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  1. Rhodes A, Vallikkannu N, Jayalakshmi P
    Br J Biomed Sci, 2017 Apr;74(2):65-70.
    PMID: 28367736 DOI: 10.1080/09674845.2016.1220709
    BACKGROUND: Ovarian cancer is particularly lethal due to late stage at presentation. The subtypes behave differently with respect to their biology and response to treatment. Two recent markers reported to be useful in assisting in the diagnosis are WT1 and PAX8. Malaysia, with its multi-ethnic population provides an opportunity to study the expression of these biomarkers in ovarian cancer in the three most populous ethnicities in Asia and ascertain their usefulness in the diagnosis of ovarian carcinoma.

    MATERIALS AND METHODS: Tissues from ovarian epithelial neoplasms diagnosed between 2004 and 2012 were tested using antibodies to WT1 and PAX8. The slides were assessed to determine levels of marker expression and related to ethnicity, ovarian tumour type, grade and stage.

    RESULTS: Serous tumours were the main histological type (n = 44), the remaining being endometrioid (n = 15), mucinous (n = 15) and clear cell tumours (n = 7). Late stage at diagnosis was significantly associated with serous (p n = 1) and clear cell carcinomas (n = 2) expressed PAX8, and none expressed WT1. There was no significant difference in the tumour expression of either WT1 or PAX8 between the three Malaysian ethnicities.

    CONCLUSIONS: In an Asian setting, PAX8 and WT1 are expressed in the vast majority of serous ovarian cancers and may be useful in distinguishing serous ovarian carcinomas from other poorly differentiated tumours.

  2. Tan PC, Suguna S, Vallikkannu N, Hassan J
    Singapore Med J, 2008 Mar;49(3):193-8.
    PMID: 18362999
    Following labour induction at term, 12 percent of neonates can expected to be admitted to the neonatal intensive care unit. We aimed to evaluate the Bishop score, pre-induction ultrasonography (US) assessment of amniotic fluid, foetal weight and cervical length, and pre-induction and intrapartum risk factors as predictors of neonatal admission.
  3. Tan PC, King AS, Vallikkannu N, Omar SZ
    Arch Gynecol Obstet, 2012 Mar;285(3):585-90.
    PMID: 21796421 DOI: 10.1007/s00404-011-2026-3
    To evaluate the effect of a single 250-mg dose of 17 alpha-hydroxyprogesterone caproate (17-OHPC) intramuscularly as adjunct to nifedipine tocolysis in preterm labor.
  4. Tan PC, Khine PP, Vallikkannu N, Omar SZ
    Obstet Gynecol, 2010 May;115(5):975-981.
    PMID: 20410771 DOI: 10.1097/AOG.0b013e3181d99290
    OBJECTIVE: To compare the effects of promethazine with those of metoclopramide for hyperemesis gravidarum.

    METHODS: Women at their first hospitalization for hyperemesis gravidarum were approached when intravenous antiemetic therapy was needed. They were randomly assigned to receive 25 mg promethazine or 10 mg metoclopramide every 8 hours for 24 hours in a double-blind study. Primary outcomes were vomiting episodes by diary and well-being visual numerical rating scale score (10-point scale) in the 24-hour main study period. Participants also filled out an adverse-effects questionnaire at 24 hours and a nausea visual numerical rating scale score at recruitment and at 8, 16, and 24 hours.

    RESULTS: A total of 73 and 76 women, randomized to metoclopramide and promethazine, respectively, were analyzed. Median vomiting episodes were one (range 0-26) compared with two (range 0-26) (P=.81), and well-being visual numerical rating scale scores were 8 (range 1-10) compared with 7 (range 2-10) (P=.24) for metoclopramide and promethazine, respectively. Repeat-measures analysis of variance of the nausea visual numerical rating scale scores showed no significant difference between study drugs (F score=0.842, P=.47). Reported drowsiness (58.6% compared with 83.6%, P=.001, number needed to treat to benefit [NNTb] 5), dizziness (34.3% compared with 71.2%, P

  5. Tan PC, Vallikkannu N, Suguna S, Quek KF, Hassan J
    Clin Exp Obstet Gynecol, 2009;36(1):35-9.
    PMID: 19400416
    OBJECTIVE: To evaluate the predictive value for successful labor induction of transvaginal ultrasound (TVS) of cervical length according to parity.

