Counseling in fetal medicine: Congenital cytomegalovirus infection.

Although the clinical work-up of CMV in pregnancy has gradually become more accurate, counseling for CMV is still challenging. Despite the potential feasibility of universal prenatal serological screening, its introduction in prenatal diagnosis continues to raise concerns related to its real cost-effectiveness. Contextually, anticipating the confirmation of fetal infection earlier in pregnancy is one of the most pressing issues to reduce the parental psychological burden. Amniocentesis is still the gold standard and recent data have demonstrated that it could be performed before 20 weeks of gestation, provided that at least 8 weeks have elapsed from the presumed date of maternal seroconversion. New approaches, such as chorionic villus sampling (CVS) and virome DNA, even if not yet validated as confirmation of fetal infection, have been studied alternatively to amniocentesis to reduce the time-interval from maternal seroconversion and the amniocentesis results. Risk stratification for sensorineural hearing loss (SNHL) and long-term sequelae should be provided according to the prognostic predictors. Nevertheless, in the era of valacyclovir, maternal high-dose therapy, mainly for first trimester infections, can reduce the risk of vertical transmission and increase the likelihood of asymptomatic newborns, but it is still unclear whether valacyclovir continues to exert a beneficial effect on fetuses with positive amniocentesis. This review provides updated evidence-based key counseling points with GRADE recommendations.

Effects of umbilical vein flow on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVES: To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. METHODS: This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (

Fetal brain development in pregnancies complicated by gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) carries an increased risk of neurocognitive impairment in offsprings. However, the contribution of maternal hyperglycemia in affecting fetal brain development is not fully elucidated yet. The aim of this study was to evaluate fetal brain and sulci development in pregnancies complicated by GDM. METHODS: Prospective observational study including 100 singleton pregnancies complicated by GDM and 100 matched controls. All fetuses underwent neurosonography at 29-34 weeks of gestation, including the assessment of the length of the corpus callosum (CC), cerebellar vermis (CV), Sylvian (SF), parieto-occipital (POF) and calcarine fissures (CF). Sub-group analysis according to the specific treatment regimen adopted (n 67 diet vs. 33 insulin therapy) was also performed. RESULTS: Fetuses from mothers with GDM under insulin therapy had a smaller CC (35.54 mm) compared to both controls (40 mm; p<0.001) and women with GDM under diet (39.26 mm; p=0.022) while there was no difference in the HC between the groups. Likewise, when corrected for HC, CV depth was smaller in fetuses with GDM both under insulin therapy (7.03 mm) and diet (7.05 mm,) compared to controls (7.36 mm; p=0.013). Finally, when assessing the sulci development of the brain SF (p≤0.0001), POF (p≤0.0001) and CF (p≤0.0001) were significantly smaller in fetuses with maternal GDM. Post-hoc analysis showed that fetuses of GDM mothers requiring insulin therapy had significantly lower values of SF (p=0.032), POF (p=0.016) and CF (p=0.001). CONCLUSIONS: Pregnancies complicated by GDM showed a peculiar pattern of fetal brain growth and cortical development and these changes, which are more evident in those requiring insulin supplementation.

Effects of gender on fetal cortical development: a secondary analysis of a prospective cross-sectional study.

OBJECTIVES: The primary objective was to evaluate the effects of fetal sex on fetal cortical development in low-risk pregnancies. Secondary objective was the evaluate the impact of gestational age. METHODS: This was a secondary analysis of a prospective cross-sectional study on low-risk fetuses undergoing fetal neurosonography between 19 and 34 weeks of gestation. The depth of Sylvian Fissure (SF), Parieto Occipital Fissure (POF) and Calcarine Fissure (CF) were evaluated and related to fetal sex. Neurosonographic variables were normalized for fetal head circumference and expressed as multiple of the median (MoM). RESULTS: A total of 344 fetuses were considered (173 male, 171 female). The baseline characteristic of the two groups were similar except a higher birthweight present in male fetuses (p=0.044). The depth SF (p=0.023) CF (p=0.014) and POF (p=0.046) showed significantly higher values in male fetuses when all the gestational age range was considered. However, when data were controlled for gestational age, these differences resulted significant only after 28 weeks. CONCLUSIONS: Differences in cortical development related to gender occur after 28 weeks of gestation with an increase depth of SF, POF and CF in male fetuses.

