Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Patient acceptance of transvaginal sonographic endometrial thickness assessment compared with hysteroscopy and biopsy for exclusion of endometrial cancer in cases of postmenopausal bleeding.

INTRODUCTION: Available examinations for women with postmenopausal bleeding include transvaginal sonography to measure endometrial thickness (TVS-ET), and invasive endometrial assessment using hysteroscopy/endometrial biopsy. However, selection of the examination method seldom involves consideration of patient preferences. The aim of this study was to examine patient preferences for the method used to investigate postmenopausal bleeding. METHODS: Women were asked to complete an interviewer-administered structured survey before they underwent clinical investigations at a university gynaecology unit from June 2016 to June 2017. Using the standard gamble approach, women were asked to choose between invasive assessment by hysteroscopy/endometrial biopsy (gold standard) or TVS-ET with a risk of missing endometrial cancer. The risk of missing endometrial cancer during TVS-ET was varied until each woman was indifferent to either option. RESULTS: The median detection rate for endometrial cancer required using TVS-ET was 95% (interquartile range=80%-99.9%). In total, 200 women completed the survey, and 77 (38.5%) women required TVS-ET to have a 99.9% detection rate for endometrial cancer. Prior hysteroscopy experience was the only factor that influenced the women's decisions: a significantly higher detection rate was required by this patient group than by patients without previous hysteroscopy experience (P=0.047). CONCLUSION: A substantial proportion of women would accept TVS-ET alone for the investigation of postmenopausal bleeding. In the era of patientcentred care, clinicians should incorporate patient preferences and enable women to make informed choices concerning the management of postmenopausal bleeding.

The relationship between visceral adiposity and cardiometabolic risk in Chinese women with polycystic ovary syndrome.

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

Impact of haemostatic sealant versus electrocoagulation on ovarian reserve after laparoscopic ovarian cystectomy of ovarian endometriomas: a randomised controlled trial.

OBJECTIVE: To evaluate the effect of haemostatic sealant compared with bipolar coagulation on ovarian reserve after laparoscopic cystectomy for ovarian endometriomas. DESIGN: Patient-blinded, randomised controlled trial. SETTING: University-affiliated tertiary hospital. POPULATION: Women aged 18-40 years with 3-8 cm unilateral or bilateral endometriomas. METHODS: Ninety-four patients were randomised to receive haemostasis by the application of haemostatic sealant (n = 47) or standard care (n = 47). MAIN OUTCOME MEASURES: Primary outcome was the effect on the antral follicular count 3 months after the operation as it captures the effect on the ovary subjected to treatment. Secondary outcomes included the change in anti-Mullerian hormone, follicular-stimulating hormone and peri-operative outcomes including haemostasis, complications, pain, and satisfaction scores. RESULTS: A total of 94 patients aged 32.36 ± 4.92 years underwent laparoscopic cystectomy for ovarian endometriomas. The average diameter of the endometrioma was 4.21 ± 1.38 cm. The increase in antral follicle count of the affected ovaries at 3 months in the intervention group (+2.36 ± 0.37) was significantly (P = 0.013) higher than that in the control group (+1.08 ± 0.36). Repeated measures analysis of variance revealed significant effect with time (P < 0.001) and of interaction of group × time (P = 0.029) for affected ovary antral follicle count. No significant difference was noted between the two groups with regard to follicular-stimulating hormone, anti-Mullerian hormone, and other secondary outcomes. CONCLUSIONS: Applying haemostatic sealant after laparoscopic cystectomy of ovarian endometriomas produced a greater increase in antral follicle count 3 months after surgery compared with the control group. TWEETABLE ABSTRACT: RCT: Haemostatic sealant in laparoscopic cystectomy of endometriomas increase in the antral follicle count after surgery.

Applicability of first-trimester combined screening for fetal trisomy 21 in a resource-limited setting in mainland China.

