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Background & Objectives: Alpha-thalassaemias are genetic disorders with high prevalence in northern Thailand. However, common genotypes and current data on the prevalence of α-thalassaemias have not been reported in this region. Therefore, the objective of the present study was to determine the prevalence of α-thalassaemia genotypes in pregnant women in northern Thailand., Methods: Genomic DNA was extracted from blood samples of pregnant women who came to Maharaj Nakorn Chiang Mai University Hospital during July 2009 to 2010. The common deletion and point mutation genotypes of α-thalassaemia were evaluated by gap- polymerase chain reaction (PCR) and PCR with restriction fragment length polymorphism (RFLP)., Results: Genotypes of 638 pregnant women were: 409 samples (64.11%) being normal subjects (αα/αα) and 229 samples (35.89%) with α-thalassaemias. these 229 samples could be classified into deletional HbH disease (--SEA/-α3.7) for 18 samples (2.82%); heterozygous α0-thalassaemia --SEA type (--SEA/αα)) for 78 (12.23%); heterozygous α+-thalassaemia - α3.7 type (-α3.7/αα) for 99 (15.52%); homozygous α+-thalassaemia - α3.7 type (-α3.7/- α3.7) for five (0.78%); heterozygous α+-thalassaemia - α4.2 type (-α4.2/αα) for two (0.31%); and heterozygous HbCS (αCSα/αα) for 27 (4.23%) cases., Interpretation & Conclusions: The prevalence of α-thalassaemias in pregnant women in northern Thailand was high. This finding supports the implementation of the prevention and control of this common genetic disorder by screening for α-thalassaemia genotypes.

Objective: To compare pregnancy outcomes of women with chronic HBV infection with those of HBV-negative women., Methods: A retrospective cohort study was undertaken to analyze singleton pregnancies of women without medical/surgical disease and with known HBsAg status. Pregnancy outcome measures were compared among the control group, women with positive HBsAg status (case group), and those with positive HBeAg status., Results: Among 26 350 enrolled pregnant women, 21 812 in the control group and 1446 in the case group were compared. Only the proportion of preterm births was significantly higher among pregnancies with positive HBsAg status (RR 1.013 [95% CI, 1.001-1.025]). Among women with positive HBsAg status who had been screened for HBeAg, GDM was significantly higher among women with positive HBeAg status (RR 1.434 [95% CI, 0.999-2.057]). Preterm births and low birth weight were also significantly higher among women with positive HBeAg status (RR 1.250 [95% CI, 1.000-1.563] and 1.258 [95% CI, 1.053-1.505], respectively)., Conclusion: Chronic carriers of HBV had a minimally increased risk of preterm birth and low birth weight but the risk was more pronounced in women with positive HBeAg status. Women with positive HBeAg status also had an increased risk of GDM., (Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of the research was to determine effectiveness of the model for prenatal control in reducing new cases of severe thalassemia., Methods: Pregnant women at six tertiary centers were recruited to follow the model, consisting of (1) carrier screening using mean corpuscular volume (for alpha-thal-1 and beta-thal) and CMU-E screen (for HbE trait), (2) carrier diagnosis, (3) the couples at risk were counseled and offered prenatal diagnosis, and (4) termination of affected pregnancy. All neonates were evaluated for thalassemia., Results: Of the 12,874 recruited pregnancies, 7008 were valid for analysis. Of them, 281 couples were identified to be at risk, Of the 281, 58 affected fetuses were identified and 55 pregnancies were terminated, whereas three did not accept pregnancy termination. All 6727 neonates at no risk were proven to be unaffected. The model had sensitivity and positive predictive value of 100% and 20%, respectively. The model could detect all of affected fetuses., Conclusion: The model could prenatally identify affected fetuses with a detection rate and negative predictive value of 100%. The model was highly effective to prenatally detect affected fetuses with an acceptable false positive rate., (© 2013 John Wiley & Sons, Ltd.)

