Liona C Y Poon - Academia.edu (original) (raw)

Papers by Liona C Y Poon

Research paper thumbnail of Contingent Screening for Small by Weight for Gestational Age Neonates

Pediatric endocrinology reviews : PER, 2016

Effective screening for small for gestational age neonates (SGA), in the absence of preeclampsia,... more Effective screening for small for gestational age neonates (SGA), in the absence of preeclampsia, can be accomplished using a contingent screening method. The basis for the contingent model is a combined assessment at 19-24 weeks gestation to stratify patients according to their risk. We can then identify prenatally over 90% of SGA neonates for a false positive rate of 10%.

Research paper thumbnail of Cervical cerclage for preterm birth prevention in twin gestations with short cervix: a retrospective cohort study

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 16, 2016

To determine if cervical cerclage reduces the rate of spontaneous early preterm birth in cases of... more To determine if cervical cerclage reduces the rate of spontaneous early preterm birth in cases of ultrasound detected short cervix in dichorionic/diamniotic (DC-DA) twins. This was a retrospective cohort study on DC-DA twins. The cases were 40 consecutive DC-DA twins at Saint Peter's University Hospital from November 2006 through May 2012 where cervical cerclage was performed for ultrasound determined cervical length of 1-24 mm at 16-24 weeks' gestation. The cases were matched with 40 controls with no cerclage for cervical length and gestational age at cervical assessment. The primary outcome measure was spontaneous birth at <32 weeks. There was no difference between the two groups in maternal age, body mass index, cigarette smoking, use of in-vitro fertilization, parity and prior spontaneous preterm birth. There were statistically more Caucasian women in the controls. In the cases, compared to controls, spontaneous delivery at <32 weeks was significantly less frequent...

Research paper thumbnail of First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing

Fetal diagnosis and therapy, 2014

To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in mate... more To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers. In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in...

Research paper thumbnail of Mean arterial pressure in the three trimesters of pregnancy: effects of maternal characteristics and medical history

Ultrasound in Obstetrics & Gynecology, 2015

To define the contribution of maternal variables which influence the measured mean arterial press... more To define the contribution of maternal variables which influence the measured mean arterial pressure (MAP) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and MAP was measured in women with singleton pregnancies attending for three routine hospital visits at 11(+0) -13(+6) , 19(+0) -24(+6) and 30(+0) -34(+6) or 35(+0) -37(+6) weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. For pregnancies delivering phenotypically normal live births or stillbirths at ≥24 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation, variables from maternal demographic characteristics and medical history important in the prediction of MAP were determined from a linear mixed effects multiple regression. MAP was measured in 75,841 cases in the first trimester, 30,447 in the second trimester and 31,673 in the third trimester. Significant independent contributions to MAP were provided by gestational age, maternal age, weight, height, Afro-Caribbean racial origin, cigarette smoking, family history of PE, history of PE in the previous pregnancy, inter-pregnancy interval, chronic hypertension and diabetes mellitus. The effects of some variables were similar and for others differed in the three different trimesters. Random effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured MAP and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates both in pregnancies that developed PE and in those without this pregnancy complication. A model was fitted to express the measured MAP into MoMs after adjustment for variables from maternal characteristics and medical history that affect this measurement.

Research paper thumbnail of Meta-analysis of second-trimester markers for trisomy 21

Ultrasound in Obstetrics & Gynecology, 2013

Objective To summarize by meta-analysis the accumulated data on the screening performance of seco... more Objective To summarize by meta-analysis the accumulated data on the screening performance of secondtrimester sonographic markers for fetal trisomy 21.