    METHOD: TVS of the cervix was performed before term labor induction. Induction was considered successful if vaginal delivery was achieved within 24 hours; 231 women were available for final analysis.

    RESULTS: Analysis of the receiver operator characteristics curve showed an optimal cut-off for cervical length of < or = 20 mm for successful induction. Following multivariate logistic regression analysis, a sonographic short cervix (AOR 5.6; p < 0.001) was an independent predictor of successful induction but not a favorable Bishop score (p = 0.47). Among multiparas with a short cervix, positive and negative predictive values for successful induction were 98% (95% CI 90-100%) and 21% (95% CI 13%-32%) and among nulliparas, predictive values were 69% (95% CI 53%-82%) and 77% (95% CI 64%-87%) respectively.

    CONCLUSION: In nulliparas, cervical length can usefully predict labor induction outcome.

  6. Tan PC, Vallikkannu N, Suguna S, Quek KF, Hassan J
    Ultrasound Obstet Gynecol, 2007 May;29(5):568-73.
    PMID: 17444553
    To compare transvaginal sonography for cervical length measurement and digital examination for Bishop score assessment in women undergoing labor induction at term, to assess their tolerability (in terms of pain) and ability to predict need for Cesarean delivery.
  7. Tan PC, Suguna S, Vallikkannu N, Hassan J
    Aust N Z J Obstet Gynaecol, 2006 Dec;46(6):505-9.
    PMID: 17116055
    To assess the relationship of ultrasound assessment for amniotic fluid, fetal weight, cervical length, cervical funneling and clinical factors on the risk of Caesarean delivery after labour induction at term.
  8. Vallikkannu N, Lam WK, Omar SZ, Tan PC
    BJOG, 2017 Jul;124(8):1274-1283.
    PMID: 27348806 DOI: 10.1111/1471-0528.14175
    OBJECTIVE: To evaluate the tolerability of cervical insulin-like growth factor binding protein 1 (IGFBP-1) and its value as a predictor of successful labour induction, compared with Bishop score and transvaginal ultrasound (TVUS) cervical length.

    DESIGN: A prospective study.

    SETTING: A tertiary hospital in Malaysia.

    POPULATION: A cohort of 193 term nulliparous women with intact membranes.

    METHODS: Prior to labour induction, cervical fluid was obtained via a vaginal speculum and tested for IGFBP-1, followed by TVUS and finally Bishop score. After each assessment the procedure-related pain was scored from 0 to 10. Cut-off values for Bishop score and cervical length were obtained from the receiver operating characteristic (ROC) curve. Multivariable logistic regression analysis was performed.

    MAIN OUTCOMES MEASURES: Vaginal delivery and vaginal delivery within 24 hours of starting induction.

    RESULTS: Bedside IGFBP-1 testing is better tolerated than Bishop score, but is less well tolerated than TVUS [median (interquartile range) of pain scores: 5 (4-5) versus 6 (5-7) versus 3 (2-3), respectively; P < 0.001]. IGFBP-1 independently predicted vaginal delivery (adjusted odds ratio, AOR 5.5; 95% confidence interval, 95% CI 2.3-12.9) and vaginal delivery within 24 hours of induction (AOR 4.9; 95% CI 2.1-11.6) after controlling for Bishop score (≥4 or ≥5), cervical length (≤29 or ≤27 mm), and other significant characteristics for which the Bishop score and TVUS were not predictive of vaginal delivery after adjustment. IGFBP-1 has 81% sensitivity, 59% specificity, positive and negative predictive values of 82 and 58%, respectively, and positive and negative likelihood ratios of 2.0 and 0.3 for vaginal delivery, respectively.

