Cell-free DNA screening for fetal aneuploidy using the rolling circle method: A step towards non invasive prenatal testing simplification.

OBJECTIVE: To assess the efficacy of cell-free (cf)DNA screening for aneuploidy using the automated system based on rolling circle replication. METHODS: A prospective study among women referred for invasive prenatal diagnosis between July 2018 and December 2019. The plasma fraction was extracted within 5 days from blood collection, stored at -20°C and cfDNA measured between January and December 2019. RESULTS: A total of 805 women were recruited; 778 with singleton pregnancies and 27 twins. There were 48 Down syndrome, 25 Edwards syndrome and 3 Patau syndrome cases. Overall, the no-call rate was 2.6% (95% confidence interval 1.6%-3.9%) which reduced from 4.7% to 1.1% after relocation of the system (p < 0.002) to ensure a constant ambient temperature below 25°C. In singletons the Down syndrome detection rate (DR) was 100% (93%-100%) and false-positive rate (FPR) 0.14% (0.00%-0.79%). The Edwards syndrome DR was 96% (80%-100%) and FPR 0.78% (0.29%-1.7%). One false-positive had a confined placental trisomy 18 and the remaining five a z-score requiring sample repetition; all the false-positives occurred before system relocation (p < 0.005). Patau syndrome DR and FPR were 67% (9.4%-99%) and 0.26% (0.03%-0.95%). CONCLUSION: The cfDNA rolling circle method yields similar results to other methods provided that room temperature is adequately controlled.

Vasa previa: when antenatal diagnosis can change fetal prognosis.

OBJECTIVES: Evaluate ultrasound diagnostic accuracy, maternal-fetal characteristics and outcomes in case of vasa previa diagnosed antenatally, postnatally or with spontaneous resolution before delivery. METHODS: Monocentric retrospective study enrolling women with antenatal or postnatal diagnosis of vasa previa at Sant'Anna Hospital in Turin from 2007 to 2018. Vasa previa were defined as fetal vessels that lay 2 cm within the uterine internal os using 2D and Color Doppler transvaginal ultrasound. Diagnosis was confirmed at delivery and on histopathological exam. Vasa previa with spontaneous resolutions were defined as fetal vessels that migrate >2 cm from uterine internal os during scheduled ultrasound follow-ups in pregnancy. RESULTS: We enrolled 29 patients (incidence of 0.03%). Ultrasound antenatally diagnosed 25 vasa previa (five had a spontaneous resolution) while four were diagnosed postnatally, with an overall sensitivity of 96.2%, specificity of 100%, positive predictive value of 96.2%, and negative predictive value of 100%. Early gestational age at diagnosis is significally associate with spontaneously resolution (p 0.023; aOR 1.63; 95% IC 1.18-2.89). Nearly 93% of our patient had a risk factor for vasa previa: placenta previa at second trimester or low-lying placenta, bilobated placenta, succenturiate cotyledon, velametous cord insertion or assisted reproduction technologies. CONCLUSIONS: Maternal and fetal outcomes in case of vasa previa antenatally diagnosed are significally improved. Our data support the evaluation of umbilical cord insertion during routine second trimester ultrasound and a targeted screening for vasa previa in women with risk factor: it allows identification of fetus at high risk, reducing fetal mortality in otherwise healthy newborns.

Arteriovenous uterine malformation developed from an interstitial pregnancy on residual tubal stump: A critical managment in a fertile woman.

Uterine arteriovenous malformations are rare conditions with diverse clinical presentation that range from asymptomatic patients to different degrees of menorrhagia, commonly associated with previous pregnancy or uterine trauma. This case report describes a 36-year-old woman who presented with ultrasound diagnosis of interstitial pregnancy on residual right tube stump 4 months after a laparoscopic salpingectomy for extrauterine pregnancy. She started treatment with methotrexate; afterwards serum human chorionic gonadotropin levels and ultrasound follow-ups were scheduled. While serum human chorionic gonadotropin levels were progressively reducing, transvaginal ultrasound follow-ups showed a persistent anechoic mass on right rube stump, with increased peripheral high flow vascularity: highly suspicious for a uterine arteriovenous malformation. A laparoscopy was performed with a tumorectomy of the mass. The histopathological exam of the specimen confirmed uterine arteriovenous malformation. Patient successfully became pregnant 2 years later, with an eventless pregnancy and a vaginal delivery without complications.

Clinical and Ultrasound Predictors of Placenta Accreta in Pregnant Women with Antepartum Diagnosis of Placenta Previa: A Multicenter Study.

