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Biomedical subjects

T N Leung

Publications and source records attributed to T N Leung.

At least 19 recordsLinked to original sources

First-trimester combined screening for trisomy 21 in a predominantly Chinese population.

OBJECTIVE: To examine the effectiveness of first-trimester fetal trisomy 21 screening using a combination of maternal age, nuchal translucency thickness (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels in a predominantly Chinese population in Hong Kong. METHODS: This was a prospective study over a 1.5-year period of 2990 women who underwent combined screening for trisomy 21 between 11+0 and 13+6 weeks of gestation in a university fetal medicine unit. NT was measured according to the criteria set by The Fetal Medicine Foundation (FMF), maternal serum free beta-hCG and PAPP-A levels were measured, and the risk of trisomy 21 was calculated using The FMF's algorithm. Fetal karyotyping was advised when the risk was 1 : 300 or above. All subjects were followed up for pregnancy and fetal outcome. RESULTS: Of the 2990 women who underwent the screening program, 99% were Chinese. There were 57 twin pregnancies, giving a total of 3047 fetuses. Thirty-one percent of the women were 35 years old or above. One hundred and eighty-five (6.1%) fetuses were screen-positive; this included 14 cases of trisomy 21 and 17 cases of other chromosomal abnormalities. The positive predictive value was 16.7%. Among the 2862 screen-negative fetuses, only 18 (0.6%) cases had an unknown fetal outcome. There were no cases in which trisomy 21 was missed and the infant was liveborn. CONCLUSION: First-trimester combined screening for fetal trisomy 21 is highly effective among Chinese subjects.

Adult↗

Identification of a Streptococcus agalactiae serotype III subtype 4 clone in association with adult invasive disease in Hong Kong.

Characterization of Streptococcus agalactiae serotype III isolates revealed a subtype 4 clone that has an indistinguishable pulsed-field gel electrophoresis pattern and possesses a C-alpha protein, IS1381, and a novel sequence type (ST), ST 283, by multilocus sequence tagging. This clone was significantly associated with diseases caused by invasive strains from nonpregnant adults (P <or= 0.01, chi-square test) and was not present in the genital tracts of pregnant mothers.

DNA Transposable Elements↗

First-trimester maternal serum levels of placental hormones are independent predictors of second-trimester fetal growth parameters.

OBJECTIVE: To determine whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of second-trimester fetal growth parameters. METHODS: This was a cohort study over a 1-year period involving 594 Chinese women who underwent both first-trimester combined screening for Down syndrome and a routine second-trimester ultrasound examination. Maternal PAPP-A and fbeta-hCG levels (expressed in log(10) of multiples of median (MoM)), crown-rump length (CRL) (expressed in standardized Z-score (Z-CRL)), and maternal height and weight, were correlated with the Z-score of biparietal diameter (Z-BPD), femur length (Z-FL) and abdominal circumference (Z-AC) measured in the second trimester, using the Pearson test, followed by multiple regression analysis. RESULTS: Z-BPD, Z-FL and Z-AC were positively correlated with log(10) PAPP-A MoM, CRL and maternal height (all P < 0.05), while log(10) fbeta-hCG MoM was negatively correlated with Z-AC (P < 0.05). After controlling for the effects of CRL, maternal height and weight, log(10) PAPP-A MoM was found to be an independent positive predictor of Z-FL (r = 0.797, P < 0.001) and Z-AC (r = 0.305, P = 0.049), and log(10) fbeta-hCG MoM was an independent negative predictor of Z-FL (r = -0.381, P = 0.023) and Z-AC (r = -0.418, P = 0.002). Neither hormonal level was related to Z-BPD. CONCLUSIONS: First-trimester PAPP-A and fbeta-hCG are independent factors that influence subsequent fetal growth. PAPP-A level is positively correlated with FL and AC in the second trimester, while fbeta-hCG level is negatively correlated with them. However, BPD is not affected by either of the hormones.

Adult↗

First-trimester maternal serum level of pregnancy-associated plasma protein-A is an independent predictor of fetal maxillary bone length.

