Effect of ethnicity on first trimester biomarkers for combined trisomy 21 screening: results from a multicenter study in six Asian countries.

OBJECTIVE: To assess differences between first trimester trisomy 21 screening markers free beta chain of the human chorionic gonadotrophin (ßhCG) and pregnancy-associated plasma protein A (PAPP-A) in pregnant women of six different Asian countries (China, Indonesia, Korea, Taiwan, Thailand, and Vietnam) and compare serum levels with those in women of European countries. METHODS: Median and multiple of median (MoM) values of free ßhCG and PAPP-A were determined in more than 3000 pregnant women from the Asian countries during their first trimester of pregnancy. Differences in MoM values between a European reference group from a previous multicenter evaluation and the Asian population were evaluated. Two different types of population correction factors for T21 risk estimation were assessed. RESULTS: An at least 10% difference of median MoMs between European and Asian PAPP-A values was found to be statistically significant (p < 0.0001). The specificity of the screening did not show a big difference in individual countries, when using the country-specific correction factor compared with the overall Asian correction factor (<1.4%). CONCLUSIONS: The use of a correction factor is recommended based on the differences in European and Asian MoM values. Developing country-specific medians in larger study populations can help identify clinical relevant differences and give the opportunity to explore a more accurate risk calculation.

Magnesium sulfate maintenance infusion in women with preeclampsia: a randomized comparison between 2 gram per hour and 1 gram per hour.

OBJECTIVE: To compare the percentages of pregnant women with preeclampsia who reached the therapeutic serum magnesium levels between those who received maintenance magnesium sulfate infusion of 2 g/hour versus I g/hour MATERIAL AND METHOD: Sixty women diagnosed of preeclampsia and magnesium sulfate that were considered for seizure prophylaxis were randomized into two groups. A loading dose of 5 g magnesium sulfate was given intravenously over 20 minutes to both groups. Maintenance doses of magnesium sulfate of 2 g/hour and 1 g/hour were given to the study and control groups, respectively. The maintenance dose was continued until 24 hours postpartum. Blood samples for serum magnesium were collected at 0, 1/2, 2, and 4 hours after the loading dose and at 2 and 12 hours after delivery. Clinical signs of magnesium toxicity were carefully monitored. Maternal and neonatal outcome were evaluated. RESULTS: Significantly more women in the present study group reached the therapeutic level of serum magnesium at 2 hours (70% vs. 23%, p = 0.001) and at 4 hours (80% vs. 17%, p = 0.00) after the loading dose and at 2 hours (60% vs. 20%, p = 0.003) and at 12 hours (80% vs. 37%, p = 0.001) after delivery. No clinical magnesium toxicity was observed There were no significant differences in maternal and neonatal outcomes between the two groups. CONCLUSION: The maintenance dose of magnesium sulfate at 2 g/hour was more likely to attain the therapeutic level of serum magnesium when compared to 1 g/hour with no detectable difference in maternal and neonatal outcomes.

Cystic malformation of lower female genital tract resulting in hydrops fetalis: a case report.

Genitourinary tract malformations causing hydrops fetalis are rare. The authors report a case of a female delivered at 32 weeks gestational age following a prenatal diagnosis of an abdominopelvic cystic mass with hydrops fetalis. The neonate was persistently hypoxic with unstable cardiovascular status and survived only 7 days. At autopsy, a cystic malformation replaced the vagina and uterus, associated with lower vaginal atresia and anorectal agenesis. The cyst had interfered with the normal process of Müllerian duct fusion, leading to a longitudinal vaginal septum and bifurcation of endocervix, with absent uterus and fallopian tubes. The urinary bladder was compressed by the cyst, resulting in bilateral hydronephrosis. The cyst impeded the inferior vena caval and umbilical venous circulations and impinged upon the thoracic cavity with resultant pulmonary hypoplasia. This malformation, which might be termed "cystic dysplasia" of the vagina, represents an extreme form of hydrometrocolpos that resulted in hydrops fetalis.

Are the cardiac dimensions spared in growth-restricted fetuses resulting from uteroplacental insufficiency?

AIM: The aim of this study was to investigate the effect of intrauterine growth restriction (IUGR), specifically from uteroplacental insufficiency, on fetal cardiac dimensions. MATERIAL AND METHODS: Cardiac circumference (CC) and cardiac area (CA) were measured in four-chamber view in 143 normal fetuses between 18 and 40 weeks of gestation. A study group comprised a homogeneous group of 49 IUGR fetuses with abnormal umbilical artery impedance. Multiple regression analysis was used to compare the cardiac dimensions between normal and IUGR fetuses and to determine if there were differences in cardiac measurements between those with normal and with abnormal ductus venosus Doppler. RESULTS: Fetal cardiac dimensions did not differ significantly between normal and IUGR fetuses. In IUGR fetuses, cardiac dimensions were not statistically different between those with normal and abnormal ductus venosus Doppler. CONCLUSION: Cardiac dimensions are spared and may be used for gestational age estimation in growth-restricted fetuses resulting from uteroplacental insufficiency.