BACKGROUND/AIMS: Abnormally invasive placenta (AIP) includes placenta accreta, increta, and percreta and represents major complications of pregnancy. This study was designed to assess the role of ultrasonography in the identification of AIP among pregnant women with antepartum diagnosis of placenta previa. METHODS: A cross-sectional study was performed between May 2015 and April 2016 in 11 centers, including 242 women with antepartum diagnosis of placenta previa. RESULTS: Ninety-eight out of 242 (40.49%) women had a histological diagnosis of placenta accreta. A higher number of caesarean deliveries (p = 0.001) and curettages (p = 0.027) and older age of the woman at the delivery (p = 0.031) were identified as risk factors for placenta accreta. The presence of irregularly shaped placental lacunae (vascular spaces) within the placenta (p = 0.008), protrusion of the placenta into the bladder (p < 0.0001), and turbulent blood flow through the lacunae on Doppler ultrasonography (p = 0.008) were predictors of placenta accreta. CONCLUSIONS: Women with a prior delivery by caesarean section have a high incidence of placenta accreta among women with antepartum diagnosis of placenta previa.

Maternal outcomes in first and second trimester termination of pregnancy: which are the risk factors?

AIMS: To evaluate maternal complications of first trimester and second trimester termination of pregnancy (TOP) performed after first or second trimester positive prenatal diagnosis (PD). RESULTS: We performed a retrospective study from January 2007 to December 2011, on 844 patients, who underwent a TOP after positive amniocentesis or chorionic villus sampling (CVS) for foetal aneuploidies, performed for maternal age ≥35 years of age, positive prenatal screening (PS) or for genetic reasons. Exclusions criteria were gestational age >22+0 weeks, twin pregnancy and co-existing maternal pathologies. We compared maternal complications of first trimester and second trimester TOP and we established which risk factors were correlated to higher maternal complications (haemorrhages, transfusion, repeated uterine curettage and infections). Maternal complications were significantly higher in second trimester TOP. Previous uterine surgery is a significant risk factor for maternal complications in second trimester TOP, but not in first trimester TOP. Six uterine ruptures and three hysterectomies occurred, all in multiparous women with second trimester TOP. All uterine ruptures occurred in women with previous caesarean sections. CONCLUSIONS: First trimester TOP in women with risks factors for maternal complications guarantees better maternal outcomes and less health costs. Thus, in these women we should prefer a first trimester PS and PD.

Development of customized fetal growth charts in twins.

BACKGROUND: Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. OBJECTIVE: The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. STUDY DESIGN: Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Società Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. RESULTS: The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2-8) observations per pregnancy in dichorionic and 6 in (range, 2-11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. CONCLUSION: Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for gestation constructed in this study may provide a useful tool for a more accurate assessment of fetal growth in twin pregnancies.

Consensus Document of the Italian Association of Hospital Cardiologists (ANMCO), Italian Society of Pediatric Cardiology (SICP), and Italian Society of Gynaecologists and Obstetrics (SIGO): pregnancy and congenital heart diseases.

The success of cardiac surgery over the past 50 years has increased numbers and median age of survivors with congenital heart disease (CHD). Adults now represent two-thirds of patients with CHD; in the USA alone the number is estimated to exceed 1 million. In this population, many affected women reach reproductive age and wish to have children. While in many CHD patients pregnancy can be accomplished successfully, some special situations with complex anatomy, iatrogenic or residual pathology are associated with an increased risk of severe maternal and fetal complications. Pre-conception counselling allows women to come to truly informed choices. Risk stratification tools can also help high-risk women to eventually renounce to pregnancy and to adopt safe contraception options. Once pregnant, women identified as intermediate or high risk should receive multidisciplinary care involving a cardiologist, an obstetrician and an anesthesiologist with specific expertise in managing this peculiar medical challenge. This document is intended to provide cardiologists working in hospitals where an Obstetrics and Gynecology Department is available with a streamlined and practical tool, useful for them to select the best management strategies to deal with a woman affected by CHD who desires to plan pregnancy or is already pregnant.

Customized Fetal Growth Charts for Parents' Characteristics, Race, and Parity by Quantile Regression Analysis: A Cross-sectional Multicenter Italian Study.

