Papers by Basky Thilaganathan
American Journal of Obstetrics and Gynecology, 2015
Hypertension, Jan 14, 2015
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 18, 2015
Heart (British Cardiac Society)
Objective: To evaluate the effectiveness of adding outlet views to the four chamber view in routi... more Objective: To evaluate the effectiveness of adding outlet views to the four chamber view in routine prenatal ultrasound screening for major congenital heart defects (CHD) as performed by trained sonographers, and to compare the procedure with current practice. Design and setting: Prospective observational study at a London teaching hospital. Participants and methods: 9277 women booked at a single institution (80% had first trimester nuchal translucency measurement) due to have routine fetal cardiac screening using the four chamber and outflow tract views at > 18 weeks of gestation. Main outcome measure: Identification of major CHD in chromosomally normal and abnormal pregnancies antenatally or postnatally. Results: There were 40 abnormalities (4.3/1000), of which 30 were chromosomally normal (3.3/1000). The overall antenatal detection rate was 75% (95% confidence interval (CI) 59% to 87%) and 70% (95% CI 51% to 85%) for euploid pregnancies. Abnormal cardiac views accounted for 70% of all prenatal diagnoses, 30% of which were made at < 18 weeks. The sensitivity of cardiac views during the first scan at > 18 weeks was 52%. Of all patients undergoing nuchal translucency screening, 34 had major CHD, nine with increased nuchal translucency (26.5%). Factors influencing the results of this screening programme were training and audit of operators, adequate equipment for antenatal examination, ease of access, and low threshold for referral to specialised fetal echocardiography. Conclusion: Adding ventricular outlet views to the four chamber assessment of the heart at routine fetal anomaly scans at > 18 weeks is the most effective technique to detect CHD prenatally. The success of such a programme depends on an infrastructure committed to continuous in house training of obstetric ultrasonographers coupled with feedback from specialised fetal cardiologists, as well as adequate resource allocation to obstetric hospitals involved with antenatal screening.
American journal of obstetrics and gynecology, Jan 20, 2015
The aims of this study were evaluation of the association of reduced fetal movements (RFM) and sm... more The aims of this study were evaluation of the association of reduced fetal movements (RFM) and small-for-gestational-age (SGA) birth at term and to explore if fetal and maternal outcomes are different with single vs repeated episodes of RFM and normal fetal assessment test results. This was a retrospective cohort study of all singleton pregnancies referred for RFMs at a tertiary fetal medicine unit from January 2008 through September 2014. Ultrasound and Doppler indices were obtained from a computerized ultrasound database and pregnancy outcome was collected from hospital records. Of the 21,944 women with a singleton pregnancy booked for maternity care during the study period, 1234 women (5.62%) reported RFMs >36+0 weeks. Of these, 1029 women (83.4%) reported a single episode of RFM and 205 (16.6%) had ≥2 presentations for RFM. Women with repeated RFMs had a significantly higher mean uterine artery pulsatility index in the second trimester. The prevalence of SGA baby at birth in ...
Ultrasound in Obstetrics & Gynecology, 2015
Placental insufficiency contributes to the risk of stillbirth. Cerebroplacental ratio (CPR) is an... more Placental insufficiency contributes to the risk of stillbirth. Cerebroplacental ratio (CPR) is an emerging marker of placental insufficiency. The aim of this study was to evaluate the association between fetal CPR, uterine artery Doppler recorded in the third trimester, estimated fetal weight (EFW) and stillbirth. This was a retrospective cohort study including 2812 singleton pregnancies, which underwent an ultrasound scan in the third trimester. EFW were converted into centiles and Dopplers (uterine and CPR) into multiples of the median (MoM), adjusting for gestation. Regression analysis was performed to identify and adjust for potential confounders, while the ROC curve analysis was used to assess the predictive value. Adjusting for EFW centile and uterine artery mean PI MoM, CPR MoM remained an independent predictor of stillbirth and perinatal mortality (OR: 0.02, 95% CI 0.00-0.36; p=0.008 and 0.005, 95% CI 0.00-0.05, 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;lt;0.001, respectively). Uterine artery mean PI≥1.5MoM was significantly associated with low CPR MoM, even after adjusting for EFW centile or small for gestational age (SGA) (OR 5.22, 95% CI 3.88-7.04 and 4.73, 95% CI 3.49-6.41; 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;lt;0.001 for both). These associations remained significant excluding pregnancies with SGA or including only cases where Dopplers were recorded at term (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;lt;0.01). For stillbirth, the area under the curve (AUC) using the combination of these three parameters was 0.85 (95% CI 0.67-1.00), sensitivity 70.0%, specificity 92.1%, positive likelihood ratio (LR) 8.89, and the negative LR 0.33. Third trimester CPR is an independent predictor of stillbirth/perinatal mortality. The role of uterine Doppler, CPR and EFW in assessing risk of adverse pregnancy outcome should be evaluated prospectively.