Research paper thumbnail of Competing Risks Model in Screening for Preeclampsia by Biophysical and Biochemical Markers at 30-33 Weeks' Gestation

Fetal Diagnosis and Therapy, 2014

To assess the risk for preeclampsia (PE) by maternal characteristics, uterine artery pulsatility ... more To assess the risk for preeclampsia (PE) by maternal characteristics, uterine artery pulsatility index (Ut-PI), mean arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 30-33 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. This was a screening study in singleton pregnancies including 2,140 that developed PE and 83,615 that were unaffected by PE. We developed a survival time model for the time of delivery for PE by combining maternal characteristics and history with Ut-PI, MAP, PlGF and sFlt-1 multiple of the median (MoM) values (combined test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE, and 13,878 unaffected pregnancies and data on PlGF and sFlt-1 were available in 118 cases of PE and 3,734 unaffected pregnancies. Modelled detection rate of all PE and PE requiring delivery within 4 and 6 weeks of the visit was estimated. Screening by the combined test would detect 66, 98 and 86% of all PE and PE requiring delivery within 4 and 6 weeks of the visit, respectively, at a false positive rate of 5%. Screening by biophysical and biochemical testing at 30-33 weeks could identify most pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Research paper thumbnail of Competing Risk Model in Screening for Preeclampsia by Mean Arterial Pressure and Uterine Artery Pulsatility Index at 30-33 Weeks' Gestation

Fetal Diagnosis and Therapy, 2014

To assess risk for preeclampsia (PE) based on maternal characteristics, mean arterial pressure (M... more To assess risk for preeclampsia (PE) based on maternal characteristics, mean arterial pressure (MAP) and uterine artery pulsatility index (Ut-PI) at 30-33 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. Screening study in singleton pregnancies including 2,140 that subsequently developed PE and 83,615 that were unaffected by PE, gestational hypertension or delivery of small-for-gestational-age neonates (normal group). We developed a survival time model for the time of delivery for PE by combination of maternal characteristics and history with MAP and Ut-PI multiple of the median (MoM) values (biophysical test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE and 13,878 of the normal group. The detection rate of PE requiring delivery within 4, 6 and 8 weeks of the visit was estimated. In pregnancies with PE the log10 MoM values of MAP and Ut-PI were inversely related to gestational age at delivery. Biophysical testing detected 90, 65 and 53% of PE with delivery within 4, 6 and 8 weeks of the visit, at a fixed false-positive rate of 5%. Testing by maternal characteristics, Ut-PI and MAP at 30-33 weeks could identify 90% of pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Research paper thumbnail of Is high fetal nuchal translucency associated with submicroscopic chromosomal abnormalities on array CGH?

Ultrasound in Obstetrics & Gynecology, 2014

Objective To examine the possible association between high fetal nuchal translucency thickness (N... more Objective To examine the possible association between high fetal nuchal translucency thickness (NT) and pathogenic chromosomal copy number variants (CNVs) detected by array comparative genomic hybridization (CGH) in pregnancies with normal fetal karyotype.

Research paper thumbnail of How feasible is expectant management of interstitial ectopic pregnancy?

Ultrasound in Obstetrics & Gynecology, 2014

Methods We identified all women with an ultrasound diagnosis of interstitial pregnancy seen withi... more Methods We identified all women with an ultrasound diagnosis of interstitial pregnancy seen within a 9year period (January 2004 to April 2013. The clinical history, ultrasound findings and biochemical results were reviewed. The outcome of all interstitial pregnancies managed conservatively was recorded. Treatment was considered as successful when the serum β-human chorionic gonadotropin (β-hCG) level declined below 20 IU/L without the need for further intervention.

Research paper thumbnail of Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: relation to maternal and fetal characteristics

Ultrasound in Obstetrics & Gynecology, 2013

Objective To examine the possible effects of maternal and fetal characteristics on the fetal frac... more Objective To examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free (cf) DNA at 11-13 weeks' gestation and estimate the proportion of pregnancies at high risk of non-invasive prenatal testing (NIPT) failure because the fetal fraction is less than 4%.

Research paper thumbnail of OP04.10: Tetralogy of Fallot in the fetus in the current era

Ultrasound in Obstetrics and Gynecology, 2006

Research paper thumbnail of Cervical length and maternal factors in expectantly managed prolonged pregnancy: prediction of onset of labor and mode of delivery

Ultrasound in Obstetrics and Gynecology, 2008

Objective To examine the value of combining cervical length and maternal characteristics in a pro... more Objective To examine the value of combining cervical length and maternal characteristics in a prolongedpregnancy clinic in the prediction of the probability of firstly, spontaneous onset of labor within the subsequent 10 days and secondly, the need for Cesarean section.