Ectrodactyly-ectodermal dysplasia-clefting syndrome. Prenatal prospective ultrasound diagnosis.

OBJECTIVE: Prenatal diagnosis of the Ectrodactyly-Ectodermal dysplasia-clefting (EEC) syndrome has been based upon the detection of ectrodactyly, in association with facial clefting and/or positive family history. Our aim is to describe other ultrasonographic features indicating the presuntive diagnosis, regardless of genetic diagnosis, especially in cases of negative family history. MATERIALS AND METHODS: A case report and a review of the literature was assessed. RESULTS: Our case report showed a singleton foetus "lobster claw" deformities of hands and feet. Paternal history revealed bilateral agenesia of two fingers. Through literature, 15 case reports of prenatal diagnosis of EEC syndrome were found, 14 of which were eligible for our systematic review. The 33% of cases (5/15) had a familiar history of EEC, thus, we found one case of consanguinity of parents. Anomalies EEC-related were recognized in the 40% of cases (6/15). An association with genitourinary anomalies was found in 30% (5/15) of them. CONCLUSIONS: A strong suspicion of final diagnosis of EEC may be done in the presence of ectrodactyly, facial clefting and urinary malformation especially in cases of negative family history. More attention should be given to a genetic counseling, especially to understand a possible relation to other genetic syndromes.

Modeling fetal cortical development by quantile regression for gestational age and head circumference: a prospective cross sectional study.

OBJECTIVES: To develop charts for fetal brain cortical structures following a proposed standardized methodology and using quantile regression. METHODS: Prospective cross-sectional study including 344 low-risk singleton pregnancies between 19 and 34 weeks of gestation. The depth of Sylvian (SF), Parieto-occipital (POF) and Calcarine fissures (CF) were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). RESULTS: The measurements of SF, POF and CF depth significantly increased with gestation. Linear models better described the changes of cortical variables with GA and HC. When the fit of sulci depth with GA and HC were compared, a close relationship was highlighted for the latter variable. CONCLUSIONS: We provided prospective charts of fetal cortical development using quantile regression and following a strict standardized methodology These new charts may help in better identifying cases at higher risk of abnormal cortical neurodevelopment.

Evaluation of an artificial intelligent algorithm (Heartassist™) to automatically assess the quality of second trimester cardiac views: a prospective study.

OBJECTIVES: The aim of this study was to evaluate the agreement between visual and automatic methods in assessing the adequacy of fetal cardiac views obtained during second trimester ultrasonographic examination. METHODS: In a prospective observational study frames of the four-chamber view left and right outflow tracts, and three-vessel trachea view were obtained from 120 consecutive singleton low-risk women undergoing second trimester ultrasound at 19-23 weeks of gestation. For each frame, the quality assessment was performed by an expert sonographer and by an artificial intelligence software (Heartassist™). The Cohen's κ coefficient was used to evaluate the agreement rates between both techniques. RESULTS: The number and percentage of images considered adequate visually by the expert or with Heartassist™ were similar with a percentage >87 % for all the cardiac views considered. The Cohen's κ coefficient values were for the four-chamber view 0.827 (95 % CI 0.662-0.992), 0.814 (95 % CI 0.638-0.990) for left ventricle outflow tract, 0.838 (95 % CI 0.683-0.992) and three vessel trachea view 0.866 (95 % CI 0.717-0.999), indicating a good agreement between the two techniques. CONCLUSIONS: Heartassist™ allows to obtain the automatic evaluation of fetal cardiac views, reached the same accuracy of expert visual assessment and has the potential to be applied in the evaluation of fetal heart during second trimester ultrasonographic screening of fetal anomalies.

Expert ultrasonographic evaluation in fetuses with spina bifida: An essential prerequisite to select candidate to fetal surgery.

Suggested management flowchart in presence of a prenatal diagnosis of open spina bifida.

Fetal brain biometry and cortical development after maternal SARS-CoV-2 infection in pregnancy: A prospective case-control study.