OBJECTIVE: To assess the feasibility and performance of the first-trimester combined screening test for trisomy 21 in a resource-limited setting in mainland China. DESIGN: Prospective observational cohort study. SETTING: First Affiliated Hospital of Kunming Medical University, China. POPULATION: Ten thousand four hundred and forty-two pregnant women requesting first-trimester screening. METHODS: The combined screening test was performed from May 2012 to December 2014. Women with a high-risk result (≥1:600) were offered further confirmatory tests after counselling. The threshold for high risk was determined by Monte Carlo simulation to achieve a 5% false-positive rate according to the local age distribution. Pregnancy outcome and screening results were recorded for all women and monthly audits were conducted. MAIN OUTCOME MEASURES: Sensitivity, screen positive rate, cost per case of Down syndrome detected. RESULTS: Six hundred and ten women (5.8% of the total screened) had a high-risk screening test, of whom 274 (44.9%) underwent a diagnostic test and 169 (27.7%) opted for a noninvasive prenatal screening test (NIPT); 160 (26.2%) declined further testing after counselling. The pregnancy outcome was available for 10 174 (97.4%) of the women. The observed incidence of Down syndrome was 0.13% (1/750). All 14 women with a trisomy 21 pregnancy had a high-risk screening test result. The cost per Down syndrome detected was RMB596 686 compared with RMB1.79 million if all had been screened by NIPT. CONCLUSIONS: The combined screening test appears to be a more cost-effective strategy in mainland China. Screening performance in China would be improved by adopting Chinese-specific models, external quality control and assurance, and establishing risk thresholds appropriate for the age distribution of the population. TWEETABLE ABSTRACT: Combined first-trimester Downs screening in China was improved by adopting Chinese-specific models and external QC.

Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB). DESIGN: Retrospective cohort study. SETTING: One-stop PMB clinic in a Hong Kong teaching hospital. POPULATION: A cohort of 4383 women with PMB. METHODS: Transvaginal ultrasonic measurement of ET and endometrial biopsies were obtained in women presenting with PMB between 2002 and 2013. Endometrial histology was used as the reference standard to calculate accuracy estimates. MAIN OUTCOME MEASURES: Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. RESULTS: Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%). CONCLUSIONS: Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

Maternal hepatitis B surface antigen status and incidence of pre-eclampsia.

The relationship between chronic hepatitis B virus (HBV) infection with atherosclerosis and cardiovascular disorders remains unclear, and the impact of maternal HBV infection on the development of pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) is also controversial. This retrospective cohort study was conducted to examine the relationship between maternal hepatitis B surface antigen (HBsAg) status with PIH and PE in singleton pregnancies that delivered at 24 weeks of gestation and beyond. Among the 86 537 cases in the cohort, 10% were HBsAg positive, and overall 2.0% had PIH, of whom 56.3% developed PE. HBsAg-positive women had higher weight and body mass index (BMI), but lower incidences of advanced age, nulliparity, PIH (1.6% vs 2.0%, P = 0.007) and PE (0.8% vs 1.1%, P = 0.005). On multiple logistic regression analysis adjusting for the effects of nulliparity, advanced age, high BMI, and underlying renal, cardiac and autoimmune diseases, HBsAg carriage was associated with significantly reduced incidence of PIH (aOR 0.79, 95% CI 0.66-0.95) and PE (aOR 0.71, 95% CI 0.56-0.91). Our results indicate that maternal HBsAg carriage is independently associated with reduced PE. As chronic HBV infection alters the immune response of the individual, our observation could be related to enhanced maternal immunotolerance of the foetus and hence a reduction in the incidence of PE. The implications of our findings on the long-term health outcome of the infected women, from cardiovascular morbidity to malignancies, warrant further studies.

Maternal HBsAg status and infant size--a Faustian bargain?