Research paper thumbnail of Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre-eclampsia

Ultrasound in Obstetrics and Gynecology, 2008

Objective To investigate the potential value of maternal serum placental growth factor (PlGF) in ... more Objective To investigate the potential value of maternal serum placental growth factor (PlGF) in first-trimester screening for pre-eclampsia (PE). Methods The concentration of PlGF at 11 + 0 to 13 + 6 weeks' gestation was measured in samples from 127 pregnancies that developed PE, including 29 that required delivery before 34 weeks (early PE) and 98 with late PE, 88 cases of gestational hypertension (GH) and 609 normal controls. The distributions of PlGF multiples of the median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to determine the factors with a significant contribution for predicting PE. Results In the control group significant independent contributions for log PlGF were provided by fetal crown-rump length, maternal weight, cigarette smoking and racial origin, and after correction for these variables the median MoM PlGF was 0.991. In the early-PE and late-PE groups PlGF (0.611 MoM and 0.822 MoM, respectively; P < 0.0001) and pregnancyassociated plasma protein-A (PAPP-A) (0.535 MoM; P < 0.0001 and 0.929 MoM; P = 0.015, respectively) were reduced but in GH (PlGF: 0.966 MoM; PAPP-A: 0.895 MoM) there were no significant differences from controls. Significant contributions for the prediction of PE were provided by maternal characteristics and obstetric history, serum PlGF and uterine artery pulsatility index (PI) and with combined screening the detection rates for early PE and late PE were 90% and 49%, respectively, for a false-positive rate of 10%. Conclusion Effective screening for PE can be provided by a combination of maternal characteristics and obstetric history, uterine artery PI and maternal serum PlGF at 11 + 0 to 13 + 6 weeks' gestation.

Research paper thumbnail of First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing

Ultrasound in Obstetrics & Gynecology, 2013

Objective To define risk cut-offs with corresponding detection rates (DR) and false-positive rate... more Objective To define risk cut-offs with corresponding detection rates (DR) and false-positive rates (FPR) in screening for trisomy 21 using maternal age and combinations of first-trimester biomarkers in order to determine which women should undergo contingent maternal blood cell-free (cf) DNA testing. (DV-PIV) at 11 + 0 to 13 + 6 weeks' gestation and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and alpha-fetoprotein (AFP) at 8 + 0 to 13 + 6 weeks. Estimates of risk cutoffs, DRs and FPRs were derived for combinations of biomarkers and these were used to define the best strategy for contingent cfDNA testing.

Research paper thumbnail of Maternal serum placental growth factor at 11-13 weeks in chromosomally abnormal pregnancies

Ultrasound in Obstetrics and Gynecology, 2009

Objectives To investigate the potential value of maternal serum placental growth factor (PlGF) in... more Objectives To investigate the potential value of maternal serum placental growth factor (PlGF) in first-trimester screening for trisomy 21 and other major chromosomal abnormalities.

Research paper thumbnail of First-trimester maternal serum tumor necrosis factor receptor-1 and pre-eclampsia

Ultrasound in Obstetrics and Gynecology, 2009

Objectives To examine whether the maternal serum concentration of the soluble receptor-1 of tumor... more Objectives To examine whether the maternal serum concentration of the soluble receptor-1 of tumor necrosis factor-α (TNF-R1) at 11-13 weeks of gestation in pregnancies that subsequently develop pre-eclampsia is different from that in women without this complication.

