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Papers by Baskaran Thilaganathan

Research paper thumbnail of Agreement between predicted risk and prevalence of Down syndrome in first trimester nuchal translucency screening

Prenatal Diagnosis, 2002

The agreement between predicted risks of Down syndrome and observed prevalence was investigated i... more The agreement between predicted risks of Down syndrome and observed prevalence was investigated in a population of 11 847 singleton pregnancies screened by first trimester nuchal translucency at a single institution. Twenty-seven cases of Down syndrome were observed; 20 were detected prenatally by nuchal translucency and maternal age screening, three by other means and four postnatally. The screened women were grouped according to their predicted risk of having an affected pregnancy, and this was compared with the observed prevalence. A significant correlation between predicted and observed prevalences was noted, thus demonstrating that risk estimates for Down syndrome based on first trimester nuchal translucency screening are accurate. Copyright © 2002 John Wiley & Sons, Ltd.

Research paper thumbnail of Platelet size and glycoprotein Ib and IIIa expression in normal fetal and maternal blood

Our purpose was to study platelet size and surface glycoprotein expression in normal fetal and ma... more Our purpose was to study platelet size and surface glycoprotein expression in normal fetal and maternal blood throughout pregnancy. A cross-sectional study was performed at the Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London. Fetal and maternal blood samples were obtained from uncomplicated pregnancies at 8 to 42 weeks' gestation (n = 101 and n = 117, respectively) and from 30 nonpregnant controls. Flow cytometry was used to determine platelet size and glycoprotein Ib and IIIa expression both before and after stimulation with adenosine diphosphate. Mean platelet size in both fetal and maternal blood was significantly lower than that of nonpregnant controls and decreased with advancing gestation. The surface density of glycoprotein Ib in maternal and fetal platelets was significantly lower than in nonpregnant controls but did not change with gestation. Adenosine diphosphate stimulation of maternal platelets resulted in increased percentage expression and surface density of all glycoproteins, whereas stimulation of control platelets resulted in increased surface density of glycoprotein Ib and percentage expression of glycoprotein IIIa. Adenosine diphosphate stimulation of fetal platelets resulted in increased surface density of glycoprotein Ib and IIIa. Pregnancy is associated with increased thrombocytopoiesis in both the mother and fetus. Maternal platelet glycoprotein expression and responsiveness to adenosine diphosphate stimulation is increased. Fetal platelets are phenotypically mature from at least 12 weeks' gestation and respond in an adultlike fashion to stimulation with adenosine diphosphate.

Research paper thumbnail of Labor: An immunologically beneficial process for the neonate

Leukocyte counts and lymphocyte subpopulations were measured in umbilical cord blood obtained fro... more Leukocyte counts and lymphocyte subpopulations were measured in umbilical cord blood obtained from normal pregnancies delivered either vaginally or by elective cesarean section. In the group delivered vaginally there were significantly higher median values for neutrophils, monocytes, and natural killer cells. The leukocytosis associated with labor is selective for mediators of nonspecific or innate immunity. Labor may be an immunologically beneficial process for the neonate. (AM J OSSlET GVNECOL 1994; 171 : 1271-2.)

Research paper thumbnail of Doppler assessment and biophysical profile in growth restricted fetuses (IUGR): Interaction of test parameters

Research paper thumbnail of 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial

The Lancet, 2015

Background No consensus exists for the best way to monitor and when to trigger delivery in mother... more Background No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV).

Research paper thumbnail of Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia

Journal of leukocyte biology, 2015

During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua)... more During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor bl...

Research paper thumbnail of Recurrence of hypertensive disorders of pregnancy, an Individual Patient Data Meta-Analysis

American journal of obstetrics and gynecology, Jan 9, 2015

We performed an Individual Participant Data (IPD) meta-analysis to calculate the recurrence risk ... more We performed an Individual Participant Data (IPD) meta-analysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. We performed an electronic literature search for cohort studies that reported on women suffering from HDP and who had a subsequent pregnancy. The principal investigators were contacted, informed and requested for their original study data. The obtained data were merged to form one combined database. The results will be presented as % with 95% confidence interval (CI) and odds ratios (OR) with 95% CI. Out of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies using published data (IPD where available) showed a recurrence rate of 18.1% (N=152,213, 95% CI: 17.9 - 18.3). In the 22 studies included in our IPD, the recurrence rate of a HDP was 20.7% (95%CI: 20.4 - 20.9). Recurrence manifested as preeclampsia (PE) in 13.8% (95%CI: ...

