Veronica Cozzi

Maternal and foetal resistin and adiponectin concentrations in normal and complicated pregnancies

Objective   The aim of this study was to evaluate how resistin and adiponectin (ApN) are involved in maternal energy metabolism and foetal growth.

Infertility as a cancer risk factor - a review.

Ovarian, endometrial and breast cancers are associated with several risk factors, such as low parity, infertility, early age at menarche, and late age at menopause. Frequently most of these risk factors coexist in infertile patients and some studies suggested that the different infertility causes can be involved in cancer risk development. In particular case-control and cohort studies investigated the possible role of ovulatory disorders, endometriosis and unexplained infertility in increasing the risk of this disease. Most studies have shown no overall increased risk in invasive ovarian cancer in subfertile patients, although nulliparity has been consistently associated with increased rates of ovarian tumor, in particular with borderline and endometrioid cancers in patients with a history of endometriosis. Different studies reported that infertile women are not at risk for breast cancer. However, women affected by infertility may be more at risk for endometrial cancer, particularly if affected by ovulatory disorders. Moreover, infertility is now often treated with medical devices that could by themselves modify the hormonal environment and be cofactors in the cellular changes towards cancer development. However, although early studies suggested that infertility medications were associated to increased risk in ovarian cancer, subsequent studies have been mainly reassuring, although suggesting that type and duration of medical treatment can increase the malignancy risk. An increased risk of endometrial cancer in patients undergoing infertility treatment has been reported, as expected by the similar structure shared by clomiphene and tamoxiphene. Since breast cancer is widely recognized as having a hormonal etiology, a possible role of fertility medications to promote cancer has been hypothesized. However, many large studies were not able to find an associated risk of breast cancer. In conclusion, nowadays, firm answers about the precise effects of infertility and its treatment on cancer risk are not available but findings are generally reassuring. Further studies about fertility drug treatments on larger populations may offer in the future longer follow-up and more precise data with better adjustments for confounding factors.

Maternal and Fetal Fatty Acid Profile in Normal and Intrauterine Growth Restriction Pregnancies With and Without Preeclampsia

The aim of this study was to evaluate maternal and fetal lipid profile in intrauterine growth restriction (IUGR) pregnancies with and without preeclampsia (PE). Thirteen normal pregnancies studied during the third trimester (control M) and 29 at elective cesarean section (control CS) were compared with 18 pregnancies complicated by IUGR (IUGR only) and with seven pregnancies complicated by both IUGR and PE (IUGR-PE). Total plasma fatty acids, triglycerides, cholesterol, and nonesterified fatty acids (NEFA) were determined in maternal and fetal plasma. Nutritional intake was analyzed. IUGR only mothers had lower percentage of linoleic acid (LA) and higher arachidonic acid (AA) than controls, partly explained by higher AA dietary intake. Higher levels of NEFA were observed both in IUGR only and in IUGR-PE mothers whereas triglyceride levels were increased in IUGR-PE mothers only. In IUGR-PE fetuses, LA and AA were significantly decreased, whereas triglyceride and NEFA concentrations were significantly increased compared with normal fetuses. In conclusion, IUGR only is associated with altered fatty acids profile not completely accounted by dietary changes. We hypothesize that the differences observed in IUGR with PE for triglycerides and other lipids could be related to a difference in maternal phenotype.

First trimester PTX3 levels in women who subsequently develop preeclampsia and fetal growth restriction.

Pentraxin 3 (PTX3) and C‐reactive protein (CRP) levels were measured in the first trimester of pregnancy in women who subsequently developed preeclampsia (PE, n = 16) and fetal growth restriction (FGR, n = 12) requiring iatrogenic delivery before 37 weeks, and those who had uncomplicated pregnancies delivering at term (n = 60). Mean PTX3 levels were significantly higher in women who subsequently developed PE (7.31 ng/ml, SD = 4.12) when compared to those with normal pregnancy outcome (4.92 ng/ml, SD = 1.94, p = 0.0046). There were no significant differences between PTX3 levels in women with FGR (4.82 ng/ml, SD = 2.35) compared to normal pregnancy outcome (p = 0.88). The median CRP levels did not vary significantly between the three groups (p = 0.26). PTX3 levels in women who subsequently develop PE are already elevated in the first trimester, but not in those that develop FGR. This supports the hypothesis of an excessive maternal inflammatory response to pregnancy in the etiology of PE.

