National strategic advocacy to manage patients with inherited bleeding disorders in low and lower-middle income countries.

INTRODUCTION: Inherited bleeding disorders (IBDs) including hemophilia, von Willebrand disease, platelet disorders, mucocutaneous bleeding disorders and coagulation factor deficiencies are rarely found and under-recognized in low and lower-middle-income countries. Some patients succumbed to serious bleeding without diagnosis and treatment during childhood. AREA COVERED: Diagnosis, management, and prevention should be integrated into the existing health care system. Although some countries have not implemented appropriate health care infrastructure, an initiative plan should be set up by cooperation of experienced experts and health care providers. Identification of patients with IBDs should be started in the antenatal setting to search for females at risk of carrier state. The investigations include bleeding assessment, mixing venous clotting time, coagulogram, coagulation factor assay and mutation detection. Genotypic analysis is helpful for confirming the definite diagnosis, carrier detection as well as prenatal diagnosis for females at risk of bearing an offspring with severe bleeding manifestations. Management involves replacement therapy ranging from blood component to virus-inactivated factor concentrate. Appropriate research is an essential backbone for improving patients' care. EXPERT OPINION: Effective national strategic advocacy to manage patients with IBDs requires intensive collaboration among policy makers, health care providers, patients, and family members.

Treatment of obstructive sleep apnea in high risk pregnancy: a multicenter randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) during pregnancy is a risk factor for preeclampsia possibly through a link to placental physiology. This study evaluates the efficacy of continuous positive airway pressure (CPAP) on the modulation of blood pressure and the reduction in preeclampsia in women with high-risk pregnancy and OSA. METHODS: A multicenter open-label, randomized controlled trial comparing CPAP treatment versus usual antenatal care was conducted in three academic hospitals in Bangkok, Thailand. Participants included singleton pregnant women aged older than 18 years with any high-risk condition (i.e., chronic hypertension, obesity, history of preeclampsia or gestational diabetes in the previous pregnancy, or diabetes), and OSA (respiratory disturbance index 5-29.99 events/hour by polysomnography), who presented either in the first trimester (gestational age, GA 0-16 weeks) or subsequently developed OSA during the 2nd trimester (GA 24-28 weeks). The primary endpoint was blood pressure during antenatal care. Secondary endpoints included the incidence of preeclampsia. An intention-to-treat analysis was performed with additional per-protocol and counterfactual analyses for handling of nonadherence. RESULTS: Of 340 participants, 96.5% were recruited during the first trimester. Thirty participants were later excluded leaving 153 and 157 participants in the CPAP and usual-care groups for the modified-intention-to-treat analysis. CPAP adherence rate was 32.7% with average use of 2.5 h/night. Overall, CPAP treatment significantly lowered diastolic blood pressure (DBP) by - 2.2 mmHg [95% CI (- 3.9, - 0.4), p = 0.014], representing approximately - 0.5 mmHg per hour of CPAP use [95%CI (- 0.89, - 0.10), p = 0.013]. CPAP treatment also altered the blood pressure trajectory by continuously lowering DBP throughout pregnancy with mean differences (95% CI) of - 3.09 (- 5.34, - 0.93), - 3.49 (- 5.67, - 1.31) and - 3.03 (- 5.20, - 0.85) mmHg at GA 18-20, 24-28, and 32-34 weeks, respectively compared to 0-16 weeks. Preeclampsia rate was 13.1% (20/153 participants) in the CPAP and 22.3% (35/157 participants) in the usual-care group with a risk difference (95% CI) of - 9% (- 18%, - 1%, p-value = 0.032) and a number-needed-to-treat (95% CI) of 11 (1, 21). CONCLUSIONS: CPAP treatment in women with even mild-to-moderate OSA and high-risk pregnancy demonstrated reductions in both DBP and the incidence of preeclampsia. CPAP treatment also demonstrated a sustained reduction in DBP throughout gestation. Trial registration ClinicalTrial.GovNCT03356106, retrospectively registered November 29, 2017.