Background: The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown., Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6-12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcg·hr(-1)·mL(-1)) and a trough concentration of 1 mcg/mL., Results: Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9-42.9) years, weight 69.0 (40-130) kg, and gestational age 32.9 (30.1-38.7) weeks. Median (range) EFV AUC(0-24), C(max), and C(24 hours) were 55.4 mcg·hr(-1)·mL(-1) (13.5-220.3), 5.4 mcg/mL (1.9-12.2), and 1.6 mcg/mL (0.23-8.13), respectively. EFV AUC and C(max) did not differ during pregnancy and postpartum but C(24 hours) was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37-0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported., Conclusions: Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy.

Objective: To assess the outcomes of pregnancies complicated by systemic lupus erythematosus (SLE) and evaluate the clinical course of the disease during pregnancy., Material and Method: The database of high-risk pregnancies between 1995 and 2006 was prospectively collected and searched for pregnancies with SLE. The medical records were reviewed, Results: Sixty-eight pregnant women were identified during the period of the present study. Of 61 (89.7%) live births, 27 (39.7%) had preterm delivery and 20 (29.4%) had fetal growth restriction. Mean gestational age was 35.6 +/- 4.2 weeks. Mean neonatal birth weight was 2322 +/- 781 grams. There were seven (10.3%) perinatal deaths. Maternal SLE flares occurred in 20 (29.4%), seven in the first trimester, eight in the second trimester five in the third trimester, and none in the post partum period. Preeclampsia is the most common maternal complication (20.6%). There was a higher rate of flares if the pregnancy occurred while the disease was active. The predictor of poor pregnancies outcomes included flare-up of the disease, renal involvement, hypertension, and conception while the disease is active., Conclusion: Active SLE prior to pregnancy is associated with a less favorable maternal and fetal outcome. Hypertension increased the risk of fetal loss and adverse outcome.

Antiretroviral treatment with zidovudine (ZDV) from the 14th week until the end of pregnancy has markedly reduced the vertical transmission rate of HIV-1 in Europe and North America. A shorter duration of treatment has reduced this rate in Africa and Southeast Asia to a lesser degree. In Southeast Asia, subtype E is the major subtype rather than subtype B as in Western countries. The goals of this study were to determine the optimal duration of ZDV prophylaxis for subtype E and to confirm its effectiveness at the histologic level. Fifty pregnant women seropositive for HIV-1 subtype E were given ZDV prophylaxis consisting of 300 mg administered twice daily, switching to 300 mg administered every 3 hours from the onset of labor until delivery. Twenty-seven received "short-term" ZDV lasting 14 to 35 days before delivery, whereas the other 23 received "long-term" ZDV lasting 62 to 92 days. The effectiveness of ZDV prophylaxis was assessed by detection of HIV-1 in the placenta using in situ polymerase chain reaction (PCR). All babies in this study were tested up to one year of age. Three were not positive until after one month of age, but one was positive as a neonate. Four neonates were positive for HIV-1 as detected by PCR on peripheral blood, including one in the neonatal period. All cases were from the short-term prophylaxis group. Decidual glandular epithelial cells were the only cell type in the placenta that expressed HIV proviral DNA under ZDV prophylaxis. Sixty-seven percent of placentas in the short-term ZDV group showed more than occasional positive cells compared with 22% in the group receiving long-term ZDV prophylaxis (P < 0.02). This is first study to compare the effectiveness of short-term and long-term ZDV prophylaxis with respect to the presence of HIV in the placenta. Our study shows that longer (at least 60 days) prophylaxis is more effective in reducing HIV expression in the placenta and is associated with reduced transmission to neonates.