OBJECTIVES: To assess cerebral growth and the development of fetal cortex using neurosonography in fetuses from pregnancies experiencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) according to infection timing. METHODS: Pregnancies with by SARS-CoV-2 during first and second trimesters were prospectively studied and matched with unaffected controls. Enclosed women underwent neurosonography at 30-34 weeks of gestation and corpus callosum (CC) and cerebellar vermis (CV) lengths measured. Further Sylvian fissure (SF), insula. Parieto-occipital fissure (POF), and calcarine sulci fissures (CSF) depths were obtained. The ultrasonographic variables considered were normalized with fetal head size. RESULTS: One hundred and seventy four consecutive pregnancies experiencing SARS COV 2 infection (81 before 14 weeks and 93 later) and 131 not affected pregnancies were considered. General and pregnancy characteristics were similar between the three groups of women. No significant differences existed in CC and CV lengths across groups. Similarly, insula, SF, POF And CSF depth did not result changed in fetuses of affected mothers. CONCLUSIONS: SARS-CoV-2 infection does nor resulted associate with differential fetal cortical development or brain growth in mildly symptomatic pregnant women. This information may be useful to reassure infected mothers on the health of their fetuses.

Fetal brain biometry and cortical development in congenital heart disease: A prospective cross sectional study.

OBJECTIVE: To evaluate brain biometry and cortical development by neurosonography in fetuses with congenital heart defect (CHD) and evaluate differences among different type of CHD. METHODS: In a prospective cross sectional study singleton fetus with CHD were matched with controls and grouped into two categories according to the predicted severity of cerebral arterial oxygen deficit induced by the CHD: Group A mildly reduced or normal and Group B moderately to severely reduced. Neurosonography was done at 30-33 weeks to obtain measurements of corpus callosum (CC), cerebellar vermis (CV), Sylvian fissure (SF) insula, parieto-occipital fissure (POF), and calcarine sulci fissures (CSF). All the neurosonographic parameters were adjusted by head circumference (HC). RESULTS: A total of 78 fetuses with CHD (group A 30; group B 48) and 80 matched controls form uncomplicated pregnancies were considered. CHD fetuses have significantly smaller CC, CV, SF, and POF and bigger insula when compared to control fetuses. These differences are more marked in group B fetuses. These differences remained significant after correction for HC values. CONCLUSION: Fetuses with CHD have an impaired cortical development and these variations are more evident in those with a predicted lower oxygen delivery to the brain.

Which is the best time to perform balloon valvuloplasty in critically fetal aortic stenosis: Prenatally or after birth?

Fetal aortic valvuloplasty may prevent the progression of severe fetal aortic stenosis to hypoplastic left heart syndrome at birth. Since it is an high risk procedure a careful selection of fetuses that can benefit from the prenatal treatment instead of waiting for postnatal intervention.

Placental Volume and Uterine Artery Doppler in Pregnancy Following In Vitro Fertilization: A Comprehensive Literature Review.

The number of pregnancies achieved using in vitro fertilization (IVF) is rapidly increasing around the world. The chance of obtaining a successful pregnancy is also significantly improved due to technological advances and improvement in infertility treatment. Despite this success, there is evidence that pregnancy conceived by IVF has an increased risk of adverse maternal and perinatal outcome mainly represented by the development of hypertensive diseases, pre-eclampsia, and fetal growth restriction. Although different cofactors may play a role in the genesis of these diseases, the development of the placenta has a pivotal function in determining pregnancy outcomes. Advances in ultrasound technology already allows for evaluation in the first trimester, the impedance to flow in the uterine artery, and the placental volume using Doppler and three-dimensional techniques. This review article aims to describe the modification occurring in placental volume and hemodynamics after IVF and to summarize the differences present according to the type of IVF (fresh vs. frozen-thawed embryos).

Modeling Pulsatility Index nomograms from different maternal and fetal vessels by quantile regression at 24-40 weeks of gestation: a prospective cross-sectional study.