PTX3 as a potential endothelial dysfunction biomarker for severity of preeclampsia and IUGR.

Endothelial dysfunction typical of preeclampsia (PE) is the result of an excessive maternal inflammatory response to pregnancy. We investigated PTX3 in maternal, fetal and placental compartments in complicated pregnancies. Maternal blood samples were collected during the third trimester in 53 PE, 43 IUGR (intrauterine growth restriction) and 50 normal pregnancies. Fetal samples were collected from the umbilical vein in 26 PE, 23 IUGR and 26 normal pregnancies at elective cesarean section. Pattern and site of expression of PTX3 were studied by immunohistochemistry (IHC) on placenta, decidual bed and maternal peritoneum. PE and IUGR pregnancies had significantly higher maternal PTX3 levels compared to normal pregnancies, with IUGR significantly lower than PE. Maternal peritoneum expressed a significantly higher signal in the endothelium of pathological compared to normal pregnancies. The maternal increase of PTX3 correlated with the severity of disease with higher PTX3 concentrations in severe PE. Increased PTX3 levels in PE and IUGR mothers, together with IHC data represent the expression of altered endothelial function on the maternal side. IUGR fetuses had higher PTX3 values than controls and the increase was related to IUGR severity, likely reflecting the hypoxic environment. These data confirm the relevance of PTX3 in support the hypothesis that PE is a disease associated with altered maternal endothelial function. The PTX3 increase in IUGR fetuses deserves further investigation.

Fetal Development after Assisted Reproduction—A Review

Despite the success of assisted reproduction technologies (ART) in allowing conception in couples with infertility problems, a growing body of evidence points to implication of ART on fetal birth weight alterations, fetal malformations, chromosomal aneuploidies and syndromes related to genomic imprinting modifications. Different causes can be accounted for to explain the increased risk of fetal defects. Pregnancies generated by ART differ from spontaneously achieved pregnancies in that gametes and embryos are cultured in vitro, more than one conceptus is transferred into the uterine cavity, and the time of transfer is different to what occurs in normal conditions. Epigenetic reprogramming of gene expression has been advocated in relation to the gamete and embryo manipulation, with a significant role of genomic imprinting in determining changes in fetal growth. Moreover, the maternal environment, with the ovarian hyperstimulation of the beginning of pregnancy, could alter the maternal response to the early phases of trophoblast invasion. There are suggestions that placental weights and placental/fetal weight ratios are increased in these pregnancies resembling the model of maternal undernutrition in the early phases of pregnancy. Therefore concern has also arisen around the possible long term and transgenerational effects of assisted reproduction procedures and studies should be carried out to evaluate these possibilities.

Estimation of fetal oxygen uptake in human term pregnancies

Objective. Umbilical oxygen (O2) uptake is a parameter of basic physiologic interest. It has been extensively studied in chronically catheterized animals but very few data have been obtained acutely in humans. Recent developments in ultrasound technology allow the estimation of umbilical venous blood flow in utero. Methods. In all, 26 normal term pregnancies were studied at the time of elective cesarean section in order to evaluate fetal O2 uptake as the product of umbilical blood flow and umbilical O2 veno-arterial difference. An ultrasound evaluation was performed within 1 h from delivery: umbilical vein area and flow velocity were recorded to calculate umbilical vein volume flow (Qumb). Blood samples from the umbilical vein (uv) and artery (ua) were obtained at the time of fetal extraction for respiratory gases and acid–base evaluation. Results. Umbilical O2 uptake was calculated as Qumb • (uv-ua)O2 content: an average value of 0.84 ± 0.40 mmol/min was obtained. Umbilical O2 uptake per kg was 0.25 ± 0.12 mmol/kg/min, significantly related to fetal O2 delivery. Conclusions. We estimated umbilical blood flow by ultrasound and we measured umbilical O2 uptake at term obtaining a value of umbilical O2 uptake/kg similar to what previously reported in human pregnancies and chronically catheterized animals.