Human Reproduction
Is there an association between discordance in embryonic growth and fetal loss at the time of the... more Is there an association between discordance in embryonic growth and fetal loss at the time of the 11-14-week scan in twin pregnancies? Regardless of the chorionicity, crown rump length (CRL) discordance at 7(+0)-9(+6) weeks is predictive of subsequent single fetal demise in the first trimester. Previous small studies have reported a variable association between discordance in embryonic growth and subsequent fetal loss. Retrospective study of all twin pregnancies of known chorionicity from a large regional cohort over a 10-year period. A total of 1356 twin pregnancies (288 monochorionic and 1068 dichorionic) were included in the study. Women presenting to the early pregnancy unit were included in the study. Logistic regression, ROC curve and Kaplan-Meier analyses were performed to evaluate the association between CRL discordance at 7(+0)-9(+6) weeks and spontaneous single fetal loss diagnosed at the 11-14-week scan. A systematic review was also performed using MEDLINE, EMBASE, Cinahl...
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, Jan 29, 2015
To assess the predictive accuracy for stillbirth of second trimester uterine artery Doppler. We s... more To assess the predictive accuracy for stillbirth of second trimester uterine artery Doppler. We searched MEDLINE, EMBASE and Cochrane databases from inception until March 2015 without language restrictions. Included studies were those that assessed the association of abnormal uterine artery Doppler parameters and stillbirth. Two independent reviewers selected studies, extracted data and assessed quality. Results for studies that were performed in the 2(nd) trimester were pooled and summary estimates of sensitivity, specificity, likelihood ratios and their 95% confidence intervals were obtained. Overall summary of test accuracy was provided by the diagnostic odds ratio. Literature searches returned 338 relevant citations with 32 considered in full. Thirteen studies met our search criteria, (85, 846 women, 508 stillbirths) and were included in the review. Bivariate pooled estimate for sensitivity was 65% (95% CI 38 - 85%) and for specificity it was 82% (95% CI 72- 88%). The positive l...
