Jeffrey K. Pollard

Tumor necrosis factor alpha stimulates amnion prostaglandin biosynthesis primarily via an action on fatty acid cyclooxygenase

The purpose of this study was to determine how tumor necrosis factor alpha (TNF alpha) stimulates prostaglandin E2 production in human amnion. Amnion cells were isolated from term placentae and grown to confluence in culture. Incubations were conducted in quadruplicate wells for 16 hours with TNF alpha and protein synthesis inhibitors cycloheximide and actinomycin D, or arachidonic acid, acetylsalicylic acid (ASA), or staurosporine or H7 which inhibit protein kinase C activity. Prostaglandin E2 (PGE2) was measured by radioimmunoassay and cellular protein determined. The stimulatory action of TNF alpha on amnion PGE2 production was blocked by protein synthesis inhibitors, and the addition of arachidonic acid always enhanced the stimulatory properties of TNF alpha. TNF alpha consistently induced more rapid recovery from ASA treatment, and protein kinase C inhibition attenuated the stimulatory effects of TNF alpha. These results suggest that the stimulatory action of TNF alpha on amnion PGE2 production is likely at the level of induction of fatty acid cyclooxygenase activity and is partially dependent upon activation of protein kinase C.

Mechanism of cytokine stimulation of prostaglandin biosynthesis in human decidua

OBJECTIVE: The purpose of this study was to determine the mechanism of action of the cytokines tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) on the stimulation of prostaglandin (PG) production in human decidua. METHODS: Decidual cells from term placentas were grown in culture until confluent. Incuba tions were performed with TNFα or IL-1β, and with cycloheximide, actinomycin D, arachidonic acid, or acetylsalicylic acid (ASA). Prostaglandin E2 was measured by radioimmunoassay and cellular protein determined. RESULTS: The concentration-related stimulation of decidual PGE2 production by IL-1β and TNFα was completely abrogated by cycloheximide and actinomycin D treatment. Although arachidonic acid alone stimulated decidual PGE2 biosynthesis, the addition of IL-1β or TNFα consistently augmented this effect. Both cytokines induced recovery of PGE2 biosynthesis from ASA pretreatment more rapidly than controls. CONCLUSIONS: Interleukin-1β and TNFα both act on decidual PG biosynthesis in a manner requiring new protein synthesis. In combination with our other results, this suggests that IL-1β and TNFα act to induce PG endoperoxide synthase activity. (J Soc Gynecol Invest 1994;1: 31-6)

Effects of Gestational Age on Prostaglandin Production and Its Regulation in Human Myometrial Cells

The objective of this study was to evaluate the effects of known stimulants of prostaglandin production on cultured myometrial cells from women who are at various gestational ages. To evaluate this, myometrial segments were obtained from 12 patients at 27-40 weeks gestation at cesarean delivery. Myometrial cells were then isolated and grown to confluence in culture. Incubations were conducted in quadruplicate for 16 hours with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), or ionomycin. Prostaglandins E2, F2 alpha, and 6-keto F1 alpha (the stable metabolite of prostacyclin) were measured by radioimmunoassay and cellular protein determined. The results revealed that cultured myometrial cells produced prostaglandins in response to IL-1 beta, TNF-alpha, EGF, PMA, and ionomycin at all gestational ages tested at a significantly increased rate (P < 0.05 vs controls at and above 10 ng/ml of IL-1 beta, TNF alpha, and EGF; 1 microM for PMA, and 5 microM for ionomycin). The major prostaglandin produced in response to each stimulant was 6-keto-PGF1 alpha. Cultured human myometrial cells respond to known stimulants of prostaglandin production throughout the third trimester of pregnancy in the absence of labor. The myometrium may therefore be a source of prostaglandins that influences uterine activity.

Eclampsia in Southern Alberta: Is There a Role for Seizure Prophylaxis in All Women with Gestational Hypertension?

OBJECTIVE To evaluate the predictability of eclampsia and explore the role for seizure prophylaxis in a population with a low frequency of seizure prophylaxis. METHODS A retrospective review was conducted of all women with eclampsia registered at the Foothills Hospital in Calgary, Alberta, between 1991 and 2000. The data collected included timing of seizure in relation to diagnosis of gestational hypertension (GHTN) and delivery, method of seizure prophylaxis (if any), and maternal characteristics. RESULTS During the study period, 3075 of 38,577 women (8.0%) were diagnosed with GHTN, with or without proteinuria or adverse conditions. Three percent had received magnesium sulfate for seizure prophylaxis. Of these 3075 women, 17 (0.6%) developed eclampsia, none of whom was receiving magnesium sulfate for seizure prophylaxis at the time. Of these, 10 women (59%) exhibited GHTN prior to their first seizure, including 6 women with GHTN with adverse conditions, 3 with GHTN with proteinuria but without adverse conditions, and 1 with GHTN without proteinuria or adverse conditions. Five of the 17 women had seizures that occurred prior to labour, 6 were intrapartum, and 6 were postpartum. Nine (53%) of the 17 women with eclampsia had their initial seizure after the diagnosis of GHTN and before 24 hours postpartum. CONCLUSION Seizure prophylaxis for all the women with GHTN, from the time of diagnosis through 24 hours postpartum, may have been able to prevent as many as 53% of eclamptic episodes. Three hundred and seven women with GTHN would have to receive seizure prophylaxis to prevent one seizure.

