Burnout and well-being in young doctors in Hong Kong: a territory-wide cross-sectional survey.

INTRODUCTION: This territory-wide study evaluated the level of burnout and health status among young doctors in Hong Kong. METHODS: All young doctors in Hong Kong, defined as residents-in-training or doctors within 10 years of their specialist registration, were invited to participate in an online cross-sectional survey. This survey used standardised questionnaires including the Copenhagen Burnout Inventory (CBI) for burnout, Patient Health Questionnaire-9 for depression, and general health questionnaires. RESULTS: In total, 514 doctors completed the survey; 284 were doctors within 10 years of their specialist registration, while 230 were residents-in-training. There were 277 women (54%); among all respondents, the mean age was 33.7 ± 6.1 years. Using a CBI subscale cut-off score of ≥50 (moderate and higher), 72.6% (n=373) of respondents reported personal burnout; 70.6% (n=363) of respondents reported work-related burnout; and 55.4% (n=285) of respondents reported client-related burnout. Furthermore, 24% (n=125) of respondents were "somewhat dissatisfied" with their present job position; 4% (n=19) of respondents were "very dissatisfied" with their present job position. The prevalence of depression among respondents was 21% (n=110). CONCLUSIONS: In this territory-wide cross-sectional survey of young doctors in Hong Kong, a high prevalence of burnout was identified among young doctors; respondents exhibited a considerable level of depression and substantial dissatisfaction with their current positions. Strategies to address these problems must be formulated to ensure the future well-being of the medical and dental workforce in Hong Kong.

Clinical and biochemical characteristics of infants with prolonged neonatal jaundice.

INTRODUCTION: Protocols for investigating neonatal prolonged jaundice vary and the yield from screening has not been assessed. International guidelines recommend establishing cholestasis before proceeding to investigate the underlying pathology. However, in most hospitals administered by the Hospital Authority, full liver function is checked at the first neonatal jaundice clinic visit. To study the diagnostic yield of this approach, we carried out a retrospective study of all infants referred for prolonged jaundice. METHODS: Attendance records from the neonatal jaundice clinic at the Tuen Mun Hospital, Hong Kong, the clinical management system, and electronic patient records were used to retrieve epidemiological, clinical, and laboratory data, and patients' clinical progress. RESULTS: During the 8-month study period from 8 July 2015 to 8 March 2016, 1164 infants were referred to the neonatal jaundice clinic for prolonged jaundice. Among them, 16 (1.4%) infants had conjugated hyperbilirubinaemia. Diagnoses included biliary atresia (n=1), cytomegalovirus (CMV) infection (n=3), neonatal hepatitis syndrome (n=2), and transient cholestasis (n=10). In total, 98 (8.42%) infants had elevated alanine transaminase levels. Diagnoses included biliary atresia (n=1), hepatic congestion related to congestive heart failure (n=1), CMV infection (n=5), neonatal hepatitis syndrome (n=16), and non-specific elevated alanine transaminase (n=75). In total, 59 infants had elevated alkaline phosphatase levels. CONCLUSIONS: A stepwise approach is recommended, in which full liver function is checked and the underlying cause of jaundice is investigated only after confirming cholestasis.

Autophagic adaptation is associated with exercise-induced fibre-type shifting in skeletal muscle.

AIM: Acute exercise is known to activate autophagy in skeletal muscle. However, little is known about how basal autophagy in skeletal muscle adapts to chronic exercise. In the current study we aim to, firstly, examine whether long-term habitual exercise alters the basal autophagic signalling in plantaris muscle and, secondly, examine the association between autophagy and fibre-type shifting. METHODS: Adult female Sprague-Dawley rats aged 2 months were randomly assigned to control and exercise groups. Animals in exercise group were kept in cages equipped with free access running wheels to perform habitual exercise for 5 months. Animals in the control group were caged in the absence of running wheels. Animals were sacrificed after the 5-month experimental period. Plantaris muscle tissues were harvested for analysis. RESULTS: We showed that long-term habitual exercise enhanced basal autophagy, but without altering expressions of autophagy proteins in plantaris muscle. Interestingly, sirtuin protein, a possible regulator of autophagy, was upregulated in plantaris muscle. Furthermore, we suspected that different types of muscle fibre adapted to chronic exercise in different ways. Long-term habitual exercise resulted in fibre-type shifting from type IIX to IIA in both gastrocnemius muscle and plantaris muscle. Intriguingly, our analysis demonstrated that LC3-II protein abundance is positively correlated with the proportion of type IIA fibre whereas it was negatively correlated with the proportion of type IIX fibre in plantaris muscle. PGC-1α protein abundance was positively associated with the proportion of type IIA fibre and LC3-II in plantaris muscle. CONCLUSION: These results suggest that basal autophagy is enhanced in plantaris muscle after long-term habitual exercise and associated with fibre-type shifting.

