Research

Research Highlights

Singapore Preconception Study of Long-term Maternal and Child Outcomes (S-PRESTO)

Recent findings show the importance of pre-conceptual health and peri-conceptual nutrition for pregnancy outcomes such as gestational length,birth size, and offspring health. It is now evident that there is a potentially important clinical window for the induction of relevant epigenetic signals occurring both before and soon after conception that was not investigated. These considerations underscore the urgent need for studies of peri-conceptual nutrition in Asia. The approach is critical for the establishment of effective prevention studies since the influences of maternal health on offspring phenotype can occur very early in development prior to any contact with obstetric health services. The study aims to test the following primary hypothesis: That nutrition, lifestyle, and maternal emotional health prior to pregnancy and/or during the first trimester alter the expression of metabolic or neurodevelopmental endophenotypes with accompanying effects on the epigenome/transcriptome of the offspring.

In this prospective preconception cohort study, 900 women who plan to get pregnant will be recruited and they will be assessed metabolically, nutritionally and epigenetically, then monitored them from their first missed menses with nutritional surveys and assays and repeated bio-sampling to birth followed by assessment in the women of lactation and lactational nutrition. Epigenetic analyses will be done on the cord and placenta at birth and in buccal smears at frequent postnatal intervals. Phenotypic measures of body composition and core neurodevelopmental measures will be followed in the offspring until 2 years of age.

The OBGYN Faculty involved in the study are Assoc Prof Jerry Chan, Prof Kenneth Kwek, Adj Assoc Prof Bernard Chern, Adj Assoc Prof Tan Heng Hao, Adj Prof George Yeo, Prof Tan Kok Hian and Adj Asst Prof Ang Seng Bin. The study is conducted in collaboration with Singapore Institute for Clinical Sciences (SICS, A*STAR) and National University Hospital (NUH).

For more information, please visit http://www.s-presto.sg/.

 

Clinical and Translational Research in Endometriosis

Endometriosis affects 6 to 10% of women, and 50% of the affected group presenting with infertility. The pathophysiology has not been well studied. The executive committee of the grant led by Adj Assoc Prof Bernard and Dr Peter Barton Smith aims to utilize the fund to establish an Endometriosis research network for clinical and translational research. It enables a multi-disciplinary approach to define epidemiology, develop understanding of its pathophysiology and derive biomarkers for diagnosis and monitoring purpose. Understanding of its pathophysiology and derive biomarkers for diagnosis and monitoring purpose. The funding will be used to establish outcome-linked clinico-pathological database or bio-repository, including prospective recruitment, rigorous phenotyping of cases, tissue banking and longitudinal assessment of clinical outcomes in pain and fertility.

 

Preclinical Studies in Intrauterine Gene Therapy and Haemopoietic Stem Cell Therapy in a Non-human Primate Model

Extensive research has been done in trying to determine the efficacy and immune responses of adeno-associated viral vector (AAV)-mediated intrauterine gene transfer (IUGT) in both early and late gestation. Aside from varying the timepoints of IUGT, a few serotypes of AAV have also been tried out, along with differentiating both sites and methods of delivery. Hypothetically, it is believed that intervention in early gestation affords the benefits of immune tolerance, as there is a fetal immune system is still immature. Also, the small size of the fetus gives the added advantage of achieving a higher vector to cell ratio, which is hoped to be more effective. Infant NHPs are hand-reared and show no abnormal developmental characteristics. More in-depth studies will have to be conducted to determine the safety profile of this proposed treatment which, once developed, will contribute greatly to the treatment of a variety of single-gene disorders worldwide.

The principal investigator, Assoc Prof Jerry Chan Kok Yen (Senior Consultant, Department of Reproductive Medicine; Director, KK Research Centre – KKH) received an award from the National Medical Research Council (NMRC) to support the research for a period of 3 years up to November 2015.

 

Selected  2014 Publications:

