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Biomedical subjects

T Y Khong

Publications and source records attributed to T Y Khong.

At least 19 recordsLinked to original sources

Foetal and neonatal autopsy rates and use of tissue for research: the influence of 'organ retention' controversy and new consent process.

AIM: To examine whether the 'organ retention' controversy and new autopsy consent process had any effect on foetal and neonatal autopsy rates and on permitting the use of tissue for scientific research and education. METHODS: An audit of perinatal autopsy rates in a tertiary hospital prior to (1999-2001) and subsequent to the 'organ retention' controversy (2001-2002), and the introduction of a new consenting process (2002-2004). Rates were compared also with those a decade earlier (1990-1993). RESULTS: Overall autopsy rates have been falling significantly between the three study periods (1999-2001 71.7%; 2001-2002 61.5%; 2003-2004 50.5%). Autopsy rates have fallen significantly between 1990-1993 and 1999-2001 (P<0.00005) and between 1990-1993 and 1999-2004 (P<0.0000001). The autopsy rates for stillbirths and neonatal deaths have fallen significantly further since the 'organ retention' controversy but not significantly so following the new consenting process. Significantly fewer autopsies are performed on foetuses less than 20 weeks gestation in recent years than a decade ago (P<0.0000001). There were more external or limited autopsies in later years (P=0.015). Permission for the use of tissue for education and research is less frequent following the 'organ retention' controversy and particularly following the introduction of the new consenting process. CONCLUSION: Perinatal autopsy rates have fallen over the past 10 years. Fewer autopsies are being performed following the 'organ retention' controversy and use of tissue for research and education is permitted even less frequently following the introduction of the new consenting process.

Autopsy↗

Is endomyometrial injury during termination of pregnancy or curettage following miscarriage the precursor to placenta accreta?

AIMS: To determine the frequency with which myometrium is removed during vacuum terminations of pregnancy or dilatation and curettage after miscarriage, and to relate these findings to subsequent placenta accreta or its proxies. METHODS: Archival tissues from vacuum termination of pregnancy or dilatation and blunt curettage after miscarriage were examined for the presence of myometrium. The subsequent obstetric histories were scrutinised for manual removal of placenta, postpartum haemorrhage, or retained placenta. A retrospective study comparing the frequency of miscarriage and termination in women who had or did not have a manual removal was also performed. RESULTS: Myometrium was seen in the products of conception in 44% and 35% of termination and miscarriage tissues, respectively. One of nine women with myometrium at miscarriage had a postpartum haemorrhage in a subsequent pregnancy whereas, of the 21 women without myometrium at miscarriage, three required manual removal and seven had a postpartum haemorrhage afterwards. A past history of termination and/or miscarriage was more frequent in multigravid women who had a manual removal than those who did not. CONCLUSIONS: Endomyometrial injury is frequent at termination or dilatation and curettage after miscarriage, but the relation to subsequent placenta accreta remains unclear. Women requiring a manual removal of the placenta were likely to have had a past history of termination and/or miscarriage.

Abortion, Induced↗

On an anatomical basis for the increase in birth weight in second and subsequent born children.

OBJECTIVE: Structural changes of the spiral arteries needed for the pregnancy do not completely resolve following parturition. We tested the hypothesis that these anatomical changes are related to the number of previous pregnancies. METHODS: Video image analysis was performed on Masson-stained sections from 28 hysterectomy specimens, examining the proportion of non-muscular tissue within the spiral arterial walls. Semi-quantitative analysis of changes of the internal elastic lamina was performed on orcein-stained sections. The extent of changes was tested for correlation with parity using regression analysis. RESULTS: Duplication and fragmentation of the internal elastic lamina increased with increasing parity (P=0.019) with differences between nulliparity and parity 1, 2, 3 or 4 but not between other parity pairings. The proportion of non-muscular tissue increased with increasing parity (P=0.010). CONCLUSIONS: These results suggest that pregnancy results in permanent anatomical changes in the spiral arteries that may modify subsequent vascular remodelling in the next pregnancy. This could provide an anatomical basis to explain the epidemiological data showing an increasing birth weight with increasing parity, particularly of the second born.

Adult↗

Provider attitudes about gaining consent for perinatal autopsy.