The frequency and the cellular basis for HIV-1 transmission from mother to child in the early gestational period are poorly understood. We compared the placentas of 24 women seropositive for HIV-1 subtype E and who had not received any antiretroviral drugs, to placentas of 25 seronegative women. All placentas were obtained during therapeutic abortion at 6-23 weeks gestation. Placentas and fetal organs were examined by routine light microscopy, immunostaining for p24 capsid protein, and in situ PCR to localize which cells were infected with HIV-1 subtype E. The number of previous abortions was not a factor in placental HIV infection since this number was higher in seronegative women (P < 0.01). There were no significant differences between the placentas of the two groups with respect to presence of chorioamnionitis, villitis, villous stromal fibrosis, infarction, abnormal villous maturation, deciduitis or decidual necrosis. HIV-1 subtype E was detected in up to 83% of placentas, either by immunostaining or in situ PCR, in trophoblast, villous stromal cells, Hofbauer cells, decidual and decidual glandular epithelium. Fetal organs were positive for HIV in 30% (6/20) of cases. There was a significant association between transmission of HIV to the fetus and the histologic findings of chorioamnionitis, plasmacellular deciduitis and decidual cell necrosis. This is the first report showing an association of chorioamnionitis with early in utero transmission of HIV-1 subtype E. This may help explain the cases of in utero transmission that persist despite antiretroviral prophylaxis, given that therapy is started in the late gestational period.

Since HbF and HbA are not found in fetuses with Hb Bart's hydrops fetalis the feasibility of prenatal diagnosis of homozygous alpha-thalassemia 1 by fetal hemoglobin typing was examined. Blood samples were obtained from fetuses at 18 to 22 weeks of gestation by cordocentesis in 32 pregnant women at risk of having a child with homozygous alpha-thalassemia 1 (alpha-thal-1). The samples were analyzed by a PCR-based method for the diagnosis of alpha-thal-1 (SEA type) and the proportion of hemoglobin fractions were determined by automated HPLC. DNA analysis showed that 8 of the 32 fetuses were homozygotes for alpha-thal-1, 17 were heterozygous for alpha-thal-1 (alpha-thal-1 trait), and a normal complement of four a-globin genes was found in 7 cases. The Hb typing in fetuses with homozygous alpha-thal-1 showed a peak of unbound Hb (Hb Bart's and Hb Portland) and no HbF, HbA and HbA The alpha-thal-1 trait chromatograms showed unbound Hb, pre HbF, HbF and HbA peaks. The chromatogram of normal fetuses showed HbF and HbA peaks without HbA2. In these cases the HbA proportion is between 3% and 10% with no apparent differences between the 18h and 22nd week of gestation. As the analysis of fetal Hb types by HPLC is facile and speedy and the results correspond with those obtained by DNA analysis, fetal Hb typing by automated HPLC is a convenient prenatal diagnostic method for homozygous alpha-thal-1. The method is recommended for prenatal diagnosis in populations with a high frequency of alpha-thal-1.

Objective: To describe the sonographic characteristics of fetuses with trisomy 21., Design: A prospective descriptive analysis., Setting: Department of Obstetrics and Gynecology, Faculty of Medicine, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University., Subjects: Pregnancies at risk of trisomy 21 between 14-27 weeks' gestation., Results: Thirty-six fetuses with subsequently proven trisomy 21 were prenatally evaluated by ultrasound in the second trimester. The main indications for detailed ultrasound examinations were advanced maternal age and abnormal findings on routine ultrasound. All of them had chromosome analysis by amniocentesis or cordocentesis. Nineteen (52.78%) had one or more abnormal findings. The common sonographic findings included thickened nuchal fold (33.33%), short femur (19.44%), and mild pyelectasis (22.22%). The other uncommon abnormalities included major anomalies (cardiac malformations, ventriculomegaly, duodenal atresia, esophageal atresia), hyperechoic bowel, echogenic intracardiac foci, abnormalities of extremities. In this study, rare minor markers but more specific markers including sandal gap, clinodactyly and mid-phalanx hypoplasia of the fifth finger were demonstrated., Conclusion: About half of the fetuses with trisomy 21 had abnormal sonographic findings in the second trimester. The most common marker was thickened nuchal fold. Although prenatal ultrasound can not permit a definite diagnosis of trisomy 21, about half of them have sonographic markers, warranting cytogenetic testing.