Sensitivity and specificity of modified 100-g oral glucose tolerance tests for diagnosis of gestational diabetes mellitus.

OBJECTIVE: To study the sensitivity and specificity of the modified 100-g oral glucose tolerance test for diagnosis of gestational diabetes mellitus (GDM). MATERIAL AND METHOD: Medical records of pregnant women attending the antenatal clinic of King Chulalongkorn Memorial Hospital, Thailand, who underwent a 100-g oral glucose tolerance test (OGTT) during March 2004 to September 2009, were retrospectively reviewed. Three modified criteria were proposed for diagnosis of GDM. The screening efficacy of the modified criteria were assessed, using the National Diabetes Data Group (NDDG) criterion as gold standard. RESULTS: A total of 729 records were reviewed, 511 were included for analysis. Using the NDDG criterion as the gold standard, the modified II criterion has the highest sensitivity of 96.8%, and the highest accuracy of 90.8%. The modified II criterion can detect the same proportion of maternal and neonatal complications, compared to the NDDG criterion. CONCLUSION: The modified II criterion, using the fasting plasma glucose and 2-hour plasma glucose measurements, showed high sensitivity and accuracy, with moderate specificity for diagnosis of GDM. Its potential use as an alternative to standard 100-g OGTT should be evaluated in the prospective study.

Fetal facial sonographic markers for second trimester Down syndrome screening in a Thai population.

OBJECTIVE: To assess the efficacy of using facial sonographic markers for screening fetuses in the second trimester for Down syndrome (DS) in a high-risk Thai population. METHOD: Frontomaxillary facial angle (FMF) and nasal bone length (NBL) were measured prospectively in pregnant women at high-risk for DS who were undergoing genetic amniocentesis from November 2008 to October 2009. The receiver operator characteristic (ROC) curves were constructed to assess the screening efficacy of FMF angle and NBL. RESULT: A total of 460 pregnant women were recruited, and a mid-sagittal facial profile was obtained for 403 fetuses. There were 386 fetuses with normal chromosomes, 10 fetuses with DS, 1 fetus with trisomy 13, and 1 fetus with trisomy 18. The remaining 5 fetuses had balanced translocation (n = 2), deletion (n = 1), and mosaic Turner (n = 2). Two different combinations of FMF angle and biparietal diameter to nasal bone length (BPD:NBL) ratio for DS screening in the second trimester achieved 50% and 90% detection rates and 4.4% and 14.0% false positive rates, respectively. CONCLUSION: The combination of FMF angle and BPD:NBL ratio has a high sensitivity and specificity for screening for DS in the second trimester in a high-risk Thai population.

Placental cord drainage and the effect on the duration of third stage labour, a randomized controlled trial.

OBJECTIVE: To assess the effect of placental cord drainage on the duration of third stage labor, and to clarify the safety of this method regarding to postpartum hemorrhage, retained placenta, incidence of manual removal of placenta, and the need for blood transfusion. DESIGN: Randomized controlled trial. SETTING: King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: One hundred women in the third stage of labour after vaginal delivery were randomized. In the study group, placental cord drainage was performed. In both groups, the placenta was delivered by Brandt Andrew method. One case of placenta succenturiata was subsequently excluded. The duration of third stage was compared as the primary outcome. The incidence of postpartum hemorrhage, retained placenta, manual removal of placenta, and the need for blood transfusion were compared. RESULTS: In 99 cases with normal placentas, 49 cases were assigned to the study group, 50 cases were assigned to the control group. The third stage of labor was significantly shorter after placental cord drainage (5.1 +/- 2.4 minutes vs. 7.0 +/- 6.1 minutes). There was no postpartum hemorrhage, uterine atony, hypovolemic shock, or the need for blood transfusion in neither groups. CONCLUSION: Placental cord drainage shortens the duration of third stage labour. This method appears to be safe and does not increase postpartum complication.

Maternal periodontal disease and risk of preeclampsia: a case-control study.

