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The usefulness of limited placental sampling in stillbirths

Hayati AR, Khong TY, Zainul R

Malays J Pathol, 1998 Dec;20(2):99-102.
PMID: 10879270

144 placentas were sampled from all cases of stillbirth weighing 500 g and above seen over a period of thirteen months in the UKM Unit of the Maternity Hospital, Kuala Lumpur. Sampling was limited to 1-3 blocks per placenta for histological study. Placental abnormalities were found in 121 (85%) placentas, 78 of which had definite lesions known to contribute to foetal death while the remainder showed lesions suggestive of an underlying disease. This study supports the usefulness of limited sampling of the placenta in the face of unavailability of complete placental examination and autopsy for assessment of the cause of stillbirth.
Fulltext SARS-CoV-2 Transplacental Transmission: A Rare Occurrence? An Overview of the Protective Role of the Placenta

Wong YP, Tan GC, Khong TY

Int J Mol Sci, 2023 Feb 25;24(5).
PMID: 36901979 DOI: 10.3390/ijms24054550

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global public health crisis, causing substantial concern especially to the pregnant population. Pregnant women infected with SARS-CoV-2 are at greater risk of devastating pregnancy complications such as premature delivery and stillbirth. Irrespective of the emerging reported cases of neonatal COVID-19, reassuringly, confirmatory evidence of vertical transmission is still lacking. The protective role of the placenta in limiting in utero spread of virus to the developing fetus is intriguing. The short- and long-term impact of maternal COVID-19 infection in the newborn remains an unresolved question. In this review, we explore the recent evidence of SARS-CoV-2 vertical transmission, cell-entry pathways, placental responses towards SARS-CoV-2 infection, and its potential effects on the offspring. We further discuss how the placenta serves as a defensive front against SARS-CoV-2 by exerting various cellular and molecular defense pathways. A better understanding of the placental barrier, immune defense, and modulation strategies involved in restricting transplacental transmission may provide valuable insights for future development of antiviral and immunomodulatory therapies to improve pregnancy outcomes.
Low perinatal autopsy rate in Malaysia: time for a change

Tan GC, Hayati AR, Khong TY

Pediatr Dev Pathol, 2010 Sep-Oct;13(5):362-8.
PMID: 20367214 DOI: 10.2350/09-03-0623-OA.1

Our objectives were to determine the perinatal autopsy rate in a tertiary hospital in Malaysia and to quantify the value of the perinatal autopsy. All stillbirths, miscarriages, therapeutic abortions, and neonatal deaths between January 1, 2004, and August 31, 2009, were identified from the archives. The autopsy findings were compared with the clinical diagnoses. The autopsy reports were also reviewed to determine if it would be possible to improve the quality of the autopsies. There were 807 perinatal deaths, of which 36 (4.5%) included an autopsy. There were ethnic differences in the rate of autopsy, with the lowest rate among the Malays. The autopsy provided the diagnosis, changed the clinical diagnosis, or revealed additional findings in 58.3% of cases. Ancillary testing, such as microbiology, chromosomal analysis, and biochemistry, could improve the quality of the autopsy. This study provides further data on the perinatal autopsy rate from an emerging and developing country. It reaffirms the value of the perinatal autopsy. Attempts must be made to improve on the low autopsy rate while recognizing that the performance of autopsies can be enhanced through the use of ancillary testing.
Distribution of cord inflammation in cases with clinical suspicion of chorioamnionitis

Wong YP, Tan GC, Khong TY

Malays J Pathol, 2024 Apr;46(1):41-49.
PMID: 38682843

INTRODUCTION: Identification of acute funisitis, a sign of foetal inflammatory response (FIR), is crucial as their presence is associated with ominous neonatal outcomes. Recommendation on which part of umbilical cord should be sampled to facilitate optimal identification of acute funisitis is limited.
METHODS: This is a retrospective cross-sectional study over a seven-month duration recruiting all patients with clinical suspicion of chorioamnionitis and/or maternal intrapartum pyrexia. The distribution and the degree of cord inflammation were assessed. The cases were also evaluated for maternal inflammatory response (MIR) and chorionic vasculitis (CV).
RESULTS: Of the 191 placentas, 88 (46.1%) had some degree of cord inflammation. Forty-nine (55.7%) had a differential in cord inflammation, with distal cord section (n = 38) demonstrating significant greater inflammation than that of proximal cord section (n = 11) (p<0.001). There were 20 cases with phlebitis only and 8 cases demonstrated arteritis only in either proximal or distal cord sections. Increasing magnitude of cord inflammation was significantly associated with increasing severity of MIR and the rate of CV (p<0.001). CV was observed in 25 (24.3%) cases showing absence of cord inflammation, while 12 (13.6%) cases with cord FIR demonstrated no CV.
DISCUSSION: Inflammatory reaction can occur variably throughout the length of the umbilical cord and chorionic plate vessels, with greater inflammation seen in the distal cord section. We affirm the current Amsterdam recommendation of submitting at least two cross sections of the cord representing proximal and distal sites and two sections from placental parenchyma to facilitate the identification of FIR.
The value of umbilical cord insertion site sampling in detecting maternal and/or fetal inflammatory response