The Correlation Between Three-Dimensional Ultrasound Measurement of Fetal Adrenal Gland and Maternal Serum Fructosamine Level in Gestational Diabetes Mellitus: Prospective Cohort Study.

Objective: Gestational diabetes mellitus (GDM) has an impact on fetal adrenal gland size and volume, which are greater in the GDM population. This study used 2D and 3D ultrasound scanning to determine the correlation of fetal adrenal gland size and volume with fructosamine levels, HbA1c levels, estimated fetal weight (EFW), and neonatal birth weight in GDM patients. Methods: This study included eighty singleton pregnant women diagnosed with GDM between 24-28 weeks of gestation. During weeks 32-34 of gestation, the length, width, and depth of the fetal zone and total adrenal gland were measured using transabdominal 2D ultrasound. Virtual organ computer-aided analysis (VOCAL) software was used to evaluate fetal zone and total adrenal gland volume in 3D ultrasound. All the participants were followed until delivery. Pearson's correlation analysis was conducted to examine the correlation between fetal adrenal gland ultrasound measurements and the factors of interest. Results: The study consisted of sixty-six (82.5%) pregnant women with diet-controlled GDM (GDMA1) and fourteen (17.5%) pregnant women with insulin-managed GDM (GDMA2). There was no difference in fetal adrenal gland measurements between the diet-controlled (GDMA1) and the insulin-managed (GDMA2) groups. All the participants had achieved optimal glucose levels at the time of ultrasound acquisition. The total adrenal gland length and fetal zone volume had statistically significant positive correlations with EFW (r = 0.69, p = 0.02 and r = 0.84, p = 0.01, respectively). After adjusting for EFW, only the fetal zone volume was significantly correlated with fructosamine levels (adjusted-OR = 2.4, 95% CI: 1.5, 3.9, p = 0.01) and HbA1c levels (adjusted-OR = 2.5, 95% CI: 1.6, 4.3, p = 0.01). Conclusion: The fetal zone volume is correlated with EFW, fructosamine levels, and HbA1c levels. This non-invasive technique may be beneficial as an indirect marker for glycemic monitoring in GDM.

A Comparison of Shear Wave Elastography between Normal Myometrium, Uterine Fibroids, and Adenomyosis: A Cross-Sectional Study.

BACKGROUND: The differential diagnosis between uterine fibroid and adenomyosis is sometimes difficult; a precise diagnosis is required in women with infertility because of the different choice of treatments. Ultrasound elastography (UE) is a novel technique to evaluate the elasticity or the stiffness of the tissue of interest. The present study aims to compare UE shear wave velocity (SWV) among normal uterine myometrium, uterine fibroid, and adenomyosis, and assess the accuracy of shear wave elastography in the diagnosis of adenomyosis. MATERIALS AND METHODS: This cross-sectional study recruited 25 subjects for each group (control, adenomyosis, and fibroid) from April 2019 to April 2020. Transvaginal UE using an Aplio 500 (Toshiba Medical Systems, Japan) with ultrasound mapping for point of tissue biopsy was performed for all subjects. The diagnosis was confirmed by histology. Masson's trichrome staining for collagen was performed and quantified. RESULTS: The mean ± standard deviation (SD) for SWV was 3.44 ± 0.95 m/seconds (control group), 4.63 ± 1.45 m/ seconds (adenomyosis group), and 4.53 ± 1.07 m/seconds (fibroid group). The mean SWV differed when comparing normal myometrium and adenomyosis after adjustments for age and endometrial pathology (P=0.019). The cut-off point of SWV at 3.465 m/seconds could differentiate adenomyosis from the normal uterus with an 80% sensitivity, 80% specificity, and an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.68-0.93) (P<0.001). No significant difference in SWV between the adenomyosis and fibroid groups was detected. CONCLUSION: Shear wave elastography could be an alternative tool to distinguish between normal myometrium and adenomyosis; however, it could not differentiate adenomyosis from uterine fibroid or uterine fibroid from normal myometrium.