Information on the impact of maternal hepatitis B virus (HBV) infection on pregnancy outcome is conflicting. Some studies reported an association with increased infant birthweight, which could be interpreted as advantageous to pregnancy. A retrospective study was performed to compare birthweight outcome between 6261 and 55,817 singleton pregnancies in mothers screened positive and negative for hepatitis B surface antigen (HBsAg), respectively. The HBsAg positive women were younger, had higher body mass index (BMI) and incidence of overweight, but less gestational weight gain, and were associated with increased macrosomia (birthweight ≥4000 g) in mothers <35 years (odds ratio, OR, 1.28), BMI ≥25 kg/m(2) (OR 1.24), without gestational diabetes mellitus (GDM, OR 1.19), and in male infants (OR 1.18). It was also associated with increased large-for-gestational age (LGA, birthweight >90th percentile) infants in nulliparas (OR 1.13), age <35 years (OR 1.12), BMI ≥25 kg/m(2) (OR 1.19), with (OR 1.36) and without (OR 1.09) GDM, and in male infants (OR 1.13). When the effects of high BMI, advanced age, GDM, and male infants were controlled for, positive HBsAg was significantly associated with macrosomic (adjusted odds ratio, aOR, 1.15) and LGA (aOR 1.11) infants. In view of the latest findings on the association between high infant birthweight with increased risk of obesity, diabetes mellitus, and various forms of malignancies from childhood to adulthood, further studies are warranted to determine if maternal hepatitis B infection would impact adversely on the long-term health of the offspring through its effect on increasing birthweight.

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.

First-trimester fetal nasal bone length in an ethnic Chinese population.

OBJECTIVES: To determine reference ranges of fetal nasal bone length (NBL) in a Chinese population and to assess the value of NBL measurement in screening for chromosomal defects in the first trimester. METHODS: In this prospective study the fetal profile was examined and the fetal NBL and crown-rump length (CRL) were measured in Chinese women presenting with singleton pregnancies for first-trimester screening for aneuploidy between January 2004 and June 2007. Screening was performed on the basis of nuchal translucency (NT) measurement and maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A levels. RESULTS: NBL was measured in 7543 fetuses, of which 7517 were euploid. The best fit equation for median NBL in euploid fetuses in relation to CRL was: NBL (mm) = 0.4593 + (0.0186 x CRL(mm)). The NBL for gestational age (GA, in days) was given by the equation NBL(mm) = 0.2392 + (0.0027 x GA). There was no correlation between log(10)(NBL multiples of the median (MoM)) and log(10)(NT MoM) in unaffected pregnancies (r = - 0.009; P = 0.43). Only two of the 11 cases with trisomy 21 had an NBL outside the 5(th) or 95(th) centiles of the reference range for euploid fetuses. CONCLUSION: Reference ranges for NBL in a Chinese population suitable for screening for aneuploidy between 11 and 13 + 6 weeks' gestation have been derived. The NBL in Chinese fetuses is similar to that of other ethnic groups. However, unlike the determination of presence vs. absence of the nasal bone, NBL measurement is unlikely to further improve screening for aneuploidy.

Medians and correction factors for biochemical and ultrasound markers in Chinese women undergoing first-trimester screening for trisomy 21.

OBJECTIVE: To establish normative values and distribution parameters of first-trimester maternal serum free beta-human chorionic gonadotropin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness in Chinese women and to examine the effects of covariates on their levels. METHODS: Maternal serum free beta-hCG, PAPP-A and fetal NT were measured in 9762 women presenting for first-trimester combined screening for Down syndrome at 11 to 14 weeks of gestation. Individuals' markers were converted to multiples of the median (MoM) using expected medians estimated by performing a weighted regression analysis. Multivariate regression analysis was performed to assess the influence of maternal weight, parity, ethnicity, chorionicity in twin pregnancies, smoking, insulin-dependent diabetes and mode of conception on individual marker MoM levels. RESULTS: Both free beta-hCG and PAPP-A median values demonstrated an exponential relationship with gestational age in days. Multivariate regression analysis indicated that free beta-hCG MoM was statistically significantly dependent on maternal weight (P < 0.0001) and chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001), that PAPP-A MoM was dependent on maternal weight (P < 0.0001), parity (P < 0.0001), chorionicity in twin pregnancy (both monochorionic and dichorionic P < 0.0001) and mode of conception (P = 0.002), and that fetal NT-MoM was dependent on maternal weight (P = 0.0006) and mode of conception (P = 0.012). CONCLUSION: Normative values have been generated to allow conversion of NT, free beta-hCG and PAPP-A to their MoM equivalents and correction factors have been determined to adjust for maternal and pregnancy characteristics for use in ethnic Chinese women undergoing first-trimester screening for aneuploidy.

