PP035. Placental klotho protein in preeclampsia: A possible link to long term outcomes.

INTRODUCTION: An aging-suppressor gene, klotho, is a candidate factor for vascular disease because its deficiency leads to impaired endothelium-dependent vasodilation and impaired angiogenesis. Although klotho protein is predominantly expressed in the kidney, it is detected in a limited number of other tissues, such as the placenta, ovary, prostate gland, and small intestine. This protein is involved in several metabolic pathways such as calcium and phosphate homeostasis, the insulin-like growth factor 1 (IGF-1), apoptosis, angiotensin-II-induced events in the kidney and oxidative stress. OBJECTIVES: The aim was to assess the expression of the klotho gene in the placenta from pregnancies affected by severe preeclampsia. METHODS: Placentas were collected from normal pregnancies (n=12) and pregnancies complicated by preeclampsia (n=12), matched for gestational age. Klotho mRNA and protein were determined using real-time quantitative polymerase chain reaction (PCR) and Western blot, respectively. RESULTS: Real-Time PCR analyses demonstrated a significant (p=0.005) 83% down-regulation of Klotho in patients with Preeclampsia versus Controls. Results of Western Blot agreed with those from Real-Time PCR. CONCLUSION: Klotho mRNA expression in the placenta is decreased in preeclamptic pregnancies. Given its role in cardiovascular disease in aging, it may link preeclamptic mothers and their offsprings to long term cardiovascular outcomes.

PP093 Maternal and fetal outcomes in oocyte donor pregnancies.

INTRODUCTION: The history of oocyte donation is relatively new in the framework of in vitro fertilization (IVF) techniques, and little has been discussed about the obstetric outcomes of such pregnancies. OBJECTIVES: The aim of this study is to assess the obstetric outcomes of pregnancy following in vitro fertilization with embryo transfer (IVF-ET) using donor oocytes and compare them to the outcomes from autologous IVF-ET and to spontaneous pregnancy in women with advanced age (AMA) to identify possible criticalities and help in counseling women and their doctors. METHODS: The study included a total of 70 delivered pregnancies. The study group included 14 oocyte donors IVF-ET (d-IVF-ET) from women aged 32-52years. The results from the study group were compared to the next two consecutive deliveries from the autologous IVF-ET (IVF-ET group) (n=28; age 30-46years) and with two more consecutive deliveries from women older than 40years (Advanced Maternal Age: AMA) (n=28, age 40-45years). We evaluated the occurrence of pregnancy-induced hypertension (PIH), preeclampsia (PE), fetal growth restriction (IUGR), the gestational age at birth, placental anomalies, the mode of delivery, birth weight and the neonatal Apgar score. The fetal weight was corrected with the gestational age at the time of delivery according to Gardosi. Statistical analysis was performed with the Chi-squared test. RESULTS: Oocyte donor pregnancies had significantly higher rates of PE (d-IVF-ET 21.4%, IVF-ET 0%, AMA 0%, p<0.011). They also had higher rates of PIH and IUGR (d- IVF-ET 21.4%, IVF-ET 0%, AMA 3.6% p<0.011) (d- IVF-ET 21.4%, IVF-ET 7.1%, AMA 3.6% p<0.011 respectively). We found placental anomalies only in the d-IVF-ET group; the incidence of placental accretism was 28.6%, (p<0.003). There are not significant differences in the gestational age at birth, placental anomalies, the mode of delivery, birth weight and the neonatal Apgar score between the groups. CONCLUSION: This is the first study that compares the obstetric outcomes of donor pregnancies to the outcomes of autologous IVF-ET pregnancies and to advanced maternal age. The advanced maternal age criterion assumes that most women requiring oocyte donation are older. Hypertensive disorders were surprisingly not related to maternal age or to the in vitro fertilization technique. Obstetricians that deal with pregnancies from oocyte donation need to be aware of the more severe obstetric outcomes, especially placenta accrete and pregnancy-related hypertensive disorders. This warrants close blood pressure monitoring and an accurate placenta ultrasound. All women who conceive through oocyte donation should be counselled as early as the pre-conception period and referred to specific centres for high-risk pregnancies.

Placental overexpression of transforming growth factor-beta3 in the HELLP syndrome.

