Umbilical artery Thrombosis: A case report of prenatal diagnosis and systematic review of the literature.

Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still unclear but it is often associated with anatomical cord abnormalities that leads to blood stasis and thrombosis formation. Other possible risk factors are maternal thrombophilia, autoimmune disease, gestational diabetes, hypertension disorders of pregnancy and Rh-alloimmunization. The most common clinical symptom is the reduction of fetal movements. The diagnosis is histopathological, but it can be suspected by clinical and prenatal ultrasound findings. Generally, the first choice therapy is the immediate delivery with cesarean section. This study reported a case of a spontaneous intrauterine UAT in a low-risk pregnancy and a systematic review of the literature on clinical, ultrasound and histopathological findings of UAT, in order to help clinicians in the diagnostic process and management of this rare complication.

Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

Asymptomatic CMV infection at birth following maternal primary infection despite valacyclovir treatment and a subsequent negative amniocentesis. Case report.

Valacyclovir is currently the only pharmacological intervention demonstrated to reduce the risk of vertical CMV congenital infection within a randomized clinical trial in case of primary infection during pregnancy. So far, no data are available on the prognosis of children with congenital CMV infection diagnosed at birth after a negative amniocentesis whose mother were treated with valacyclovir during pregnancy, therefore it is essential to carry out a rigorous neurocognitive follow-up in these children in order to investigate the potential clinical consequence.

Invasive prenatal diagnosis in the era of cell-free fetal DNA: experience at a single center.

BACKGROUND: We aimed to assess procedure-related risk of fetal loss associated with amniocentesis and chorionic villus sampling and compare amniocentesis and chorionic villus sampling with cell-free fetal DNA in identifying chromosomal abnormalities. METHODS: A retrospective observational study on 4712 women with singleton pregnancy who underwent invasive prenatal diagnosis, from January 2010 to December 2019. Postprocedural miscarriage rate (before 24+0 weeks gestation) was determined for the whole population and for the group of women aged ≥35 years who underwent the procedure for the sole maternal age. RESULTS: Miscarriage rate following amniocentesis and chorionic villus sampling were 0.50% and 1.25%, respectively. In our population of women undergoing invasive procedure for advanced maternal age cell-free fetal DNA would have identified only the 49 cases of trisomy 21, 13 and 18, whereas the other 21 more subtle chromosomal anomalies, diagnosed by amniocentesis and chorionic villus sampling, would have been missed. CONCLUSIONS: Patients who opt for cell-free fetal DNA test should be informed of the screening nature of the test and the possibility of false positive results. Invasive prenatal testing has probably lower risks than previously reported and has unquestionable advantages such as the certainty of diagnosis and the ability to detect a higher number of chromosomal abnormalities, when compared with cell-free fetal DNA.

Small-for-gestational-age fetus diagnosed in the second trimester: Possible etiologies and short-term neonatal outcomes.

INTRODUCTION: The aim of our study was to investigate the causes of fetal growth <10th centile diagnosed <26 weeks' gestation in singleton pregnancies and compare pregnancy outcomes in relation to the identified etiology. MATERIAL AND METHODS: Historical cohort study conducted in two Italian hospitals which included all small-for-gestational-age fetuses diagnosed between 18+0 and 26+0 weeks over a 10-year period. Fetuses were divided into three groups depending on the prenatally suspected etiology: chromosomal abnormalities (Group 1), malformations (Group 2) and isolated (Group 3). These groups were compared regarding pregnancy outcomes. Fetuses in Group 3 were divided into small-for-gestational-age and fetal growth restriction following the Delphi Consensus criteria and the outcomes were further compared. Fisher's Exact or Mann-Whitney test were used for comparison of groups. RESULTS: In all, 435 fetuses were included. Of these, 20 cases (4.6%) were associated with chromosomal abnormalities (Group 1), 98 (22.5%) with fetal malformations (Group 2) and 317 (72.9%) were isolated (Group 3). A higher percentage of live births was reported for Group 3 (P < 0.001). Termination of pregnancy was more common in Group 1 (P < 0.001). No differences in gestational age at delivery, birthweight, intrauterine death or neonatal death were detected within groups. Growth-restricted fetuses had lower gestational age at delivery, birthweight and number of live births (P < 0.001), higher rates of termination of pregnancy, intrauterine death (P < 0.001) and neonatal death <10 days (P = 0.002) compared to small-for-gestational-age. In 17 cases a chromosomal abnormality, genetic syndrome or adverse neurological outcome was diagnosed after birth: six from Group 2 (11.3% of live births in this group) and 11 from Group 3 (4.3%). CONCLUSIONS: We report that fetal growth <10th percentile diagnosed before 26 weeks is not isolated before birth in 27% of cases. Malformations and chromosomal abnormalities are common etiologies; therefore, detailed anomaly scans and invasive testing should be offered. In addition, there is a residual risk of neonatal death and postnatal diagnosis of a genetic syndrome or neurodevelopmental impairment despite normal prenatal tests. These results expand the small amount of information on the outcome of cases with very early diagnosis of impaired fetal growth currently available and highlight the importance of detailed counseling with couples.