Ultrasound in Obstetrics & Gynecology, 2015
The aim of this systematic review and meta-analysis was to explore the pregnancy outcome in fetus... more The aim of this systematic review and meta-analysis was to explore the pregnancy outcome in fetuses with prenatal diagnosis of isolated posterior fossa anomalies. Medline and Embase were searched electronically utilizing combinations of the relevant medical subject heading for &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;posterior fossa&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;, and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;outcome. The posterior fossa anomalies analysed were: Dandy Walker malformation (DWM), mega cisterna magna (MCM), Blake&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;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;s pouch cyst (BPC) and vermian hypoplasia (VH). The outcomes observed were: the rate of chromosomal abnormalities, additional anomalies detected only at pre-natal magnetic resonance imaging (MRI), additional anomalies detected only at post-natal imaging and concordance between pre-natal and post- diagnosis. Only isolated cases of posterior fossa anomalies were included in the analysis, defined as having no cerebral or extra-cerebral additional anomalies detected at the scan. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale (NOS) for cohort studies. We used meta-analyses of proportions to combine data and fixed or random effects models according to the heterogeneity of the results. A total of 22 studies including 531 fetuses with posterior fossa anomalies were included in the systematic review. The prevalence of chromosomal abnormalities in fetuses with isolated DWM was 16.3% (95% CI 8.7-25.7). The prevalence of additional CNS abnormalities detected only at prenatal MRI but missed at ultrasound was 13.7 (95% CI 0.2-42,6), while those of additional CNS and extra-CNS anomalies missed at prenatal imaging and detected only after birth were 18.2% (95% CI 6.2-34.6) and 18,9 (6,3-36,2) respectively. Prenatal diagnosis was not confirmed in 28.2% (95% CI 8.5-53.9) of the cases (Table 4). None of the fetuses with isolated MCM tested prenatally were found to have a chromosomal abnormality (0%, 95% CI 0-4,7). There were no significant associations with associated anomalies detected at pre-natal MRI, nor with associated CNS and extra-CNS anomalies detected after birth and missed pre-natally. Prenatal diagnosis was not confirmed in 7.1% (95% CI 2.3-14.5) of the cases. The rate of chromosomal anomalies in fetuses with isolated BPC was 5.2% (95% CI 0.9- 12.7) and there was no associated CNS anomaly detected only at prenatal MRI and missed at the scan (0%, 95% CI 0-6,4). Likewise, no associated CNS or extra-CNS anomalies were detected only after birth. Prenatal diagnosis of BPC was not confirmed after birth in 9.8% (95% CI 2.9-20.1) of the cases. The rate of chromosomal anomalies in fetuses with isolated VH was 6.5% (95% CI 0.8-17.1) and no additional anomalies were detected at prenatal MRI and missed at the scan (PP: 0%, 95% CI 0-45,9). Finally, the proportions of cerebral and extra-cerebral anomalies detected only after birth were 14.2% (95% CI 2.9-31.9) and 0% (95% CI 0-18,5), respectively. Prenatal diagnosis was not confirmed in 32.4% (95% CI 18.3-48.4) of the cases. Isolated DWM is a condition at high risk of chromosomal and associated structural anomalies. Isolated MCM and BPC have a low risk of aneuploidy or associated structural anomalies. The small number of cases with isolated VH precludes drawing any robust evidence regarding their management.
Blood, 1994
The anion transport activity of the human erythrocyte anion transporter (band 3; AE1) has been ex... more The anion transport activity of the human erythrocyte anion transporter (band 3; AE1) has been examined in both normal and glycophorin A (GPA)-deficient (MkMk) human red blood cells (RBCs). The sulfate transport activity of MkMk cells (from two ethnically diverse sources) was approximately 60% that of normal erythrocytes under the transport assay conditions used. However, MkMk and normal RBCs contained similar amounts of band 3. The reduction in sulfate transport activity was shown to be caused by an increase in the apparent Km for sulfate in MkMk RBCs, suggesting the band 3 in the MkMk RBCs has a lowered binding affinity for sulfate anions. The size of the N-glycan chain on band 3 of the MkMk cells was larger than that on band 3 from normal RBCs. In contrast, the size of the N-glycan chain on the glucose transporter (GLUT1) from MkMk cells was smaller than that on GLUT1 from normal cells. The possible role of GPA in the biosynthesis and anion transport activity of band 3 in normal ...
Blood, 1996
The bilateral trafficking of nucleated cells between the fetus and the mother was studied using p... more The bilateral trafficking of nucleated cells between the fetus and the mother was studied using polymerase chain reaction (PCR)-based systems sensitive enough to detect 1 target cell in 100,000 background cells. Sixty-six mother-baby pairs were recruited; maternal and cord blood samples were collected at delivery for DNA extraction. Cell trafficking was studied in informative cases using PCR-genotyping of polymorphic regions in the beta-globin cluster, the glutathione S-transferase M1 locus and the angiotensin converting enzyme gene. In addition, Y-PCR was also used in conjunction with these systems for the detection of fetal cells in maternal circulation. Fetal cells were detected in maternal peripheral blood in 26 of 51 cases whereas maternal cells were detected in 16 of 38 fetal umbilical cord blood samples. The proportion of umbilical samples with detectable maternal sequences was much higher than previously reported. In the 28 cases informative for both mother and baby, there w...
