Performance of an ancillary test for cervical cancer that measures miRNAs and cytokines in serum and cervical mucus.

Currently, human papillomavirus tests and cytology are used to screen for cervical cancer. However, more accurate ancillary screening tests are needed. MicroRNAs (miRNAs) and cytokines are promising biomarkers that are aberrantly expressed in cervical cancer. Therefore, the potential of developing new screening markers based on the levels of miRNAs and cytokines in serum and local mucus samples from the same patients with cervical neoplasia was investigated. miRNA screening was performed by microarray and measurement using real-time reverse-transcriptase PCR. Cytokine were measured using multiplex bead assay, and changes in expressions were analyzed based on disease severity. As lesions progressed, miR-20b-5p, -155-5p, -144-3p, -451a, and -126-3p expression levels were increased in mucus, and miR-16-5p, -223-3p, and -451a expression levels were decreased in serum. Regarding cytokines, IL-6, IL-8, monocyte chemoattractant protein-1, Eotaxin, interferon-γ, and RANTES were increased, whereas granulocyte-colony-stimulating factor (G-CSF) was significantly decreased in mucus. miRNAs and cytokines in serum did not have high diagnostic accuracy. However, a combination of miR-20b-5p, -451a, -126-3p, Eotaxin, as well as G-CSF in mucus samples, had high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.989 (0.979-0.999). Our results suggest that using mucus for this ancillary test is more beneficial than serum.

Metabolomic and microbiome analysis of cervicovaginal mucus in in vitro fertilization-embryo transfer: Toward predicting pregnancy success.

Purpose: In the context of in vitro fertilization-embryo transfer (IVF-ET), factors other than egg quality may be key determinants of treatment success, in particular, maternal factors related to uterine endometrial receptivity and unidentified factors. We therefore aimed to analyze the metabolome and microbiome in IVF-ET patients who did and did not achieve pregnancy. Methods: Cervicovaginal mucus was collected from patients undergoing IVF-ET. Metabolite analysis was conducted by liquid chromatography-mass spectrometry and the microbiota were determined by the polymerase chain reaction using universal 16S-rRNA gene bacterial primers by MiSeq sequencing. Patients were classified as pregnant (N = 10) or nonpregnant (N = 13). Metabolic pathways were examined by MetaboAnalyst. Results: Three metabolic pathways, including alanine-aspartate-glutamate metabolism, arginine biosynthesis, and cysteine-methionine metabolism, were commonly decreased at the time of embryo transfer irrespective pregnant outcomes. Notably, pyruvate was decreased in the pregnant group. Amino acid metabolites showed inverse correlations with the presence of anaerobic microbiota in the nonpregnant group. Conclusions: Metabolism decreased during embryo transplantation, with a notable decrease in pyruvate metabolism, particularly in patients who became pregnant. The behavior of metabolites in the pregnant and nonpregnant groups suggests that metabolome analysis in the cervicovaginal mucus may be a diagnostic marker for predicting pregnancy.

Effect of delivery mode on postnatal platelet count dynamics in neonates born to mothers with immune thrombocytopenia.

We aimed to determine the effect of delivery mode on postnatal platelet count dynamics in neonates born to mothers with immune thrombocytopenia (ITP). This single-center, retrospective study included 41 mothers with ITP and their 65 infants born by vaginal delivery (VD, n = 30) and cesarean section (CS, n = 35) between January 1997 and March 2022. The median difference in platelet counts from day 0 to day 2 (ΔPlt [D 0-2]) was significantly lower in the VD group (- 39 × 109/L, interquartile range [IQR]: - 47 to - 24 × 109/L) than the CS group (15 × 109/L, IQR: - 6.5 to 33 × 109/L) (p < 0.001). The median ΔPlt (D 0-5) was significantly lower in the VD group (- 55 × 109/L, IQR: - 85 to - 31 × 109/L) than the CS group (33 × 109/L, IQR: 1-69 × 109/L) (p < 0.001). Multivariate analysis also showed a significant association of delivery mode with ΔPlt (D 0-2) and ΔPlt (D 0-5) (both p < 0.001). VD neonates with platelet counts ≥ 100 × 109/L at birth were significantly more likely than CS neonates to develop thrombocytopenia < 100 × 109/L at nadir (1/26 vs. 6/25) (p = 0.0496). Our findings indicate that mode of delivery is a useful predictor of postnatal platelet count dynamics in neonates born to mothers with ITP.