  1. Lee YH, Tan CW, Venkatratnam A, Tan CS, Cui L, Loh SF, Griffith L, Tannenbaum SR, Chan JK. Dysregulated sphingolipid metabolism in endometriosis. Journal of Endocrinology and Metabolism. 2014 Oct;99(10): e1913-e1921. (JIF: 6.310)
  2. Tan CW, Lee YH, Tan HH, Lau MS, Choolani M, Griffith L, Chan JK. CD26/DPPIV down-regulation in endometrial stromal cell migration in endometriosis. Fertility and Sterility. 2014 Jul;102(1):167-177. (JIF: 4.295)
  3. Tan KH, Sim Tan S, Sze S, Ryan Lee W, Jack Ng M, Kiang Lim S. Plasma biomarker discovery in preeclampsia using a novel differential isolation technology for circulating extracellular vesicles. American Journal of Obstetrics and Gynecology. 2014 Oct;211(4):380.e1-380.e13 (JIF: 3.800)
  4. Dighe N, Khoury M, Mattar C, Chong M, Choolani M, Chen JK, Antoniou MN, Chan JK. Long-term reproducible expression in human fetal liver hematopoietic stem cells with a UCOE-based lentiviral vector. Journal of Endocrinology. 2014 Aug 12; 9(8):1.e104805-8.e104805 (JIF: 3.534)
  5. Fan Y, Marcy G, Lee ES, Rozen S, Mattar CN, Waddington SN, Goh EL, Choolani M, Chan JK. Regionally-Specified Second Trimester Fetal Neural Stem Cells Reveals Differential Neurogenic Programming. PLOS ONE. 2014 Sept;9(9):1.e105985-12.e105985 (JIF: 3.534)
  6. Saraswat L, Ashok PW, Mathur M. Medical management of miscarriage. The Obstetrician & Gynaecologist 2014;16(2):79–85 (JIF: 3.437)
  7. Salomon LJ, Alfirevic Z, Audibert F, Kagan KO, Paladini D, Yeo GSH, Raine-Fenning N, and on behalf of the ISUOG Clinical Standards Committee. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound Obstet Gynecol. 2014; 44: 122–123 (JIF: 3.140)
  8. Ling LP, Phoon JW, Lau MS, Chan JK, Viardot-Foucault V, Tan TY, Nadarajah S, Tan HH. GnRH agonist trigger and ovarian hyperstimulation syndrome: relook at 'freeze-all strategy'. Reproductive BioMedicine Online. 2014 Jun;29(3):392-394 (JIF: 2.980)
  9. Chong MF, Wong JX, Colega M, Chen LW, van Dam RM, Tan CS, Lim AL, Cai S, Broekman BF, Lee YS, Saw SM, Kwek K, Godfrey KM, Chong YS, Gluckman P, Meaney MJ, Chen H; GUSTO study group. Relationships of maternal folate and vitamin B12 status during pregnancy with perinatal depression: The GUSTO study. Journal of Psychiatric Research. 2014 Aug;55:110-116 (JIF: 2.682)
  10. Chong YS, Cai S, Lin H, Soh SE, Lee YS, Leow MK, Chan YH, Chen L, Holbrook JD, Tan KH, Rajadurai VS, Yeo GSH, Kramer MS, Saw SM, Gluckman PD, Godfrey KM, Kwek K; GUSTO study group. Ethnic differences translate to inadequacy of high-risk screening for gestational diabetes mellitus in an Asian population: a cohort study. BMC Pregnancy and Childbirth. 2014 Oct 2;14(345):1-7 (JIF:2.150)
  11. Lim WY, Lee YS, Tan CS, Kwek K, Chong YS, Gluckman PD, Godfrey KM, Saw SM, Pan A. The association between maternal blood pressures and offspring size at birth in Southeast Asian women. BMC Pregnancy & Childbirth. 2014 Dec 2;14(403):1-10 (JIF: 2.150)
  12. Chong Y, Chan M, Tan HH, Nadarajah S. Human embryo cryopreservation: one-step slow freezing does it all?. Journal of Assisted Reproduction and Genetics. 2014 Jul;31(7):921-925 (JIF: 1.772)
  13. Tay S, Cheong M. Evidence for ethnic and environmental contributions to frequency of ovarian clear cell carcinoma. Australian and New Zealand Journal of Obstetrics and Gynaecology. 2014 Jun;54(3):225-230 (1.620)
  14. Tan LS, Chio MT, Sen P, Lim YK, Ng J, Ilancheran A, Low JJ, Yeoh YS, Chan RK, Luo N.Assessment of psychosocial impact of genital warts among patients in Singapore. Sex Health. 2014 Sep;11(4):313-318 (JIF: 1.576)
  15. Ong XH, Koh E, Yong KL. Single-port access laparoscopic re-staging with bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection for endometrial cancer. Journal of Minimally Invasive Gyneocoloy Case Reports. 2014 Aug;3(3):97–99 (JIF: 1.575)
  16. Lee JM, Huang CY, Wu KY, Yen CF, Chern BSM, Lee CL. Novel technique of neovagina creation with uterine serosa in the treatment of vaginal agenesis associated with mullerian agenesis. Journal of Minimally Invasive Gyneocoloy. 2014 May; 3(2):50-53 (JIF: 1.575)
  17. Ong XH, Mathur M, Kew C, Chern BSM. Surgical management of cesarean scar pregnancies – A single tertiary experience.  Journal of Minimally Invasive Gyneocoloy. 2014 Aug; 3(3):82-88 (JIF: 1.575)
  18. Ng QJ, Abdul Rahman MF, Lim ML, Chee JJ, Tan KH. Single versus combination tocolytic regimen in the prevention of preterm births in women: a prospective cohort study : Journal of Perinatal Medicine. 2014 Nov 1. [Epub ahead of print] (JIF: 1.425)
  19. Ee TX, Allen JC Jr, Malhotra R, Koh H, Østbye T, Tan TC. Determining optimal gestational weight gain in a multiethnic Asian population. The Journal of Obstetrics and Gynaecology Research, 2014 Apr;40(4):1002-1008 (JIF: 1.221)
  20. Viardot-Foucault V, Tai BC, Prasath EB, Lau MS, Chan JK, Loh SF.Younger women with ovulation disorders and unexplained infertility predict a higher success rate in superovulation (SO) intrauterine insemination (IUI). Ann Acad Med Singapore. 2014 Apr;43(5):225-231 (JIF: 1.221)

 

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