Wong YP, Tan GC, Khong TY

APMIS, 2025 Jan;133(1):e13496.
PMID: 39509086 DOI: 10.1111/apm.13496

The 2016 Amsterdam Placental Workshop Group Consensus Statement recommends sampling a block of the placenta close to the umbilical cord insertion site (UCIB) for histopathological evaluation. This piece of placenta at the umbilical cord insertion is presumed to give a better yield of inflammation (if present). We aimed to investigate the utility of the UCIB in the detection of maternal and/or fetal inflammatory responses (MIR and/or FIR), in comparison with the other sections of the placental parenchyma. This is a retrospective cross-sectional study including all placentas with histologic chorioamnionitis. The histopathological slides of placentas were reviewed as per Amsterdam consensus guidelines. Diagnostic performance of UCIB in identifying MIR and/or FIR, relative to the other placental sections, was assessed. UCIB revealed diagnostic sensitivity, specificity, and diagnostic accuracy of 79.2% (95% CI: 74.2-83.6%), 100.0% (95% CI: 95.6-100.0%), and 83.6% (95% CI: 79.5-87.2%), respectively, in the detection of FIR, while showing a low sensitivity of 52.6% (95% CI: 47.5-57.6%) in detecting MIR. In 59 (24.6%) cases, FIR was not seen in the corresponding placental parenchymal sections but was detected in the UCIBs. This study is the first study to confirm that a section from the UCIB is essential for the detection of FIR, which affirms the Amsterdam consensus sampling recommendations.
Diagnostic utility of p57 immunohistochemistry and DNA ploidy analysis by fluorescence in situ hybridisation in hydatidiform moles

Wong YP, Chia WK, Selimin A, Chia PY, Mustangin M, Shuib S, et al.

Malays J Pathol, 2021 Dec;43(3):341-351.
PMID: 34958055

INTRODUCTION: Hydatidiform moles (HMs) include complete and partial moles, are the result of abnormal fertilisation. The accurate classification of HMs and its distinction from non-molar specimens is utmost important for clinical management and risk assessment. It is diagnostically challenging if the distinction is based solely on histomorphology with poor interobserver reproducibility, especially in early gestations. This study aimed to investigate the diagnostic ability of combined p57 immunohistochemistry and DNA ploidy analysis to distinguish between complete moles, partial moles and non-molar abortus.
MATERIALS AND METHODS: We included all HMs cases diagnosed in our centre over a six-year period. p57 immunohistochemistry stain was performed. Only nuclear immunoreactivity in >50% of cytotrophoblasts and villous stromal cells was regarded as positive for p57. DNA ploidy status was determined by fluorescence in situ hybridisation. A total of 250 cells from five chorionic villi were counted and were scored as diploid or triploid if more than 10% of nuclei demonstrated two or three signals, respectively.
RESULTS: A total of 51 cases originally diagnosed by histomorphology as complete mole (n = 18), partial mole (n = 24) and non-molar abortus (n = 9) were recruited. The cases were reclassified based on the p57 immunostaining pattern and DNA ploidy status, into 27 complete moles (p57-/diploid), 9 partial moles (p57+/triploid) and 15 non-molar abortus (p57+/diploid). The diagnostic accuracy by histomorphological features alone in each category: complete moles, partial moles and non-molar abortus was 78.4%, 70.6% and 88.2% respectively.
CONCLUSION: This study highlighted the importance of the utility of combined p57 immunostain and DNA ploidy analysis in arriving at an accurate diagnosis in HMs. An algorithmic approach utilising these ancillary techniques is advocated in routine diagnostic workup for a more refined diagnostic approach to HMs.
MicroRNA profiling in complete and partial hydatidiform moles