    CONCLUSION: IGFBP-1 better predicted vaginal delivery than BS or TVUS, and may help guide decision making regarding labour induction in nulliparous women.

    TWEETABLE ABSTRACT: IGFBP-1: a stronger independent predictor of labour induction success than Bishop score or cervical sonography.

  9. Khairudin MN, Vallikkannu N, Gan F, Hamdan M, Tan PC
    Am J Obstet Gynecol MFM, 2024 Mar 04;6(4):101324.
    PMID: 38447674 DOI: 10.1016/j.ajogmf.2024.101324
    BACKGROUND: Labor pain varies significantly among pregnant women, ranging from mild to extremely distressing. Nonpharmacologic pain relief methods during vaginal birth are increasingly popular, either as a complement to pharmacologic agents or, at times, as the primary method of pain relief. Multiple trials have reported that manual or by-hand massage reduces labor pain. The effectiveness of full-body mechanical massage using electric massage chairs on labor pain remains unexplored.

    OBJECTIVE: This study aimed to evaluate mechanical massage using an electric massage chair on labor pain in nulliparous women.

    STUDY DESIGN: A randomized counterbalanced crossover trial was conducted in a university hospital in Malaysia from August 2022 to February 2023. Eligible nulliparas in labor with a minimum labor pain score of 5 (0-10 numerical rating scale) were enrolled. Participants were randomized to 30 minutes on the massage chair with mechanical massage followed by 30 minutes on the massage chair without mechanical massage or the other way around in the massage sequence. The primary outcome was a change in pain score comparing pain with and without mechanical massage as a paired comparison for the entire trial participants. The secondary outcomes were across arms analyses of maternal and neonatal outcomes. The paired t test, t test, Mann-Whitney U test, chi-square test, and Fisher exact test were used as appropriate for the data.

    RESULTS: Overall, 208 women were randomized: 104 to each intervention. Data were available from 204 participants (103 randomized to massage first and 101 to no massage first). The primary outcomes of change in labor pain scores (0-10 numerical rating scale) after massage and no massage (all participants included after crossover, paired t test analysis) were 4.51±2.30 and 5.38±2.10, respectively (mean difference, -0.87; 95% confidence interval, -1.14 to -0.59; P

  10. Tan PC, Khine PP, Sabdin NH, Vallikkannu N, Sulaiman S
    J Ultrasound Med, 2011 Feb;30(2):227-33.
    PMID: 21266561
    OBJECTIVES: The purpose of this study was to evaluate cervical length changes after membrane sweeping and the effect of cervical shortening on pregnancy outcomes.

    METHODS: Low-risk women at 40 weeks' gestation undergoing membrane sweeping to expedite labor were recruited. Participants were scheduled for labor induction at 41 weeks' gestation. Transvaginal ultrasonography was performed immediately before and after membrane sweeping to measure the cervical length. Three presweep and postsweep cervical lengths were measured. The shortest lengths before and after the sweep were taken as the representative lengths. The effect of membrane sweeping on cervical length was analyzed. Multivariable logistic regression analysis was performed to evaluate the effect of cervical shortening on labor induction and the mode of delivery.

    RESULTS: For the 160 participants, the mean presweep cervical length ± SD was 21.0 ± 10.0 mm; the postsweep length was 23.8 ± 10.9 mm, an average increase of 2.8 ± 0.6 mm (P < .001). Cervical shortening after membrane sweeping was noted in 53 of 160 cases (33%). Cervical shortening was associated with a reduction in all-cause cesarean delivery but not labor induction on bivariate analysis. After adjustment for maternal age, parity, presweep Bishop score, postsweep cervical length, oxytocin augmentation, epidural analgesia, and meconium-stained fluid, cervical shortening after membrane sweeping was independently predictive of a reduction in cesarean deliveries (adjusted odds ratio, 0.24; 95% confidence interval, 0.06-0.90; P = .034).