Research paper thumbnail of Thresholds for intervention in severe early onset growth restriction (IUGR)

American Journal of Obstetrics and Gynecology, 2004

Research paper thumbnail of Uterine artery Doppler, birthweight and timing of preeclampsia onset: providing insights into the dual etiology of late-onset preeclampsia

Ultrasound in Obstetrics & Gynecology, 2014

To investigate the relationship between uterine artery Doppler ultrasound indices and birth weigh... more To investigate the relationship between uterine artery Doppler ultrasound indices and birth weight in women with early-, intermediate- and late-onset pre-eclampsia as compared with women with uneventful pregnancy outcome. In a retrospective, observational cohort study, uterine artery Doppler assessment was carried out at 18+0 to 23+6 weeks' gestation in 26,893 women attending for routine antenatal care in a tertiary care center. The mean resistance index (RI) and its relationship to the outcome of pregnancy and birth-weight centiles were evaluated. Uterine artery RI showed a significant, negative correlation with birth weight (r= -0.20, P<0.0001). Patients with early-onset pre-eclampsia had an increased prevalence of high uterine artery mean RI, above the 90(th) centile, corresponding to an increased proportion of small-for-gestational age (SGA) neonates with a birth weight below the 10(th) centile. In late-onset pre-eclampsia, however, there was an unexpectedly higher proportion of large-for-gestational-age (LGA) neonates with a birth weight above the 90(th) centile without a concurrent increase in the prevalence of low uterine artery mean RI below the 10(th) centile. The finding of a bimodal skewed distribution of birth weight, with neonates exhibiting a higher prevalence of both LGA and SGA with late-onset pre-eclampsia, indicates that there are two types of late-onset pre-eclampsia. These findings explain the poor performance of mid-trimester uterine artery Doppler in predicting pre-eclampsia at term and provide insights into the placental origins of the early and late forms of pre-eclampsia.

Research paper thumbnail of First-trimester nuchal translucency, nasal bones, and trisomy 21 in selected and unselected populations

American Journal of Obstetrics and Gynecology, 2006

Objective: The purpose of this study was to assess the role of fetal nasal bones evaluation in fi... more Objective: The purpose of this study was to assess the role of fetal nasal bones evaluation in firsttrimester screening for trisomy 21 in selected and unselected pregnancies. Study design: Visualization of the nasal bones was attempted in women attending for routine nuchal translucency screening (unselected population, n = 7116, 12 cases of trisomy 21), as well as in high-risk pregnancies referred to our tertiary care center (selected population, n = 510, 23 cases of trisomy 21). Results: The sensitivity, specificity, positive and negative predictive value of absent nasal bones for trisomy 21 were 16.7%, 97.3%, 1.1%, 99.8% and 47.6%, 95.3%, 33.3%, 97.4% in the unselected and selected population, respectively. At logistic regression analysis including nuchal translucency and nasal bones findings, the latter resulted to be an independent predictor of trisomy 21 in the selected but not in the unselected population. Conclusion: First-trimester nasal bones assessment for trisomy 21 screening has a very different performance in selected and unselected pregnancies.

Research paper thumbnail of Decreased endovascular trophoblast invasion in first-trimester pregnancies with high-resistance uterine artery doppler indices

American Journal of Obstetrics and Gynecology - AMER J OBSTET GYNECOL, 2003

BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis o... more BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis of preeclampsia. This study investigates the relationship between Doppler assessment of uterine artery resistance and endovascular trophoblastic invasion in the ®rst trimester of pregnancy. METHODS: Patients undergoing termination of pregnancy for non-medical reasons were categorized as having a low-or high-resistance uterine artery blood¯ow pattern by transabdominal Doppler ultrasound. Products of conception were examined histologically with regard to the extent of decidual endovascular trophoblast invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine artery blood¯ow pregnancies identi®ed at 10±14 weeks of gestation. Normal intradecidual endovascular trophoblast invasion was identi®ed with a similar frequency in both groups (P = 0.79). However, the proportion of decidual vessels with endovascular trophoblast invasion was signi®cantly higher in the low-resistance pregnancies (49%) compared with the high-resistance ones (34%, P = 0.02). CONCLUSIONS: The ®ndings of this study support the use of uterine artery Doppler investigation for the non-invasive assessment of trophoblast invasion in early pregnancy. Further studies are necessary to clarify the biological signi®cance of these observations and their potential clinical applications.