Fetal diagnosis and therapy
Flow cytometry was used to determine the number of circulating natural killer (NK) cells in 170 p... more Flow cytometry was used to determine the number of circulating natural killer (NK) cells in 170 pregnancies undergoing cordocentesis for prenatal diagnosis at 17-38 weeks gestation and 16 undergoing cardiocentesis before social termination of pregnancy at 13-17 weeks. The number of NK cells decreased exponentially with gestation from a mean of 0.26 x 10(9)/l at 13 weeks to 0.09 x 10(9)/l at 38 weeks (r = -0.356, p < 0.001). When expressed as a percentage of the total number of lymphocytes, the proportion of NK cells decreased from a mean of 29% at 13 weeks to 6% at 38 weeks (r = 0.680, p < 0.0001). These data suggest that in early pregnancy the fetal immune response is dependent on innate rather than adaptive mechanisms.
American Journal of Obstetrics and Gynecology, 2015
Impaired fetal growth might be better evaluated in twin pregnancies by assessing the inter-twin d... more Impaired fetal growth might be better evaluated in twin pregnancies by assessing the inter-twin discordance rather than the individual fetal size. The aim of this study was to investigate the prediction of perinatal loss in twin pregnancy using discordance in fetal biometry and Doppler. This was a retrospective cohort study in a tertiary referral centre. The estimated fetal weight (EFW), umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebroplacental ratio (CPR) and their discordance recorded at the last ultrasound assessment before delivery or demise of one or both fetuses were converted into centiles or multiples of the median (MoM). The discordance was calculated as the larger value-smaller value/larger value. Logistic regression analysis was performed to identify, and adjust for, potential confounders. The predictive accuracy was assessed using ROC curve analysis. The analysis included 620 (464 dichorionic diamniotic and 156 monochorionic diamniotic) twin pregnancies (1240 fetuses). Perinatal loss of one or both fetuses complicated 16 (2.6%) pregnancies. The combination of EFW discordance and CPR discordance had the best predictive performance (AUC: 0.96, 95% CI 0.92-1.00) for perinatal mortality. The detection rate, false positive rate, positive likelihood ratio (LR) and negative LR were 87.5%, 6.7%, 13.08 and 0.13, respectively. The EFW centile, EFW below the 10th centile (small for gestational age), UA PI discordance, MCA PI discordance and MCA PI MoM were significantly associated with the risk of perinatal loss on univariate analysis, but these associations became non-significant after adjusting for other confounders (p=0.097, p=0.090, p=0.687, p=0.360 and p=0.074, respectively). The UA PI MoM, CPR MoM, EFW discordance and CPR discordance were all independent predictors of the risk of perinatal loss, even after adjusting for potential confounders (p=0.022, p=0.002, 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;lt;0.001 and p=0.010, respectively). EFW discordance and CPR discordance are independent predictors of the risk of perinatal loss in twin pregnancies. Their combination could identify the majority of twin pregnancies at risk of perinatal loss. These findings highlight the importance of discordance in Doppler indices of fetal hypoxia, as well as fetal size, in assessing the risk of perinatal mortality.