Feasibility and learning curve of performing first trimester fetal anatomy screening among operators with varying experience using the protocol of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG).

OBJECTIVE: To compare the feasibility of performing a complete first trimester fetal anatomy screening between two operators with different levels of experience using the protocol of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), and to compare the duration of scan and learning curve of each operator as secondary outcomes. METHODS: A prospective study was conducted on singleton pregnancies at 11+0-13+6 weeks of gestation. Transabdominal ultrasound anatomy screening was performed by a maternal fetal medicine (MFM) staff (operator 1) or a first year MFM fellow (operator 2) following ISUOG guidelines. The visibility of fetal structures and time taken by each operator were recorded and analyzed. RESULTS: Data from 98 participants in operator 1 group and 96 participants in operator 2 group were analyzed. The success rate of visualizing all structures was feasible in 87.8% and 91.7% (p = .370) of cases in operator 1 and operator 2, respectively. The significant improvement in visualization success rate was observed between the first 50 and the last 50 scans in both groups (p = .004 vs. p = .006). Average time spent on the exam by operator 1 was significantly shorter than the time spent by operator 2 (11.3 ± 4.8 min vs. 15.0 ± 6.2 min; p < .001). CONCLUSION: Completeness of first trimester fetal anatomy screening following ISUOG protocol were feasible with no statistical difference between the two different levels of experienced operators. Moreover, time allocatable with a brief learning curve were demonstrated in both groups.

Calcium Consumption During Pregnancy: A Multicenter Study in a Middle-Income Country in Southeast Asia.

OBJECTIVE: To perform a cross-sectional observational study of calcium consumption among pregnant women from multicenter tertiary care hospitals in the middle-income country in Southeast Asia. STUDY DESIGN: A cross-sectional observational study. SETTING: The study was conducted in four geographical regions (northern, northeastern, southern, and central) of Thailand. Five participating hospitals consisted of one university hospital in each region and one additional tertiary care hospital in the central region. MATERIALS AND METHODS: A cross-sectional study was performed nationwide from 1st November 2017 to 31st January 2019. All singleton aged 19-40 years were included. Exclusion criteria were any conditions that influenced calcium-containing food consumption. Dietary intake self-records immediately after eating for two working days and one holiday were analyzed via INMUCAL-NV3.0 dietary program. RESULTS: The 1549 records were obtained. The mean age was 29 ± 5.7 years. Most participants were primigravida (48.6%). The average gestational age was 20.6 ± 8.8 weeks. Mean calcium consumption was 602.4 mg/day (95% CI; 589.2615.6 mg/day) mg/dL. Inadequate calcium consumption prevalence based on the Thai dietary reference intake (less than 800 mg/day) and US Institute of Medicine (less than 1000 mg/day) were 82.0% and 93.4%, respectively. CONCLUSION: The mean calcium consumption among pregnant women in the middle-income country in Southeast Asia was 602.4 mg/day (95% CI 589.2-615.6 mg/day). Inadequate calcium consumption of Thai pregnant women prevalence was 82.0% and 93.4% according to Thai dietary reference intake in pregnancy and the US Institute of Medicine.

The Comparative Study of Cervical Shear Wave Elastography Between Twin and Singleton Pregnancy.