BACKGROUND: We examined whether pregnant women with periodontal disease have an increased risk of preeclampsia, and we empirically evaluated the extent to which associations between periodontal disease and preeclampsia are dependent upon diagnostic criteria used to define periodontal disease operationally. METHODS: One hundred and fifty preeclampsia cases and one-fifty normotensive controls who delivered a singleton infant at term were enrolled. Periodontal examinations were performed within 48 h after delivery. Participants' periodontal health status was classified, a priori, into four categories according to the extent and severity of periodontal disease. Putative risk factors for periodontal disease and preeclampsia were ascertained during in-person postpartum interviews using a structured questionnaire and by medical record abstraction. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: No clinically meaningful differences were observed between cases and controls with regard to periodontal parameters. After controlling for known confounders, severe clinical periodontal disease was not associated with an increased risk of preeclampsia (OR = 0.92, 95% CI: 0.26-3.28). In addition, there was no evidence of a linear increase in risk of preeclampsia with increasing severity of periodontal disease (P for trend = 0.65). When different diagnostic criteria previously used in other studies were used, the prevalence of periodontal disease varied substantially. However, the magnitude and direction of associations between periodontal disease and preeclampsia were largely similar regardless of the diagnostic criteria used to define periodontal disease. CONCLUSIONS: This study provides no convincing evidence that periodontal disease is associated with preeclampsia risk among Thai women.

Is maternal periodontal disease a risk factor for preterm delivery?

Several studies have suggested an association between maternal periodontal disease and preterm delivery, but this has not been a consistent finding. In 2006-2007, the authors examined the relation between maternal periodontal disease and preterm delivery among 467 pregnant Thai women who delivered a preterm singleton infant (<37 weeks' gestation) and 467 controls who delivered a singleton infant at term (> or =37 weeks' gestation). Periodontal examinations were performed within 48 hours after delivery. Participants' periodontal health status was classified into 4 categories according to the extent and severity of periodontal disease. Logistic regression was used to estimate odds ratios and 95% confidence intervals. Preterm delivery cases and controls were similar with regard to mean probing depth, mean clinical attachment loss, and mean percentage of sites exhibiting bleeding on probing. After controlling for known confounders, the authors found that severe clinical periodontal disease was not associated with an increased risk of preterm delivery (odds ratio = 1.20, 95% confidence interval: 0.67, 2.16). In addition, there was no evidence of a linear increase in risk of preterm delivery or its subtypes associated with increasing severity of periodontal disease (P(trend) > 0.05). The results of this case-control study do not provide convincing evidence that periodontal disease is associated with preterm delivery or its subtypes among Thai women.

Excursion index of the septum primum as a parameter for diastolic function assessment of Thai fetuses: at 32 to 35 weeks' gestation.

OBJECTIVE: To establish the normal value of fetal diastolic function by the measurement of the excursion index of the septum primum (EISP) from 32 to 35 weeks' gestation in Thai fetuses. MATERIAL AND METHOD: Fetuses of normal Thai pregnant women were recruited for 2-dimensional echocardiographic measurements of the EISP (the ratio between the linear displacement of the flap valve and the left atrial diameter) from 32 to 35 weeks' gestation. All had a confirmed gestational age, normal structural scanning, and negative diabetic screening at 24 to 28 weeks' gestation. The 5th, 50th and 95th percentile of the EISP were demonstrated The relationship between the EISP and gestational age were determined RESULTS: Three hundred twenty-seven measurements were obtained The normal values of the EISP according to gestational age were presented as 5th, 50th, and 95th percentile ranks. The correlation coefficients (r) between the EISP and gestational age were 0.03. The EISP were not statistically different with advancing gestation. The 5th, 50th, and 95th of the EISP were 0.32, 0.45, and 0.59 respectively. The intra-observer variability was 5.5%. CONCLUSION: The normal values of fetal EISP in the Thai population from 32 to 35 weeks' gestation were established This could serve as a baseline data in detection of the alteration of left ventricular diastolic function during fetal life.

Nasal bone hypoplasia in trisomy 21 at 15 to 24 weeks' gestation in A high risk Thai population.

OBJECTIVE: To assess the utility of nasal bone hypoplasia in the detection of fetuses with trisomy 21 in the second trimester in a high risk Thai population. MATERIAL AND METHOD: A prospective study involving pregnant women undergoing amniocentesis due to increased risk of aneuploidy from January 2005 to December 2005. Fetal biometry and nasal bone measurements were obtained at the time of amniocentesis. Linear regression model and diagnostic tests were analyzed using the SPSS computer program. RESULTS: A total of 407 fetuses were evaluated. In euploid fetuses, the Nasal Bone Length (NBL) increased linearly with advancing gestational age. Fetuses with Down syndrome had a significantly higher proportion of NBL below the 5th centile when compared with normal fetuses (p < 0.05). The optimal nasal bone threshold associated with trisomy 21 is a BiParietal Diameter/Nasal Bone Length (BPD/NBL) ratio of 10 or greater, yielded a sensitivity of 80%, specificity of 86% for detection of trisomy 21. CONCLUSION: Nasal bone hypoplasia is associated with an increased risk of Down syndrome in the presented population.