Impact of nuchal cord on fetal outcomes, mode of delivery, and management: a questionnaire survey of pregnant women.

OBJECTIVES: To explore pregnant women's views on the impact of nuchal cord on fetal outcomes, mode of delivery, and management. DESIGN: Questionnaire survey. SETTING: Antenatal clinic of two regional hospitals in Hong Kong. PARTICIPANTS: A questionnaire survey of all pregnant women at their first visit to the antenatal clinic of United Christian Hospital and Tseung Kwan O Hospital in Hong Kong was conducted between August and October 2012. RESULTS: Most participants (71.8%) were worried about nuchal cord, and 78.3% and 87.7% of them thought that nuchal cord could cause intrauterine death and fetal death during labour, respectively. Approximately 87.5% of participants thought that nuchal cord would reduce the chance of successful vaginal delivery and 56.4% thought that it would increase the chance of assisted vaginal delivery. Most (94.1%) participants thought that it was necessary to have an ultrasound scan at term to detect nuchal cord. In addition, 68.8% thought that it was necessary to deliver the fetus early and 72.8% thought that caesarean section must be performed in the presence of nuchal cord. Participants born in Mainland China were significantly more worried about the presence of nuchal cord than those born in Hong Kong. However, there was no difference between participants with different levels of education. CONCLUSION: Most participants were worried about the presence of nuchal cord. Many thought that nuchal cord would lead to adverse fetal outcomes, affect the mode of delivery, and require special management. These misconceptions should be addressed and proper education of women is needed.

Autophagic Adaptations to Long-term Habitual Exercise in Cardiac Muscle.

Autophagy has been shown to be responsive to physical exercise. However, the effects of prolonged habitual exercise on autophagy in cardiac muscle remain unknown. The present study aimed to examine whether long-term habitual exercise alters the basal autophagic signalling in cardiac muscle. Female Sprague-Dawley rats aged 2 months were randomly assigned to control and exercise groups. Animals in exercise group were kept in cages with free access exercise wheels to perform habitual exercise for 5 months. Animals in the control group were placed in cages without exercise wheels. Ventricular muscle tissues were harvested for analysis after 5 months. Phosphorylation statuses of upstream autophagic regulatory proteins and protein expressions of downstream autophagic facts remained unchanged in the cardiac muscle of exercise animals when compared to control animals. Intriguingly, the protein abundance of microtubule-associated protein-1 light chain -3 II (LC3-II), heat shock protein 72 (HSP72) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) were significantly increased in cardiac muscle of exercise rats relative to control rats. 5 months of habitual exercise causes the adaptive increase in LC3-II reserve without altering autophagic flux, which probably contributes to the elevation of cellular autophagic capacity and efficiency of cardiac muscle.

High levels of LDL-C combined with low levels of HDL-C further increase platelet activation in hypercholesterolemic patients

High levels of low-density lipoprotein cholesterol (LDL-C) enhance platelet activation, whereas high levels of high-density lipoprotein cholesterol (HDL-C) exert a cardioprotective effect. However, the effects on platelet activation of high levels of LDL-C combined with low levels of HDL-C (HLC) have not yet been reported. We aimed to evaluate the platelet activation marker of HLC patients and investigate the antiplatelet effect of atorvastatin on this population. Forty-eight patients with high levels of LDL-C were enrolled. Among these, 23 had HLC and the other 25 had high levels of LDL-C combined with normal levels of HDL-C (HNC). A total of 35 normocholesterolemic (NOMC) volunteers were included as controls. Whole blood flow cytometry and platelet aggregation measurements were performed on all participants to detect the following platelet activation markers: CD62p (P-selectin), PAC-1 (GPIIb/IIIa), and maximal platelet aggregation (MPAG). A daily dose of 20 mg atorvastatin was administered to patients with high levels of LDL-C, and the above assessments were obtained at baseline and after 1 and 2 months of treatment. The expression of platelets CD62p and PAC-1 was increased in HNC patients compared to NOMC volunteers (P<0.01 and P<0.05). Furthermore, the surface expression of platelets CD62p and PAC-1 was greater among HLC patients than among HNC patients (P<0.01 and P<0.05). Although the expression of CD62p and PAC-1 decreased significantly after atorvastatin treatment, it remained higher in the HLC group than in the HNC group (P<0.05 and P=0.116). The reduction of HDL-C further increased platelet activation in patients with high levels of LDL-C. Platelet activation remained higher among HLC patients regardless of atorvastatin treatment.

