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Biomedical subjects

Euan M Wallace

Publications and source records attributed to Euan M Wallace.

At least 19 recordsLinked to original sources
PubMed2006

The effects of maternal betamethasone administration on the intrauterine growth-restricted fetus.

Intrauterine growth restriction (IUGR) is associated with altered fetal cardiovascular function to ensure adequate perfusion of essential organs. IUGR fetuses are at risk of preterm delivery and so are likely to receive antenatal glucocorticoids to promote lung maturation. Because glucocorticoids alter vascular tone, we questioned whether such treatment may induce fetal cardiovascular alterations. Using pregnant sheep carrying twins, we induced IUGR at approximately 0.7 gestation by single umbilical artery ligation in one twin, using the other twin as a control. In each fetus, we monitored carotid blood flow and arterial blood gases. We administered 11.4 mg betamethasone (n = 5) or vehicle (n = 4) to the ewe on d 5 (BM1) and 6 (BM2) postsurgery. On d 7, fetal brains were collected for immunohistochemistry. In control fetuses, carotid blood flow decreased 3.5 h post-BM1 by 24% (P < 0.001), returning to baseline at 5.5 h. In IUGR fetuses, carotid flow decreased 2.5 h post-BM1 by 27% and then increased by 25% over baseline, peaking at 11 h (P < 0.001). Compared to control + saline, we observed a significant increase in oxidative damage (4-hydroxynonenal-positive cells) in the fetal hippocampus and subcallosal area of all treatment groups (IUGR + BM > IUGR + saline = control + BM). There was a significant correlation between carotid blood flow reperfusion after betamethasone and the number of 4-hydroxynonenal-positive cells in the cortex and hippocampus. These data suggest that antenatal betamethasone may induce brain injury in the IUGR fetus but not in the normally grown fetus.

Animals↗
PubMed2006

Distinct expression and localization of serine protease HtrA1 in human endometrium and first-trimester placenta.

Mammalian embryos cannot survive without the placenta. Development of the human placenta requires trophoblast proliferation, differentiation, and invasion as well as highly coordinated modulation of the maternal uterus. HtrA1 is a member of the recently identified mammalian HtrA (high temperature requirement factor A) serine protease family with a high level of expression in the placenta. In this study, we examined whether HtrA1 expression (mRNA and protein) is associated with placental development in the human. HtrA1 is up-regulated in both endometrial glands and decidual cells during endometrial preparation for embryo implantation and during first-trimester pregnancy at placentation. HtrA1 expression was also detected in certain trophoblast subtypes during early pregnancy. The villous syncytiotrophoblast and cytotrophoblast showed the strongest expression while the interstitial extravillous trophoblast showed the lowest or no expression of HtrA1. The distinct distribution of HtrA1 at the maternal-trophoblast interface suggests that HtrA1 may play a role in placental development.

Decidua↗
PubMed2006

Association between low day 16 hCG and miscarriage after proven cardiac activity.

OBJECTIVE: To investigate an association between low human chorionic gonadotrophin (hCG) levels at the end of the first week of implantation and later clinical miscarriage occurring after ultrasound confirmation of a live pregnancy. METHODS: This was an observational retrospective study of 1,054 women who underwent in vitro fertilization and achieved an ultrasound-confirmed live singleton pregnancy with cardiac activity. The incidence of miscarriage diagnosed at 8-19 weeks +6 days of gestation was estimated in these 3 subgroups according to their hCG concentrations at day 16 after conception: less than the 25th, 25th-75th, and more than the 75th percentiles. RESULTS: The overall incidence of miscarriage was 11.1% (117/1,054), and the median gestational age at diagnosis was 10 weeks and 4 days. The median (95% confidence interval) day 16 hCG level in the miscarriage group was 182 mIU/mL (157-211), significantly lower than the median level in those who had an ongoing pregnancy (223 mIU/mL [213-233], P < .003). There was an increasing risk of miscarriage associated with decreased hCG levels (8.0% at > 75th percentile; 9.9% at 25th-75th percentiles; 16.7% at < 25th percentile; P = .003). CONCLUSION: Low hCG levels in very early pregnancy are associated with an increased risk of miscarriage occurring after the clinical recognition of pregnancy. The mechanisms underlying late first-trimester and second-trimester miscarriages may have begun as early as the first week of implantation. LEVEL OF EVIDENCE: III.

Abortion, Spontaneous↗
PubMed2006

Maternal serum activin A and the prediction of intrauterine growth restriction.