Red Blood Cell Alloimmunization: Principles and Management in Pregnancy

Abstract Despite significant advances in immunohematology, including the discovery of the Rhesus factor and the subsequent development of nationwide Rh immune globulin prophylaxis programs, the incidence of Rhesus alloimmunization is one to two per 1000 Rh-negative women. This is largely due to the lack of administration of Rh immune globulin in high risk situations. The identification of a sensitized pregnant patient requires an initial antibody screen with appropriate antibody titres and paternal red blood cell antigen pheno-typing. Fetuses, identified at high risk due to critical antibody titre levels, require invasive action with serial amniocenteses plus amniocyte antigen testing. Percutaneous umbilical blood sampling or intrauterine fetal transfusion may be dictated in severe situations.

Signal Averaging in Wolff-Parkinson-White Syndrome: Evidence That Fractionated Activation Is Not Necessary for Body Surface High Frequency Potentials

It is commonly assumed that the presence of high frequency components in body surface potentials implies that fractionated activation fronts, caused by heterogeneously viable tissue, are present in the heart. However, it is possible that non‐fractionated activation fronts can also give rise to high frequency surface potentials and that the relative amount of high frequency power is related to the complexity of the activation sequence. In a test of this idea, averaged body surface potentials were recorded during the entire QRS complex of nine Wolff‐Parkinson‐White (WPW) patients in situations in which fractionated activation fronts should not have been present, but which represent increasing degrees of complexity of ventricular activation: (1) postoperative entopic pacing from subepicardial wires placed during surgery, when a single coherent activation front was present throughout most of the QRS; (2) Preoperative preexisted rhythm, when a single coherent activation front was present for one portion of the QRS (the delta wave); and (3) postoperative normal rhythm, when two or more activation fronts were present in the ventricles throughout most of the QRS. For comparison, averaged body surface potentials were also analyzed during the last 40 ms of the QRS complex and the ST segment of 14 postinfarction patients with chronic ventricular tachycardia. In the patients with WPW syndrome, relatively high frequency content increased (attenuation ‐36.7 vs ‐27.2 vs 18.3 dB) and QRS width decreased (160.7 vs 125.9 vs 94.1 ms) significantly from paced to preoperative to postoperative beats. Significant high frequency content was present in all cases, showing that coherent activation fronts can give rise to high frequencies. Interestingly, the postoperative QRS of WPW patients contained a larger proportion of high frequency power than did the late potentials of the patients with ventricular tachycardia. Thus, while the presence of late fractionated body surface potentials may be a marker for ventricular tachycardia, these potentials by themselves do not necessarily signify that the underlying cardiac activation giving rise to these signals is fractionated.

OC31: Women's satisfaction with the OSCAR (One‐Stop Clinic Assessment of Risk) model of first‐trimester combined screening

Objectives: This study evaluated women’s satisfaction with the OSCAR (One-Stop Clinic Assessment of Risk) first-trimester combined screening (FTS) model introduced in Calgary, Canada in March 2006. Methods: The FTS OSCAR model provides pretest counseling, phlebotomy, blood assay for fβ-hCG, PAPP-A (Delfia TM Xpress), nuchal translucency (NT) scan, the FTS risk calculation (Astraia) and post-test counseling during a 90-min appointment. A satisfaction survey was developed to measure expectations and satisfaction with these various components of service. Additional information collected included the women’s demographics, their recall of their screen result (positive or negative) and whether they felt reassured with testing. Between 13 March 2006–2007, all women referred for the 11–13 + 6 week FTS who agreed to complete the survey were included. Results: Response rate was 75% (3763/5013). Overall, 98.1% of the women were either very satisfied or satisfied and 95.6% felt their expectations were met. These results were independent of maternal age, parity and education. Most women were reassured by testing regardless of results (99.3% and 82.1% of the screen-negative and screen-positive (≥1/300 women, respectively). Most (93%) stated that screening early in pregnancy and receiving test results at the same visit (95.6%) was very important. Conclusions: The FTS OSCAR model meets women’s expectations and is associated with a high degree of satisfaction in terms of timing of screening and rapid availability of results. A high proportion of women were reassured by their results regardless of whether they were screen negative or positive. There was also a relatively low uptake of prenatal diagnosis among the screen-positive women (49%). This may imply that women favor the personal risk assessment and benefit from the 1-1 post-counseling of the OSCAR model. Further research is under way to address these questions.