OBJECTIVE: To derive a nomogram of fetal maxillary bone length (MAX) for a Chinese population and to study whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) is an independent predictor of fetal MAX. METHODS: This was a prospective observational study over 10 months examining Chinese women with a singleton pregnancy who attended the first-trimester screening program for Down syndrome. The subjects had the fetal crown-rump length (CRL), nuchal translucency, MAX, maternal serum PAPP-A and free beta-human chorionic gonadotropin (fbeta-hCG) levels measured. A nomogram of MAX was derived using normal pregnancies with reliable dates. The correlations between MAX, CRL, PAPP-A and fbeta-hCG levels were studied, after correction for gestational dependency using Z-score transformation for the ultrasound markers (Z-MAX and Z-CRL), and logarithmic transformation of multiple of gestation-specific medians for the biochemical markers (log10PAPP-A multiples of the median (MoM) and log10fbeta-hCG MoM), using the Pearson test and multiple regression analysis. RESULTS: During the study period, 607 Chinese women met the inclusion criteria. The mean gestational age at the first-trimester screening was 12 + 4 weeks (SD, 4 days). Curve estimation analysis showed that a linear relationship fit best between MAX and CRL (MAX (mm) = -0.01 + 0.101 * CRL (mm); r = 0.826; P < 0.0001), and between MAX and gestational age (MAX (mm) = -8.465 + 0.170 * gestational age (day); r = 0.754; SD = 0.71; P < 0.0001). There were significant positive correlations between Z-MAX and Z-CRL (r = 0.627; P = < 0.0001), Z-MAX and log10PAPP-A MoM (r = 0.239; P = < 0.0001). Multiple regression analysis showed that both Z-CRL (P = < 0.0001) and log10 PAPP-A MoM (P = 0.048) were independent predictors for Z-MAX. CONCLUSION: Both CRL and maternal levels of PAPP-A are independent predictors of the fetal MAX measured during the first trimester. The positive correlation between PAPP-A levels and fetal MAX is consistent with the known biological function of PAPP-A on bone growth. This association must be adjusted for when both PAPP-A and MAX are combined for screening of Down syndrome.

Asian People↗

Fetal intra-abdominal umbilical vein varix: what is the clinical significance?

OBJECTIVE: To assess the clinical significance of fetal intra-abdominal umbilical vein (FIUV) varix. METHODS: We reviewed all cases of FIUV varix diagnosed in a university hospital from 1994 to 2003 and searched the English literature for cases of prenatal diagnosis of FIUV varix. The FIUV was considered dilated when the measurements were above 2 SD of the mean for gestational age. Cases reported in the literature were included if they met the diagnostic criteria for FIUV varix. RESULTS: Between 1994 and 2003, 13 fetuses were diagnosed in our hospital as having FIUV varix. Review of the literature revealed an additional 80 cases. Fetal outcome was available for analysis in 91 cases. Additional sonographic abnormalities were detected prenatally in 29 cases (31.9%), most commonly anomalies of the cardiovascular system (including structural and functional abnormalities), hydropic features and anemia. There were nine (9.9%) cases of chromosomal abnormalities. All except one had associated sonographic abnormalities. There were 12 (13%) perinatal losses. Only 54 cases (59.3%) of fetuses with FIUV varix had a normal obstetric outcome. In the 62 cases with isolated FIUV varix, there were five unexplained intrauterine deaths (8.1%) occurring between 29 and 38 weeks of gestation. The incidence of complications, which included intrauterine death, thrombosis of the umbilical vein and abnormal antenatal cardiotocogram, were significantly higher (P = 0.01, Fisher's exact test) if the diagnosis of FIUV varix was made before 26 weeks. CONCLUSIONS: FIUV varix is associated with a high incidence of fetal anomalies and obstetric complications. Detailed sonography is necessary to exclude fetal anomalies. Karyotyping should be offered when additional fetal abnormalities are detected. Intensive surveillance including color Doppler ultrasound should be started from the moment of diagnosis until delivery, especially in those cases presenting early in pregnancy.

Abdomen↗

Cervical length at 18-22 weeks of gestation for prediction of spontaneous preterm delivery in Hong Kong Chinese women.

OBJECTIVE: To assess the value of a single cervical length measurement by transvaginal sonography (TVS) at the time of mid-trimester anomaly scan for predicting spontaneous preterm delivery (SPD) among Chinese women. METHODS: A prospective observational study was carried out involving 2880 subjects with singleton pregnancies and confirmed gestational age. Cervical length was measured at 18-22 weeks of gestation. RESULTS: The incidence of SPD < 34 weeks and < 37 weeks were 0.7% and 3.7%, respectively. Women with SPD < 34 weeks and SPD < 37 weeks had shorter median cervical lengths (32.6 mm and 36.2 mm, respectively) than those with term deliveries (37.6 mm) (P = 0.006 and 0.025, respectively). The predictive performance of cervical length was better for SPD < 34 weeks compared with < 37 weeks. A cervical length < or = 27 mm, which corresponded to the 4th centile, occurred in 36.8%, 62.5% and 100% of those with SPD < 34, < 30 and < 26 weeks, respectively. The positive likelihood ratio (LR) of a cervical length < or = 27 mm in predicting SPD < 34 weeks was 9.8. Using logistic regression, both short cervix and funneling were independent predictors for SPD < 34 weeks of gestation. The coexistence of funneling and a cervical length < or = 27 mm gave a positive predictive value (PPV) and LR of SPD < 34 weeks of 14.7% and 26.0, respectively. CONCLUSIONS: Mid-trimester cervical length is predictive of SPD in Chinese women. However, given the low PPV of a short cervical length, its clinical utility is still limited in low-risk populations.