BACKGROUND: Differentiating between the small healthy fetus and the high risk growth restricted fetus remains a significant obstetric challenge. It has been previously shown that maternal activin A levels are increased in association with fetal growth restriction. AIM: To evaluate maternal serum activin A as a marker of fetal growth restriction. METHODS: Prospective cohort study of 62 women referred for fetal assessment because of a clinical suspicion of a small for gestation fetus. Maternal serum levels of activin A were measured with an ELISA. RESULTS: Activin A levels, expressed as median (95% CI) MoMs, were similar in the women with a normal-sized fetus and in those with a healthy small for gestational age fetus, 1.14 (95% CI 1.0-1.5) and 1.31 (95% CI 0.8-2.1), respectively (P = 0.97). Compared to the women with a normal-sized fetus or a healthy small fetus, activin A levels were significantly elevated in the women who had an intrauterine fetal growth restriction fetus 2.37 (95% CI 1.6-3.7; P = 0.01 compared to normal and P = 0.04 compared to healthy small). CONCLUSIONS: These data confirm that circulating activin A is increased in association with fetal growth restriction. However, a single blood sample for activin A will not efficiently discern between healthy and compromised small fetuses.

Activins↗
PubMed2006

Compliance with a risk factor-based intrapartum prophylaxis program for neonatal group B streptococcal disease.

AIM: The US Centre for Disease Control (CDC) recently amended their guidelines for the prevention of early-onset group B streptococcal disease (EOGBSD) of the newborn to recommend bacteriological screening, rather than risk factor-based screening, as the preferred method of identifying 'at risk' mother-infant pairs. This recommendation was derived from population data suggesting that the effectiveness of bacteriological screening was superior to a risk-factor approach because antibiotic compliance was better with the former. Whether poor compliance and therefore impaired prevention is inherent in risk-factor screening has not been widely tested. METHODS: For a 6-month period we audited compliance with an established risk-factor EOGBSD prophylaxis program. RESULTS: During the audit period, 1243 women delivered, of whom 287 (23%) had at least one risk factor. Of these women, 193 (67%), representing 15% of all women giving birth, received antibiotics. Thus, there were 94 women who were eligible for antibiotics but did not receive prophylaxis. There were sound clinical reasons for withholding antibiotics in 68 of these. Therefore, the corrected compliance rate within our program was 73%. CONCLUSION: This compares favourably with published compliance rates with bacteriological-based programs, but we have suggested mechanisms to improve compliance further.

Antibiotic Prophylaxis↗
PubMed2005

Serine peptidase HTRA3 is closely associated with human placental development and is elevated in pregnancy serum.

HTRA3 is a newly identified serine peptidase of the mammalian HTRA (high-temperature requirement factor A) family, that is upregulated dramatically during mouse placental development. The current study determined whether HTRA3 was involved in human placentation. During the menstrual cycle, HTRA3 was expressed primarily in the endometrial glands, being significantly upregulated toward the mid- to late secretory phases; prominent expression in the stroma detected only in the decidual cells in the late secretory phase. Thus, overall endometrial HTRA3 expression was highest in the late secretory phase, when the endometrium is prepared for maternal-trophoblast interaction. During the first trimester of pregnancy, both glandular and decidual HTRA3 expression increased further with the decidual upregulation being highly significant. The strong link between HTRA3 expression and endometrial stromal cell decidualization was further established in an in vitro model using primary endometrial stromal cells. HTRA3 was also expressed by certain trophoblast subtypes in the first-trimester placenta: strongly in the villous syncytiotrophoblast, trophoblast shell, and endovascular trophoblast and weakly in the distal portion of the trophoblast cell columns but not in villous cytotrophoblast, the proximal region of the cell columns, or interstitial trophoblast. Upregulation of HTRA3 expression in association with placental development was revealed by a significant elevation of this protein in the maternal serum during the first trimester. We thus propose that HTRA3 is a previously unrecognized factor closely associated with and potentially important for human placentation. This study established crucial groundwork for future investigations toward establishing the physiological roles of HTRA3 in human placentation.

Antibody Specificity↗
PubMed2005

Identification of kynurenine pathway enzyme mRNAs and metabolites in human placenta: up-regulation by inflammatory stimuli and with clinical infection.