Nomogram for predicted probability of cervical cancer and its precursor lesions using miRNA in cervical mucus, HPV genotype and age.

Cervical cancer is the fourth most common cancer in women worldwide. Although cytology or HPV testing is available for screening, these techniques have their drawbacks and optimal screening methods are still being developed. Here, we sought to determine whether aberrant expression of miRNAs in cervical mucus could be an ancillary test for cervical neoplasms. The presence of miRNAs in 583 and 126 patients (validation and external cohorts) was determined by real-time RT-PCR. Performance of a combination with five miRNAs (miR-126-3p, -451a -144-3p, -20b-5p and -155-5p) was estimated by ROC curve analysis. Predicted probability (PP) was estimated by nomograms comprising -ΔCt values of the miRNAs, HPV genotype and age. A combination of five miRNAs showed a maximum AUC of 0.956 (95% CI: 0.933-0.980) for discriminating cancer. Low PP scores were associated with good prognosis over the 2-year observation period (p < 0.05). Accuracy for identifying cancer and cervical intraepithelial neoplasia (CIN) 3 + by nomogram was 0.983 and 0.966, respectively. PP was constant with different storage conditions of materials. We conclude that nomograms using miRNAs in mucus, HPV genotype and age could be useful as ancillary screening tests for cervical neoplasia.

Lower accuracy of cytological screening for high-grade squamous intraepithelial neoplasia in women over 50 years of age in Japan.

BACKGROUND: As the population ages in developed countries, the number of Pap smears for cervical cancer screening of older women is increasing. There is concern that cervical atrophy may cause misinterpretation of results for this segment of the population. The present study evaluated the accuracy of screening for high-grade intraepithelial lesions (HSILs) in women younger or older than 50 years, to determine whether aging affects cytological interpretation. METHODS: Patients with HSIL cytology (N = 1565) were dichotomized into those aged 20-49 years or aged ≥ 50 years. Association between histology results and age was examined. Pearson's chi-squared test and Cochran-Armitage trend test were used for statistical analysis. RESULTS: The positive predictive value (PPV) for cervical intraepithelial neoplasia (CIN)2 and worse was 65.2% (62/95) in older women but 87.3% (482/552) in younger women (p < 0.001). Older patients had a significantly lower PPV (p = 1.69 × 10-8). Separately analyzing chronic cervicitis, CIN1 and overt cancer grouped together, compared with another group composed of CIN2 and CIN3, we found that the PPV for CIN2 and CIN3 was lower in older than in younger women [44.2% (42/95)-vs-82.4% (455/552), p < 0.001], respectively. CONCLUSIONS: HSILs are associated with a wide range of disease categories as age increases, and the accuracy of HSIL interpretation is lower in older women.

Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia.

Persistent HPV infection associated with immune modulation may result in high-grade squamous intraepithelial lesions (CIN)2/3. Currently, there is little information on the cervicovaginal microbiome, local cytokine levels and HPV infection related to CIN. Follow-up of patients after local surgery provides an opportunity to monitor changes in the cervicovaginal environment. Accordingly, we undertook this longitudinal retrospective study to determine associations between HPV genotypes, cervicovaginal microbiome and local cytokine profiles in 41 Japanese patients with CIN. Cervicovaginal microbiota were identified using universal 16S rRNA gene (rDNA) bacterial primers for the V3/4 region by PCR of genomic DNA, followed by MiSeq sequencing. We found that Atopobium vaginae was significantly decreased (p < 0.047), whereas A. ureaplasma (p < 0.022) increased after surgery. Cytokine levels in cervical mucus were measured by multiplexed bead-based immunoassays, revealing that IL-1ß (p < 0.006), TNF-α (p < 0.004), MIP-1α (p < 0.045) and eotaxin (p < 0.003) were significantly decreased after surgery. Notably, the level of eotaxin decreased in parallel with HPV clearance after surgery (p < 0.028). Thus, local surgery affected the cervicovaginal microbiome, status of HPV infection and immune response. Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia may be important for understanding the pathogenesis of CIN in future.

Late onset group B streptococcus disease manifesting as acute suppurative parotitis.