OBJECTIVE: To compare the cervical shear wave elastography (SWE) by using transvaginal ultrasound (TVS) between twin and singleton pregnant women. MATERIALS AND METHODS: This was a prospective cohort study involving the twin and singleton pregnant women who attended the antenatal care at Ramathibodi Hospital, Bangkok, Thailand. The participants who met the inclusion criteria were serially measured the shear wave speed (SWS) by using TVS at early, mid-, and third trimester. The changes in SWS with advancing gestational age between twin and singleton pregnancies were evaluated. The gestational age at delivery and spontaneous preterm delivery rate were also analyzed. RESULTS: A total of 36 twin pregnancies and 38 singleton pregnancies were analyzed. No significant difference in baseline characteristics, except the age of participants (twin pregnancies 33.1±4.6 years, singleton pregnancies 29.9±5.4 years, p-value = 0.006) was observed. The cervical SWS decreased with advancing gestational age in both twin and singleton pregnancy, but there was a statistically significant difference of cervical SWS at the lower point in mid-trimester (twin pregnancies 2.27±0.4, singleton pregnancies 2.71±0.6 m/s, p-value = 0.001). However, no significant difference in cervical SWS at the upper point and the lower point in the early and third trimester was demonstrated. Even though the gestational age at delivery between both groups revealed a significant difference (twin pregnancies 35.9±2.8, singleton pregnancies 37.6±2.9 wk., p-value = 0.008) but the spontaneous preterm delivery rate did not differ significantly (twin pregnancies 22.2%, singleton pregnancies 15.8%, p-value = 0.483). CONCLUSION: The mid-trimester cervical SWS measurement at the lower point detects the difference in cervical softness between twin pregnancies and singleton pregnancies. The cervical SWS might be an additional option for monitoring the change in cervical softness in twin pregnancies.

The Effect of Umbilical Cord Milking Compared with Delayed Cord Clamping in Term Neonates: A Randomized Controlled Trial.

OBJECTIVE: To study the effect of intact umbilical cord milking (I-UCM) procedure in comparison with the procedure of delayed cord clamping (DCC) in term neonates. STUDY DESIGN: A randomized controlled trial. SETTING: Department of Obstetrics and Gynecology and Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University. MATERIALS AND METHODS: The study was performed from June 2017 to March 2018. Singleton term pregnant women (37-42 weeks' gestation) were recruited. Neonates were randomized into DCC and I-UCM groups. Umbilical cord was 3 times milked toward the neonate in 25 cm length from umbilical stump which was still attached to the placenta before cutting the cord in I-UCM group. Delay in cord clamping for 60 seconds was performed before the cord cutting in DCC group. Neonatal and maternal outcomes were recorded. RESULTS: Of 168 neonates included in this trial, 84 cases were randomized into each group. The baseline characteristics of both groups were comparable. No statistical difference was found in terms of the mean of hemoglobin levels in the DCC and I-UCM groups which were 16.9 (±1.6) g/dl and 17.0 (±1.9) g/dl, respectively (P-value 0.75). There was no difference in terms of adverse neonatal and maternal outcomes in both groups. CONCLUSION: Both I-UCM and DCC revealed a comparable effect on hematologic status without deleterious effects on neonatal and maternal outcomes at the age of 48-72 hours in term neonates.

Effects of probiotic supplements on insulin resistance in gestational diabetes mellitus: A double-blind randomized controlled trial.

AIMS/INTRODUCTION: To evaluate the effect of probiotic supplements on insulin resistance in pregnant women with diet-controlled gestational diabetes mellitus. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was carried out between June 2016 and February 2017. Pregnant women with diet-controlled gestational diabetes mellitus were enrolled in the study at 24-28 weeks-of-gestation and randomized to receive either probiotic supplements containing Bifidobacterium and Lactobacillus or a placebo daily for four consecutive weeks. Primary outcomes were mean differences in insulin resistance (homeostatic model assessment for insulin resistance), fasting insulin and fasting plasma glucose between the two groups. Secondary outcomes were changes in maternal weight after the intervention. RESULTS: Data from 28 patients in the probiotic group and 29 in the placebo group were analyzed. The changes in metabolic parameters after randomization showed significant improvement in glucose metabolism in the probiotic group compared with the placebo group, including fasting plasma glucose (0.68 ± 5.88 vs 4.620 ± 7.78 mg/dL, mean difference -3.94 mg/dL, 95% confidence interval -7.62, -0.27, P = 0.034), fasting plasma insulin (1.11 ± 1.71 vs 3.77 ± 1.70 mIU/L, mean difference -2.67 mIU/L, 95% confidence interval -3.57, -1.76, P = 0.001) and homeostatic model assessment for insulin resistance (0.25 ± 0.37 vs 0.89 ± 0.46, mean difference -0.63, 95% confidence interval -0.86, -0.41, P = 0.001). Weight gain during randomization was similar between the two groups. CONCLUSIONS: Four weeks of probiotic supplements in women with diet-controlled gestational diabetes in the late second and early third trimester lowered fasting glucose and increased insulin sensitivity. Probiotic supplements may be considered as an adjunct treatment for glycemic control in these patients.

