Higher rate of early-onset preeclampsia in pregnancies following oocyte donation according to increasing maternal age.

OBJECTIVE: To assess the influence of maternal age on the incidence of early-onset preeclampsia requiring delivery before 34 weeks of gestation in pregnancies obtained after oocyte donation. METHODS: We carried out a prospective cohort analysis of 431 single and twin pregnancies, admitted to 3 Tertiary Referral Hospital in Northern Italy between 2008 and 2017. The rate of early-onset PE was calculated and stratified according to maternal age (from 30 to 49 years). A reference population of 11,197 single pregnancies collected prospectively at the first trimester of pregnancy in the same geographic area of Italy and in same hospitals was used to calculate the expected incidence of early-onset PE. RESULTS: In women who delivered after 24 weeks of gestation, the rate of early-onset PE was much higher in oocyte-donation pregnancies, reaching 6.7% (29/431), than the expected rate of 0.5% of the cohort of reference. The mean early PE rate was 4.1% (10/242) in singletons and 10.1% (19/189) in twin pregnancies. According to maternal age, the rate of early PE was 1.16% and 3.12% at 30 years, and 4.98% and 13.14% at 49 years in single and twin pregnancies obtained after oocyte donation, respectively. CONCLUSION: Pregnancies obtained after oocyte donation delivering after 24 weeks had a higher risk of early-onset PE requiring delivery before 34 weeks of gestation, than the general population. The risk is directly correlated with the increase of maternal age and is also higher in twin pregnancies.

Comparison of two "a priori" risk assessment algorithms for preeclampsia in Italy: a prospective multicenter study.

PURPOSE: To compare the performance of the algorithms proposed by the Fetal Medicine Foundation in 2012 and BCNatal in 2013 in an Italian population. METHODS: A multicentric prospective study was carried out which included pregnancies at 11-13 weeks' gestation from Jan 2014 through May 2017. Two previously published algorithms were used for the calculation of the "a priori" risk of preeclampsia (based on risk factors from medical history) in each individual. RESULTS: In a study population of 11,632 cases, 67 (0.6%) developed early preeclampsia and 211 (1.8%) developed late preeclampsia. The detection rates (95% CI) for early and late preeclampsia were 58.2% (45.5-70.2) vs. 41.8% (29.6-54.5) (p value < 0.05) and 44.1% (37.3-51.1) vs. 38% (31.3-44.8) (p value < 0.05) for the Fetal Medicine Foundation and BCNatal, respectively (at a 10% false positive rate). The associated risk was 1:226 and 1:198 (p value ns) for early PE, and 1:17 and 1:24 (p value ns) for late PE for the Fetal Medicine Foundation and BCNatal, respectively. CONCLUSIONS: The Fetal Medicine Foundation screening for preeclampsia at 11-13 weeks' gestation scored the highest detection rate for both early and late PE. At a fixed 10% false positive rate, the estimated "a priori" risks of both the Fetal Medicine Foundation and the BCNatal algorithms in an Italian population were quite similar, and both were reliable and consistent.

Maternal hemodynamic profile during pregnancy and in the post-partum in hypertensive disorders of pregnancy and fetal growth restriction.