Adult↗

The Randomized Nitric Oxide Tocolysis Trial (RNOTT) for the treatment of preterm labor.

OBJECTIVE: This study was undertaken to assess the effectiveness of glyceryl trinitrate (GTN) patches in comparison with beta2 sympathomimetics (beta2) for the treatment of preterm labor. STUDY DESIGN: A multicenter, multinational, randomized controlled trial was conducted in tertiary referral teaching hospitals. Women in threatened preterm labor with positive fetal fibronectin or ruptured membranes between 24 and 35 weeks' gestation were recruited and randomly assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong contractions persisted at 2 hours. Obstetric and neonatal outcomes were assessed. RESULTS: Two hundred thirty-eight women were recruited and randomly assigned, 117 to beta2 and 121 to GTN. On a strict intention-to-treat basis, there was no significant difference in the time to delivery using Kaplan-Meier curves (P = .451). At 2 hours, 27% of women receiving beta2 had moderate or stronger contractions compared with 53% in the GTN group (P < .001). This led to 35% of women in the GTN group receiving rescue treatment. If delivery or requirement for beta2 rescue are regarded as treatment failure, then a significant difference was observed between the 2 arms (P = .0032). There were no significant differences in neonatal outcomes. CONCLUSION: GTN is a less efficacious tocolytic compared with ss2 sympathomimetics.

Adrenergic beta-2 Receptor Agonists↗

A validation study of ultrasonic foetal weight estimation models for Hong Kong Chinese singleton pregnancies.

OBJECTIVE: To validate the published regression models for ultrasonic foetal weight estimation in Hong Kong Chinese singleton pregnancies. DESIGN: Prospective cohort study. SETTING: Regional hospital, Hong Kong. PARTICIPANTS: One hundred and fourteen Hong Kong Chinese women with singleton pregnancy at term (37-42 weeks). MAIN OUTCOME MEASURES: The birth weight of the neonate was used to validate the ultrasonic foetal weight estimation models. The ultrasound used to collect the data was performed within 2 days prior to delivery. RESULTS: Foetal weight estimation models published by Hadlock and Woo have a high intraclass correlation coefficient of 0.86. Woo's regression model has the least mean difference (0.2 g; 95% limits of agreement, -569.4 to 569.8 g) and Hadlock 3 has the smallest limits of agreement (-114.6 g; 95% limits of agreement, -663.4 to 434.2 g) among the models tested. CONCLUSIONS: Woo's regression model of foetal weight estimation gave the least mean difference and the actual birth weight for our local population were within the acceptable limits of agreement.

Cohort Studies↗

Customizing fetal biometric charts.

OBJECTIVE: To study the effects of maternal and pregnancy characteristics on fetal biometric size using longitudinal ultrasound measurements and to construct customized models for fetal biometric size charts. METHODS: A cohort of 533 healthy pregnant women with normal singleton pregnancies were recruited for regular ultrasound examination for fetal biometry between 24 and 40 weeks' gestation. Multilevel modeling was used to construct models of fetal head size, femur length and abdominal circumference. Variables of maternal and pregnancy characteristics including booking weight and height, age, parity and fetal sex were included in the construction of the customized fetal biometric size charts. RESULTS: Increased fetal head size and abdominal circumference were significantly associated with extremes of maternal age. Maternal height had a statistically significant influence on biparietal diameter. Maternal booking weight had an influence on fetal abdominal circumference and femur length. Fetal sex was found to have a statistically significant influence on the final regression models of biparietal diameter, head circumference and femur length. Parity had an influence on fetal head circumference and abdominal circumference. CONCLUSIONS: Maternal and pregnancy characteristics have a significant influence on in-utero fetal biometry. We produced models to construct customized fetal biometric size charts. Further validation studies are necessary to evaluate the clinical usefulness of such customized fetal biometric size charts.