OBJECTIVE: To examine the attitudes of neonatologists, obstetricians, midwives, and neonatal nurses toward perinatal autopsy and survey physicians about whom they perceive influence women's decisions on autopsy consent. METHODS: A postal survey that incorporated a questionnaire of eight fictitious case scenarios and combined three factors (confidence of antemortem diagnosis, intention to have future pregnancy, and parental attitude toward autopsy) in various permutations was sent to various Australian physicians and nurses (all consultant neonatologists working in neonatal intensive care units and a sample of consultant obstetricians, midwives, and neonatal nurses in level III maternity hospitals). Respondents were asked to rate how likely they were to seek consent for or suggest autopsies on a seven-point Likert scale (1 = certainly will not, 7 = certainly will). Interactions between factors and respondents were measured by analysis of variance, and differences were compared using Mann-Whitney U, chi(2), and generalized estimating equation tests. RESULTS: The overall response rate was 70% (neonatologists 57%, obstetricians 62%, midwives 77%, and neonatal nurses 75%). Neonatologists (median score 7, interquartile range 7, 7) were more likely to ask for autopsies than neonatal nurses (5; 2, 6) (P <.001), as were obstetricians (7; 7, 7) compared with midwives (6; 3, 7) (P <.001). Physicians rated midwives and neonatal nurses as having some to substantial influence on mothers' decisions about consent for autopsy. CONCLUSION: Physicians are not averse to seeking consent for perinatal autopsies. Midwives and nurses are influenced by the three factors studied, which might negatively influence the consent rate for perinatal autopsies. Intervention strategies aimed at changing nurses' attitudes should be considered.

Attitude of Health Personnel↗

Altered placental structure induced by maternal food restriction in guinea pigs: a role for circulating IGF-II and IGFBP-2 in the mother?

Maternal feed restriction may restrict fetal growth in part indirectly by impairing placental functional development. Such actions could be mediated by the insulin-like growth factors (IGF), which are important modulators of placental growth and differentiation and more generally, are influenced by nutrient availability. While a role for the fetal IGF axis has been demonstrated, less is known of the influence, if any, of that in the mother. This study aimed to determine whether alterations in the maternal IGF axis and placental functional and structural development due to maternal food restriction are related. We therefore examined the associations between placental structural parameters, the ratios of maternal to fetal plasma glucose and fetal to maternal plasma urea concentration, and maternal circulating IGF-I, IGF-II and IGFBP-2 in ad libitum fed and food restricted (70-90 per cent of the ad libitum intake) pregnant guinea pigs. In mid-gestation, fetal weight (r = 0.65, P = 0.008, n = 17), volume of the maternal blood space (r = 0.58, P = 0.048, n = 17), and surface density of syncytiotrophoblast (r = 0.65, P = 0.023, n = 17), were positively correlated, and syncytiotrophoblast thickness was negatively correlated, with maternal plasma IGF-II concentration (r = -0.69, P = 0.014, n = 17). Late in gestation, fetal weight, placental weight and total exchange surface area in the placenta were each negatively correlated with maternal plasma IGFBP-2 concentration (all P < 0.01), while the arithmetic mean thickness of syncytiotrophoblast was positively correlated with maternal plasma IGFBP-2 concentration. Late in gestation, the ratio of maternal to fetal plasma glucose was positively correlated with fetal weight (r = 0.54, P = 0.038, n = 15) and the ratio of fetal to maternal plasma urea concentration was positively correlated with placental weight (r = 0.52, P=0.046, n=15). Maternal feed restriction reduced the ratio of maternal plasma IGF-II to IGFBP-2 in late gestation by 75 per cent (P = 0.001) and this ratio was positively correlated with fetal weight (r = 0.56, P = 0.01, n = 20), placental weight (r = 0.59, P = 0.006), placental diameter (r = 0.621, P = 0.003), placental volume (r = 0.57, P=0.009), weight of trophoblast (r = 0.51, P=0.037), weight of fetal capillaries (r = 0.49, P = 0.046), syncytiotrophoblast surface density (r = 0.611, P = 0.009) and negatively correlated with syncytiotrophoblast thickness (r = -0.55, P = 0.021). Our results suggest that in mid-pregnancy, maternal circulating IGF-II promotes placental structural development, while later in pregnancy, IGFBP-2 inhibits it, and their relative abundance and interaction strongly influences placental structure and function near term.

Animals↗

Vasoactive effects of 8-epi-prostaglandin F(2alpha)in isolated human placental conduit and resistance blood vessels in vitro.