Interventricular septal thickness of Thai fetuses: at 32 to 35 weeks' gestation.

OBJECTIVE: To establish the normal value of fetal InterVentricular Septal Thickness (IVST) from 32 to 35 weeks' gestation in Thai fetuses. MATERIAL AND METHOD: Thai pregnant women with normal fetuses were recruited for prenatal 2-dimensional M-mode echocardiographic measurements of fetal IVST at 32 to 35 weeks' gestation. All had a confirmed gestational age, normal structural scanning and negative diabetic screening at 24 to 28 weeks 'gestation. The IVST was measured from the 4-chamber view during diastole and systole. The 5th, 50th and 95th percentile of the IVST during Diastole (IVSD) and the IVST during Systole (IVSS) were demonstrated The relationship between the IVSD and IVSS and gestational age were determined RESULTS: A total of 410 measurements were obtained. The normal values of the IVSD and IVSS according to gestational age were presented as 5th, 50th and 95th percentile ranks. The correlation coefficients (r) between the IVSD and IVSS and gestational age were 0.11 and 0.12, respectively. The IVSD and IVSS were not statistically different with advancing gestation. The 95th, percentile of the IVSD was 4.51 millimeters (mm) (range = 4.26 to 4.74 mm) and IVSS was 6.23 mm (range = 5.96 to 6.68 mm). The intraobserver variability was 7.6%. CONCLUSION: The normal values of fetal IVSD and IVSS in a Thai population from 32 to 35 weeks' gestation were established. This could be used as a baseline data in detecting the asymmetrical septal hypertrophy during fetal life.

Intrauterine therapy for fetal supraventricular tachycardia in a twin pregnancy.

A case of a twin pregnancy in which one fetus developed hydrops secondary to supraventricular tachycardia was detected at 21 weeks' gestation. Transplacental digoxin therapy successfully converted the supraventricular tachycardia to a normal sinus rhythm without evidence of maternal or fetal side-effects. The pregnancy proceeded to term and elective cesarean section was carried out at 37 weeks' gestation.

The management of acardiac twins at King Chulalongkorn Memorial Hospital: case series.

Acardiac twin is a rare event with high perinatal mortality rate and the management strategies remain controversial. The authors report 4 cases of twin pregnancies associated with one acardiac twin diagnosed at King Chulalongkorn Memorial Hospital during the period 1993 to 2002. Two cases were expectantly managed and intrauterine interventions were performed in order to occlude umbilical artery of the acardiac twin in 2 cases, by using Guglielmi detachable coil (GDC) embolization and absolute alcohol injection. Overall, the perinatal mortality rate for the pump twin was 50% and the survival rate of expectant management in the present series was 100%. GDC embolization was judged to be technically successful since it completely occluded the circulation to the acardiac twin. However, the pump twin was dead which might have resulted from the compromised state due to cardiac failure. At present, it seems that conservative management with close antenatal surveillance is the treatment of choice when the twin-weight ratios are substantially less than 70%. Invasive techniques should be considered when there is ultrasound evidence of hydramnios or congestive heart failure of the pump twin at a previable gestational age.

Predicting the risk of preeclampsia and small for gestational age infants by uterine artery Doppler in low-risk women.

The objective was to assess the value of uterine artery notching as a screening test for preeclampsia and fetal growth restriction in a low-risk population of healthy pregnant women. Color Doppler ultrasound was used to examine both uterine arteries in 322 healthy pregnant women at 24.9 +/- 1.9 (range 22-28) weeks of gestation. The criterion for abnormal results was a unilateral or bilateral presence of an early diastolic notch. The major end points were preeclampsia and small for gestational age (SGA) infants. Of the 322 women, 19 (5.9%) developed preeclampsia and six of them (1.9%) delivered SGA infants. An early diastolic notch was detected in 58 women (18%). The risk of developing preeclampsia and SGA infants in an abnormal Doppler study group was found to be greater than in that of a normal group (P<0.05). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting preeclampsia were 36.8, 83.2, 12.1, and 95.5%, respectively; whereas detecting SGA infants were 67, 82.9, 6.9, and 99.2%, respectively. Women with an early diastolic notch have considerably a higher risk of developing preeclampsia and SGA infants. On the other hand, women with normal uterine artery waveforms are unlikely to develop preeclampsia and SGA infants. The test may be useful to minimize unnecessary interventions.