Research paper thumbnail of Maternal Thyroid Function at Gestational Weeks 11–13 in Twin Pregnancies

Thyroid, 2013

Thyroid disease during pregnancy may be associated with increased risk of various pregnancy compl... more Thyroid disease during pregnancy may be associated with increased risk of various pregnancy complications. It is known that serum thyrotropin (TSH) is suppressed because of the increased hormone production induced by human chorionic gonadotrophin (hCG) in early pregnancy, and that higher hCG levels in twin pregnancies may cause a more pronounced physiologic suppression. The recognition of this phenomenon is important in order to avoid unnecessary concerns and to correctly establish the diagnosis of overt thyroid disease in twin pregnancies. The aim of this study was to establish reference ranges of maternal serum TSH and free thyroxine (FT4) at gestational weeks 11-13 in twin pregnancies. This is a case series of 177 dichorionic and 58 monochorionic twin pregnancies with normal outcomes, and 19 monochorionic pregnancies complicated by severe twin-twin transfusion syndrome. Maternal serum concentrations of TSH, FT4, antithyroperoxidase, and antithyroglobulin antibodies were measured at gestational weeks 11-13. The measured TSH and FT4 were converted to multiple of median (MoM) of normal singleton pregnancies and MoM values in the different groups were compared. In the antibody-negative twin pregnancies with normal outcomes, compared to singletons, serum TSH MoM was lower (median 0.62 [interquartile range [IQR 0.16-1.18] vs. 1.01 [IQR 0.61-1.51]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), FT4 MoM was not significantly different (median 0.98 [IQR 0.91-1.08] vs. 0.99 [IQR 0.91-1.09]; p = 0.975), and free β-hCG MoM was higher (median 1.91 [IQR 1.33-2.59] vs. 0.98 [IQR 0.66-1.50]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). In the antibody-positive group (n = 37), compared to the negative group (n = 198), the median TSH was higher, but FT4 and free β-hCG were not significantly different. In the twin-twin transfusion syndrome group, compared to normal twin pregnancies, TSH, FT4, and free β-hCG were not significantly different. In twins, compared to singleton pregnancies, TSH is lower but FT4 is not significantly different. These reference ranges of thyroid hormones in twins can form the basis for the study of early thyroid function in pathological pregnancies and the investigation of the consequences of overt and subclinical hypothyroidism on twin pregnancy outcome.

Research paper thumbnail of Demographic factors that can be used to predict early-onset pre-eclampsia

Journal of Maternal-Fetal and Neonatal Medicine, 2014

Objective: To define the maternal demographic factors that predicts the risk of developing early-... more Objective: To define the maternal demographic factors that predicts the risk of developing early-onset pre-eclampsia (requiring delivery before 34 weeks' gestation) in an Australian population. These are compared to risk factors described in a British population to determine whether the Fetal Medicine Foundation (FMF) risk algorithm for predicting early-onset pre-eclampsia needs to be modified for an Australian population. Methods: A secondary analysis of prospective cohorts in Australia and in the United Kingdom was conducted. Demographic details and past medical history were obtained. Odds ratios (ORs) for the development of early-onset pre-eclampsia were calculated for maternal factors in both populations. Forest plots were used to compare the two sets of odds ratios. Results: In the Australian population, pre-existing hypertension (OR 19.89, and body mass index 440 kg/m 2 (OR 9.04, 95% CI 1.13-72.40) predicted risk of developing early-onset pre-eclampsia. There were no significant differences in the odds ratios for maternal factors in the two populations.

Research paper thumbnail of Reference range of birth weight with gestation and first-trimester prediction of small-for-gestation neonates

Prenatal Diagnosis, 2011

Objective Firstly, to establish a reference range of birth weight with gestation at delivery; sec... more Objective Firstly, to establish a reference range of birth weight with gestation at delivery; secondly, to identify maternal characteristics that are significantly associated with birth weight; and thirdly, to determine if combinations of maternal characteristics, fetal nuchal translucency thickness (NT), and serum concentrations of free beta-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) are significant predictors of small-for-gestational-age (SGA) neonates in the absence of preeclampsia.

Research paper thumbnail of Maternal serum retinol-binding protein-4 at 11–13weeks’ gestation in normal and pathological pregnancies

Metabolism, 2013

Objective. To examine maternal serum levels of retinol-binding protein-4 (RBP4) at 11-13 weeks' g... more Objective. To examine maternal serum levels of retinol-binding protein-4 (RBP4) at 11-13 weeks' gestation in normal and pathological pregnancies.