Chia WK, Yeoh HXY, Mustangin M, Khong TY, Wong YP, Tan GC

Malays J Pathol, 2023 Dec;45(3):353-362.
PMID: 38155377

INTRODUCTION: Hydatidiform mole is one of the gestational trophoblastic disease and comprises complete (CM) and partial moles (PM), which carries a risk of developing persistence disease, invasive mole or choriocarcinoma. MicroRNAs (miRNAs) have been discovered in various tissues, including neoplastic tissues. Its role in the pathogenesis of molar pregnancy or as biomarkers are still largely uncertain. The aim of this study is to identify the differentially expressed miRNAs in CM and PM.
MATERIALS AND METHODS: Using next-generation sequencing, the miRNAs profiles of CM (n=3) and PM (n=3) moles, including placenta of non-molar abortus (n=3) as control were determined. The differentially expressed miRNAs between each group were analysed. Subsequently, bioinformatics analysis using miRDB and Targetscan was utilised to predict target genes.
RESULTS: We found 10 differentially expressed miRNAs in CMs and PMs, compared to NMAs, namely miR- 518a-5p, miR-423-3p, miR-503-5p, miR-302a-3p, and miR-1323. The other 5 miRNAs were novel, not listed in the known database. The 3 differentially expressed miRNAs in CMs were predicted to commonly target ZTBT46 and FAM73B mRNAs.
DISCUSSION: miR-518 was consistently observed to be downregulated in CM versus PM, and CM versus NMA. Further bioinformatic analysis to provide insight into the possible role of these miRNAs in the pathogenesis of HMs, progression of disease and as potential diagnostic biomarkers as well as therapeutic targets for HMs is needed.
Fulltext A Review of Placenta and Umbilical Cord-Derived Stem Cells and the Immunomodulatory Basis of Their Therapeutic Potential in Bronchopulmonary Dysplasia

Chia WK, Cheah FC, Abdul Aziz NH, Kampan NC, Shuib S, Khong TY, et al.

Front Pediatr, 2021;9:615508.
PMID: 33791258 DOI: 10.3389/fped.2021.615508

Bronchopulmonary dysplasia (BPD) is a devastating lung disorder of preterm infants as a result of an aberrant reparative response following exposures to various antenatal and postnatal insults. Despite sophisticated medical treatment in this modern era, the incidence of BPD remains unabated. The current strategies to prevent and treat BPD have met with limited success. The emergence of stem cell therapy may be a potential breakthrough in mitigating this complex chronic lung disorder. Over the last two decades, the human placenta and umbilical cord have gained increasing attention as a highly potential source of stem cells. Placenta-derived stem cells (PDSCs) and umbilical cord-derived stem cells (UCDSCs) display several advantages such as immune tolerance and are generally devoid of ethical constraints, in addition to their stemness qualities. They possess the characteristics of both embryonic and mesenchymal stromal/stem cells. Recently, there are many preclinical studies investigating the use of these cells as therapeutic agents in neonatal disease models for clinical applications. In this review, we describe the preclinical and clinical studies using PDSCs and UCDSCs as treatment in animal models of BPD. The source of these stem cells, routes of administration, and effects on immunomodulation, inflammation and regeneration in the injured lung are also discussed. Lastly, a brief description summarized the completed and ongoing clinical trials using PDSCs and UCDSCs as therapeutic agents in preventing or treating BPD. Due to the complexity of BPD, the development of a safe and efficient therapeutic agent remains a major challenge to both clinicians and researchers.
Non-hypertensive gestational diabetes mellitus: Placental histomorphology and its association with perinatal outcomes

Lai YM, Tan GC, Shah SA, Abd Rahman R, Mohd Saleh MF, Mansor S, et al.

Placenta, 2024 Mar 06;147:21-27.
PMID: 38278001 DOI: 10.1016/j.placenta.2024.01.012

INTRODUCTION: Gestational diabetes mellitus (GDM) exerts a great impact on the placenta and reflects changes on placentas both morphological and functionally. The aims of this study are to evaluate the prevalence of placental histopathological lesions in pregnancies complicated by GDM compared to gestational age-matched controls, and their association with maternal and fetal complications.
METHODS: Fifty-four singleton GDM-complicated pregnancies were recruited and compared to 33 consecutive normal pregnancies. Two pathologists, blinded to all clinical data, reviewed and evaluated all histological samples of the placentas in accordance with Amsterdam criteria. Relevant demographic, clinical data and primary birth outcomes were recorded.
RESULTS: A myriad of histomorphological abnormalities, including chronic inflammation (n = 9/54, p = 0.031), histological chorioamnionitis (n = 23/54, p