Neonatal Outcomes of Term Infants Born with Meconium-Stained Amniotic Fluid.

Background Meconium-stained amniotic fluid (MSAF) is considered an alarming sign of possible fetal compromise and it has recently been reported that neonatal outcome correlates with the degree of meconium thickness. Methods We retrospectively studied 400 term infants allocated in clear amniotic fluid and grade 1, 2, and 3 MSAF groups on the basis of color and thickness of AF. Multivariable logistic regression analysis was performed to evaluate the potential independent effect of delivery with MSAF of different severity on the risk of a composite adverse neonatal outcome. Results We found that delivery with grade 2 (OR 16.82, 95% Cl 2.12-33.52; p = 0.008) and 3 (OR 33.79, 95% Cl 4.24-69.33; p < 0.001) MSAF is independently correlated with the risk of adverse neonatal outcome, such as the occurrence of at least one of the following: need of resuscitation in the delivery room, blood cord pH < 7.100, occurrence of meconium aspiration syndrome (MAS), persistent pulmonary hypertension (PPH), transient tachypnea of the newborn (TTN), acute respiratory distress syndrome (ARDS), hypoxic-ischemic encephalopathy (HIE), and sepsis. Conclusions There is a positive correlation between the severity of amniotic fluid meconium staining and thickness and the outcomes of term infants. Therefore, the evaluation and grading of MSAF during labor is useful in order to plan for the presence of a neonatologist at delivery for immediate and proper neonatal care.

Elevated nuchal translucency, is it time to discuss the cut off?

OBJECTIVE: We aimed to evaluate pregnancy and postnatal outcomes of fetuses with NT between 95th and 99th percentile at first trimester and whether they could benefit from further investigations rather that routine scans. METHODS: Multicenter retrospective observational study which involved all cases with NT between 95th and 99th percentile from January 2015 to December 2020. Unfavorable outcome was considered as: miscarriage or intrauterine fetal death (IUFD), chromosomal abnormality/genetic syndrome, major malformation or neurodevelopmental delay. Study population outcomes were compared with general population. RESULTS: The rate of unfavorable outcome was 25.44% (167 out of 667). We reported: 6 (0.90%) second trimester miscarriage or IUFD, 90 (13.49%) chromosomal abnormalities/genetic syndromes, 57 (8.55%) major malformations, 13 (1.95%) cases of neurodevelopmental delay. The incidence of chromosomal abnormalities/genetic syndromes and major malformations were significantly higher (OR 6.99 (IC 95% 4.33-11.28), P < 0.001 and OR 17.77 (IC 95%7.22-43.75), P < 0.001 respectively) compared to the general population. The incidence of neurodevelopmental delay was not increased (OR of 0.64 CI 95% 0.33-1.24 P = 0.185). CONCLUSIONS: Fetuses with NT between 95th and 99th percentile have an increased risk of pregnancy and postnatal adverse outcomes. According to our data it is reasonable to consider a lower cut of NT (NT > 95th percentile) for offering further investigations such as detailed ultrasound scan, fetal echocardiography and counseling where the option of performing fetal karyotype and CGH array should be discussed.

Increased nuchal translucency with normal karyotype and genomic microarray analysis: A multicenter observational study.