OBJECTIVE: The purpose of this study was to determine whether placental-derived kynurenines (neuroactive metabolites that are derived from tryptophan) contributes to infection-mediated fetal cerebral injury. STUDY DESIGN: Placentae and cord blood were obtained from term deliveries (n = 16) and preterm deliveries with or without intrauterine bacterial infection (n = 8 per group). We investigated whether the placenta expressed messenger RNAs of kynurenine metabolite-forming enzymes, the effects of infection in vivo on the expression of these enzymes by the placenta, the in vitro effects of bacterial endotoxin lipopolysaccharide on expression and kynurenine metabolite output by the placenta, and the kynurenine metabolite levels in umbilical cord blood. RESULTS: Placentae expressed messenger RNA of tryptophan-degrading enzymes and synthesized several compounds. The expression of several enzymes increased significantly in placentae that were exposed to infection and/or lipopolysaccharide. Lipopolysaccharide also induced significant increases in placental kynurenine and quinolinic acid output. Kynurenine and quinolinic acid in cord blood of fetuses who were exposed to infection were elevated significantly. CONCLUSION: Inflammatory mediated release of kynurenines from placentae exposes the fetus to significant amounts of potentially neurotoxic substances.

Case-Control Studies↗
PubMed2005

Uterine artery Doppler velocimetry for the detection of adverse obstetric outcomes in patients with elevated mid-trimester beta-human chorionic gonadotrophin.

AIM: The aim of this study is to review the clinical usefulness of Doppler velocimetry of the uterine artery for the detection of adverse obstetric outcome in a population of women with elevated mid-trimester serum beta-human chorionic gonadotrophin (betahCG). METHODS: Women with an unexplained elevated mid-trimester betahCG level (> or = 4.0 multiples of the median) are offered uterine artery Doppler assessment at 22-24 weeks of gestation. We have audited the clinical usefulness of this practice by reviewing the prevalence of the adverse outcomes of gestational hypertension, intrauterine growth restriction (IUGR) and preterm birth and the predictive capacity of the test when applied to this subgroup of high-risk patients. RESULTS: Sixty-two women had an elevated serum betahCG and underwent Doppler study of uterine artery flow velocity waveform. Notching afforded better predictive utility for any outcome than the resistance index alone or in combination with notching. For a composite adverse outcome of any or all of gestational hypertension, birthweight < or = 10th centile, and preterm delivery, the presence of a uterine notch alone had sensitivity of 30.7% and specificity of 93.8%. For the identification of severe fetal growth restriction (< 5th centile) and/or preeclampsia, the presence of a notch offered a sensitivity of 50%, specificity of 96.3%, a positive likelihood ratio of 13.5, and a negative likelihood ratio of 0.5. CONCLUSIONS: The identification of uterine artery notching by means of Doppler ultrasound as a component of the surveillance of women with unexplained elevated betahCG levels significantly improves the prediction of preeclampsia and/or severe IUGR, although the low prevalence of 13% of these adverse outcomes limits the usefulness of the test in routine clinical practice.

Adult↗
PubMed2005

Testing for Down syndrome in the older woman: a risky business?

For over 30 years, antenatal diagnosis of Down syndrome has been offered on the basis of advanced maternal age. While this was appropriate in the 1970s, developments in antenatal screening have rendered this a most inefficient strategy that is associated with excessive costs and procedure-related pregnancy losses. In this article we argue for a review of how we test for Down syndrome in the older woman.

Adult↗
PubMed2005

Iodine status in pregnant women living in Melbourne differs by ethnic group.

The iodine status of pregnant women from different ethnic groups in an Australian population was determined by measuring urinary iodine concentration (UIC) from stored spot urine samples. Study subjects were selected from pregnant women participating in a Down Syndrome screening study at Monash Medical Centre in Melbourne, Australia. In total, 263 Vietnamese, 262 Indian/Sri Lankan (ISL) and 277 Caucasian women were included. The median UIC of Caucasian women (52 microg/L) was significantly lower than that of both Vietnamese women (58 microg/L, P <0.01) and ISL women (61 microg/L, P = 0.03). The proportion of women who had a UIC below 50 microg/L was 48.4% of the Caucasian women, 38.4% of the Vietnamese women and 40.8% of the ISL women. These data are consistent with mild iodine deficiency for each of the groups of pregnant women. The evidence for mild iodine deficiency in these groups of pregnant women is consistent with recent Australian studies in pregnant and non-pregnant individuals. The association of ethnicity with iodine status is most likely due to differences in dietary behaviours. Understanding the factors that influence iodine nutrition in a multiethnic population will be important for identifying the most useful approaches to improving iodine status, evaluating different strategies and the development of appropriate monitoring programs. Action to improve iodine status in the Australian population should include consideration of ethnic differences in diet.

Australia↗
PubMed2004

Serum concentrations of macrophage inhibitory cytokine 1 (MIC 1) as a predictor of miscarriage.