The effects of 8-epi-prostaglandin F(2alpha)(8-epi-PGF(2alpha)) and the thromboxane A(2)-mimetic U46619 were examined on isolated human fetal placental arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit and resistance arteries. 8-epi-PGF(2alpha)was found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2alpha)were 4.10x10(-7) m (2.02-8.35x10(-7) m) (mean, 95 per cent CI and 2.05x10(-6) m (0.43-9.89 x10(-6) m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF(2alpha)(112+/-17 per cent), (relative to maximum KCl induced vasoconstriction) in conduit vessels was significantly less than that caused by U46619 (152+/-20 per cent). In resistance vessels the maximum vasoconstrictor effects to 8-epi-PGF(2alpha)(208+/-10 per cent) and U46619 (201+/-19 per cent) were similar, and in both cases significantly greater than the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit (EC(50)=1.21x10(-9) m, 0.58-2.51x10(-9) m) and resistance arteries [EC(50)=5.95x10(-9) m, (0.81-43.60x10(-9) m] as was found for 8-epi PGF(2alpha). 8-epi-PGF(2alpha)was equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC(50)=1.25x10(-6) m, 0.25-6.17x10(-6) m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF(2alpha)in placental resistance arteries was significantly reduced (99+/-20 per cent) in vessels obtained from severely pre-eclamptic compared with normal pregnancies. These results indicate that 8-epi-PGF(2alpha)displays differential vasoconstrictor activity in the fetal-placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2alpha)are reduced in pre-eclampsia, the effect being selective to placental resistance vessels. This reduction may occur as a result of more serious disturbances in the placental microcirculation with the disease process in pre-eclampsia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

A topographical and clinical approach to examination of the placenta.

Placental examination can be frustrating because of a perceived lack of usefulness and other limitations. A systematic examination employing a topographic approach that will eliminate gross omissions is described. This approach is used at the time of gross and histological examination. Histologically, the umbilical cord is examined from the surface to the inside, while the amniochorial membranes and placental disc are examined from the foetal to maternal surfaces. It is possible to accrue useful information when the placenta is examined this way. This information then can be correlated with the clinical details and indications for the placental examination.

Australia↗

Myometrial fibers in the placental basal plate can confirm but do not necessarily indicate clinical placenta accreta.

Placental basal plate myometrial fibers reflect mild placenta accreta. We tested the hypotheses that a macroscopically disrupted area relates to an area where the placenta is focally adherent and that the incidence of placenta accreta is higher than stated in the literature. Sagittal blocks were taken from the basal plate from macroscopically intact, disrupted, and mixed (viz, at the junction of intactness and disruption) areas, together with an en face block from 90 singleton placentas. Histologic examination revealed that 11 of 23 placentas with a macroscopically disrupted maternal surface and 16 of 67 with a macroscopically intact maternal surface had placental basal plate myometrial fibers, a significant difference. More cases were detected with sampling from the mixed than from the intact area, while sampling from the wholly disrupted area was unrewarding. The en face block also was helpful for detecting myometrial fibers. Extensive and selective sampling of the basal plate revealed a much higher incidence of placental basal plate myometrial fibers. Clinical chart review affirmed that their presence can confirm but does not necessarily correlate with a clinical diagnosis of mild placenta accreta.

Adolescent↗

Chorangioma with trophoblastic proliferation.

Only two examples of the entity of chorangiocarcinoma, in which there is a proliferation of both the vascular and epithelial components of the placental villi, have been reported in the literature. To test the hypothesis that chorangiocarcinomas are actually more common than implied by the literature, histological sections of chorangiomas were reviewed. Syncytiotrophoblast and cytotrophoblast proliferation, with nuclear atypia, similar to that found in trophoblastic neoplasia, were seen in 15 of 23 cases. Thus, 65% of chorangiomas fulfilled the diagnostic criteria to warrant re-assignment as "chorangiocarcinoma". The proliferation index of the cytotrophoblast in the tumor as measured by MIB-1 (Ki-67) immunostaining was significantly higher in "chorangiocarcinoma" than chorangioma (35.4% vs 15.7%, P<0.02). The following factors had no relationship to the presence or absence of trophoblastic proliferation: vascularity, cellularity, infarction, size or location of the chorangioma, or age of the patient. Five of the 15 chorangiomas with trophoblastic proliferation were of the chorangiomatosis variety. No formal follow-up was performed, as this was a retrospective study, but there is no recorded case of persistent gestational trophoblastic disease in this cohort, although one woman with "chorangiocarcinoma" had a history of previous hydatidiform molar pregnancies. An apparently benign clinical course is seen. These lesions, best described as chorangiomas with trophoblastic proliferation, are more common than suggested by the rarity of reported cases.

Adult↗

Chronic deciduitis in the placental basal plate: definition and interobserver reliability.