Customized birth weight: coefficients and validation of models in a UK population.

OBJECTIVES: To produce a customized birth weight model in a UK population. METHODS: This was a population-based, multiethnic, retrospective cohort study of 42,583 women with uncomplicated singleton pregnancies resulting in a live birth at 37-42 weeks of gestation between 1997 and 2005. Multivariate analysis was undertaken and a double cross-over approach was employed to validate the models estimating customized birth weight. RESULTS: Coefficients confirmed the findings of previous studies, indicating that birth weight was strongly influenced by maternal ethnicity, age, parity, body mass index, smoking, fetal gender and gestational age at delivery. CONCLUSIONS: We have derived models to determine customized or predicted birth weight in a UK population that are both robust and reproducible.

Prediction of birth weight by fetal crown-rump length and maternal serum levels of pregnancy-associated plasma protein-A in the first trimester.

OBJECTIVE: To determine whether the first trimester crown-rump length (CRL), maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of birth weight. METHODS: This was an observational study over 1.5 years in Chinese patients who underwent first-trimester combined screening for Down syndrome in a University fetal medicine unit. After excluding cases with multiple pregnancies, congenital malformations and in-utero deaths, the relationship between fetal CRL (expressed as standardized Z-score (Z-CRL)), maternal PAPP-A and fbeta-hCG levels (expressed as log(10) of multiples of the median) and birth weight (Z-BW) were analyzed by Pearson's correlation test followed by multiple regression to check for their independency. The predictive power of the independent predictors for small-for-gestational age (SGA, defined as birth weight < 10(th) centile) was then assessed using receiver-operating characteristics (ROC) curves, and the likelihood ratios were derived. RESULTS: A total of 2760 cases were included. Z-CRL, log(10) PAPP-A(MoM), and log(10) fbeta-hCG were positively correlated with Z-BW (P < 0.0001), but only Z-CRL and log(10) PAPP-A(MoM) were independent predictors (P < 0.0001). The areas under the ROC curves of PAPP-A(MoM) and Z-CRL were 0.608 and 0.593, respectively (P < 0.0001). Likelihood ratios increased with decreasing PAPP-A(MoM) and Z-CRL, but were around 1 when the markers were at or above the mean. CONCLUSION: First-trimester CRL and PAPP-A are independent factors that influence final birth weight. The lower the PAPP-A and the smaller the CRL, the higher the risk of a fetus becoming SGA. However, their predictive powers are not sufficiently good for them to be used alone for SGA screening.

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.

Gene expression pattern associated with radiotherapy sensitivity in cervical cancer.