OBJECTIVE: To evaluate the placental expression of transforming growth factor-beta3 (TGF-beta3) in patients with HELLP syndrome and pre-eclampsia compared to controls, and its correlation to Doppler velocimetry analysis of the utero-placental blood flow. STUDY DESIGN: Real-time PCR analysis was performed, after cesarean section, in placental samples from 10 women affected by HELLP syndrome, 10 women with pre-eclampsia and 10 controls. Pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries were measured. RESULTS: The mean TGF-beta3 expression was significantly higher in patients with HELLP syndrome compared with the control group (p < 0.001), and no difference was observed in the pre-eclampsia group. TGF-beta3 expression correlated positively with umbilical PI (p < 0.001). CONCLUSIONS: TGF-beta3 may play a key role as regulator of a variety of cellular events occurring during HELLP syndrome, high local expression of this growth factor may be responsible for remodeling of the placental structure, which results in the dysfunction of maternal-fetal circulation.

Ultrasound measurement of pregnancy-induced changes in maternal bone mass: a longitudinal, cross-sectional and biochemical study.

Our objective was to investigate the changes in maternal bone status in pregnancy. Amplitude-dependent speed of sound (AD-SoS) by quantitative ultrasound was measured in 100 healthy, White, pregnant women at term, and 100 White, healthy, non-pregnant and premenopausal women matched for age, as controls. In a subgroup of 50 women a longitudinal evaluation throughout pregnancy was performed. A significant reduction of AD-SoS was observed during pregnancy (controls: 2170 +/- 55 m/s; first trimester: 2118 +/- 46 m/s; second trimester: 2085 +/- 49 m/s; third trimester: 2081 +/- 51 m/s), showing a negative correlation with body mass index (r -0.31; p < 0.05) and a positive correlation with daily calcium intake (r 0.33; p < 0.05). Increased levels of urinary markers of bone resorption confirmed bone turnover (p < 0.05). Ultrasonographic study of bone is a simple, low-cost and safe method for measuring maternal bone mass in pregnancy. During pregnancy, there was a significant loss in AD-SoS that is an indicator of bone status; this decrease was higher in the second and third trimesters (p < 0.05), associated with a high bone turnover. It was more intense in women with a low calcium intake (p < 0.05).

Prediction of gestational hypertension or intrauterine fetal growth restriction by mid-trimester 24-h ambulatory blood pressure monitoring.

OBJECTIVES: To investigate clinical impact of 24-h ambulatory blood pressure monitoring (ABPM) on the prediction of hypertensive disorders of pregnancy and IUGR. METHODS: ABPM was performed in 334 normotensive non-proteinuric nulliparous women at 20 weeks' gestation. Arterial blood pressure patterns were analyzed by chronobiometry. RESULTS: Women who developed idiopathic IUGR (21) or PIH (33) showed a 24-h diastolic blood pressure mean significantly higher than the controls (69.2+/-1.8 mmHg and 73.5+/-6.2 vs. 62.2+/-1.5). Women with subsequent IUGR also showed a modification in BP rhythm. The most effective cut-off levels of 24-h diastolic blood pressure mean proved to be 67 for IUGR and 68 for hypertension. CONCLUSIONS: ABPM in the second trimester reliably predicts idiopathic IUGR and PIH. Both patients destined to develop gestational hypertension and those destined to develop IUGR show similar elevations in 24-h diastolic mean at 20 weeks' gestation.

Prospects for vaccination against malaria in man.

Rodents have been successfully protected against a challenge of viable Plasmodium berghei by employing as vaccine: (1) the irradiated blood stages of the same parasite, or (2) the water-insoluble fraction of the blood stages, or (3) irradiated sporozoites; all these vaccines were shown to be stage-specific. A method is outlined for testing in the field, in the absence of any risks, the efficacy of analogous vaccines against falciparum malaria in man. It is emphasized that: (1) the efficacy of the vaccines can be tested in no model but only against P. falciparum in man; (2) the protection should be measured in terms of (a) prevention of morbidity, and (b) prevention of mortality; and (3) research must be intensified in order to meet, as needed, the requirements of mass production of merozoites and/or sporozoites, and to find ways to increase the human immune response to a higher level of protection against P. falciparum.