Few patients with acute suppurative parotitis (ASP) due to group B streptococcus (GBS) have been documented. Limited data on clinical and microbiological features and infectious route are available. We present a 21-day-old boy with invasive GBS disease manifesting as ASP. The patient was admitted because of irritability, fever, and erythematous swelling over the right parotid area. No purulent material exuded from the Stensen's duct. Ultrasonography and computed tomography of the neck showed findings indicative of ASP. On the day after admission, blood culture yielded GBS. The isolate was determined as GBS serotype Ia and sequence type-23, and the patient was successfully treated with intravenous ampicillin for 10 days. A review of the literature revealed 11 GBS ASP infants including ours with age at onset between 13 days and 12 weeks. All infants had bacteremia while pus from the Stensen's duct was detected in only one case. This finding remarkably contrasts with ASP caused by pathogens other than GBS, where the infection usually spreads via a retrograde route from Stensen's duct. The present case and literature review indicate GBS ASP primarily arises from bloodstream infection, and that ASP should be included in an infectious focus as late onset GBS disease.

MicroRNA­126­3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway.

We previously reported that relative to normal cervical mucus, microRNA 126­3p (miR­126­3p) is present in significantly greater amounts in the cervical mucus of patients with overt cervical cancer or precursor lesions. Here, we investigated the effects of enforced miR­126­3p expression in the cervical cancer cell line, HeLa, on proliferation, migration, invasion, apoptosis and protein expression. We transfected HeLa cells with miR­126­3p miRNA and found that proliferation, migration and invasion by cell counting, wound healing, cell migration and invasion assay were significantly reduced in these cells relative to those transfected with a negative control mimic. The levels of phosphoinositide 3 kinase (PI3K), phosphorylated 3­phosphoinositide­dependent protein kinase­1 (p­PDK1) and p­AKT proteins were lower in the miR­126­3p­transfected cells. Phosphorylated 70S6K (p­p70S6K), phosphorylated glycogen synthase kinase 3ß (p­GSK3ß), phosphorylated S6K (p­S6K), cyclin D1, phosphorylated p21­activated kinase 1 (p­PAK1), Rho associated coiled­coil containing protein kinase 1 (ROCK1), myotonic dystrophy­related CDC42­binding kinases α (MRCKα) and phospholipase C γ1 (p­PLCγ1) were also downregulated. This suggests that downstream effectors of the PI3K/PDK1/AKT pathway are targets for inhibition by miR­126­3p. In contrast, apoptotic­related proteins including the BCL­2­associated agonist of cell death (Bad), B­cell lymphoma­extra­large (Bcl­xL) and BCL­2­associated X (Bax), were all upregulated by miR­126­3p, resulting in increased caspase 3/7 activity and apoptosis. Thus, enforced expression of miR­126­3p inhibited cell migration and invasion and also induced apoptosis by regulating the PI3K/PDK1/AKT pathway in HeLa cells. Hence, high levels of miR­126­3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR­126­3p could represent a new approach for treating patients with cervical cancer.

Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions.

Human papillomavirus (HPV) infection can persist in the cervical epithelium without provoking a strong host immune response, leading to the development of cervical cancer. Cytokines, which mediate innate and adaptive immune activities, are secreted in the cervical mucus; however, there is currently no appropriate method for assessing cytokine levels in mucus specimens. Here, we employed multiplexed bead-based immunoassays to examine cytokine levels in cervical mucus using both weighted-volume and total protein concentration methods to adjust for different specimen volumes in individual patients. Out of 18 cytokines initially examined in the primary cohort patient group (n = 28), 14 were detected in more than 10% of the samples. Of these 14 cytokines, expression levels of interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), RANTES, and eotaxin were significantly increased with the disease severity in the secondary cohort patient group (n = 235). We also examined associations between cytokine levels and clinical parameters, such as cytology and HPV genotype. Of the 14 cytokines, granulocyte colony-stimulating factor (G-CSF) was downregulated in HPV-positive specimens. Examination of co-expression patterns of cytokines in relation to HPV infection status revealed that several pairs of cytokines were simultaneously upregulated in HPV-positive cases, including INF-γ and interleukin (IL)-17A, GM-CSF and monocyte chemoattractant protein-1 (MCP-1), GM-CSF and RANTES, IL-17A and RANTES, and MCP-1 and eotaxin. Interestingly, upregulation of GM-CSF and RANTES might reflect a shift in immuno-regulatory cytokines in HPV-positive specimens, potentially associated with more severe cervical neoplasia.

Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia.

microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). The levels of miRNA in the mucus were quantified by miRNA array and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The performance for detecting diseases was statistically analysed. The expression of miRNAs was further validated in the surgical tissues of enrolled patients. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) were significantly up-regulated in SCC and AD compared with normal, and their expression levels correlated with disease severity and high-risk human papillomavirus infection. Receiver operating characteristic curve analyses revealed that the area under the curve values for miR-126-3p, -20b-5p, -451a, and -144-3p were 0.89, 0.90, 0.94, and 0.93, respectively, for SCC plus AD compared with normal, showing high accuracy of cancer detection. Real-time RT-PCR analyses confirmed the expression of these four miRNAs in frozen tissues from cervical cancer. miR-126-3p, -20b-5p, -451a, and -144-3p in cervical mucus are promising biomarkers for cervical cancer and high-grade CINs.

A novel mutation in SLC1A3 causes episodic ataxia.

Episodic ataxias (EAs) are rare channelopathies characterized by recurrent ataxia and vertigo, having eight subtypes. Mutated genes were found in four of these eight subtypes (EA1, EA2, EA5, and EA6). To date, only four missense mutations in the Solute Carrier Family 1 Member 3 gene (SLC1A3) have been reported to cause EA6. SLC1A3 encodes excitatory amino-acid transporter 1, which is a trimeric transmembrane protein responsible for glutamate transport in the synaptic cleft. In this study, we found a novel missense mutation, c.383T>G (p.Met128Arg) in SLC1A3, in an EA patient by whole-exome sequencing. The modeled structural analysis suggested that p.Met128Arg may affect the hydrophobic transmembrane environment and protein function. Analysis of the pathogenicity of all mutations found in SLC1A3 to date using multiple prediction tools showed some advantage of using the Mendelian Clinically Applicable Pathogenicity (M-CAP) score. Various types of SLC1A3 variants, including nonsense mutations and indels, in the ExAC database suggest that the loss-of-function mechanism by SLC1A3 mutations is unlikely in EA6. The current mutation (p.Med128Arg) presumably has a gain-of-function effect as described in a previous report.

Invasive meningococcal disease due to ciprofloxacin-resistant Neisseria meningitidis sequence type 4821: The first case in Japan.

We present a 4-year-old girl who developed invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup C sequence type (ST)-4821. She was hospitalized due to fever, vomiting, rash and altered consciousness. Serogroup C N. meningitidis was isolated from blood culture taken on admission and was confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a biochemical test, and molecular microbiological analysis. The patient was successfully treated with 50 mg/kg ceftriaxone every 12 hours for 7 days without any complications. The isolate was susceptible to a wide variety of ß-lactams and rifampin but was resistant to ciprofloxacin. The isolate harbored gyrA T91I and parC S87I mutations at the quinolone-resistance-determining regions. Multi-locus sequence typing revealed the isolates as ST-4821, which was identical to an endemic clone frequently detected in China. However, neither the patient nor her family members had traveled abroad. To our knowledge, this report is the first to describe an IMD patient caused by ciprofloxacin-resistant N. meningitidis ST-4821 in Japan, and is the first community-acquired IMD case due to this strain outside of China. The high proportion of ciprofloxacin resistance and hypervirulent features of this ST-4821 strain raise special public health concerns. We still consider ciprofloxacin is still appropriate drug for post-exposure chemoprophylaxis in Japan. However, nationwide surveillance for susceptibility of IMD isolates is necessary to establish the regional antibiogram, and thereby to avoid chemoprophylaxis failure.

Long-term follow up of hospitalized pediatric anorexia nervosa restricting type.