OP25.01: First trimester combined screening: prospective evaluation of performance in an OSCAR setting

Objectives: The study was performed to assess whether hemodynamic effects on the fetus occur in late-pregnancy mice when ultrasound contrast agent (UCA) (SonoVue TM ) is used for clinical applications in obstetrical ultrasonography. Methods: Sixty late-pregnancy mice (Wister mice, median weight, 300 (range, 260–330) g; median gestational age, 19 (range, 16–21) days) were selected and divided into three experimental groups – Group A, the control group, were injected with physiologic saline solution, Group B were injected with a diagnostic dose of UCA − 0.06 mg/kg body weight – and Group C were injected with a high dose of UCA − 12 mg/kg. From each group a random selection of one mouse was made and it was examined by ACUSON Sequoia 512 with contrast pulse sequencing (CPS) technology. Maternal and fetal heart rate, pulsatility index (PI), resistance index (RI), and systolic: diastolic ratios (S/D) were measured in the fetal middle cerebral artery, umbilical artery, and uterine artery before and after administration of UCA or physiologic saline solution. Results: There were no significant differences in maternal and fetal heart rate, PI, RI, and S/D ratios in the fetal middle cerebral artery, umbilical artery and uterine artery between the different dosage groups of UCA or physiologic saline solution (ANOVA, P > 0.05). A significant decrease in the maternal and fetal heart rate, measured in the uterine artery and in the fetal middle cerebral artery, before and after injection of UCA or physiologic saline solution was found (t-test, P 0.05). Conclusions: The SonoVue TM UCA did not produce any harmful fetal or placental effects in late pregnancy and was shown to be safe in this study. The decreases in maternal and fetal heart rates was probably caused by the stress of the procedure.

P01.22: Nuchal translucency screening in the detection of Down syndrome

Methods: Between 3/2002 and 2/2006, 712 consecutive patients presented for routine prenatal care in a private clinic at approximately 11 to 14 weeks gestation. A sonologist, who is certified for NT measurement by the Fetal Medicine Foundation, performed all the first-trimester scans. Given the un-established reliability and the low acceptance of first-trimester biochemical marker testing in Lebanon, an NT ≥ 2.5 mm was considered a positive screening result. Results: All patients accepted NT screening and outcomes are available on 557 (78%). Missed abortions occurred in 6, fetal death in utero beyond the first trimester occurred in 7, 13 patients were lost to follow up and 129 patients are still undelivered. NT ≥ 2.5 mm occurred in 18 (3.2%) cases. Our screened population had 3 fetuses with trisomy 21 and one fetus with trisomy 18. An NT ≥ 2.5 mm detected the trisomy 18 fetus and 2 of 3 trisomy 21 fetuses. The trisomy 21 fetus that was missed on NT screening was detected in the second trimester because of duodenal atresia on ultrasound. The resulting sensitivity in our population is 75% with a false positive rate of 13/551 (2.4%). In addition, 2 cases of cystic hygromas were detected. Conclusions: To date, this represents the first and largest study of NT screening in Lebanon. Our results suggest that first-trimester screening using NT is feasible and highly acceptable in Lebanon and provided a sensitivity of 75% with a false positive rate of less than 5%. These findings are comparable to reports from other centers.

Characteristics and Outcomes of Low Birth Weight Infants from In Vitro Fertilization and Natural Conceptions

Abstract Objective: To compare characteristics and outcomes (0–18 months) between surviving low birth weight ( in vitro fertilization (IVF) infants, and low birth non-IVF infants born between 1991 and 1997. Design: Retrospective case-controlled study. Setting: The Regional Fertility Program (RFP) and Southern Alberta Perinatal Follow-up Program (PNFU) in Calgary, Alberta. Participants: Fifteen infants born with birth weight less than 1250 g after IVF at the RFP and seen at the PNFU. Three controls per case were matched for year of birth, birth weight, and gender. Main Outcome Measures: Neonatal intensive care unit data, hospitalizations, medications, disabilities, developmental outcomes, and parental demographics. Results: IVF infants were significantly more likely to have older mothers (mean 31.80 vs. 28.00 years, p=0.005), ventriculomegaly (26.7% vs. 4.4%, p=0.030), been given non-prescription medications (91.7% vs. 52.6%, p=0.018), a non-vertex presentation at delivery (72.7% vs. 45.2%, p=0.027), and to be of multiple birth (80.0% vs. 26.7%, p Conclusions: Eighteen month outcomes of IVF and non-IVF infants less than 1250 g did not differ dramatically. Long-term comparisons of extremely low birth weight IVF and non-IVF infants with regard to mental and physical development are essential. IVF pregnancies are known to increase the risk of low birth weight, preterm delivery, multiple birth, and coexistent morbidities. These risk factors are of social and economic importance to parents and health care providers.