OBJECTIVES: The purpose of this study was to construct fetal biometric charts between 16 and 40 weeks' gestation that were customized for parental characteristics, race, and parity, using quantile regression analysis. METHODS: In a multicenter cross-sectional study, 8070 sonographic examinations from low-risk pregnancies between 16 and 40 weeks' gestation were analyzed. The fetal measurements obtained were biparietal diameter, head circumference, abdominal circumference, and femur diaphysis length. Quantile regression was used to examine the impact of parental height and weight, parity, and race across biometric percentiles for the fetal measurements considered. RESULTS: Paternal and maternal height were significant covariates for all of the measurements considered (P < .05). Maternal weight significantly influenced head circumference, abdominal circumference, and femur diaphysis length. Parity was significantly associated with biparietal diameter and head circumference. Central African race was associated with head circumference and femur diaphysis length, whereas North African race was only associated with femur diaphysis length. CONCLUSIONS: In this study we constructed customized biometric growth charts using quantile regression in a large cohort of low-risk pregnancies. These charts offer the advantage of defining individualized normal ranges of fetal biometric parameters at each specific percentile corrected for parental height and weight, parity, and race. This study supports the importance of including these variables in routine sonographic screening for fetal growth abnormalities.

Myths about nutrition in pregnancy.

Many women have incorrect knowledge about nutrition in pregnancy owing to false beliefs derived from popular practices. More than 90% of our cohort of pregnant women during early pregnancy (<12 weeks of gestational age) gave at least one incorrect answer to the five questions relative to common myths about nutrition in pregnancy. Education was inversely associated with the percentage of incorrect answers, and the lowest percentage of any mistakes was found in the small number of women who received nutritional information by a dietician. In conclusion, the usual sources of information about nutrition in pregnancy are not adequate to overcome the false beliefs acquired by traditions.

Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications.

Karyotyping and aCGH are routinely used to identify genetic determinants of major congenital malformations (MCMs) in fetal deaths or terminations of pregnancy after prenatal diagnosis. Pathogenic rearrangements are found with a variable rate of 9-39% for aCGH. We collected 33 fetuses, 9 with a single MCM and 24 with MCMs involving 2-4 organ systems. aCGH revealed copy number variants in 14 out of 33 cases (42%). Eight were classified as pathogenic which account for a detection rate of 24% (8/33) considering fetuses with 1 or more MCMs and 33% (8/24) taking into account fetuses with multiple malformations only. Three of the pathogenic variants were known microdeletion syndromes (22q11.21 deletion, central chromosome 22q11.21 deletion, and TAR syndrome) and 5 were large rearrangements, adding up to >11 Mb per subject and comprising strong phenotype-related genes. One of those was a de novo complex rearrangement, and the remaining 4 duplications and 2 deletions were 130-900 kb in size, containing 1-7 genes, and were classified as variants of unknown clinical significance. Our study confirms aCGH as a powerful technique to ascertain the genetic etiology of fetal major congenital malformations.

Maternal Risk Factors for Respiratory Syncytial Virus Lower Respiratory Tract Infection in Otherwise Healthy Preterm and Term Infants: A Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVE: To date, there is no published, formal assessment of all maternal risk factors for respiratory syncytial virus lower respiratory tract infection (RSV-LRTI) in infants. A systematic literature review and meta-analysis were undertaken to ascertain: What maternal risk factors are associated with an increased risk of RSV-LRTI in infants? METHODS: The systematic literature review used explicit methods to identify, select and analyze relevant data. PubMed, Embase and the Cochrane Library were searched (November 2022) using terms regarding: (1) RSV/LRTI; (2) risk factors; (3) pregnant/postpartum population. Bayesian meta-analysis compared RSV hospitalization (RSVH) risk in infants born to mothers with or without certain risk factors. RESULTS: A total of 2353 citations were assessed and 20 were included in the final review (10 individual studies; 10 pooled analyses). In 10 studies examining infants (<1 year) without comorbidities (primary outcome), 10 maternal risk factors were associated with RSV-LRTI/RSVH in multivariate analyses. Meta-analysis revealed smoking while pregnant increased infant RSVH risk by 2.01 (95% credible interval: 1.52-2.64) times, while breast-feeding was protective (0.73, 95% credible interval: 0.58-0.90). Risk scoring tools have reported that maternal risk factors contribute between 9% and 21% of an infant's total risk score for RSVH. CONCLUSIONS: A greater understanding of maternal risk factors and their relative contribution to infant RSV-LRTI will enable more accurate assessments of the impact of preventive strategies.

Could the contraceptive counselling improve contraceptive choice after abortion? A multicentric study to evaluate patients' perception.