A Randomized Controlled Trial of Immediate versus Delayed Umbilical Cord Clamping in Multiple-Birth Infants Born Preterm.

BACKGROUND: Delayed cord clamping (DCC) improves placental transfusion and increases blood volume in preterm infants when compared with immediate cord clamping (ICC). However, evidence to support DCC in multiple-birth preterm infants is still lacking. OBJECTIVE: To compare the outcomes of ICC versus DCC in preterm infants of multiple births. STUDY DESIGN: Women with a multiple pregnancy, including twins and triplets with a gestational age of 28-36 weeks, were randomized to receive ICC (23 women and 50 infants) or DCC for 30-60 s (24 and 51 infants). The infants' hematocrit on admission, superior vena cava (SVC) flow measured within 24 h, and hematocrit at 8 weeks of age were compared. The use of uterotonic agents during delivery was not controlled in this study. RESULT: All infants were delivered by cesarean section (CS) except for 2 sets of twins, 1 in each group. Maternal and infant baseline characteristics in both groups were comparable. There were no significant differences between the groups in admission hematocrit, SVC flow measured within 24 h, hematocrit at 8 weeks of age, or any other neonatal outcomes. The incidence of maternal postpartum hemorrhage (PPH) was higher in the DCC group (4.3% in ICC vs. 25% in DCC, p = 0.04). CONCLUSION: DCC for 30-60 s did not improve placental transfusion or increase systemic blood flow in multiple-birth infants born preterm, mostly by CS, when compared with ICC. The finding of a higher PPH rate in the DCC group raises concerns about the maternal safety of this procedure in this patient population.

Continuous Positive Airway Pressure Therapy in Gestational Diabetes With Obstructive Sleep Apnea: A Randomized Controlled Trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with gestational diabetes mellitus (GDM). This study assessed the effects of continuous positive airway pressure (CPAP) in obese pregnant females with GDM and OSA. METHODS: A randomized controlled trial was conducted (April 2014 - June 2016). Obese females at 24 to 34 weeks gestation and with diet-controlled GDM were screened for OSA. Those with OSA were randomly assigned to receive 2 weeks nightly CPAP or be part of a waitlist control group. After 2 weeks, all patients were offered CPAP. The primary outcome was glucose metabolism, obtained from an oral meal tolerance test (MTT) at baseline and 2 weeks. Pregnancy outcomes were collected. RESULTS: Eighteen patients were randomized to CPAP and 18 to control groups. There were no significant changes between groups in fasting glucose, glucose response to MTT, and insulin sensitivity or secretion after 2 weeks. Those adherent to CPAP had significantly improved insulin secretion (P = .016) compared to the control group. When a counterfactual instrumental variable approach was applied to deal with nonadherence, the CPAP group had significantly improved insulin secretion (P = .002) and insulin sensitivity (P = .015). Lower rates of preterm delivery (P = .002), unplanned cesarean section (P = .005), and neonatal intensive care unit admissions (P < .001) were observed among those who used CPAP longer than 2 weeks. CONCLUSIONS: Two weeks of CPAP in females with GDM and OSA did not result in improved glucose levels, but insulin secretion improved in those adherent to CPAP. Continued CPAP use was possibly associated with improved pregnancy outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea and Gestational Diabetes: Incidence and Effects of Continuous Positive Airway Pressure Treatment on Glucose Metabolism; Identifier: NCT02108197; URL: https://clinicaltrials.gov/ct2/show/NCT02108197.

Obstructive sleep apnea and diet-controlled gestational diabetes.