Research paper thumbnail of Agreement between predicted risk and prevalence of Down syndrome in first trimester nuchal translucency screening

Prenatal Diagnosis, 2002

The agreement between predicted risks of Down syndrome and observed prevalence was investigated i... more The agreement between predicted risks of Down syndrome and observed prevalence was investigated in a population of 11 847 singleton pregnancies screened by first trimester nuchal translucency at a single institution. Twenty-seven cases of Down syndrome were observed; 20 were detected prenatally by nuchal translucency and maternal age screening, three by other means and four postnatally. The screened women were grouped according to their predicted risk of having an affected pregnancy, and this was compared with the observed prevalence. A significant correlation between predicted and observed prevalences was noted, thus demonstrating that risk estimates for Down syndrome based on first trimester nuchal translucency screening are accurate. Copyright © 2002 John Wiley & Sons, Ltd.

Research paper thumbnail of Platelet size and glycoprotein Ib and IIIa expression in normal fetal and maternal blood

Our purpose was to study platelet size and surface glycoprotein expression in normal fetal and ma... more Our purpose was to study platelet size and surface glycoprotein expression in normal fetal and maternal blood throughout pregnancy. A cross-sectional study was performed at the Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London. Fetal and maternal blood samples were obtained from uncomplicated pregnancies at 8 to 42 weeks' gestation (n = 101 and n = 117, respectively) and from 30 nonpregnant controls. Flow cytometry was used to determine platelet size and glycoprotein Ib and IIIa expression both before and after stimulation with adenosine diphosphate. Mean platelet size in both fetal and maternal blood was significantly lower than that of nonpregnant controls and decreased with advancing gestation. The surface density of glycoprotein Ib in maternal and fetal platelets was significantly lower than in nonpregnant controls but did not change with gestation. Adenosine diphosphate stimulation of maternal platelets resulted in increased percentage expression and surface density of all glycoproteins, whereas stimulation of control platelets resulted in increased surface density of glycoprotein Ib and percentage expression of glycoprotein IIIa. Adenosine diphosphate stimulation of fetal platelets resulted in increased surface density of glycoprotein Ib and IIIa. Pregnancy is associated with increased thrombocytopoiesis in both the mother and fetus. Maternal platelet glycoprotein expression and responsiveness to adenosine diphosphate stimulation is increased. Fetal platelets are phenotypically mature from at least 12 weeks' gestation and respond in an adultlike fashion to stimulation with adenosine diphosphate.

Research paper thumbnail of Labor: An immunologically beneficial process for the neonate

Leukocyte counts and lymphocyte subpopulations were measured in umbilical cord blood obtained fro... more Leukocyte counts and lymphocyte subpopulations were measured in umbilical cord blood obtained from normal pregnancies delivered either vaginally or by elective cesarean section. In the group delivered vaginally there were significantly higher median values for neutrophils, monocytes, and natural killer cells. The leukocytosis associated with labor is selective for mediators of nonspecific or innate immunity. Labor may be an immunologically beneficial process for the neonate. (AM J OSSlET GVNECOL 1994; 171 : 1271-2.)

Research paper thumbnail of Doppler assessment and biophysical profile in growth restricted fetuses (IUGR): Interaction of test parameters

Research paper thumbnail of 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial

The Lancet, 2015

Background No consensus exists for the best way to monitor and when to trigger delivery in mother... more Background No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction. We aimed to assess whether changes in the fetal ductus venosus Doppler waveform (DV) could be used as indications for delivery instead of cardiotocography short-term variation (STV).

Research paper thumbnail of Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia

Journal of leukocyte biology, 2015

During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua)... more During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor bl...

Research paper thumbnail of Recurrence of hypertensive disorders of pregnancy, an Individual Patient Data Meta-Analysis

American journal of obstetrics and gynecology, Jan 9, 2015

We performed an Individual Participant Data (IPD) meta-analysis to calculate the recurrence risk ... more We performed an Individual Participant Data (IPD) meta-analysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. We performed an electronic literature search for cohort studies that reported on women suffering from HDP and who had a subsequent pregnancy. The principal investigators were contacted, informed and requested for their original study data. The obtained data were merged to form one combined database. The results will be presented as % with 95% confidence interval (CI) and odds ratios (OR) with 95% CI. Out of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies using published data (IPD where available) showed a recurrence rate of 18.1% (N=152,213, 95% CI: 17.9 - 18.3). In the 22 studies included in our IPD, the recurrence rate of a HDP was 20.7% (95%CI: 20.4 - 20.9). Recurrence manifested as preeclampsia (PE) in 13.8% (95%CI: ...