    CONCLUSIONS: Membrane sweeping was associated with lengthening of the cervix. A shortened cervix after sweeping was independently predictive of vaginal delivery.

  11. Hamdan M, Shuhaina S, Hong JGS, Vallikkannu N, Zaidi SN, Tan YP, et al.
    Acta Obstet Gynecol Scand, 2021 Nov;100(11):1977-1985.
    PMID: 34462906 DOI: 10.1111/aogs.14247
    INTRODUCTION: Multiparous labor inductions are typically successful, and the process can be rapid, starting from a ripened cervix with a predictable response to amniotomy and oxytocin infusion. Outpatient Foley catheter labor induction in multiparas with unripe cervixes is a feasible option as the mechanical process of ripening is usually without significant uterine contractions and well tolerated. Labor contractions can be initiated by amniotomy and titrated oxytocin infusion in the hospital for well-timed births during working hours as night birth are associated with adverse events. We sought to evaluate outpatient compared with inpatient Foley catheter induction of labor in multiparas for births during working hours and maternal satisfaction.

    MATERIAL AND METHODS: A randomized trial was conducted in the University of Malaya Medical Center. A total of 163 term multiparas (no dropouts) with unripe cervixes (Bishop score ≤5) scheduled for labor induction were randomized to outpatient or inpatient Foley catheter. Primary outcomes were delivery during "working hours" 08:00-18:00 h and maternal satisfaction on allocated care (assessed by 11-point visual numerical rating score 0-10, with higher score indicating more satisfied).

    CLINICAL TRIAL REGISTRATION: ISRCTN13534944.

    RESULTS: Comparing outpatient and inpatient arms, delivery during working hours were 54/82 (65.9%) vs. 48/81 (59.3%) (relative risk 1.1, 95% CI 0.9-1.4, p = 0.421) and median maternal satisfaction visual numerical rating score was 9 (interquartile range 9-9) vs. 9 (interquartile range 8-9, p = 0.134), repectively. Duration of hospital stay and membrane rupture to delivery interval were significantly shorter in the outpatient arm: 35.8 ± 20.2 vs. 45.2 ± 16.2 h (p = 0.001) and 4.1 ± 2.9 vs. 5.3 ± 3.6 h (p = 0.020), respectively. Other maternal and neonatal secondary outcomes were not significantly different.

    CONCLUSIONS: The trial failed to demonstrate the anticipated increase in births during working hours with outpatient compared with inpatient induction of labor with Foley catheter in parous women with an unripe cervix. Hospital stay and membrane rupture to delivery interval were significantly shortened in the outpatient group. The rate of maternal satisfaction was high in both groups and no significant differences were found.

  12. Vallikkannu N, Laboh N, Tan PC, Hong JGS, Hamdan M, Lim BK
    Arch Gynecol Obstet, 2022 Jan 09.
    PMID: 34999923 DOI: 10.1007/s00404-021-06383-2
    PURPOSE: To evaluate Foley catheter and controlled release dinoprostone insert compared to foley catheter alone on induction to delivery interval and maternal satisfaction.

    METHODS: A randomized trial was conducted in a university hospital in Malaysia from December 2018 to May 2019. Term nulliparas with unfavorable cervix (Bishop score ≤ 5) scheduled for labor induction were randomized to Foley catheter and controlled release dinoprostone insert simultaneously or Foley catheter alone. Primary outcomes were induction to delivery interval (hours) and maternal satisfaction on birth experience (assessed by 11-point Visual Numerical Rating Scale VNRS 0-10, higher score more satisfied).