Macrophage inhibitory cytokine 1 (MIC 1) is thought to have immunomodulatory actions favouring fetal viability. We measured serum concentrations of MIC 1 in asymptomatic women at 6-13 weeks' gestation who subsequently miscarried or who had already miscarried. MIC 1 concentrations in the miscarriage cohort (n=100), were a third of those who had ongoing pregnancies (n=197). Multiples of the median for miscarriage was 0.32 (95% CI 0.23-0.32) versus 1.00 (0.93-1.06) for ongoing pregnancies; p<0.0001. Concentrations were just as low 3 weeks before diagnosis as on the day of diagnosis. That MIC 1 serum concentrations seem to be low weeks before miscarriage suggests possible predictive and causative roles, as well as therapeutic potential.

Abortion, Spontaneous↗
PubMed2004

Maternal serum and amniotic fluid levels of macrophage inhibitory cytokine 1 in Down syndrome and chromosomally normal pregnancies.

OBJECTIVES: To measure maternal serum and amniotic fluid levels of macrophage inhibitory cytokine-1 (MIC-1) in Down syndrome and normal pregnancies, assessing the utility of MIC-1 as a prenatal marker of Down syndrome. METHODS: Stored serum from 64 Down syndrome and 399 control pregnancies, collected at 8 to 17 weeks of pregnancy, and stored amniotic fluid from 17 Down syndrome and 53 controls, collected at 15 to 19 weeks of pregnancy, were retrieved for analysis. MIC-1 was measured using an established in-house ELISA, blinded to sample type. RESULTS: In maternal serum, MIC-1 levels are not altered in Down syndrome in either the first or second trimester. Levels, expressed as median (95% CI) multiples of the median (MoM), in the Down syndrome cases and controls were 1.07 (0.9-1.1) MoM and 1.0 (0.95-1.03) MoM respectively. In amniotic fluid, MIC-1 levels were significantly decreased compared to controls, 0.52 (0.44-0.64) MoM versus 1.0 (0.85-1.08) MoM (p < 0.0001). CONCLUSION: MIC-1 is decreased in amniotic fluid but not in maternal serum in Down syndrome pregnancies. MIC-1 will not be useful as a prenatal marker of Down syndrome.

Amniotic Fluid↗
PubMed2004

First trimester levels of inhibins and activin A in normal and failing pregnancies.

OBJECTIVE: Miscarriage is the commonest complication of human pregnancy. We undertook this study to assess whether inhibin A, pro-alphaC inhibin and/or activin A, products of the corpus luteum and placenta, might be useful in either the prediction or diagnosis of miscarriage. DESIGN: Case-control study. PATIENTS: Ninety-eight asymptomatic women at 6-13 weeks gestation who subsequently had a miscarriage and 198 gestation-matched women with a normal singleton pregnancy. MEASUREMENTS: Maternal serum levels of inhibin A, pro-alphaC inhibin, activin A and human chorionic gonadotrophin (hCG) were measured. RESULTS: Inhibin A, pro-alphaC and hCG, expressed as multiples of the normal median (MoM; +/-95% confidence intervals) in the miscarriage cases were significantly lower than in the viable controls, 0.56 (0.48-0.69) MoM vs. 1.00 (0.98-1.13) MoM, 0.55 (0.51-0.84) MoM vs. 1.0 (0.86-1.22) MoM and 0.34 (0.23-0.36) MoM vs. 1.00 (0.94-1.08) MoM, respectively (P < 0.0001 for all). Of the three analytes, hCG was the most discriminating between cases and controls. Levels of activin A in the miscarriage cases were not significantly different from controls, 0.96 (0.86-1.07) vs. 1.0 (0.95-1.08). CONCLUSIONS: These data suggest that inhibin A, pro-alphaC inhibin and activin A will not be useful in either the prediction or diagnosis of early pregnancy miscarriage.

Abortion, Spontaneous↗
PubMed2004

Fetal activin A: associations with labour, umbilical artery pH and neonatal outcome.