Research paper thumbnail of Contingent Screening for Small by Weight for Gestational Age Neonates

Pediatric endocrinology reviews : PER, 2016

Effective screening for small for gestational age neonates (SGA), in the absence of preeclampsia,... more Effective screening for small for gestational age neonates (SGA), in the absence of preeclampsia, can be accomplished using a contingent screening method. The basis for the contingent model is a combined assessment at 19-24 weeks gestation to stratify patients according to their risk. We can then identify prenatally over 90% of SGA neonates for a false positive rate of 10%.

Research paper thumbnail of Cervical cerclage for preterm birth prevention in twin gestations with short cervix: a retrospective cohort study

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 16, 2016

To determine if cervical cerclage reduces the rate of spontaneous early preterm birth in cases of... more To determine if cervical cerclage reduces the rate of spontaneous early preterm birth in cases of ultrasound detected short cervix in dichorionic/diamniotic (DC-DA) twins. This was a retrospective cohort study on DC-DA twins. The cases were 40 consecutive DC-DA twins at Saint Peter's University Hospital from November 2006 through May 2012 where cervical cerclage was performed for ultrasound determined cervical length of 1-24 mm at 16-24 weeks' gestation. The cases were matched with 40 controls with no cerclage for cervical length and gestational age at cervical assessment. The primary outcome measure was spontaneous birth at <32 weeks. There was no difference between the two groups in maternal age, body mass index, cigarette smoking, use of in-vitro fertilization, parity and prior spontaneous preterm birth. There were statistically more Caucasian women in the controls. In the cases, compared to controls, spontaneous delivery at <32 weeks was significantly less frequent...

Research paper thumbnail of First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing

Fetal diagnosis and therapy, 2014

To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in mate... more To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers. In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in...

Research paper thumbnail of Mean arterial pressure in the three trimesters of pregnancy: effects of maternal characteristics and medical history

Ultrasound in Obstetrics & Gynecology, 2015

To define the contribution of maternal variables which influence the measured mean arterial press... more To define the contribution of maternal variables which influence the measured mean arterial pressure (MAP) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and MAP was measured in women with singleton pregnancies attending for three routine hospital visits at 11(+0) -13(+6) , 19(+0) -24(+6) and 30(+0) -34(+6) or 35(+0) -37(+6) weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. For pregnancies delivering phenotypically normal live births or stillbirths at ≥24 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation, variables from maternal demographic characteristics and medical history important in the prediction of MAP were determined from a linear mixed effects multiple regression. MAP was measured in 75,841 cases in the first trimester, 30,447 in the second trimester and 31,673 in the third trimester. Significant independent contributions to MAP were provided by gestational age, maternal age, weight, height, Afro-Caribbean racial origin, cigarette smoking, family history of PE, history of PE in the previous pregnancy, inter-pregnancy interval, chronic hypertension and diabetes mellitus. The effects of some variables were similar and for others differed in the three different trimesters. Random effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured MAP and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates both in pregnancies that developed PE and in those without this pregnancy complication. A model was fitted to express the measured MAP into MoMs after adjustment for variables from maternal characteristics and medical history that affect this measurement.

Research paper thumbnail of Meta-analysis of second-trimester markers for trisomy 21

Ultrasound in Obstetrics & Gynecology, 2013

Objective To summarize by meta-analysis the accumulated data on the screening performance of seco... more Objective To summarize by meta-analysis the accumulated data on the screening performance of secondtrimester sonographic markers for fetal trisomy 21.

Research paper thumbnail of Competing Risks Model in Screening for Preeclampsia by Biophysical and Biochemical Markers at 30-33 Weeks' Gestation