BACKGROUND: Maternal cardiovascular changes, occurring since the beginning of pregnancy, are necessary for normal placentation and regular evolution of pregnancy. OBJECTIVE: This study aimed to compare the hemodynamic profiles and cardiac remodeling of women with hypertensive disorders of pregnancy and either appropriate for gestational age fetuses or growth-restricted fetuses, women with normotensive pregnancies complicated by fetal growth restriction, and women with uncomplicated pregnancies, during pregnancy and the postpartum period. STUDY DESIGN: A prospective longitudinal case-control design was used for this study. Over the study period, 220 eligible women with singleton pregnancies were selected for the analysis and divided into 4 groups: (1) hypertensive disorders of pregnancy with appropriate for gestational age fetuses; (2) hypertensive disorders of pregnancy with fetal growth restriction; (3) normotensive fetal growth restriction; and (4) controls. Ultrasound fetal biometry and fetoplacental Doppler velocimetry were performed at recruitment. Maternal hemodynamic assessment using transthoracic echocardiography was performed at the time of recruitment by a dedicated cardiologist blinded to maternal clinical data. The same assessments were performed in 104 patients at 32 weeks (interquartile range, 24-40) after delivery by the same cardiologist. RESULTS: During pregnancy, women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction group showed significantly lower cardiac output and increased compared with those in the control group. These values were associated with concentric remodeling of the left ventricle owing to relatively increased wall thickness, which was not accompanied by an increase in left ventricular mass. Isolated fetal growth restriction presented similar but less important hemodynamic changes; however, there was no change in relative wall thickness. At postpartum follow-up, the hemodynamic parameters of women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and isolated-fetal-growth-restriction groups reverted to values similar to those of the control group. Only 8.3% of women in these groups experienced hypertension even in the postpartum period, and asymptomatic stage-B cardiac failure was observed for 17% at echocardiography. In the group of women with hypertensive disorders of pregnancy and appropriate for gestational age fetuses, cardiac output increased as in normal pregnancies, but total vascular resistance was significantly higher; hypertension then occurred, along with ventricular concentric hypertrophy and diastolic dysfunction. At postpartum follow-up, women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed significantly higher mean arterial pressure, total vascular resistance, and left ventricular mass compared with those in the control group. Persistent hypertension and asymptomatic stage-B cardiac failure were observed in 39.1% and 13% of women in the former group, respectively. CONCLUSION: Pregnancies with hypertensive disorders of pregnancy and fetal growth restriction and normotensive pregnancies with fetal growth restriction were associated with the hemodynamic profile of lower heart rate and cardiac output, most likely because of abnormal adaptation to pregnancy, as confirmed by abnormal changes from pregnancy to the postpartum period. The heart rates and cardiac output of women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed changes opposite to those observed in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and fetal-growth-restriction groups. Obesity and other metabolic risk factors, significantly prevalent in women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group, predispose to hypertension and cardiovascular diseases during pregnancy and the postpartum period, potentially offering a window for personalized prevention. Such preventive strategies could differ in women with hypertensive disorders of pregnancy and fetal growth restriction characterized by poor early placental development.

Hypertensive Disorders of Pregnancy and Fetal Growth Restriction: Clinical Characteristics and Placental Lesions and Possible Preventive Nutritional Targets.

BACKGROUND: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control pregnancies. METHODS: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. RESULTS: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. CONCLUSIONS: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR.

Second trimester uterine arteries pulsatility index is a function of placental pathology and provides insights on stillbirth aetiology: A multicenter matched case-control study.

INTRODUCTION: The aim of this study was to investigate the relationships between maternal vascular malperfusions (MVM) and second trimester uterine arteries pulsatility index (UtA-PI) in cases of stillbirth (SB), compared to live-birth (LB) matched controls. METHODS: This was a multicentre, observational, matched case-control study performed at five referral maternity centres over a 4-year period including SB and LB control pregnancies at high-risk for preeclampsia (PE) and/or fetal growth restriction (FGR), matched and stratified for UtA-PI MoM quartiles values of the SB cases. Logistic regression was used to assess the rates of each MVM finding, within each increasing MoM quartile subcategory in SB and matched LB controls. RESULTS: 82 SB and 82 LB matched high-risk pregnancies were included. Placental hypoplasia, placental infarction, retroplacental hematoma, distal villous hypoplasia and accelerated villous maturation showed a significant correlation with UtA-PI. At univariable analysis, placental infarction and distal villous hypoplasia were more highly associated with the increasing quartile uterine Doppler measurements (odds ratio 2.24 and 2.23, respectively). Logistic regressions showed a significant positive and independent association between rates of retroplacental hematoma or distal villous hypoplasia and stillbirth within corresponding UtA-PI MoM quartiles (odds ratio 5.21 and 2.28, respectively). DISCUSSION: We are providing evidence for characterization of two major etiological stillbirth categories, characterized by a positive or absent association with UtA-PI impairment and specific histopathological placental MVM lesions. Our results support a strict third trimester follow-up of cases with increased second trimester UtA-PI, in order to improve the reproductive chances of these pregnant patients.

Italian Advisory Board: sFlt-1/PlGF ratio and preeclampsia, state of the art and developments in diagnostic, therapeutic and clinical management.

Extensive research has been published, showing the usefulness of angiogenic markers in both diagnosis and subsequent prediction and management of preeclampsia and placenta-related disorders. Recent evidence provides a helpful cut off for the Elecsys ratio sFlt-1 to PlGF, that predicts preeclampsia development in women with sign and symptoms, before its clinical onset in the short term. In Europe, no accordance exists for the use of such kind of test in clinical practice; only German guidelines have recently taken it into account, as a diagnostic aid for preeclampsia, in conjunction with other clinical findings. This panel of Italian experts recently met, in order to review the literature and to promote the evaluation of the clinical utility of sFlt-1/PlGF ratio at the Italian country level, as regards: prediction of preeclampsia during the first trimester, prediction or exclusion of new onset or recurrence in patients with risk factors for preeclampsia, triage of patients suffering from gestational hypertension, evaluation of disease severity, prediction of adverse maternal and fetal outcomes.