels were positively correlated. CONCLUSION: Decreased levels of placental TRAIL-R2 and previous history of cesarean section were found to be significantly associated with placenta accreta, suggesting a possible role of apoptosis in abnormal trophoblast invasion.