Fetal Diagnosis and Therapy, 2014

To assess the risk for preeclampsia (PE) by maternal characteristics, uterine artery pulsatility ... more To assess the risk for preeclampsia (PE) by maternal characteristics, uterine artery pulsatility index (Ut-PI), mean arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) at 30-33 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. This was a screening study in singleton pregnancies including 2,140 that developed PE and 83,615 that were unaffected by PE. We developed a survival time model for the time of delivery for PE by combining maternal characteristics and history with Ut-PI, MAP, PlGF and sFlt-1 multiple of the median (MoM) values (combined test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE, and 13,878 unaffected pregnancies and data on PlGF and sFlt-1 were available in 118 cases of PE and 3,734 unaffected pregnancies. Modelled detection rate of all PE and PE requiring delivery within 4 and 6 weeks of the visit was estimated. Screening by the combined test would detect 66, 98 and 86% of all PE and PE requiring delivery within 4 and 6 weeks of the visit, respectively, at a false positive rate of 5%. Screening by biophysical and biochemical testing at 30-33 weeks could identify most pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Research paper thumbnail of Competing Risk Model in Screening for Preeclampsia by Mean Arterial Pressure and Uterine Artery Pulsatility Index at 30-33 Weeks' Gestation

Fetal Diagnosis and Therapy, 2014

To assess risk for preeclampsia (PE) based on maternal characteristics, mean arterial pressure (M... more To assess risk for preeclampsia (PE) based on maternal characteristics, mean arterial pressure (MAP) and uterine artery pulsatility index (Ut-PI) at 30-33 weeks&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; gestation. Screening study in singleton pregnancies including 2,140 that subsequently developed PE and 83,615 that were unaffected by PE, gestational hypertension or delivery of small-for-gestational-age neonates (normal group). We developed a survival time model for the time of delivery for PE by combination of maternal characteristics and history with MAP and Ut-PI multiple of the median (MoM) values (biophysical test). Data on third-trimester MAP and Ut-PI were available in 350 cases of PE and 13,878 of the normal group. The detection rate of PE requiring delivery within 4, 6 and 8 weeks of the visit was estimated. In pregnancies with PE the log10 MoM values of MAP and Ut-PI were inversely related to gestational age at delivery. Biophysical testing detected 90, 65 and 53% of PE with delivery within 4, 6 and 8 weeks of the visit, at a fixed false-positive rate of 5%. Testing by maternal characteristics, Ut-PI and MAP at 30-33 weeks could identify 90% of pregnancies developing PE and requiring delivery within the subsequent 4 weeks.

Research paper thumbnail of Is high fetal nuchal translucency associated with submicroscopic chromosomal abnormalities on array CGH?

Ultrasound in Obstetrics & Gynecology, 2014

Objective To examine the possible association between high fetal nuchal translucency thickness (N... more Objective To examine the possible association between high fetal nuchal translucency thickness (NT) and pathogenic chromosomal copy number variants (CNVs) detected by array comparative genomic hybridization (CGH) in pregnancies with normal fetal karyotype.

Research paper thumbnail of How feasible is expectant management of interstitial ectopic pregnancy?

Ultrasound in Obstetrics & Gynecology, 2014

Methods We identified all women with an ultrasound diagnosis of interstitial pregnancy seen withi... more Methods We identified all women with an ultrasound diagnosis of interstitial pregnancy seen within a 9year period (January 2004 to April 2013. The clinical history, ultrasound findings and biochemical results were reviewed. The outcome of all interstitial pregnancies managed conservatively was recorded. Treatment was considered as successful when the serum β-human chorionic gonadotropin (β-hCG) level declined below 20 IU/L without the need for further intervention.

Research paper thumbnail of Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: relation to maternal and fetal characteristics

Ultrasound in Obstetrics & Gynecology, 2013

Objective To examine the possible effects of maternal and fetal characteristics on the fetal frac... more Objective To examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free (cf) DNA at 11-13 weeks' gestation and estimate the proportion of pregnancies at high risk of non-invasive prenatal testing (NIPT) failure because the fetal fraction is less than 4%.

Research paper thumbnail of OP04.10: Tetralogy of Fallot in the fetus in the current era

Ultrasound in Obstetrics and Gynecology, 2006

Research paper thumbnail of Cervical length and maternal factors in expectantly managed prolonged pregnancy: prediction of onset of labor and mode of delivery

Ultrasound in Obstetrics and Gynecology, 2008

Objective To examine the value of combining cervical length and maternal characteristics in a pro... more Objective To examine the value of combining cervical length and maternal characteristics in a prolongedpregnancy clinic in the prediction of the probability of firstly, spontaneous onset of labor within the subsequent 10 days and secondly, the need for Cesarean section.