OBJECTIVE: To define the ontogeny of umbilical artery activin A at term and to evaluate activin A as a potential marker of perinatal hypoxia. DESIGN: A cohort study. SETTING: A university teaching hospital delivery suite. POPULATION: A convenience sample of 141 term pregnancies. METHODS: At delivery, umbilical artery and vein bloods were collected for blood gas measurements and subsequent measurement of activin A. Activin A levels were correlated with blood gas measurements and with labour and neonatal outcomes. MAIN OUTCOME MEASURES: Umbilical arterial activin A and pH. RESULTS: The median (95% CI) umbilical arterial activin A level at delivery was 1.38 (1.34-1.70) ng/mL. Levels varied significantly across gestation (P= 0.03), increasing from 36 to 38 weeks, thereafter decreasing to a nadir at 41 weeks. In 60 matched samples, the median (95% CI) venous and arterial activin A levels were 0.89 (0.81-1.06) ng/mL and 1.38 (1.21-1.61) ng/mL, respectively (P < 0.0001). Mean umbilical arterial pH was 7.20 (7.06-7.38; 5-95th centiles) and was not significantly correlated with log10 activin A (r=- 0.01; P= 0.68). Compared with healthy controls, there was no difference in arterial activin A in neonates identified as having suffered significant intrapartum asphyxia (P= 0.96). Fetal activin A levels were significantly lower in cases delivered by emergency caesarean section for complications during the first stage of labour compared with cases delivered vaginally (P= 0.003). CONCLUSIONS: Umbilical artery activin A does not appear to be a sensitive marker of fetal oxygenation or of risk of hypoxic-ischaemic encephalopathy.

Activins↗
PubMed2004

Hypoxia induced activin secretion by the fetoplacental unit: differential responses related to gestation.

OBJECTIVE: To determine whether activin A levels reflect oxygen availability in basal and hypoxic conditions in the late pregnant fetus and newborn lamb. DESIGN: In vivo animal experimental study. SETTING: Department of Physiology, Monash University. POPULATION: Chronically catheterised fetal sheep in late gestation. METHODS: Fetal hypoxia was induced at 125 (n = 4), 135 (n = 4) or 145 days ('term'; n = 3) gestational age by maternal nitrogen exposure, for 4 hours, during which maternal and fetal arterial, and amniotic fluid samples were collected. Lambs (age one, five and eight days; n = 3) were exposed to 1 hour of hypoxia via nitrogen exposure. MAIN OUTCOME MEASURES: Activin A, prostaglandin E2 (PGE2) and cortisol were analysed in plasma and amniotic fluid, and whole blood was used to determine Pao2, Paco2, %O2, lactate and pH. RESULTS: Basal activin A concentrations in the fetal arterial circulation remained unchanged between 125 days (0.230 [0.10] ng/mL) and term (0.28 [0.10] ng/mL), as did fetal oxygen saturation (59.11% [4.74%] to 52.25% [4.84%]) and pH (7.35 [0.02] to 7.37 [0.02]). Moderate fetal hypoxia (50% fall in fetal arterial %O2) produced a significant increase in circulating activin A (2.05 [0.67] ng/mL) and a significant decrease in pH (7.27 [0.03]) at 125 days of gestation, however, at 135 and 145 days, activin A and pH remained unchanged. Fetal activin A concentration was significantly correlated with pH (P = 0.036) but not %O2 (P = 0.072). Hypoxia in the lambs did not alter circulating activin A. CONCLUSIONS: In response to hypoxia, activin A is increased in the circulation of 125-day-old fetuses, but not in older fetuses. Fetal arterial activin A levels sensitively reflect pH but not oxygen saturation, with increasing activin A in conditions of metabolic acidosis.

Activins↗
PubMed2004

Maternal and neonatal outcomes in 54 triplet pregnancies managed in an Australian tertiary centre.

BACKGROUND: To provide current data on maternal and neonatal outcomes in triplet pregnancies in an Australian population. METHODS: Retrospective case note review of all triplet pregnancies managed within a single Australian tertiary centre. RESULTS: Fifty-four sets of triplets were managed from January 1996 to October 2002. A total of 59% resulted from the use of assisted reproductive technologies. The median gestation at delivery was 32.5 weeks (range: 21-36 weeks); 14% delivered prior to 28 weeks and 43% delivered before 32 weeks. Preterm labour and preterm rupture of membranes were the most common antenatal complications occurring in 57 and 22% of pregnancies, respectively. A total of 93% of pregnancies were delivered by Caesarean section and 37% of mothers experienced at least one post-partum complication. A total of 96% of neonates were liveborn, with a median birthweight of 1644 g (range: 165-2888 g). The two most common neonatal complications were jaundice and hypoglycaemia in 52 and 43% of liveborn neonates, respectively. A total of 28% of neonates were below the 10th centile for gestational age and sex. A total of 8% of neonates demonstrated congenital anomalies. The perinatal mortality at a gestational age of 20-24 weeks was 100%, 22% at 25-28 weeks and zero for those babies born at 29 weeks or beyond. CONCLUSION: Assisted reproductive technologies contribute significantly to the incidence of triplet pregnancies. Gestational age at delivery and perinatal mortality is comparable to published international data. Triplets born in a tertiary centre beyond 28 weeks gestation have a very favourable prognosis in the newborn period.

Adult↗