OBJECTIVE: To define the residual risk of morbidity-related outcome in fetuses with nuchal translucency (NT) of 3.5 mm or more after normal genetic testing and mid-trimester anomaly scan. METHODS: A total of 114 fetuses with isolated NT of 3.5 mm or more, normal karyotype, and array-based comparative genomic hybridization (array-CGH) were included and divided in three groups: NT 3.5-4.5 mm, NT 4.5-6 mm, and NT greater than 6 mm. RASopathy testing and ultrasound follow up were performed in all fetuses. We evaluated: (1) incidence of genetic disorders; (2) incidence of structural abnormalities; (3) pregnancy outcome; (4) long-term pediatric outcome before (point 1) and after (point 2) a normal RASopathy testing and mid-trimester anomaly scan. RESULTS: After normal karyotype and array-CGH the residual risk of morbidity-related outcome was 24.64% for NT 3.5-4.5 mm, 25% for NT 4.5-6 mm and 76.47% for NT more than 6 mm. After a normal RASopathy testing and mid-trimester anomaly scan the residual risks decreased to 7.14%, 8.69%, and 33.3% in the three groups, respectively. CONCLUSION: In fetuses with an NT of 3.5 mm or more and both normal karyotype and array-CGH, the rate of morbidity-related outcome depends on NT size. A normal RASopathy testing and mid-trimester ultrasound are reassuring but the residual risk of morbidity-related outcome is increased compared with the general population, particularly if NT is greater than 6 mm.

Urine Biochemistry of a Human Fetus with Urinary Tract Obstruction - A Case Report.

INTRODUCTION: Fetal lower urinary tract obstruction (LUTO) can be mild or severe with oligohydramnios, renal dysplasia and pulmonary hypoplasia. Fetal urine biochemical markers correlate with fetal prognosis and, if favorable, surgical intervention is feasible. METHODS: We report a patient in her 18th gestational week whose fetus was diagnosed with LUTO and underwent fetal urine sampling for calcium, sodium, chloride, beta2-microglobulin and total protein of the routine LUTO panel, with the addition of creatinine, glucose, phosphate, urea, ammonia, albumin, and NGAL. RESULTS: Although the routine fetal urine biochemistry seemed to be favorably trending favorably, sodium, beta2-microglobulin, glucose, and urea did not decrease to the reference ranges, and ammonia and creatinine were lower than the reference ranges. Ultrasound demonstrated no improvement of the obstruction. CONCLUSIONS: This case highlights the need to acquire further experience with biochemical fetal urine markers in order to better manage LUTO.

Obstetric and Neonatal Outcomes in Mild Idiopathic Polyhydramnios.

Background: Idiopathic polyhydramnios is a controversial clinical condition, as data on perinatal outcomes are conflicting and vary depending on the severity of the condition. The aim of the present study was to compare obstetric and neonatal outcomes between pregnant women with mild idiopathic polyhydramnios and a control population. Methods: A retrospective cohort study was performed at a single university hospital comparing the obstetrics and neonatal outcomes of pregnancies with mild idiopathic polyhydramnios (n = 109) and control pregnancies (n = 2550). Results: Cesarean section (CS) was significantly increased in the group with polyhydramnios compared to controls (46% vs. 32%, respectively, p = 0.047) due to a higher rate of emergency CS in the polyhydramnios group (p = 0.041) because of abnormal cardiotocography (7.3% vs. 2.9%; p = 0.018) or labor dystocia (8.2% vs. 2.9%; p = 0.006). No statistically significant difference was found in the Apgar score, in the rate of neonatal hypoxia, or in the incidence of macrosomia between groups. In four cases, additional diagnoses of anomalies were made after birth, with a rate of 3.2%, which is comparable to the general population. Conclusion: Besides an increased risk of CS, patients with mild idiopathic polyhydramnios should be reassured regarding maternal and feto-neonatal outcomes. The management of pregnancies with stable mild idiopathic polyhydramnios should not differ from uncomplicated pregnancies, except for the need for increased labor surveillance.

Trophoblast microRNAs (miRNAs), preeclampsia and intrauterine growth restriction.

MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that play a role in regulating gene expression in a tissue-specific manner. Placental miRNAs expression pattern dynamically changes during pregnancy influencing cell proliferation, differentiation and apoptosis. Changes of specific miRNA levels have been described in pregnancies complicated by hypertensive disorders or gestational diabetes and a growing interest in understanding miRNA role on placental development and placental disorders is currently going on. The present review evaluates the possible roles of miRNAs in trophoblastic invasion and placental development as well as their potential role as biomarkers for the prediction of placental disorders focusing the attention on intrauterine growth restriction.

Difference in cardiac remodeling between female athletes and pregnant women: a case control study.