Research paper thumbnail of Maternal serum placental growth factor at 11 + 0 to 13 + 6 weeks of gestation in the prediction of pre-eclampsia

Ultrasound in Obstetrics and Gynecology, 2008

Objective To investigate the potential value of maternal serum placental growth factor (PlGF) in ... more Objective To investigate the potential value of maternal serum placental growth factor (PlGF) in first-trimester screening for pre-eclampsia (PE). Methods The concentration of PlGF at 11 + 0 to 13 + 6 weeks' gestation was measured in samples from 127 pregnancies that developed PE, including 29 that required delivery before 34 weeks (early PE) and 98 with late PE, 88 cases of gestational hypertension (GH) and 609 normal controls. The distributions of PlGF multiples of the median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to determine the factors with a significant contribution for predicting PE. Results In the control group significant independent contributions for log PlGF were provided by fetal crown-rump length, maternal weight, cigarette smoking and racial origin, and after correction for these variables the median MoM PlGF was 0.991. In the early-PE and late-PE groups PlGF (0.611 MoM and 0.822 MoM, respectively; P < 0.0001) and pregnancyassociated plasma protein-A (PAPP-A) (0.535 MoM; P < 0.0001 and 0.929 MoM; P = 0.015, respectively) were reduced but in GH (PlGF: 0.966 MoM; PAPP-A: 0.895 MoM) there were no significant differences from controls. Significant contributions for the prediction of PE were provided by maternal characteristics and obstetric history, serum PlGF and uterine artery pulsatility index (PI) and with combined screening the detection rates for early PE and late PE were 90% and 49%, respectively, for a false-positive rate of 10%. Conclusion Effective screening for PE can be provided by a combination of maternal characteristics and obstetric history, uterine artery PI and maternal serum PlGF at 11 + 0 to 13 + 6 weeks' gestation.

Research paper thumbnail of First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing

Ultrasound in Obstetrics & Gynecology, 2013

Objective To define risk cut-offs with corresponding detection rates (DR) and false-positive rate... more Objective To define risk cut-offs with corresponding detection rates (DR) and false-positive rates (FPR) in screening for trisomy 21 using maternal age and combinations of first-trimester biomarkers in order to determine which women should undergo contingent maternal blood cell-free (cf) DNA testing. (DV-PIV) at 11 + 0 to 13 + 6 weeks' gestation and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and alpha-fetoprotein (AFP) at 8 + 0 to 13 + 6 weeks. Estimates of risk cutoffs, DRs and FPRs were derived for combinations of biomarkers and these were used to define the best strategy for contingent cfDNA testing.

Research paper thumbnail of Maternal serum placental growth factor at 11-13 weeks in chromosomally abnormal pregnancies

Ultrasound in Obstetrics and Gynecology, 2009

Objectives To investigate the potential value of maternal serum placental growth factor (PlGF) in... more Objectives To investigate the potential value of maternal serum placental growth factor (PlGF) in first-trimester screening for trisomy 21 and other major chromosomal abnormalities.

Research paper thumbnail of First-trimester maternal serum tumor necrosis factor receptor-1 and pre-eclampsia

Ultrasound in Obstetrics and Gynecology, 2009

Objectives To examine whether the maternal serum concentration of the soluble receptor-1 of tumor... more Objectives To examine whether the maternal serum concentration of the soluble receptor-1 of tumor necrosis factor-α (TNF-R1) at 11-13 weeks of gestation in pregnancies that subsequently develop pre-eclampsia is different from that in women without this complication.