High levels of LDL-C combined with low levels of HDL-C further increase platelet activation in hypercholesterolemic patients.

High levels of low-density lipoprotein cholesterol (LDL-C) enhance platelet activation, whereas high levels of high-density lipoprotein cholesterol (HDL-C) exert a cardioprotective effect. However, the effects on platelet activation of high levels of LDL-C combined with low levels of HDL-C (HLC) have not yet been reported. We aimed to evaluate the platelet activation marker of HLC patients and investigate the antiplatelet effect of atorvastatin on this population. Forty-eight patients with high levels of LDL-C were enrolled. Among these, 23 had HLC and the other 25 had high levels of LDL-C combined with normal levels of HDL-C (HNC). A total of 35 normocholesterolemic (NOMC) volunteers were included as controls. Whole blood flow cytometry and platelet aggregation measurements were performed on all participants to detect the following platelet activation markers: CD62p (P-selectin), PAC-1 (GPIIb/IIIa), and maximal platelet aggregation (MPAG). A daily dose of 20 mg atorvastatin was administered to patients with high levels of LDL-C, and the above assessments were obtained at baseline and after 1 and 2 months of treatment. The expression of platelets CD62p and PAC-1 was increased in HNC patients compared to NOMC volunteers (P<0.01 and P<0.05). Furthermore, the surface expression of platelets CD62p and PAC-1 was greater among HLC patients than among HNC patients (P<0.01 and P<0.05). Although the expression of CD62p and PAC-1 decreased significantly after atorvastatin treatment, it remained higher in the HLC group than in the HNC group (P<0.05 and P=0.116). The reduction of HDL-C further increased platelet activation in patients with high levels of LDL-C. Platelet activation remained higher among HLC patients regardless of atorvastatin treatment.

Acylated and unacylated ghrelin inhibit doxorubicin-induced apoptosis in skeletal muscle.

AIM: Doxorubicin, a potent chemotherapeutic drug, has been demonstrated previously as an inducer of apoptosis in muscle cells. Extensive induction of apoptosis may cause excessive loss of muscle cells and subsequent functional decline in skeletal muscle. This study examined the effects of acylated ghrelin, a potential agent for treating cancer cachexia, on inhibiting apoptotic signalling in doxorubicin-treated skeletal muscle. Unacylated ghrelin, a form of ghrelin that does not bind to GHSR-1a, is also employed in this study to examine the GHSR-1a signalling dependency of the effects of ghrelin. METHODS: Adult C57BL/6 mice were randomly assigned to saline control (CON), doxorubicin (DOX), doxorubicin with treatment of acylated ghrelin (DOX+Acylated Ghrelin) and doxorubicin with treatment of unacylated ghrelin (DOX+Unacylated Ghrelin). Mice in all groups that involved DOX were intraperitoneally injected with 15 mg of doxorubicin per kg body weight, whereas mice in CON group received saline as placebo. Gastrocnemius muscle tissues were harvested after the experimental period for analysis. RESULTS: The elevation of apoptotic DNA fragmentation and number of TUNEL-positive nuclei were accompanied with the upregulation of Bax in muscle after exposure to doxorubicin, but all these changes were neither seen in the muscle treated with acylated ghrelin nor unacylated ghrelin after doxorubicin exposure. Protein abundances of autophagic markers including LC3 II-to-LC3 I ratio, Atg12-5 complex, Atg5 and Beclin-1 were not altered by doxorubicin but were upregulated by the treatment of either acylated or unacyated ghrelin. Histological analysis revealed that the amount of centronucleated myofibres was elevated in doxorubicin-treated muscle while muscle of others groups showed normal histology. CONCLUSIONS: Collectively, our data demonstrated that acylated ghrelin administration suppresses the doxorubicin-induced activation of apoptosis and enhances the cellular signalling of autophagy. The treatment of unacylated ghrelin has similar effects as acylated ghrelin on apoptotic and autophagic signalling, suggesting that the effects of ghrelin are probably mediated through a signalling pathway that is independent of GHSR-1a. These findings were consistent with the hypothesis that acylated ghrelin inhibits doxorubicin-induced upregulation of apoptosis in skeletal muscle while treatment of unacylated ghrelin can achieve similar effects as the treatment of acylated ghrelin. The inhibition of apoptosis and enhancement of autophagy induced by acylated and unacylated ghrelin might exert myoprotective effects on doxorubicin-induced toxicity in skeletal muscle.