This study tested whether concordance could be achieved for abnormal inflammation in the basal decidua of placental specimens among 6 pathologists experienced in placental pathology. Thirty microscope slides were evaluated by the pathologists for chronic deciduitis. They also scored the severity and extent of inflammation and the presence of plasma cells. No definition of chronic deciduitis was provided. Concordance (5/6 or 6/6 agreement) was achieved in 23 cases (76%). Spearman's rank correlation showed that the diagnosis of chronic deciduitis was almost identical to the assessment of the severity of the inflammation. A regression analysis showed that the perception of severity (and hence chronic deciduitis) was influenced by the other 2 variables, extent and plasma cells. The results were shared with the pathologists, and 25 cases (excluding those with previous 6/6 consensus) were reevaluated. Concordance was now achieved in the 83% of those remaining cases. Using a threshold based on the severity and the extent of lymphocytes, and the presence of plasma cells, pathologists are able to diagnose chronic deciduitis with sufficient concordance to be of value in clinical correlation studies.

Adult↗

Haematopoietic indicators of fetal metabolic acidosis.

We aimed to study the haematopoietic response in normal and acidotic deliveries following vaginal and abdominal delivery and to compare this to the surrogate markers of perinatal acidosis. Blood gas analyses, complete blood pictures and erythropoietin assays were performed on umbilical or early neonatal blood samples. Placental sections were examined for the presence of nucleated red blood cells. Perinatal clinical risk factors and major neonatal outcomes were collected. The control population was 78 deliveries where the cord arterial pH was > 7.10. Controls born after labour were compared to those born prior to the onset of labour and to 14 acidotic infants born after labour. Nucleated red blood cells did not increase with labour in the control groups but were significantly higher (p < 0.05) in the acidotic group. Erythropoietin did not significantly change with either labour or acidosis. The predictive values from nucleated red blood cell counts were higher than those from low Apgar scores, atypical cardiotocograph traces, meconium-stained amniotic fluid, erythropoietin and the presence of nucleated red blood cells in placental sections. Nucleated red blood cell counts may be a useful surrogate marker of acidosis where blood gas analysis is unavailable. Further studies are required to examine the timing of the increase of erythropoiesis to help define the onset of the stimulus.

Acidosis↗

The placenta in maternal hyperhomocysteinaemia.

It is becoming increasingly apparent that mild or moderate hyperhomocysteinaemia may be associated with adverse perinatal complications and outcomes. The placental pathology in 14 pregnancies from 11 women diagnosed retrospectively to have hyperhomocysteinaemia, following a recent history of intrauterine fetal growth restriction, abruption or of thromboembolic disease, were reviewed. Most of the placental findings indicated abnormal placentation but these were not specific to maternal hyperhomocysteinaemia nor found in every placenta. Features observed included absence of trophoblast-induced physiological vascular changes, acute atherosis, intraluminal endovascular trophoblast in the third trimester, infarction, retroplacental haematoma formation and accelerated villous maturity. Uteroplacental vascular thrombosis was also seen. Three of the women had a subsequent pregnancy where they were treated empirically with folic acid, and these resulted in improved perinatal outcomes. The finding of placental pathology warrants investigation of the woman for hyperhomocysteinaemia. Further randomised controlled trials of folic acid supplementation in preventing pregnancy complications associated with hyperhomocysteinaemia should be conducted.

Adolescent↗

Pregnancies complicated by retained placenta: sex ratio and relation to pre-eclampsia.

Pre-eclampsia and placenta accreta have opposite histological features of placentation. This study set out to test the hypotheses that the sex ratios in these two pregnancy complications are opposite and that these conditions are mutually exclusive. A population-based database covering all deliveries in South Australia between 1986 and 1995 and the hospital-based obstetric database of the Adelaide Women's and Children's Hospital, covering 8549 births between 1993 and 1995, were used to ascertain the sex ratios in singleton pregnancies and the sex ratios in those pregnancies in which there was retained placenta, hypertension in pregnancy, or pre-eclampsia. The likelihood of independence of occurrence or mutual exclusivity of retained placenta and hypertension in pregnancy or pre-eclampsia were also examined. The male:female sex ratio in the South Australian population was 1.077. In pregnancies with hypertension in pregnancy it was 1.165 (P<0.001) and in pregnancies with retained placenta it was 0.883 (P<0.0001). There was a trend to an increased sex ratio in pre-eclamptic pregnancy (1.248 in primigravid and 1.092 in multigravid women) but there was insufficient power to detect significance (P=0.207 and 0.470, respectively). Neither hypertension in pregnancy nor pre-eclampsia were mutually exclusive of placenta accreta: hypertensive disorders of pregnancy and placenta accreta occurred independently of each other. Our findings suggest that sex-linked antigens are unlikely to influence maternofetal interactions consistently to give rise to one but not the other pregnancy complication.

Adult↗