Ultrasound and Endoscopic Surgery in Obstetrics and Gynaecology, 2003
To determine the accuracy with which uterine artery Doppler in the first trimester of pregnancy p... more To determine the accuracy with which uterine artery Doppler in the first trimester of pregnancy predicts pre-eclampsia and fetal growth restriction, particularly early-onset disease. We searched MEDLINE (1951-2012), EMBASE (1980-2012) and the Cochrane Library (2012) for relevant citations without language restrictions. Two reviewers independently selected studies that evaluated the accuracy of first-trimester uterine artery Doppler to predict adverse pregnancy outcome and performed data extraction to construct 2 × 2 tables. We synthesized sensitivity and specificity for various Doppler indices using a bivariate random-effects model. From 1866 citations, we identified 18 studies (55,974 women). The sensitivity and specificity of abnormal uterine artery flow velocity waveform (FVW) in the prediction of early-onset pre-eclampsia were 47.8% (95% CI: 39.0-56.8) and 92.1% (95% CI: 88.6-94.6), and in the prediction of early-onset fetal growth restriction were 39.2% (95% CI: 26.3-53.8) and 93.1% (95% CI: 90.6-95.0), respectively. The sensitivities for predicting any pre-eclampsia and fetal growth restriction were 26.4% (95% CI: 22.5-30.8) and 15.4% (95% CI: 12.4-18.9), respectively, and the specificities were 93.4% (95% CI: 90.4-95.5%) and 93.3% (95% CI: 90.9-95.1), respectively. The number needed to treat (NNT) with aspirin to prevent one case of early-onset pre-eclampsia fell from 1000 to 173 and from 2500 to 421 for background risks varying between 1% and 0.4%, respectively. First-trimester uterine artery Doppler is a useful tool for predicting early-onset pre-eclampsia, as well as other adverse pregnancy outcomes. Based on the NNT, abnormal uterine artery Doppler in low-risk women achieves a sufficiently high performance to justify aspirin prophylaxis in those who test positive.
The Journal of thoracic and cardiovascular surgery, Jan 15, 2014
Pathology of the aortic valve and ascending thoracic aorta is an uncommon but life-threatening co... more Pathology of the aortic valve and ascending thoracic aorta is an uncommon but life-threatening complication of pregnancy. Cardiac surgery during pregnancy is known to carry a high risk of mortality to both the mother and fetus. We present our experience of performing aortic surgery during the patients' pregnancy. All patients undergoing aortic surgery during pregnancy at St George's Hospital, from January 2004 until October 2013, were identified. Surgery was performed using cardiopulmonary bypass at 36°C, with pulsatile perfusion at 70 mm Hg. Fetal blood flow parameters were serially monitored during surgery, via transabdominal and/or transvaginal Doppler ultrasonography. Surgery was performed in the second trimester when possible to allow completion of organogenesis and minimize hemodynamic compromise. Eleven patients underwent aortic surgery. The median age was 28 years (range, 26-31 years), with gestational age 19 weeks (range, 16-21 weeks). Six patients had aortic root d...
American Journal of Obstetrics and Gynecology, 2014
OBJECTIVE: We sought to evaluate the association between fetal cerebroplacental ratio (CPR) and i... more OBJECTIVE: We sought to evaluate the association between fetal cerebroplacental ratio (CPR) and intrapartum fetal compromise and admission to the neonatal unit (NNU) in term pregnancies.
American Journal of Obstetrics and Gynecology, 2014
Fetal diagnosis and therapy, Jan 5, 2015
Objectives: A third-trimester fetal weight discordance of 25% has been proposed as an independent... more Objectives: A third-trimester fetal weight discordance of 25% has been proposed as an independent predictor of fetal loss in twin pregnancies. As fetal weight gain at this stage of pregnancy increases exponentially, it is not entirely certain whether a single cut-off for inter-twin weight discordance is appropriate. The aim of this study was to investigate whether a single weight discordance cut-off can be used or whether different cut-offs should be adopted according to the gestational age at assessment. Methods: This was a retrospective study of all twin pregnancies of known chorionicity from a large regional cohort over a 10-year period. Receiver operating characteristic curve and logistic regression analyses were used to explore the relation between estimated fetal weight (EFW) discordance detected within 4 weeks from the occurrence of the outcome and single fetal loss at different gestational age windows. Results: 957 twin pregnancies (173 monochorionic and 784 dichorionic) wer...
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Papers by Basky Thilaganathan