    RESULTS: Induction to vaginal delivery intervals was mean ± standard deviation 22.5 ± 10.4 vs. 35.1 ± 14.9 h, P =  

  13. Hamid NA, Hong JGS, Hamdan M, Vallikkannu N, Adlan AS, Tan PC
    Am J Obstet Gynecol, 2023 Oct;229(4):443.e1-443.e9.
    PMID: 37207931 DOI: 10.1016/j.ajog.2023.04.049
    BACKGROUND: A prolonged second stage of labor increases the risk of severe perineal laceration, postpartum hemorrhage, operative delivery, and poor Apgar score. The second stage is longer in nulliparas. Maternal pushing during the second stage of labor is an important contributor to the involuntary expulsive force developed by uterine contraction to deliver the fetus. Preliminary data indicate that visual biofeedback during the active second stage hastens birth.

    OBJECTIVE: This study aimed to evaluate if visual feedback focusing on the perineum reduced the length of the active second stage of labor in comparison with the control.

    STUDY DESIGN: A randomized controlled trial was conducted in the University Malaya Medical Centre from December 2021 to August 2022. Nulliparous women about to commence the active second stage, at term, with singleton gestation, reassuring fetal status, and no contraindication for vaginal delivery were randomized to live viewing of the maternal introitus (intervention) or maternal face (sham/placebo control) as visual biofeedback during their pushing. A video camera Bluetooth-linked to a tablet computer display screen was used; in the intervention arm, the camera was focused on the introitus, and in the control arm, on the maternal face. Participants were instructed to watch the display screen during their pushing. The primary outcomes were the intervention-to-delivery interval and maternal satisfaction with the pushing experience assessed using a 0-to-10 visual numerical rating scale. Secondary outcomes included mode of delivery, perineal injury, delivery blood loss, birthweight, umbilical cord arterial blood pH and base excess at birth, Apgar score at 1 and 5 minutes, and neonatal intensive care unit admission. Data were analyzed with the t test, Mann-Whitney U test, chi-square test, and Fisher exact test, as appropriate.

    RESULTS: A total of 230 women were randomized (115 to intervention and 115 to control arm). The active second stage duration (intervention-to-delivery interval) was a median (interquartile range) of 16 (11-23) and 17 (12-31) minutes (P=.289), and maternal satisfaction with the pushing experience was 9 (8-10) and 7 (6-7) (P

  14. Hong J, Raghavan S, Siti Nordiana A, Saaid R, Vallikkannu N, Tan PC
    Int J Gynaecol Obstet, 2024 Apr;165(1):265-274.
    PMID: 37846154 DOI: 10.1002/ijgo.15199
    OBJECTIVES: To evaluate expectant compared to immediate return to hospital upon outpatient Foley catheter expulsion predicated on maternal satisfaction and amniotomy-titrated oxytocin infusion to delivery interval.

    METHODS: This randomized trial was conducted in a tertiary university hospital in Malaysia from September 2020 to February 2022. A total of 330 nulliparous women at term with unripe cervices (Bishop score ≤5), singleton viable fetus in cephalic presentation, reassuring preinduction fetal heart rate tracing and intact membranes who underwent planned outpatient Foley catheter induction of labor (IOL) were included. Women were randomized to expectant or immediate return to hospital if the Foley was spontaneously expelled at home before their scheduled hospital admission the following day. Primary outcomes were amniotomy-titrated oxytocin infusion to delivery interval and maternal satisfaction on the induction process (assessed by 0-10 visual numerical rating scale [VNRS]).

    RESULTS: Amniotomy-titrated oxytocin infusion to delivery interval was 8.7 ± 4.1 versus 8.9 ± 3.9 h, P = 0.605 (mean difference - 0.228 95% CI: -1.1 to +0.6 h) and maternal satisfaction VNRS score was median (interquartile range) 8 (7-9) versus 8 (7-9), P = 0.782. Early return to hospital rates were 37/165 (22.4%) versus 72/165 (43.6%), RR 0.51 (95% CI: 0.37-0.72), P ≤ 0.001, Cesarean delivery rates were 80/165 (48.5%) versus 80/165 (48.5%), RR 1.00 (95% CI: 0.80-1.25), P = 1.00 and duration of hospital stay was 54.4 ± 22.9 versus 56.7 ± 22.8 h, P = 0.364 for the expectant versus immediate return groups respectively.