OBJECTIVES: The aim of this study was to detect possible differences in reversible cardiac remodeling occurring in sport training and twin pregnancy. BACKGROUND: cardiac remodeling occurs in athletes and pregnant women due to training and fetal requirements, respectively. These changes could be apparently similar. METHODS: 21 female elite athletes (23.2 ± 5.3 years), 25 women with twin pregnancies (35.4 ± 5.7 years) and 25 healthy competitive female athletes (controls), age-matched with pregnant women (34.9 ± 7.9 years), were enrolled. This latter group was included to minimize the effect of age on cardiac remodeling. All women evaluated through anamnestic collection, physical examination, 12 leads ECG, standard echocardiogram and strain analysis. Sphericity (SI) and apical conicity (ACI) indexes were also calculated. RESULTS: Pregnant women showed higher LA dimension (p < 0.001) compared to both groups of athletes. LV e RV GLS were significantly different in pregnant women compared to female athletes (p = 0.02 and 0.03, respectively). RV GLS was also different between pregnant women and controls (p = 0.02). Pregnant women showed significantly higher S' wave compared to female athletes (p = 0.02) but not controls. Parameters of diastolic function were significantly higher in athletes (p = 0.08 for IVRT and p < 0.001 for E/A,). SI was lower in athletes in both diastole (p = 0.01) and systole (p < 0.001), while ACIs was lower in pregnant women (p = 0.04). CONCLUSIONS: Cardiac remodeling of athletes and pregnant women could be similar at first sight but different in LV shape and in GLS, highlighting a profound difference in longitudinal deformation between athletes and pregnant women. This difference seems not to be related with age. These findings suggest that an initial maternal cardiovascular maladaptation could occur in the third trimester of twin pregnancies.

Ductus venosus Doppler assessment: do the results differ between the sagittal and the transverse approach?

OBJECTIVE: To compare the ductus venosus (DV) pulsatility index for veins (PIV) obtained in a mid-sagittal plane with that obtained in an oblique transverse plane of the fetal abdomen. METHODS: Prospective observational study in singleton uncomplicated pregnancies undergoing an ultrasound examination between 24 and 34 weeks of gestation. Pregnancies complicated by fetal anomalies, fetal growth restriction, or oligohydramnios were excluded. Two consecutive recordings of DV Doppler waveform were obtained in each woman: one in a mid-sagittal plane, and the other in an oblique transverse plane of the fetal abdomen. The peak velocity during ventricular systole (S-wave) and diastole (D-wave), the velocity during atrial contraction (a-wave), and the time-averaged maximum velocity (TAmax) were measured, and the PIV was calculated. The paired t-test was used to compare results obtained with the two approaches. A change of the DV-PIV of 0.10 or more was considered clinically relevant. RESULTS: The DV waveform was successfully obtained in 53 women (mean gestational age 28.5 weeks). The mean DV-PIV was 0.57 (±0.16 SD) in the sagittal plane and 0.54 (±0.16 SD) in the transverse plane. The mean difference (0.03) was statistically significant (p = .04), but not clinically relevant. The sagittal S-, D-, and a-wave velocities and TAmax were significantly higher in the sagittal plane compared to the transverse plane, with an increase of 12, 8, 8, and 10%, respectively (p < .05). CONCLUSIONS: The difference in the DV-PIV obtained in a mid-sagittal plane compared to a transverse plane of the fetal abdomen is small and not clinically significant. The higher DV flow velocities observed in the sagittal plane are likely the result of a better alignment with the vessel obtained using this plane. These findings have implications for clinical practice and for research.

Role of prenatal magnetic resonance imaging in fetuses with isolated severe ventriculomegaly at neurosonography: A multicenter study.

OBJECTIVE: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. METHOD: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

Primary toxoplasmosis acquired during early pregnancy: Is it currently overestimated?

OBJECTIVE: Toxoplasmosis acquired in early pregnancy is a potentially severe complication for the fetus. Evaluating the risk of transplacental infection in pregnant women accessing the Tuscany Reference Center for Infectious Diseases in Pregnancy during the last 20 years with suspected or confirmed toxoplasmosis acquired in early pregnancy was the aim of the study. STUDY DESIGN: We retrospectively enrolled all pregnant women undergoing amniocentesis for toxoplasmosis acquired in the first 16 gestational weeks in the period 1999-2019, comparing patients with certain acute infection (seroconversion occurred in pregnancy, CAIP) with those with suspected acute infection (IgG positive with low/intermediate IgG avidity index, SAIP). RESULTS: 237 patients were enrolled, 187 (78.9%) with SAIP and 50 (21.1%) with CAIP. Specific IgM was detected in 47.5% and 76.7% (p-value 0.001), and the mean IgG avidity index was 22.7% and 7.1% (p-value < 0.001) in the SAIP and in the CAIP group, respectively. The mean delay from diagnosis to antibiotic initiation was 14.6 in SAIP and 11 days in CAIP group. Toxoplasma DNA was detected in the amniotic fluid in one case in a patient with CAIP. Excluding 24 newborns with not available data, prevalence of congenital infection was 0.47% [1/213 (95% CI 0.08%-2.61%)], 0% [0/178 (95% CI 0%-2.11%)] in SAIP and 2.8% [1/35 (95% CI 0.51%-14.53%)] in CAIP group. CONCLUSIONS: Toxoplasmosis acquired in early pregnancy has a low risk of fetal infection. Actively discussing case-by-case amniocentesis indication with patients, especially when a recent toxoplasmosis is not properly confirmed, is desirable.