UNLABELLED: The objective of the present preliminary study was to determine if a difference in the pattern of gene expression exists between tumors that were subsequently found to be sensitive to radiotherapy and tumors found to be resistant to radiotherapy. PATIENTS AND METHODS: A total of 16 patients with invasive squamous cell carcinoma of the uterine cervix were included in this study. All patients were treated with standardized radiotherapy alone. Ten of the tumors were clinically radiosensitive and six were radioresistant. Total RNA, extracted from tumor specimens obtained prior to treatment, was hybridized onto an oligonucleotide microarray with probe sets complementary to over 20,000 transcripts. The genes were first subjected to a statistical filter to identify genes with statistically significant differential expression levels between those that were radiosensitive and those that were radioresistant. A back-propagation neural network was then constructed to model the differences so that patterns could be easily identified. RESULTS: Although a number of genes were found to express differentially between radiosensitive and radioresistant tumors; the 10 most discriminating genes were used to construct the model. Using the expressions from these 10 genes, we found that neural networks constructed from random subsets of the whole data were capable of predicting radiotherapy responses in the remaining subset, which appears stable within the dataset. DISCUSSION: This study shows that such an approach has the potential to differentiate tumor radiosensitivity, although confirmation of such a pattern using other larger independent datasets is necessary before firm conclusions can be drawn.

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.

Computerized analysis of acute and chronic changes in fetal heart rate variation and fetal activity in association with maternal smoking.

OBJECTIVE: To investigate the acute and chronic changes in fetal heart rate and fetal activity in association with maternal smoking by means of a computerized fetal behavior assessment program. STUDY DESIGN: In 13 term nonsmokers and 13 term smokers, fetal behavior was analyzed for 2 consecutive periods of >60 minutes. In between these 2 periods, the smokers were allowed to smoke 1 cigarette, the nonsmokers were allowed a short break of comparable time span. Fetal heart rate variation and fetal activity were recorded by a single 1.5-MHZ ultrasound transducer. The percentage of time spent in low and high fetal heart rate variation and fetal activity were analyzed by computer before and after the short break for nonsmokers and before and after the smokers smoked the 1 cigarette. Smoking-induced changes in Doppler umbilical artery recordings were also investigated. Chronic exposure to cigarette smoke was objectively evaluated by measuring the carbon monoxide concentration in expired air in all participating women after breath holding. RESULTS: Fetuses chronically exposed to cigarette smoke spent significantly more time in a low fetal heart rate variation pattern, while fetal activity was decreased both in high and low fetal heart rate variation periods. After maternal smoking, no acute changes were observed in fetal heart rate variation, yet a reduction in fetal activity was noted; however, this only reached statistical significance in periods of high fetal heart rate variation. No significant change in mean fetal heart rate was observed, yet a significant reduction in the frequency of accelerations was noted. Smoking caused an acute and transient increase in the mean pulsatility index in the umbilical artery. CONCLUSION: The computer program was able to detect changes in fetal behavioral variables in association with acute and chronic smoking. These changes may be suggestive of altered neurodevelopmental maturation possibly resulting from chronic fetal hypoxemia. This computer program offers a real possibility that analysis of fetal behavioral variables can be brought into routine clinical practice. Incorporating an analysis of these behavioral variables into smoking cessation programs may render them more successful.

Complications of laparoscopic surgery for benign ovarian cysts.

STUDY OBJECTIVE: To assess complications of laparoscopic surgery in the management of ovarian cysts. DESIGN: Prospective observational study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Consecutive patients (513) undergoing laparoscopic surgery for ovarian cysts not suspected to be malignant. INTERVENTION: Laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: A total of 587 ovarian cysts were removed from 513 women. Conversion to laparotomy was necessary in five cases (<1%). Mean +/- SD cyst diameter was 5.5+/-2.9 cm, with endometriomas (44. 5%) and dermoids (24.3%) being the two most common pathologies; 6.6% were functional. Mean +/- SD operating time was 69+/-31 minutes, and hospital stay and postoperative convalescence was 2.6+/-1.5 and 14.3 +/-9.6 days, respectively. The overall complication rate was 13.3%. Major complications occurred in three patients (0.6%): one small bowel injury and two ureter injuries. Cannula site complications were five inferior epigastric vessel injuries and four incisional hernias at the 10-mm lateral port site. CONCLUSION: Laparoscopic ovarian surgery was associated with 13.3% complications, with 0.6% being major. Careful patient selection and proper surgical training are critical to ensure safe performance of laparoscopy.