A study on in-line tablet coating--the influence of compaction and coating on tablet dimensional changes.

Prior to coating, tablets are usually stored for a definite period to enable complete strain recovery and prevent subsequent volumetric expansion-related coating defects. In-line coating is defined as the coating of tablets immediately after compaction. In-line coating will be expected to improve manufacturing efficiencies. In this study, the possibility of in-line coating was studied by evaluating the influence of compaction and coating on tablet dimensional changes. The use of tapered dies for compaction was also evaluated. Two types of tablet coaters which presented different coating environments, namely the Supercell™ coater and pan coater, were employed for coating. The extent of tablet dimensional changes was studied in real time using optical laser sensors in a controlled environment. After compaction, tablet dimensional changes were found to be anisotropic. In contrast, coating resulted in isotropic volume expansion in both the axial and radial directions. Pan coating resulted in significantly greater tablet dimensional changes compared to Supercell™ coating. There was no significant difference in dimensional changes of tablets coated in line or after complete viscoelastic strain recovery for Supercell™ coating. However, significantly different dimensional changes were observed for pan coating. The use of tapered dies during compaction was found to result in more rapid viscoelastic strain recovery and also significantly reduced tablet dimensional changes when tablets were immediately coated after compaction using the pan coater. In conclusion, the Supercell™ coater appeared to be more suitable for in-line tablet coating, while tapered dies were beneficial in reducing tablet dimensional changes when the pan coater was employed for in-line coating.

A novel way of visualizing the ductal and aortic arches by real-time three-dimensional ultrasound with live xPlane imaging.

OBJECTIVE: To describe a novel method of visualizing the ductal and aortic arches by real-time three-dimensional echocardiography with live xPlane imaging. METHODS: Live xPlane imaging was used to display the ductal- and aortic-arch views in 107 women with singleton pregnancies, including seven cases with suspected congenital heart defects (CHDs). The three vessels and trachea (3VT) view was obtained in such an orientation that either the pulmonary artery or the aorta was parallel to the direction of the ultrasound beam. The xPlane reference line was then placed across the targeted vessel, which in a normal case would provide an image of the corresponding arch view as a dual-image display. RESULTS: Once the 3VT view had been obtained, live xPlane imaging showed the aortic and ductal arches in all 100 normal cases. In seven cases with suspected CHD, the 3VT view was abnormal in five cases and normal in the other two. However, the ductal-arch view demonstrated by live xPlane imaging was abnormal in five cases of conotruncal anomalies and normal in two cases in which conotruncal anomalies were excluded. CHDs were confirmed at autopsy following termination of pregnancy in five cases and on postnatal echocardiography in one case. The heart was found postnatally to be normal in one case of suspected CHD; in this case live xPlane imaging showed that the observed abnormal 3VT view was caused by a tortuous course of the thoracic aorta associated with an abnormal diaphragm. CONCLUSION: Live xPlane imaging is a novel and relatively simple method of visualizing the ductal- and aortic-arch views, and may potentially be a useful tool in the screening of fetal conotruncal and aortic-arch anomalies.

The butterfly effect: a physical phenomenon of hypromellose matrices during dissolution and the factors affecting its occurrence.

A phenomenon was observed for the behavior of hypromellose matrices during dissolution. The tablet laminated radially, with both edges curled outwards, forming a "butterfly" shape. The butterfly effect is thus coined to describe this behavior. Due to the flamboyant shape assumed by the hydrated matrix, the apparent surface area for drug release was significantly increased. This study attempted to elucidate mechanistically the cause of this butterfly effect. Two formative mechanisms were proposed based on the behavior of moving solvent fronts and the anisotropic expansion of materials in solution. It was hypothesized that the particle size of hypromellose, applied compaction force used and proportions of both insoluble and soluble excipients contributed to the butterfly effect. The influence of the expanded shape on the mechanism and rate of drug release was also investigated. Matrix formulation was an important factor. Greater drug release was observed when the butterfly-shaped hydrated matrix was formed. The drug release profiles generally fitted the Higuchi and Korsmeyer-Peppas equations, indicating a combination of both diffusion and erosional drug release mechanisms. A combination of both fine and coarse hypromellose size fractions and adequate compaction force (more than 3 kN) were necessary for the manifestation of the butterfly effect.