Adult↗

The upregulation of angiotensin II receptor AT(1) in human preeclamptic placenta.

The human placenta has been considered to possess a locally generated renin-angiotensin system (RAS), which may play a physiological role in the regulation of uteroplacental blood circulation. The changes in the expression of such a placental RAS during pregnancy could be important for the physiological and pathophysiological aspects of some clinical disorders, such as pregnancy-induced hypertension, preeclampsia. In the present study, the alterations of expression and localization of placental angiotensin II receptor subtypes, namely AT(1) in patients with preeclampsia (elective caesarean delivery) were investigated and compared with controls (vaginal delivery and elective caesarian delivery) using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry respectively. Results from RT-PCR analysis revealed an upregulated expression of placental mRNA for AT(1) receptor subtype in patients with preeclampsia when compared with those in controls. In addition, there was also a significant activation of placental expression of angiotensinogen mRNA in patients with preeclampsia. Results from Western blot showed that the expression of AT(1) receptor was also upregulated. Immunohistochemical results further demonstrated that increased immunoreactivity for placental AT(1) receptor was predominantly localized to the thin layers of syncytiotrophoblasts and, to a less extent, the capillaries of the term placental villi. These data indicate that upregulation of placental RAS components, notably AT(1) receptor in the syncytiotrophoblasts, could play a pathophysiological role in patients with preeclampsia.

Angiotensinogen↗

Five-year compliance with hormone replacement therapy in postmenopausal Chinese women in Hong Kong.

OBJECTIVES: To assess 5-year compliance with hormone replacement therapy (HRT) in Hong Kong Chinese women and the reasons for long-term compliance or non-compliance. METHODS: A telephone survey using a standardized questionnaire was conducted in 187 postmenopausal women who had commenced HRT in a referral-only specialist clinic of a university teaching hospital 5 years previously. Over this 5-year period, the cohort had been referred out to primary care doctors once they had become stabilized on treatment. RESULTS: The 5-year compliance rate was 71.1%. The overall compliance rates were nearly the same from 2 and 5 years. 'Doctors' advice' was the most important reason for maintenance of long-term compliance, accounting for 88.0% of all compliant cases. The most frequent reason for non-compliance was that of the experience of side effects. Other important reasons were fear of cancer, fear of other side effects, and discouragement from other doctors. Overall, 16.0% of women expressed concern regarding potential side effects or risk of breast cancer. Younger age at menopause and at time of initial consultation, shorter duration of menopause at presentation and previous history of hysterectomy were associated with a higher degree of compliance at 5 years. Presence or absence of menopausal symptoms, on the other hand, was not a significant factor. CONCLUSIONS: The 5-year compliance rate in this cohort of Hong Kong Chinese women was comparable to that reported from predominantly Caucasian populations. The physicians' role in encouraging postmenopausal women to achieve long-term HRT compliance was observed.

Adult↗

Influences of perinatal factors on cord blood thyroid-stimulating hormone level.

BACKGROUND: Cord blood thyroid-stimulating hormone level is affected by various perinatal factors. The aim of this study is to investigate the relative impact of these factors on the cord blood thyroid-stimulating hormone results in singleton pregnancies. METHODS: The study group consisted of 20,086 consecutive singleton deliveries over a 3 year period. The effect of mode of delivery, infant sex, gestation at birth, birth weight, and duration of labor on the incidence of false elevation of cord blood thyroid-stimulating hormone was assessed by univariate analysis and logistic regression. RESULTS: There was an independent positive association between false elevation of cord blood thyroid-stimulating hormone (> or =15.0 mIU/L) and birth weight (p=0.005), male infant sex (p<0.001), and instrumental delivery (p<0.001). Both elective and emergency cesarean section were negatively associated with elevated cord thyroid-stimulating hormone level (p<0.001). When the cutoff level was raised to 40.0 mIU/L, none of the variables examined were significant. The incidence of false positive tests (> or =15.0 mIU/L) was higher in neonates born by cesarean section for failed instrumental delivery and fetal distress than for failure to progress of labor (34.7% vs 4.5% vs 1.3% respectively, p<0.001). CONCLUSIONS: While the incidence of false positive screening was significantly affected by various perinatal factors when the thyroid-stimulating hormone cutoff level is low, it was unaffected at a high cutoff level. The present study also provides further evidence that cord blood thyroid-stimulating hormone level reflects fetal response to perinatal stress events.