BACKGROUND: Information on long-term follow up of childhood-onset anorexia nervosa is scarce. This study investigated long-term (>10 years) course, outcome and prognostic factors for hospitalized childhood-onset anorexia nervosa restricting type (ANR). METHODS: Forty-one ANR girls admitted to a single regional center participated. Median age at first admission was 13.3 years (range, 8.6-15.6 years). The longitudinal clinical course was retrospectively determined for a median follow-up period of 17.1 years (range, 10.4-21.1 years). We analyzed physical, psychological, and social variables to predict partial remission (PR) and full remission (FR). RESULTS: The completion rate of follow up >10 years was high at 97%. At final evaluation (n = 38), distribution of prognosis was as follows: FR, n = 27 (71%); PR, n = 6 (16%); and non-remission, n = 5 (13%). The cumulative ratio of PR and FR increased during the first 5-6 years, and gradually reached a plateau at around 10 years. More than 10 years after the onset, one patient eventually achieved FR, and one patient died. Seven patients were rehospitalized and two died due to suicide during the entire follow up. On multivariate analysis, family disorders/problems rating score was a significant predictor of PR and FR. CONCLUSIONS: This study included hospitalized ANR children aged ≤15 years, the youngest cohort ever reported. Long-term prognosis is generally favorable, but the mortality rate was 5%. Careful long-term follow up >10 years is needed to evaluate outcome of childhood-onset ANR, and family therapy is important in high-risk patients with family disorders/problems.

Neurogenic pulmonary edema combined with febrile seizures in early childhood-A report of two cases.

Neurogenic pulmonary edema (NPE) is a clinical entity that can occur following central nervous system disorders. However, NPE occurs quite rarely in early childhood, and there has only been one report about pediatric NPE associated with febrile seizures. Two cases are reported here. One case involved a 2-year-old girl who presented with febrile seizures, which rapidly progressed to severe NPE. Since the NPE occurred in the emergency department room, the patient was able to be resuscitated via immediate endotracheal intubation. The other case involved an 11-month-old boy who developed respiratory distress following a 50-min episode of febrile status epilepticus. Both patients required respiratory management in the intensive care unit. However their conditions were dramatically improved within several days and fully recovered without any sequelae.

[Invasive Campylobacter jejuni/coli Infections: 9 Case Reports at a Single Center between 2000 and 2015, and a Review of Literature Describing Japanese Patients].

There have been few coherent reports on extraintestinal infection or bacteremia caused by Campylobacter jejuni (C. jejuni) or C. coli in Japan. To clarify the clinical and microbiological characteristics of invasive infections caused by these two species, we retrospectively analyzed the records of patients from whom these pathogens had been isolated from sterile sites between 2000 and 2015. During this study period, we identified 9 patients. The clinical syndrome of all of these patients was bacteremia. Three patients had underlying diseases with both liver cirrhosis and malignant neoplasm, and all of these patients were aged 60 years or older. The remaining 6 patients were immunocompetent and younger than 40 years of age. All 9 patients had a fever of 38.5 degrees C or higher. The proportion of patients with gastrointestinal symptoms was lower for the 3 patients with underlying diseases, compared with the 6 patients without underlying diseases (1/3 cases vs, 4/6 cases). Of the 8 strains evaluated for antimicrobial susceptibility, all were susceptible to imipenem/cilastatin, kanamycin and erythromycin, and 2 were resistant to levofloxacin. Antimicrobial treatment was administered to 8 patients, but one spontaneously recovered without any treatment. We were able to follow the outcomes of 8 patients, and all of these patients completely recovered without relapses. We also reviewed 14 Japanese patients reported in the Japanese and English literature and found similar clinical features consisting of a high-grade fever and an association with underlying diseases and gastrointestinal symptoms. Of note, 3 agammaglobulinemic patients presented with bacteremia and extraintestinal infections and had multiple relapses. Based on the findings of our 9 cases and previous reports, the affected patients were divided into two groups according to clinical syndrome and therapeutic intervention. One group consisted of previously healthy children or young adults showing bacteremia. Most of them had enterocolitis complications but had a good prognosis. The other group consisted of patients with underlying diseases or elderly patients who presented with bacteremia alone or bacteremia with extraintestinal infections. The latter group, especially among those with humoral immunodeficiency, should be parentally treated with antimicrobial agents and requires careful monitoring for relapse. This is the largest case series study to examine invasive C. jejuni/coli infections in Japan, and it provides important epidemiological information on this rare infection.

[Invasive Infections Caused by Nontyphoidal Salmonella sp. in Childhood Clinical Features and Incidence Trends between 1994 and 2014].