Fetoscopic laser photocoagulation in the management of twin-twin transfusion syndrome: local experience from Hong Kong.

OBJECTIVE: To review the perinatal outcome of monochorionic twin pregnancies treated by fetoscopic laser coagulation for twin-twin transfusion syndrome. DESIGN: Retrospective study. SETTING: A university teaching hospital in Hong Kong. PATIENTS: Thirty consecutive cases of fetoscopic laser coagulation of placental anastomoses for twin-twin transfusion syndrome performed in a single centre. MAIN OUTCOME MEASURES: Operative complications and perinatal survival rates. RESULTS: The median gestational age at initial presentation, laser photocoagulation, and delivery were 22 (range, 16-27) weeks, 23 (18-28) weeks, and 32 (21-37) weeks, respectively. To improve the visualisation, in three cases amnio-exchange was undertaken; the procedure was abandoned in two due to poor visualisation. The overall fetal survival rate, the double infant survival rate, and survival rate for at least one twin were 72% (43/60), 60% (18/30), and 83% (25/30), respectively. The most common peri-operative complication was bleeding from the uterine wall into the amniotic cavity, which affected three (10%) patients. CONCLUSIONS: Our results of fetoscopic laser surgery for twin-twin transfusion syndrome were similar to those in specialised centres in other countries.

Comparative study of non-destructive methods to quantify thickness of tablet coatings.

The Supercell coater is a newly introduced coater which utilizes air fluidization for tablet coating. The aim of this study was to define a suitable, fast and non-destructive method for the quantification of coat thickness for Supercell-coated tablets. Various coat thickness characterization methods were carried out on tablets coated at different process conditions. These include the use of optical microscopy, micrometer, X-ray fluorescence (XRF), Raman and near-infrared (NIR) spectroscopy. Coat thicknesses obtained from direct measurements were used to calibrate the spectral data from spectroscopic methods for model generation. The models were subsequently validated to evaluate their prediction capabilities, especially the ability to differentiate tablets coated at different conditions. XRF spectroscopy was viewed to be more suitable for the assessment of process yield and efficiency but both Raman and NIR spectroscopy were shown to be more appropriate methods for the rapid prediction and evaluation of coat thickness. However, only Raman spectroscopy was able to differentiate tablets coated under different conditions accurately. In conclusion, direct thickness measurements were more time-consuming but provided assured coat thickness data. On the other hand, XRF, Raman and NIR spectroscopy methods were viable alternatives to provide complementary information for the study of tablet coatings.

Comparison of likelihood ratios of first-trimester nuchal translucency measurements: multiples of median, delta or mixture.

OBJECTIVE: To compare the likelihood ratios (LR) determined for a measured nuchal translucency (NT) using the multiples of the median (MoM), delta-NT and mixture model approaches. METHODS: This was a retrospective study of singleton pregnancies with known outcome screened at the 12(th) week of pregnancy between January 2006 and May 2008. NT, crown-rump length (CRL) and LR for trisomy 21 using the delta-NT approach (LRNT-delta) were extracted from The Fetal Medicine Foundation trisomy 21 risk-calculation software database. NT measurements were converted into their equivalent MoM by dividing by the expected CRL-specific median NT. LR for trisomy 21 based on the MoM (LRNT-MoM) of each case was then calculated as the ratio of the Gaussian probability density functions using published trisomy 21 risk-screening parameters. The LR using the mixture model (LRNT-mixture) was calculated as the ratio of individual composite probability densities reported for trisomy 21 and unaffected pregnancies. The intraclass correlation coefficient (ICC) was used to assess the agreement between the three different approaches while the paired t-test was used to perform pairwise comparisons. RESULTS: Of the 5907 pregnancies with known outcome, 14 had trisomy 21. The ICC between the three approaches to determining an LR was 0.947 (95% CI, 0.943-0.951; P < 0.0001). Pairwise comparison indicated that differences between LR were statistically significant (P < 0.0001). Likelihood ratios determined via the delta-NT model were in general greater than those produced by both the mixture model (z = 5.58, P < 0.0001) and the MoM approaches (z = 32.8, P < 0.0001). For a 5% false-positive rate the detection rate of trisomy 21 (DR) was 78.6% (95% CI, 57.1-99.9%) The screen positive thresholds to achieve this DR were 1 : 200 for the delta-NT approach, 1 : 220 for the mixture approach and 1 : 290 for the MoM approach. CONCLUSION: No single method of determining NT-associated LR outperformed the others in its ability to detect a trisomy 21-affected pregnancy.