INTRODUCTION: 24 % of abortion in Italy are repeated procedure. The cause of repeated abortion can be traced back to the inadequacy of the contraceptive counseling during the previous admission or to the adoption of an ineffective contraception method. This study aims to evaluate the Italian situation on the perceived quality of contraceptive counselling by patients undergoing abortion. The second aim is to verify if the chosen methods were available for immediate start. STUDY DESIGN: Multicentric, prospective, non-interventional, non-randomized, non-pharmacological clinical observational study. We analyzed anonymous questionnaires on contraceptive counseling and LARC (Long Acting Reversable Contraceptives) availability and SARC (Short Acting Reversable Contraceptives) prescription at hospital discharge, distributed to women who requested abortion. RESULTS: 1074 participants on 15 hospitals through Italy. 82 % of the interviewees reported that they had received correct information regarding contraception. 74 % of the patients who chose LARC methods reported to have them inserted at the time of abortion. 73 % of women who had chosen a SARC method stated that they had received the prescription before discharge. After contraceptive counselling, we reported a significative reduction of "none or natural methods use" and a significant increase of SARC and LARC use compared to before the abortion. CONCLUSION: Contraceptive counselling could allow a better contraceptive choice in patient who required abortion and we hope that future strategies will implement LARC choice. We think that a greater availability of LARC at an affordable price at the time of abortion could improve LARC choice. In case of SARC choice, we have to implement the prescription at hospital discharged.

Sleep and sleep disorders during pregnancy and postpartum: The Life-ON study.

OBJECTIVE: to prospectively assess sleep and sleep disorders during pregnancy and postpartum in a large cohort of women. METHODS: multicenter prospective Life-ON study, recruiting consecutive pregnant women at a gestational age between 10 and 15 weeks, from the local gynecological departments. The study included home polysomnography performed between the 23rd and 25th week of pregnancy and sleep-related questionnaires at 9 points in time during pregnancy and 6 months postpartum. RESULTS: 439 pregnant women (mean age 33.7 ± 4.2 yrs) were enrolled. Poor quality of sleep was reported by 34% of women in the first trimester of pregnancy, by 46% of women in the third trimester, and by as many as 71% of women in the first month after delivery. A similar trend was seen for insomnia. Excessive daytime sleepiness peaked in the first trimester (30% of women), and decreased in the third trimester, to 22% of women. Prevalence of restless legs syndrome was 25%, with a peak in the third trimester of pregnancy. Polysomnographic data, available for 353 women, revealed that 24% of women slept less than 6 h, and 30.6% of women had a sleep efficiency below 80%. Sleep-disordered breathing (RDI≥5) had a prevalence of 4.2% and correlated positively with BMI. CONCLUSIONS: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.

Role of mode of induction and delivery and women's satisfaction after induction of labour at term: An observational study.

This cross-sectional study aimed at evaluating the impact of different modalities of induction of labour (IOL) and delivery on levels of woman' satisfaction. All women aged 18 years or older, who underwent IOL for at-term pregnancy (≥41 weeks of gestation) in randomly selected days during the study period in 6 participating centres were eligible for the study. The questionnaire investigated women's opinion regarding information about induction, pain control, length of induction, their experience about induction, labour and delivery and their attitude towards induction in a subsequent pregnancy. Women were also asked to fill in the Italian version of the Birth Satisfaction Scale-Revised (BSS-R). A total of 300 women entered the study. The answer to the question about a "positive attitude towards induction in a subsequent pregnancy was "absolutely yes" or "yes" respectively in the 77.8%, 52.8% and 48.6% of women who were induced with oral drugs, vaginal drugs and Cook balloon (heterogeneity chi-square p = 0.05). The corresponding values for women who delivered vaginally or by caesarean section (CS) were 63.3% and 36.4% (chi-square p = 0.0009). The mean BSS-R total score was higher among women who underwent IOL with oral drugs than with vaginal drugs (p < 0.0001) or Cook Balloon (p < 0.0001), and among women who delivered vaginally than in those who delivered by CS (p < 0.0001). Women were asked "What do you think is important for a method of induction?": 47.3% (95% CI 41.7%-53.0%) of women answered that "should make the induction as painless as possible", 47.0% (95% CI 41.4%-52.7%) "should induce labour quickly", 44.3% (95% CI 38.8%-50.0%) "should be safe for baby". This study showed that vaginal delivery was associated with a higher rate of satisfaction among induced women. Considering mode of induction, oral drugs were associated with a higher level of satisfaction. Control of pain and quick induction were the most appreciated characteristics.