BACKGROUND: Obstructive sleep apnea (OSA) was shown to be associated with gestational diabetes mellitus (GDM). However, prevalence of OSA in GDM women, its relationship to metabolic control, and predictive factors have not been studied. MATERIAL AND METHODS: Eighty-two obese pregnant women with diet-controlled GDM between 24 and 34 weeks of gestation participated. The Berlin questionnaire was used to assess OSA symptoms. OSA was diagnosed using an overnight monitor. Fasting glucose and hemoglobin A1c (HbA1c) were obtained. Those with OSA underwent meal tolerance test (MTT) to assess their metabolic parameters. Classification tree analysis was used to develop a screening tool for OSA. RESULTS: At a median gestational age of 29 weeks, OSA was diagnosed in 52.4% of the women, with a median apnea hypopnea index of 9.4 (interquartile range 6.4, 12.4). More severe OSA was significantly correlated with higher fasting glucose but not HbA1c. For those with OSA, sleep parameters related to oxygen desaturation significantly correlated with higher fasting insulin resistance and more severe ß-cell dysfunction, as evaluated by MTT. A screening tool involving two variables, neck circumference and Berlin Questionnaire score, was developed. The sensitivity and specificity were 86% and 51%, respectively. The overall accuracy was 70%. CONCLUSION: OSA is prevalent in obese pregnant women with diet-controlled GDM in the late second to early third trimester. OSA severity, especially the degree of oxygen desaturation, correlated with fasting glucose, insulin resistance, and ß-cell function. A simple screening tool involving the Berlin Questionnaire and neck circumference can aid in predicting OSA in this patient group.

A novel in vitro model reveals distinctive modulatory roles of Plasmodium falciparum and Plasmodium vivax on naïve cell-mediated immunity.

BACKGROUND: To date, human peripheral blood mononuclear cells (PBMCs) have been used mainly in immune stimulation assays and the interpretation of data can be influenced by the previous immunological history of donors and cross reactivity with other infectious agents. Resolving these limitations requires an alternative in vitro model to uncover the primary response profiles. METHODS: A novel in vitro model of mononuclear cells (MNCs) generated from haematopoietic stem cells (HSCs) was developed and these cells were then co-cultured with various antigens from Plasmodium falciparum and Plasmodium vivax to investigate the response of naïve immune cells to malaria antigens by flow cytometry. RESULTS: In vitro stimulation of naïve lymphocytes showed that CD4+ and CD8+ T lymphocytes were significantly reduced (P < 0.01) by exposure to lysates of infected erythrocytes or intact erythrocytes infected with P. falciparum. The depletion was associated with the expression of CD95 (Fas receptor) on the surface of T lymphocytes. Maturation of T lymphocytes was affected differently, showing elevated CD3+CD4+CD8+ and CD3+CD4-CD8- T lymphocytes after stimulation with cell lysates of P. falciparum and P. vivax, respectively. In addition, antigen presenting monocytes and dendritic cells derived from haematopoietic stem cells showed impaired HLA-DR expression as a consequence of exposure to different species of malaria parasites. CONCLUSION: These results suggest that naïve mononuclear cells differentiated in vitro from HSCs could provide a valid model for the assessment of immunity. P. falciparum and P. vivax malaria parasites could modulate various populations of immune cells starting from newly differentiated mononuclear cells.

Sonographic measurement of fetal thymus size in uncomplicated singleton pregnancies.

PURPOSE: To establish sonographic reference ranges of the normal fetal thymus size between 17 and 38 weeks of gestational age (GA). METHODS: The study was conducted between April 1 and December 31, 2013. Low-risk singleton pregnancies without obstetrical and medical complications at the GAs between 17 and 38 weeks were recruited for thymus measurement. The fetal thymus was identified on transabdominal sonography at the three-vessel view. Maximal transverse diameter, perimeter, and thymus/thoracic ratio were measured. The best-fit models in predicting thymic dimensions as a function of GA and biparietal diameter (BPD) were determined using regression analysis, and percentile charts for predicting thymic dimensions were constructed. RESULTS: A total of 296 singleton pregnancies were recruited in this study. Maximal transverse diameter, perimeter, and thymus/thoracic ratio increased throughout pregnancy. The regression equation for maximal transverse diameter of the thymus as a function of GA was as follows: Predicted mean thymus diameter (mm) = -25.904 + 2.476 × GA - 0.019 × GA2 (r = 0.915; p < 0.001) with predicted standard deviations of thymus diameter (mm) = 1.428 + 0.044 × GA (r = 0.017; p < 0.001). CONCLUSIONS: Sonographic reference ranges of the normal fetal thymic dimensions between 17 and 38 weeks of GA have been established. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:150-159, 2017.