Objective: To evaluate the effectiveness of prenatal prevention of Hb Bart's hydrops fetalis., Study Design: The study was a prospective descriptive analysis of pregnant women attending an antenatal clinic between June 1990 and June 1998. The study consisted of two periods, the first half with no prenatal diagnosis (PND) (1990-1994) and the second half with PND. During the study period, all cases of Hb Bart's hydrops fetalis were prospectively collected and postnatally confirmed. In the second period, prenatal strategy to control severe thalassemia was introduced. The strategy included (1) carrier identification by retrospective (history review for known risk) and prospective screening (simple erythrocyte osmotic fragility test) in women without known risks, (2) the couples at risk were offered genetic counseling and cordocentesis, (3) analysis of fetal blood for diagnosis, and (4) counseling for termination of pregnancy., Results: During the first half of the study, the prevalence of Hb Bart's hydrops fetalis was 0.305 (89 in 29,399 deliveries). There were no fetuses with Hb Bart's hydrops fetalis among 16,360 screened pregnancies in the second half. However, of 6,856 pregnancies in the second half not screened due to a late first visit, 10 (0.15%) fetuses had Hb Bart's hydrops fetalis. Among the screened group, cordocentesis was performed in 361 pregnancies at risk, 170 and 191 from retrospective and prospective screening, respectively; and 75 (20.8%) were proven to have Hb Bart's disease, which was diagnosed before hydropic changes occurred., Conclusion: The strategy proved effective in preventing Hb Bart's hydrops fetalis, and extensive experience with it suggests that it be considered an effective way to control severe thalassemia.

To evaluate the indications and results of prenatal diagnosis of the high risk pregnant women attending the antenatal care clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University during 1988-1998, we analysed 2,315 amniocenteses, 1,000 cordocenteses, and 11,895 obstetric ultrasound examinations. Among the amniocentesis group, 2,017 cases (87%) were done with the indication of advanced maternal age. The prevalence of major abnormal fetal chromosomes among high risk pregnancies was 1:58. Of 1,000 cases with cordocentesis, the most common indication was fetal risk of severe thalassemia (658 cases; 65.8%) and followed by fetal risk of chromosome abnormalities (272 cases; 27.2%). In the group of cordocentesis for diagnosis of thalassemia, 99 and 49 pregnancies were affected with Hb Bart's disease and homozygous beta-thalassemia, respectively. Thirty three cases with indication of chromosome analysis had fetuses with abnormal chromosomes. The major indications of ultrasonography included suspicion of intrauterine growth restriction (IUGR), determination of gestational age and screening anomalies, respectively. In conclusion, our extensive experience has enabled us to prenatally detect most fetuses with severe thalassemia, and fetuses with abnormal chromosomes as well as anomalies in a significant number, contributing a great deal to our population. Therefore, we recommend that systematic prenatal diagnosis, either amniocentesis, cordocentesis or ultrasound should be provided to every high risk pregnant woman for a healthy newborn.

Intrauterine growth curve and normogram for newborns at Maharaj Nakhon Chiang Mai Hospital are constructed. Birthweight at various gestational weeks of deliveries were determined within 24 hrs after birth. All 1,311 Thai pregnant women selected, fitted the criteria of inclusion deliveries at Maharaj Nakhon Chiang Mai Hospital from May 1983 to April 1991 (8 yrs). Their gestational age distribution was between 28 wks to 42 wks. Clinical status at birth was satisfactory. There were no obstetric or medical complications during pregnancy. Mean birthweight and standard deviation of newborns for each gestational age at delivery were calculated and presented in tabular and graphic form. Mean birthweight for 40 wks of gestation was 3.144 +/- 382 g. In addition, normogram of 10th, 50th, 90th percentile ranks of birthweight for each gestational age was constructed. These values may be useful as baseline data of intrauterine growth curve to evaluate fetal growth in our population.