Little is known about the clinical characteristics of invasive infections caused by nontyphoidal Salmonella sp. in childhood and the temporal changes of their incidence over a long period of time. In order to clarify these issues, we retrospectively analyzed the records of 17 such infected children admitted between August 1994 and December 2014 to our center. We divided the study period into the first (1994-1999), second (2000-2004), third (2005-2009), and fourth (2010-2014) periods. The ages of the 17 patients ranged from 2 days to 13 years. Clinical syndrome included bacteremia with enteritis (n = 13), followed by bacteremia or sepsis alone, (n = 2), osteomyelitis (n = 1), and meningitis (n = 1). The affected patient numbers in the first to fourth periods were 10, 5, 2, and 0, respectively, and the decreasing trend was significant (trend p < 0.001). This significant trend held up even after correction by the number of in-patients during each quarter period (trend p = 0.009). In the 14 cases of bacteremia with or without enteritis, excluding two neonatal cases and one case of osteomyelitis, most patients (n = 13, 93%) had WBC of <15,000/µL with a wide range of serum CRP levels (0.8-20.4mg/dL) on admission. Thus, it was very difficult to diagnose these bacteremia cases based on blood tests alone, and we needed to consider such risk factors of bacteremia as high fever, poor general condition, and younger age. O group serotypes of the isolates were as follows: O9 (n = 11), O7 (n = 5), and O4 (n = 1). Of the 15 strains evaluated, two strains were resistant to ampicillin and one each was resistant and intermediately resistant to fosfomycin. All strains were susceptible to cefotaxime, ofloxacin or levofloxacin, and trimethoprim-sulfamethoxazole. We were also presented with two rare cases : one involved sepsis due to vertical transmission and the other involved meningitis. The latter case had clinical relevance in that recurrence developed 3 weeks after treatment with susceptible antibiotics. In conclusion, this study is the first report on invasive infections caused by nontyphoidal Salmonella sp. in childhood in Japan, and provides important information on their clinical features and incidence trends over the last 20 years.

Successful treatment with allogenic hematopoietic stem cell transplantation of a severe congenital neutropenia patient harboring a novel ELANE mutation.

We report a 4-year-old boy with severe congenital neutropenia (SCN), who was successfully treated with hematopoietic stem cell transplantation (HSCT). The patient had frequently developed bacterial infections since 6 months of age, and showed severe neutropenia below 100/µl at 1 year and 4 months of age. The patient harbored a heterozygous missense mutation in ELANE exon 3 (p.Q73P, g.2253 A>C). This was a novel de novo mutation, and he was thus diagnosed as having SCN. Because of failure to respond to granulocyte colony-stimulating factor treatment and repeated admissions due to bacterial infections, allogeneic HSCT was performed from a serologically matched unrelated donor following the conditioning regimen: fludarabine/melphalan/anti-thymocyte globulin and a low dose of total body irradiation. Tacrolimus and a short course of methotrexate were used for graft-versus-host disease prophylaxis. Engraftment was achieved at day 12, and the patient maintained normal hematopoiesis for over 15 months after HSCT. We concluded that HSCT is a useful treatment for SCN patients, especially those who are at high risk for leukemic transformation. However, a larger number of SCN patients and longer follow-up are necessary to identify appropriate conditioning regimens and long-term prognosis.

Factors predictive of neonatal thrombocytopenia in pregnant women with immune thrombocytopenia.

To determine predictive factors for neonatal thrombocytopenia in deliveries with immune thrombocytopenia (ITP), we conducted a retrospective study at a tertiary hospital between 1997 and 2013. During this period, 30 women with ITP delivered 44 children. Neonatal thrombocytopenia (<100 × 10(9)/L) at birth was observed in seven neonates; four of these cases were severe (<50 × 10(9)/L). No cases were complicated by intracranial hemorrhage, and there was no neonatal mortality. Platelet counts at birth of neonates born to mothers, who had first been diagnosed with ITP during pregnancy were significantly higher than those born to mothers diagnosed with ITP before pregnancy. There were significant correlations between neonatal platelet counts in the first and second siblings at birth (P = 0.015) and at nadir (P = 0.035). Platelet counts of neonates born vaginally were significantly more likely to decline after birth than those delivered by cesarean section (13/16 vs. 10/23, P = 0.024). In conclusion, diagnosis of ITP before pregnancy was significantly associated with neonatal thrombocytopenia, and the platelet count of an older sibling is a strong predictor for that of the next baby. The delivery mode may be an indicator of the timing of platelet count nadir after birth.