Performance of screening questionnaires for obstructive sleep apnea during pregnancy: A systematic review and meta-analysis.

This review aims to evaluate the performance of obstructive sleep apnea (OSA) screening questionnaires during pregnancy. A systematic review and meta-analysis was performed using MEDLINE Scopus, CINAHL, and the Cochrane library. A bivariate meta-analysis was applied for pooling of diagnostic parameters. Six of the total 4719 articles met the inclusion criteria. The Berlin questionnaire (BQ, N = 604) and Epworth sleepiness scale (ESS, N = 420) were the most frequently used screening tools during pregnancy. The pooled prevalence of OSA during pregnancy was 26.7% (95%CI: 16.9%, 34.4%, I2 = 83.15%). BQ performance was poor to fair with pooled sensitivity and specificity of 0.66 (95%CI: 0.45, 0.83; I2 = 78.65%) and 0.62 (95%CI: 0.48, 0.75; I2 = 81.55%), respectively. BQ performance was heterogeneous depending on type of reference test and pregnancy. Sensitivity increased if diagnosis was based on polysomnography (0.90), and respiratory disturbance index (0.90). However, sensitivity decreased if screening was performed in early pregnancy (≤20 weeks gestation: 0.47), and high-risk pregnancy (0.44). Performance of ESS was poor with pooled sensitivity and specificity of 0.44 (95%CI: 0.33, 0.56; I2 = 32.8%) and 0.62 (95%CI: 0.48, 0.75; I2 = 81.55%), respectively. In conclusion, BQ and ESS showed poor performance during pregnancy, hence a new OSA screening questionnaire is needed. Registration: PROSPERO registration CRD42015025848.

Screening of obstructive sleep apnea during pregnancy: differences in predictive values of questionnaires across trimesters.

STUDY OBJECTIVES: Evaluation of Berlin and Stop-Bang questionnaires in detecting obstructive sleep apnea (OSA) across trimesters of pregnancy. METHODS: Pregnant women from a high-risk pregnancy clinic were recruited to complete sleep evaluations including Berlin and Stop-Bang Questionnaires. Overnight testing with Watch-PAT200 for diagnosis of OSA (cutoff point of apnea-hypopnea index ≥5 events/h) was performed. RESULTS: Seventy-two singleton pregnant women participated in the study. Enrollment consisted of 23, 24, and 25 women during first, second, and third trimesters, respectively. Of 72 pregnancies, 23 patients (31.9%) had OSA. Prevalence of OSA classified by trimesters from first to third was 30.4%, 33.33%, and 32.0%, respectively. Overall predictive values of Berlin and Stop-Bang questionnaires were fair (ROC area under curve, AUC 0.72 for Berlin, p = 0.003; 0.75 for Stop-Bang, p = 0.001). When categorized according to trimesters, predictive values substantially improved in second (AUC: 0.84 for Berlin; 0.78 for Stop-Bang) and third trimesters (AUC: 0.81 for Berlin; 0.75 for Stop-Bang), whereas performances of both questionnaires during first trimester were poorer (AUC: 0.49 for Berlin; 0.71 for Stop-Bang). Multivariate analyses show that pre-pregnancy body mass index (BMI) in first trimester, snore often in second trimester, and weight gain and pregnancy BMI in third trimester were significantly associated with OSA. CONCLUSIONS: In high-risk pregnancy, Berlin and Stop-Bang questionnaires were of limited usefulness in the first trimester. However their predictive values are acceptable as pregnancy progresses, particularly in second trimester. OSA in pregnancy seems to be a dynamic process with different predictors association during each trimester.