Valacyclovir for prevention and treatment of fetal CMV infection: inclusion in the Law 648/96 list and launch of the Italian multicentre observational prospective study "MEGAL-ITALI".

Not available.

Clinical implementation of pre-eclampsia screening in the first trimester of pregnancy.

OBJECTIVES: Early identification of preeclampia in the first trimester of pregnancy represents one of the major challenges of modern fetal medicine. The primary aim of our study was to evaluate the effectiveness of implementation of preeclampsia screening in Tuscany, Italy. The secondary aim was to evaluate pregnancy/neonatal outcome in the positive screening group compared with the negative screening group. STUDY DESIGN: Retrospective study including singleton pregnancies undergoing screening for preeclampsia. The screening test was a multiparametric algorithm based on maternal history, biochemical and biophysical parameters (Fetal Medicine Foundation algorithm). MAIN OUTCOME MEASURES: The overall performance of the test was calculated, in terms of sensitivity, specificity, positive and negative predictive value and in relation to gestational age at onset (primary aim). Pregnancy and neonatal outcomes were then compared between the positive and negative population at preeclampsia screening test (secondary aim). RESULTS: Of the 5719 patients enrolled, 4797 were included in the analysis. The sensitivity for early onset of preeclampsia (≤34 weeks) was 0.75 (CI:0.41-0.93) and specificity 0.93 (CI:0.92-0.94) for a false positive rate of 7%. The population that tested positive for preeclampsia screening showed a higher incidence of deliveries at lower gestational ages (p < 0.001), preeclampsia onset despite prophylaxis with aspirin (p < 0.001), emergency caesarean section (p < 0.001), low fetal birth weight (p < 0.001) and neonatal admission in intensive care unit (p < 0.001). CONCLUSIONS: Our data confirm the validity of first trimester screening test in identifying a category of patients at greatest risk for preeclampsia even in the presence of a post-test pharmacological prophylaxis.

Sociodemographic Differences in Prenatal Diagnosis of Chromosomal Anomalies: A Population-Based Study.

Background: In Europe, about 76% of cases of chromosomal anomalies are prenatally diagnosed. Prenatal diagnosis allows more efficient planning of postnatal treatment and helps parents for an informed decision about the continuation of pregnancy. The main aim of this study was to evaluate whether the sociodemographic maternal characteristics affect the probability of prenatal diagnosis of chromosomal anomalies. Methods: Cases of chromosomal anomalies in the period 2005-2017 came from the population-based registry of congenital anomalies of Tuscany (Italy). Differences in the proportion of cases prenatally diagnosed were investigated through the following maternal characteristics: education, geographic origin and occupation. The association between cases of termination of pregnancy after prenatal diagnosis and maternal characteristics was also analysed. Odds Ratios (OR) adjusted by maternal age were calculated using logistic regression models. Results were provided for all cases of chromosomal anomalies and for Down syndrome cases. Results: A total of 1,419 cases were included in the study. Cases prenatally diagnosed were 1,186 (83.6%). We observed a higher proportion of cases not prenatally diagnosed among cases with low maternal education compared to those with high maternal education (OR = 2.16, p < 0.001) and in women from high migratory outflow countries, compared to the Italian ones (OR = 2.85, p < 0.001). For prenatally diagnosed Down syndrome cases, we observed a higher proportion of termination of pregnancy for women with low education level (OR = 4.36, p = 0.023). Conclusions: In our study evidence of differences in the probability of prenatal diagnosis of chromosomal anomalies associated with maternal education and geographic origin was found. Population-based studies investigating sociodemographic disparities can provide essential information for targeted public health programs. Further studies are recommended to monitor the impact of the increasing availability of non-invasive screening tests.