Real-time three-dimensional ultrasound with Live xPlane imaging assists first-trimester acquisition of a true midsagittal section.

OBJECTIVE: To determine whether real-time three-dimensional (3D) ultrasound with Live xPlane imaging, which enables the simultaneous display of two real-time high-quality image planes, can assist both operators certified by The Fetal Medicine Foundation (FMF) and non-FMF-certified operators in acquiring a true midsagittal plane in the first trimester. METHODS: Eight operators, four of them FMF certified (FMF group) and the other four not (non-FMF group), were asked to acquire a fetal image that they believed to represent the true midsagittal plane using real-time 3D ultrasound with Live xPlane imaging as guidance. Each operator was asked to obtain such an image five times from each of five patients. A total of 200 images from 40 patients were obtained and stored for subsequent analysis. All pregnancies were between 11 + 0 and 13 + 6 weeks of gestation. The angle between the falx cerebri and vertical axis (angle of deviation) was then measured by a single operator. A true midsagittal section was defined as an angle of deviation equal to 0 degrees. The angle of deviation and the time taken to acquire each image were compared between FMF and non-FMF groups. RESULTS: The median angle of deviation for each operator ranged from 1.2 degrees to 3.4 degrees. There was no significant difference in this angle between those who were FMF certified and those who were not (2.0 degrees vs. 2.2 degrees, P = 0.463). The interquartile range of the angle of deviation was also similar between the FMF- and non-FMF-certified operators. Although the time taken for image acquisition was longer among the non-FMF-certified operators (median, 45.5 s vs. 32.0 s), this difference did not reach statistical significance (P = 0.107). CONCLUSION: Live xPlane imaging can provide a tool to assist the acquisition of a true midsagittal plane and to determine how true a 'midsagittal' plane really is.

Comparison of first-trimester contingent screening strategies for Down syndrome.

OBJECTIVE: To assess the relative performance of a multi-stage first-trimester screening protocol for fetal Down syndrome. METHODS: Data from 10,767 women who underwent combined ultrasound and biochemistry (BC) screening in the first trimester were reanalyzed using a contingent model approach. Amongst the 10,854 fetuses with known outcome, 32 had Down syndrome, 232 had other abnormalities and 10,590 were unaffected. Nuchal translucency (NT), BC and combined (NT-BC) gestational age-specific risks were calculated for each individual using The Fetal Medicine Foundation risk calculation algorithms (Mixture Model and Biochemistry). Individual patients were categorized as at low, high or intermediate risk according to one of the following three strategies. In 'Strategy-NT-BC' initial screening was performed using both NT and BC. In 'Strategy-BC' initial screening was undertaken using maternal serum markers followed by NT assessment in those with an intermediate risk (1 : 51 < risk

Which ultrasound or biochemical markers are independent predictors of small-for-gestational age?

OBJECTIVES: To investigate which ultrasound or biochemical markers in both the first and the second trimesters are the best predictors for fetal growth and small-for-gestational age (SGA). METHODS: This was a prospective study of 619 Chinese women with a singleton pregnancy. At 11 to 13 + 6 weeks, fetal crown-rump length (CRL), placental volume (PlaV), uterine artery pulsatility index (UtA-PI), and the maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) were measured. Fetal biparietal diameter, femur length, abdominal and head circumference, PlaV and UtA-PI were then measured at 18-22 weeks. All markers were transformed to gestational age-specific Z-scores or multiples of the median (MoM). Birth weights were also transformed to Z-scores using the individualized gestational age-related optimal weight based on a locally derived nomogram. The relationship between all markers and the customized birth weight were examined, and their predictive powers for SGA were examined by regression analysis. RESULTS: Univariate analysis revealed that all markers except free beta-hCG correlated with birth weight Z-score. After multiple linear regression analysis, only PlaV, UtA-PI and CRL in the first trimester, and PlaV and UtA-PI in the second trimester, stood out as independent markers. Logistic regression analysis showed that PlaV was the only independent first-trimester predictor of SGA, and in the second trimester both PlaV and UtA-PI were independent predictors. The sensitivity of these first- and second-trimester markers in predicting SGA were 41% and 45%, respectively, at a false-positive rate of 20%. Combining them did not significantly improve prediction of SGA. CONCLUSIONS: Among the various known ultrasound and biochemical markers, only the first-trimester PlaV and the second-trimester PlaV plus UtA-PI are independent predictors for SGA.