Normal reference of cervical blood perfusion in pregnancy.

OBJECTIVE: To develop normal reference of cervical blood perfusion in pregnancy by using 3D power Doppler-derived FMBV at 16 to 24 weeks gestation. MATERIAL AND METHOD: The present prospective cohort study recruited the normal singleton pregnant women at 16 to 24 weeks gestation who had antenatal care and midtrimester ultrasound screening at Ramathibodi Hospital between June and September 2012. Transvaginal ultrasound (TVU) measurements of cervical length (CL), cervical volume (CV), vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were performed. The pregnant women with multifetuses, severe fetal anomalies, unknown delivery status, abortion, stillbirth, and preterm birth were excluded from the present study. RESULTS: The authors recruited 168 cases but 25 cases were excluded. Only 143 cases were included into the study. The mean of gestational age at ultrasound examination and delivery was 21 and 39 weeks respectively. There were no perinatal morbidity and mortality in the present study. The average values of cervical profiles of CL, CV VI, FI, and VFI were 4.2 cm, 31.6 cm3, 6.4, 38.9, and 2.6 respectively. CONCLUSION: The normal reference of cervical blood perfusion in Thai pregnant women was established. The VI, FI, and VFI of the normal term singleton pregnancy at 16 to 24 weeks gestation were 6.4, 38.9, and 2.6 respectively.

Suppression of erythroid development in vitro by Plasmodium vivax.

BACKGROUND: Severe anaemia due to dyserythropoiesis has been documented in patients infected with Plasmodium vivax, however the mechanism responsible for anaemia in vivax malaria is poorly understood. In order to better understand the role of P. vivax infection in anaemia the inhibition of erythropoiesis using haematopoietic stem cells was investigated. METHODS: Haematopoietic stem cells/CD34+ cells, isolated from normal human cord blood were used to generate growing erythroid cells. Exposure of CD34+ cells and growing erythroid cells to P. vivax parasites either from intact or lysed infected erythrocytes (IE) was examined for the effect on inhibition of cell development compared with untreated controls. RESULTS: Both lysed and intact infected erythrocytes significantly inhibited erythroid growth. The reduction of erythroid growth did not differ significantly between exposure to intact and lysed IE and the mean growth relative to unexposed controls was 59.4 ± 5.2 for lysed IE and 57 ± 8.5% for intact IE. Interestingly, CD34+ cells/erythroid progenitor cells were susceptible to the inhibitory effect of P. vivax on cell expansion. Exposure to P. vivax also inhibited erythroid development, as determined by the reduced expression of glycophorin A (28.1%) and CD 71 (43.9%). Moreover, vivax parasites perturbed the division of erythroid cells, as measured by the Cytokinesis Block Proliferation Index, which was reduced to 1.35 ± 0.05 (P-value<0.01) from a value of 2.08 ± 0.07 in controls. Neither TNF-a nor IFN-g was detected in the culture medium of erythroid cells treated with P. vivax, indicating that impaired erythropoiesis was independent of these cytokines. CONCLUSIONS: This study shows for the first time that P. vivax parasites inhibit erythroid development leading to ineffective erythropoiesis and highlights the potential of P. vivax to cause severe anaemia.

Inhibin-A levels between 14 and 20 weeks of gestation in Thai women.

AIM: To construct a normal value for inhibin-A concentrations at 14-20 weeks of gestation for a Thai population. MATERIAL AND METHODS: Inhibin-A concentrations from pregnant women without Down's syndrome at 14-20(+6) weeks of gestation were measured. Maternal serum inhibin-A levels were analyzed according to the gestational age. RESULTS: Serum specimens from 727 Thai women were analyzed. Inhibin-A levels decreased from 14 to 17(+4) weeks and then gradually rose thereafter, giving a U-shape pattern. CONCLUSION: The data of inhibin-A concentration at 14-20 weeks of gestation for normal Thai pregnant women fitted well with quadratic regression.