    CONCLUSION: In outpatient Foley catheter IOL, expectant compared to immediate return to hospital following Foley dislodgement results in similarly high maternal satisfaction. The amniotomy-titrated oxytocin to delivery duration is non-inferior with expectant management.

  15. Vallikkannu N, Nadzratulaiman WN, Omar SZ, Si Lay K, Tan PC
    BMC Pregnancy Childbirth, 2014 Jan 28;14:49.
    PMID: 24468078 DOI: 10.1186/1471-2393-14-49
    BACKGROUND: External cephalic version (ECV) is offered to reduce the number of Caesarean delivery indicated by breech presentation which occurs in 3-4% of term pregnancies. ECV is commonly performed aided by the application of aqueous gel or talcum powder to the maternal abdomen. We sought to compare gel with powder during ECV on achieving successful version and increasing tolerability.

    METHOD: We enrolled 95 women (≥ 36 weeks gestation) on their attendance for planned ECV. All participants received terbutaline tocolysis. Regional anaesthesia was not used. ECV was performed in the standard fashion after the application of the allocated aid. If the first round (maximum of 2 attempts) of ECV failed, crossover to the opposing aid was permitted.

    RESULTS: 48 women were randomised to powder and 47 to gel. Self-reported procedure related median [interquartile range] pain scores (using a 10-point visual numerical rating scale VNRS; low score more pain) were 6 [5-9] vs. 8 [7-9] P = 0.03 in favor of gel. ECV was successful in 21/48 (43.8%) vs. 26/47 (55.3%) RR 0.6 95% CI 0.3-1.4 P = 0.3 for powder and gel arms respectively. Crossover to the opposing aid and a second round of ECV was performed in 13/27 (48.1%) following initial failure with powder and 4/21 (19%) after failure with gel (RR 3.9 95% CI 1.0-15 P = 0.07). ECV success rate was 5/13 (38.5%) vs. 1/4 (25%) P = 0.99 after crossover use of gel or powder respectively. Operators reported higher satisfaction score with the use of gel (high score, greater satisfaction) VNRS scores 6 [4.25-8] vs 8 [7-9] P = 0.01.

    CONCLUSION: Women find gel use to be associated with less pain. The ECV success rate is not significantly different.

    TRIAL REGISTRATION: The trial is registered with ISRCTN (identifier ISRCTN87231556).

  16. Sargunam PN, Bak LLM, Tan PC, Vallikkannu N, Noor Azmi MA, Zaidi SN, et al.
    BMC Pregnancy Childbirth, 2019 Dec 11;19(1):493.
    PMID: 31829138 DOI: 10.1186/s12884-019-2602-2
    BACKGROUND: Prolonged latent phase of labor is associated with adverse maternal and neonatal outcomes. Preliminary data indicate that labor induction for prolonged latent phase may reduce cesarean delivery. We performed a study powered to Cesarean delivery to evaluate labor induction compared to expectant management in full term nulliparas hospitalized for persistent contractions but non-progressive to established labor after an overnight stay.

    METHODS: From 2015 and 2017, nulliparas, ≥ 39 weeks' gestation with prolonged latent phase of labor (persistent contractions after overnight hospitalization > 8 h), cervical dilation ≤3 cm, intact membranes and reassuring cardiotocogram were recruited. Participants were randomized to immediate induction of labor (with vaginal dinoprostone or amniotomy or oxytocin as appropriate) or expectant management (await labor for at least 24 h unless indicated intervention as directed by care provider). Primary outcome measure was Cesarean delivery.

    RESULTS: Three hundred eighteen women were randomized (159 to each arm). Data from 308 participants were analyzed. Cesarean delivery rate was 24.2% (36/149) vs. 23.3%, (37/159) RR 1.0 95% CI 0.7-1.6; P = 0.96 in induction of labor vs. expectant arms. Interval from intervention to delivery was 17.1 ± 9.9 vs. 40.1 ± 19.8 h; P 

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