Research paper thumbnail of Thresholds for intervention in severe early onset growth restriction (IUGR)

American Journal of Obstetrics and Gynecology, 2004

Research paper thumbnail of Uterine artery Doppler, birthweight and timing of preeclampsia onset: providing insights into the dual etiology of late-onset preeclampsia

Ultrasound in Obstetrics & Gynecology, 2014

To investigate the relationship between uterine artery Doppler ultrasound indices and birth weigh... more To investigate the relationship between uterine artery Doppler ultrasound indices and birth weight in women with early-, intermediate- and late-onset pre-eclampsia as compared with women with uneventful pregnancy outcome. In a retrospective, observational cohort study, uterine artery Doppler assessment was carried out at 18+0 to 23+6 weeks' gestation in 26,893 women attending for routine antenatal care in a tertiary care center. The mean resistance index (RI) and its relationship to the outcome of pregnancy and birth-weight centiles were evaluated. Uterine artery RI showed a significant, negative correlation with birth weight (r= -0.20, P<0.0001). Patients with early-onset pre-eclampsia had an increased prevalence of high uterine artery mean RI, above the 90(th) centile, corresponding to an increased proportion of small-for-gestational age (SGA) neonates with a birth weight below the 10(th) centile. In late-onset pre-eclampsia, however, there was an unexpectedly higher proportion of large-for-gestational-age (LGA) neonates with a birth weight above the 90(th) centile without a concurrent increase in the prevalence of low uterine artery mean RI below the 10(th) centile. The finding of a bimodal skewed distribution of birth weight, with neonates exhibiting a higher prevalence of both LGA and SGA with late-onset pre-eclampsia, indicates that there are two types of late-onset pre-eclampsia. These findings explain the poor performance of mid-trimester uterine artery Doppler in predicting pre-eclampsia at term and provide insights into the placental origins of the early and late forms of pre-eclampsia.

Research paper thumbnail of First-trimester nuchal translucency, nasal bones, and trisomy 21 in selected and unselected populations

American Journal of Obstetrics and Gynecology, 2006

Objective: The purpose of this study was to assess the role of fetal nasal bones evaluation in fi... more Objective: The purpose of this study was to assess the role of fetal nasal bones evaluation in firsttrimester screening for trisomy 21 in selected and unselected pregnancies. Study design: Visualization of the nasal bones was attempted in women attending for routine nuchal translucency screening (unselected population, n = 7116, 12 cases of trisomy 21), as well as in high-risk pregnancies referred to our tertiary care center (selected population, n = 510, 23 cases of trisomy 21). Results: The sensitivity, specificity, positive and negative predictive value of absent nasal bones for trisomy 21 were 16.7%, 97.3%, 1.1%, 99.8% and 47.6%, 95.3%, 33.3%, 97.4% in the unselected and selected population, respectively. At logistic regression analysis including nuchal translucency and nasal bones findings, the latter resulted to be an independent predictor of trisomy 21 in the selected but not in the unselected population. Conclusion: First-trimester nasal bones assessment for trisomy 21 screening has a very different performance in selected and unselected pregnancies.

Research paper thumbnail of Decreased endovascular trophoblast invasion in first-trimester pregnancies with high-resistance uterine artery doppler indices

American Journal of Obstetrics and Gynecology - AMER J OBSTET GYNECOL, 2003

BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis o... more BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis of preeclampsia. This study investigates the relationship between Doppler assessment of uterine artery resistance and endovascular trophoblastic invasion in the ®rst trimester of pregnancy. METHODS: Patients undergoing termination of pregnancy for non-medical reasons were categorized as having a low-or high-resistance uterine artery blood¯ow pattern by transabdominal Doppler ultrasound. Products of conception were examined histologically with regard to the extent of decidual endovascular trophoblast invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine artery blood¯ow pregnancies identi®ed at 10±14 weeks of gestation. Normal intradecidual endovascular trophoblast invasion was identi®ed with a similar frequency in both groups (P = 0.79). However, the proportion of decidual vessels with endovascular trophoblast invasion was signi®cantly higher in the low-resistance pregnancies (49%) compared with the high-resistance ones (34%, P = 0.02). CONCLUSIONS: The ®ndings of this study support the use of uterine artery Doppler investigation for the non-invasive assessment of trophoblast invasion in early pregnancy. Further studies are necessary to clarify the biological signi®cance of these observations and their potential clinical applications.