Serum beta-hCG regression after laparoscopic salpingostomy in the treatment of ectopic pregnancy in Thai women.

This is a descriptive study which reviewed the regression pattern of serum beta hCG in Thai women with ectopic pregnancy after laparoscopic salpingostomy. The study group included the medical records of 21 patients who underwent laparoscopic salpingostomy between January 1991 and August 2001. The results revealed that the regression of serum beta hCG in patients with ectopic pregnancy after laparoscopic salpingostomy was about 10, 100, 1,000 times at day 6, 20 and 35 after operation. The correlation between days after operation and serum beta hCG was in the equation of log (beta hCG difference) = -0.0671 (days after operation) - 0.6187. This estimation curve can probably be used to predict the normal serum beta-hCG regression after laparoscopic salpingostomy.

Value of humerus length shortening for prenatal detection of Down syndrome in a Thai population.

OBJECTIVE: To assess the value of humerus length shortening for prenatal detection of Down syndrome in a Thai population. METHODS: A prospective study was performed on 3053 women undergoing second-trimester amniocentesis, between 16 and 24 weeks gestation, for the indications of advanced maternal age and a past history of chromosomal abnormality. Biparietal diameter (BPD) and humerus length measurements were obtained before the procedures. Regression equations relating BPD to humerus length were used to calculate observed humerus length/expected humerus length ratio in chromosomally normal and Down syndrome fetuses. Sensitivity, specificity, false-positive rate and likelihood ratio of a positive test result at various observed humerus length/expected humerus length ratios for detection of Down syndrome were calculated. A receiver-operator characteristic curve was used to determine the threshold screening ratio. RESULTS: There were 3003 chromosomally normal pregnancies and 24 fetuses with Down syndrome. The relationship between humerus length and BPD was: expected humerus length = 0.7403BPD - 5.1057, R2= 0.77, P < 0.001. Humerus length in Down syndrome fetuses was significantly shorter than in normal fetuses (P < 0.001). A ratio of 0.91 for observed humerus length/expected humerus length yielded a sensitivity of 41.7%, specificity of 88.3%, a false-positive rate of 11.7% and likelihood ratio of a positive test result of 3.63 (95% confidence interval 2.24-5.88) for detection of Down syndrome. CONCLUSIONS: Humerus length shortening in the second trimester appears to be a useful adjunctive screening parameter for fetal Down syndrome in a Thai population.

Evaluation of a culture system for enrichment of CD34+ hematopoietic progenitor cells present in maternal blood.

BACKGROUND: Clonogenic expansion of fetal cells in maternal blood is one approach to overcome the very low number of target cells available for prenatal genetic analysis. However, efficient methods of enrichment, culturing conditions and subsequent analysis of fetal cells are lacking. Optimization of this technique requires more detailed evaluation of the composition and distribution of fetal cells that cross the placenta into the maternal circulation. Previous studies by others have shown that fetal blood is rich in CD34+ progenitor cells capable of expansion in cultures supplemented with hematopoeitic growth factors. Moreover, CD34+ fetal cells have been recovered from maternal blood following enrichment. OBJECTIVE: In this study, we examine the type and frequency of hematopoietic progenitor cells detected in maternal (n = 13) and non-pregnant control (n = 4) peripheral blood specimens. METHODS: A methylcellulose-based culture system was used to perform colony assays on CD34+-enriched or non-enriched cells. Overall, a total of 2,249 colonies were scored for colony type among the 17 samples. To determine whether fetal cells were present and expanded, all colonies present in each of the 10 confirmed male-cases (n = 1,525 colonies) were examined either by PCR or FISH. RESULTS: With CD34+-enriched maternal samples, we observed a significantly higher number of burst-forming unit-erythroid (BFU-E) and a reduced number of colony-forming unit-granulocyte, macrophage (CFU-GM) colonies compared to the non-enriched samples. Of 1,067 colonies analyzed by PCR for the amelogenin locus on X and Y, none were found positive for the 250-bp Y-specific sequences. Of 458 colonies tested by FISH for presence of X and Y probe signals, no XY-male cells were detected. CONCLUSION: We conclude that hematopoiesis is enhanced during pregnancy, but the number of fetal progenitor cells is either very low or fail to expand using the enrichment techniques and culturing conditions described in this study. Further development of methods is warranted before considering this approach for prenatal diagnosis.