Birth Weight↗

Rate of rise in maternal plasma corticotrophin-releasing hormone and its relation to gestational length.

OBJECTIVE: To assess the relationship between rate of increase in maternal plasma corticotrophin-releasing hormone and gestational length. DESIGN: A prospective observational study. SETTING: Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong. METHODS: Serial venous samples taken at four to six week intervals from 81 pregnant Chinese subjects were assayed for corticotrophin-releasing hormone concentrations. The investigators responsible for the laboratory assay were blinded to the obstetric outcome. RESULTS: A total of 380 blood samples were taken. Each subject provided three to seven samples (median = 5). Seven of the 81 subjects had preterm delivery. Maternal corticotrophin-releasing hormone levels increased exponentially as gestation advanced. A negative correlation between the rate of rise of logarithmic equivalence of corticotrophin-releasing hormone concentrations (Ln-corticotrophin releasing hormone) per week and the gestational age at delivery was demonstrated (r = -0.45, P < 0.001). The rate of increase of Ln-corticotrophin releasing hormone concentrations per week was also significantly greater for those who delivered preterm before 37 weeks compared with those with uncomplicated term deliveries (0.27 Vs 0.22, P = 0.018). CONCLUSIONS: The rate of increase in maternal plasma corticotrophin-releasing hormone is inversely proportional to gestational length. Results in a Chinese population confirm and extend results from previous caucasian populations. This study provides another piece of evidence on the close link between maternal plasma corticotrophin-releasing hormone and the timing of human parturition. As the hormone is synthesized by the placenta, it supports the suggestion that the human placenta has an important role in determining gestational length.

Adult↗

Levels of cord blood thyroid stimulating hormone after external cephalic version.

OBJECTIVE: To investigate the relationship between breech presentation, external cephalic version and levels of cord blood thyroid stimulating hormone. DESIGN: Case-control study. SETTING: University teaching hospital. POPULATION: The study group consisted of 289 consecutive singleton deliveries at term over a four-year period, all of whom had an attempt at external cephalic version performed near term for breech presentation. The control group included 23,001 singleton term deliveries during the same four-year period. METHODS: Between group differences were compared with the Mann-Whitney U test or chi2 test when appropriate. MAIN OUTCOME MEASURES: Levels of cord blood thyroid stimulating hormone and the incidence of false positive screening results for congenital hypothyroidism. RESULTS: Babies who were born vaginally after prior successful external cephalic version had significantly higher median levels of cord blood thyroid stimulating hormone (6.4 vs 6.0 mlU/L, P = 0.034) and the incidence of false positive screening for thyroid stimulating hormone (12.9% vs 7.2%, P = 0.016, OR 1.9) compared with babies with spontaneous cephalic presentation. In babies with a breech presentation born by elective caesarean section, previous attempts at external cephalic version had no effect on cord blood thyroid stimulating hormone levels. There was also no difference in the levels of cord blood thyroid stimulating hormone between cephalic and breech-presenting fetuses born by elective caesarean section. However, breech-presenting babies born by emergency caesarean section after onset of labour had higher median levels of cord thyroid stimulating hormone than those with cephalic presentation (5.1 vs 4.5 mIU/L, P= 0.008). CONCLUSION: Levels of cord blood thyroid stimulating hormone are elevated in babies born vaginally after a successful external cephalic version. This finding may represent a biological difference in fetal response to the stress of labour in breech-presenting fetuses, which is not correctable by a successful external cephalic version.

Adult↗

Relationship between birthweight and repeated courses of antenatal corticosteroids.

A retrospective study was conducted in a university teaching hospital to review the association between birthweight and the number of courses of antenatal corticosteroids received in 236 singleton pregnancies. Those pregnancies complicated with pregnancy-induced hypertension, preeclampsia, diabetes mellitus and intrauterine growth restriction were excluded. The results showed that the birthweight ratio (calculated as the baby's birthweight divided by the median birthweight for that gestational age) was negatively correlated with the number of courses of corticosteroids received. Further, exposure to four or more courses of antenatal corticosteroids was associated with a significant reduction in birthweight ratio and a three-fold increase in the risk of being small-for-dates compared to those exposed to one to three courses.

Birth Weight↗

Circulating fetal RNA in maternal plasma.

The discovery of cell-free nucleic acids in plasma has opened up new possibilities for noninvasive clinical diagnosis. We demonstrate the presence of cell-free fetal RNA in maternal plasma, indicating that plasma fetal RNA might be used as a marker for noninvasive prenatal diagnosis.

Biomarkers↗