OC250: Fetal oxygen uptake in normal and IUGR pregnancies

Objectives: To examine the relationship between smallness, assessed by customized standards, and the predictive value of a normal umbilical artery Doppler. Methods: A cohort was created of 7645 singleton pregnancies without congenital anomalies. Fetuses suspected antenatally of being small for gestational age were referred for assessment by umbilical artery Doppler. The associations with adverse outcome were assessed for small-for-gestational age babies who had normal and abnormal Doppler, compared with neonates who were not small for gestational age. Perinatal outcome indicators were collected, including fetal distress requiring Cesarean section and neonatal morbidity (neonatal intensive care > 14 days, neonatal seizures, intraventricular hemorrhage Grade III or more, periventricular leucomalacia, hypoxic–ischemic encephalopathy, or necrotizing enterocolitis). Results: Of the 369 small-for-gestational age fetuses which had been identified antenatally, 70 (19%) had an abnormal umbilical artery Doppler and the babies from these pregnancies had an elevated risk of fetal distress requiring Cesarean section (OR 5.89; CI, 2.64–11.84) and neonatal morbidity (OR 3.99; CI, 1.04–11.03). However the 299 fetuses (81%) with normal umbilical artery Doppler also had elevated risk of fetal distress (OR 4.49; CI, 2.96–6.66) and neonatal morbidity (OR 2.26; CI, 1.04–4.39). Because of the higher prevalence, many more instances of adverse outcome were attributable to this group than to the group with abnormal Dopper (fetal distress – population attributable risk (PAR): normal Doppler 8.6 vs. abnormal Doppler 2.7; neonatal morbidity – PAR: normal Doppler 4.0 vs. abnormal Doppler 2.2. Conclusions: Smallness for gestational age according to customized weight standards defines a group of pregnancies with significantly elevated risk of adverse perinatal outcome. Normal antenatal umbilical artery Doppler cannot be taken as an indicator of low risk in these pregnancies.

OP07.06: 3D ultrasound assessment of placenta volume in the first trimester in pregnancies from assisted reproduction technologies (ART)

For amniocentesis there were 202 karyotype anomalies (7.8%). 110 trisomy 13,18,21; 20 sex chromosome and 13 triploidy accounted for 71% of abnormal results. Rapid karyotype by FISH was selectively used in 580 cases (22.4%). FISH was used in 95/143 cases (66.4%) potentially diagnosable with standard FISH probes. FISH was ordered in 60% of trisomy 21 cases and 85% of trisomy 18. Long-term culture confirmed the FISH results in all cases. In 0.5% culture failed. In 0.3% there were insufficient cells for FISH. Conclusions: The selective use of rapid karyotype techniques in CVS and amniocentesis produces a high detection rate but results in a significant number of cases not identified until the long-term culture (34% of potentially detectable cases for amniocentesis). For CVS specimens, rapid diagnosis alone results in a small but significant number of discordant results.

Lipoprotein Lipase (LPL) mRNA Expression in Placentas from Normal and IUGR (Intrauterine Growth Restricted) Pregnancies by Real-Time PCR.

Introduction: Adequate placental transfer is necessary for normal intrauterine growth and development of the fetus. Intrauterine growth restriction (IUGR) is a condition associated with reduced nutritional placental supply. Recently, IUGR has been associated with changes in polyunsaturated fatty acid fetal-maternal relationships, mostly for the long chain polyunsaturated fatty acids, suggesting a role for these nutrients in the pathogenesis of IUGR. Lipoprotein lipase (LPL) plays a crucial role in lipoprotein and energy metabolism: it participates in the uptake of cholesterol-rich remnant particles, by acting as a ligand for VLDL receptor, LDL receptor, LDL-receptor related protein (LRP), and it is involved in the hydrolysis of triglycerides (TG) present in chylomicrons and very lowdensity lipoprotein (VLDL) to generate fatty acids, a source of energy for peripheral tissues. This suggests that the level of LPL expression in a given tissue is the rate limiting process for the uptake of triglyceride-derived fatty acids. LPL is expressed in human placenta, where it participates in the uptake of triglyceride-derived fatty acids.