Research paper thumbnail of Maternal Thyroid Function at Gestational Weeks 11–13 in Twin Pregnancies

Thyroid, 2013

Thyroid disease during pregnancy may be associated with increased risk of various pregnancy compl... more Thyroid disease during pregnancy may be associated with increased risk of various pregnancy complications. It is known that serum thyrotropin (TSH) is suppressed because of the increased hormone production induced by human chorionic gonadotrophin (hCG) in early pregnancy, and that higher hCG levels in twin pregnancies may cause a more pronounced physiologic suppression. The recognition of this phenomenon is important in order to avoid unnecessary concerns and to correctly establish the diagnosis of overt thyroid disease in twin pregnancies. The aim of this study was to establish reference ranges of maternal serum TSH and free thyroxine (FT4) at gestational weeks 11-13 in twin pregnancies. This is a case series of 177 dichorionic and 58 monochorionic twin pregnancies with normal outcomes, and 19 monochorionic pregnancies complicated by severe twin-twin transfusion syndrome. Maternal serum concentrations of TSH, FT4, antithyroperoxidase, and antithyroglobulin antibodies were measured at gestational weeks 11-13. The measured TSH and FT4 were converted to multiple of median (MoM) of normal singleton pregnancies and MoM values in the different groups were compared. In the antibody-negative twin pregnancies with normal outcomes, compared to singletons, serum TSH MoM was lower (median 0.62 [interquartile range [IQR 0.16-1.18] vs. 1.01 [IQR 0.61-1.51]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), FT4 MoM was not significantly different (median 0.98 [IQR 0.91-1.08] vs. 0.99 [IQR 0.91-1.09]; p = 0.975), and free β-hCG MoM was higher (median 1.91 [IQR 1.33-2.59] vs. 0.98 [IQR 0.66-1.50]; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). In the antibody-positive group (n = 37), compared to the negative group (n = 198), the median TSH was higher, but FT4 and free β-hCG were not significantly different. In the twin-twin transfusion syndrome group, compared to normal twin pregnancies, TSH, FT4, and free β-hCG were not significantly different. In twins, compared to singleton pregnancies, TSH is lower but FT4 is not significantly different. These reference ranges of thyroid hormones in twins can form the basis for the study of early thyroid function in pathological pregnancies and the investigation of the consequences of overt and subclinical hypothyroidism on twin pregnancy outcome.

Research paper thumbnail of Demographic factors that can be used to predict early-onset pre-eclampsia

Journal of Maternal-Fetal and Neonatal Medicine, 2014

Objective: To define the maternal demographic factors that predicts the risk of developing early-... more Objective: To define the maternal demographic factors that predicts the risk of developing early-onset pre-eclampsia (requiring delivery before 34 weeks' gestation) in an Australian population. These are compared to risk factors described in a British population to determine whether the Fetal Medicine Foundation (FMF) risk algorithm for predicting early-onset pre-eclampsia needs to be modified for an Australian population. Methods: A secondary analysis of prospective cohorts in Australia and in the United Kingdom was conducted. Demographic details and past medical history were obtained. Odds ratios (ORs) for the development of early-onset pre-eclampsia were calculated for maternal factors in both populations. Forest plots were used to compare the two sets of odds ratios. Results: In the Australian population, pre-existing hypertension (OR 19.89, and body mass index 440 kg/m 2 (OR 9.04, 95% CI 1.13-72.40) predicted risk of developing early-onset pre-eclampsia. There were no significant differences in the odds ratios for maternal factors in the two populations.

Research paper thumbnail of Reference range of birth weight with gestation and first-trimester prediction of small-for-gestation neonates

Prenatal Diagnosis, 2011

Objective Firstly, to establish a reference range of birth weight with gestation at delivery; sec... more Objective Firstly, to establish a reference range of birth weight with gestation at delivery; secondly, to identify maternal characteristics that are significantly associated with birth weight; and thirdly, to determine if combinations of maternal characteristics, fetal nuchal translucency thickness (NT), and serum concentrations of free beta-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) are significant predictors of small-for-gestational-age (SGA) neonates in the absence of preeclampsia.

Research paper thumbnail of Maternal serum retinol-binding protein-4 at 11–13weeks’ gestation in normal and pathological pregnancies

Metabolism, 2013

Objective. To examine maternal serum levels of retinol-binding protein-4 (RBP4) at 11-13 weeks' g... more Objective. To examine maternal serum levels of retinol-binding protein-4 (RBP4) at 11-13 weeks' gestation in normal and pathological pregnancies.