Results of a Five-Year Experience in First Trimester Preeclampsia Screening.

BACKGROUND AND OBJECTIVES: The study aimed to evaluate the ability defining the risk of developing preeclampsia by a screening test carried out in the first trimester (between 11 + 0 and 13 + 6 weeks of gestational age), in order to identify high-risk women requiring more intensive health surveillance. The secondary objective was to evaluate the ability of this test to predict the risk of adverse obstetric outcomes such as fetal growth restriction, intrauterine fetal death, gestational hypertension, HELLP syndrome, placental abruption, and preterm birth. MATERIALS AND METHODS: This was a single-center study, conducted at the Operative Unit of Obstetrics of the State Hospital of the Republic of San Marino. Medical history was collected at the time of enrolment in writing. Subsequently, obstetric outcomes were collected for each enrolled woman, through the analysis of medical records. RESULTS: From October 2014 to May 2019, 589 pregnant women were recruited, of whom, 474 (80.5%) were included in the "low-risk" group, and 115 (19.5%) in the "high-risk" group. At the time of analysis of this population, the obstetric outcomes were available for 498 women (84.5%), while 91 cases (15.5%) were current pregnancies. The PI of the uterine arteries was not significantly different between the two study groups. Otherwise, a significant difference was highlighted for MAP, which is higher in the case of pregnancies at high risk based on the risk factors only, and for PAPP-A, higher in the case of low-risk pregnancies. Regarding the percentage of fetal DNA, according to the most recent literature data, in our series, we report a statistically significant difference of the average between the low and high-risk groups. CONCLUSIONS: In our study, we demonstrate that the multiparametric screening test for early PE performed well in identifying women at high risk of early PE, which certainly has the most severe maternal-fetal outcomes. The data reported that ASA intake at low doses is significantly higher in the population with high-risk tests for both early PE and late PE suggest once again that anamnestic evaluation plays an essential role in women's screening.

What women think about menopause: An Italian survey.

INTRODUCTION: Menopause is a critical period for most women who experience associated symptoms while they are still socially and individually active. OBJECTIVES: The objective of this study is to report how Italian women perceive and approach menopause. MATERIALS AND METHODS: A survey of 1028 Italian women aged 45-65 years was conducted by the Italian Center for Studies of Social Investments (CENSIS) through anonymous interviews using two methods: CATI (Computer Assisted Telephone Interviewing) and CAWI (Computer Assisted Web Interviewing). PRINCIPAL OUTCOME MEASURES: Principal outcome measures were women's perceptions and experiences of menopause and its treatments. RESULTS: The global consciousness and understanding of menopause was common (82.8 %) among Italian women and it was usually considered a physiological condition (77 %). Overall, 74.6 % of the sample were postmenopausal. Hot flushes were reported to be the most frequent (37.9 %) and bothersome symptoms (43.1 %) while 12.9 % of the women were asymptomatic. As for menopausal therapies, 24.5 % were on treatment; herbal medications were the most common remedy (63.3 %) whereas 7.6 % of the women took hormone replacement therapy (HRT). About half of the sample (50.4 %) had not sought help from the Italian National Health System (INHS). Medical expertise in the field of menopause was thought to be moderately satisfactory by 54.5 % of the sample. CONCLUSIONS: Italian women consider menopause a physiological condition. Most postmenopausal women had experienced symptoms but relied on non-hormonal treatments. The median women's satisfaction with the role of the INHS and medical competence suggests the need to improve current knowledge and awareness concerning menopause.

Breastfeeding and COVID-19 vaccination: position statement of the Italian scientific societies.

The availability of a COVID-19 vaccine has raised the issue of its compatibility with breastfeeding. Consequently, the Italian Society of Neonatology (SIN), the Italian Society of Pediatrics (SIP), the Italian Society of Perinatal Medicine (SIMP), the Italian Society of Obstetrics and Gynecology (SIGO), the Italian Association of Hospital Obstetricians-Gynecologists (AOGOI) and the Italian Society of Infectious and Tropical Diseases (SIMIT) have made an ad hoc consensus statement. Currently, knowledge regarding the administration of COVID-19 vaccine to the breastfeeding mother is limited. Nevertheless, as health benefits of breastfeeding are well demonstrated and since biological plausibility suggests that the health risk for the nursed infant is unlikely, Italian scientific societies conclude that COVID-19 vaccination is compatible with breastfeeding.