OBJECTIVE: Recent evidences highlight a considerable heterogeneity in the methodology of previously published studies reporting reference ranges for maternal and fetal Dopplers, which may have relevant implications in clinical practice. In view of these limitations, a standardized methodology to construct Doppler charts has been proposed. The aim of this study was to develop charts for pulsatility index (PI) of maternal and fetal Dopplers based upon the recently proposed standardized methodology and using quantile regression. METHODS: Prospective cross-sectional study including 2516 low-risk singleton pregnancies between 24 and 40 weeks of gestation. The mean uterine, umbilical (UA), middle cerebral (MCA) and their ratio (cerebroplacental ratio, CPR) centile values were established by quantile regression in the considered gestational interval. Interclass correlation coefficient (ICC) of each maternal and fetal vessel was also computed to assess the intra- and inter-observer agreement of the results. RESULTS: There was a good intra- and inter-observer agreement for each of the explored vessels (ICC >0.92 and >0.91 for a single and two observers, respectively). The 5th, 10th, 50th, 90th and 95th centiles of the reference range for gestation were constructed by quantile regression and compared to previously established reference charts. All the Doppler indices significantly changed with gestation. Second-degree polynomial regression models better described the changes with gestation in PCR and MCA PI values while a linear model better predicted the changes of other Doppler indices with advancing gestation. When compared to other studies reporting reference ranges for maternal and fetal Dopplers, the present charts showed similar median values but different distribution from the median. CONCLUSIONS: We provided prospective charts of maternal and fetal Dopplers based upon a previously proposed standardized methodology and using quantile regression. When compared to previously published studies, these new charts showed similar median values but different deviations from the median which may help in better differentiating cases at higher risk of placental insufficiency and adverse perinatal outcome.

Effect of SARS-CoV-2 infection on fetal umbilical vein flow and cardiac function: a prospective study.

OBJECTIVES: To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect umbilical vein blood flow (UVBF) and fetal cardiac function. METHODS: Prospective case-control study of consecutive pregnancies complicated by SARS-CoV-2 infection during the second half of pregnancy matched with unaffected women. Measurements of UVBF normalized for fetal abdominal circumference (UVBF/AC), atrial area (AA) and ventricular sphericity indices (SI) were compared between the two study groups. Chi-square and Mann-Whitney U tests were sued to analyze the data. RESULTS: Fifty-four consecutive pregnancies complicated and 108 not complicated by SARS-CoV-2 infection were included. The median gestational age at infection was 30.2 (interquartile range [IQR] 26.2 34.1). General baseline and pregnancy characteristics were similar between pregnant women with compared to those without SARS-CoV-2 infection. There was no difference in UVBF/AC (study groups z value -0.11 vs. 0.14 control p 0.751) values between pregnancies complicated compared to those not complicated by SARS-CoV-2 infection. Likewise, there was no difference in the left and right AA (left 1.30 vs. 1.28 p=0.221 and right 1.33 vs. 1.31 p=0.324) and SI (left 1.75 vs. 1.77 p=0.208 and right 1.51 vs. 1.54 p=0.121) between the two groups. CONCLUSIONS: SARS-CoV-2 infection does not affect UVBF and fetal cardiac function in uncomplicated pregnancies.

Modeling gestational age centiles for fetal umbilicocerebral ratio by quantile regression analysis: a secondary analysis of a prospective cross-sectional study.

OBJECTIVE: There is a lack of evidence on whether to favor cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) when assessing pregnancies at risk of fetal growth restriction. The Recent evidences highlight a significant heterogeneity in the methodology of previously published studies reporting reference ranges for Doppler indices, which may affect the clinical applicability of these charts. The aim of this study was to develop charts of UCR based upon a recently proposed standardized methodology and using quantile regression. METHODS: This was a secondary analysis of a prospective cross-sectional study including low-risk singleton pregnancies between 24 and 40 weeks of gestation undergoing Doppler recordings. The UCR centile values were established by quantile regression at different gestational age intervals. Quantile regression analysis was used to build the UCR chart. RESULT: 2516 low- risk singleton pregnancies were included in the analysis. UCR decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age are provided, as well as equations to allow calculation of any other percentile. CONCLUSIONS: We have established gestational age-specific normative centiles reference limits for UCR.

Sonoelastographic Assessment of the Uterine Cervix in the Prediction of Imminent Delivery in Singleton Nulliparous Women Near Term: A Prospective Cohort Study.

OBJECTIVES: To explore the role of newly developed software to assess cervical sonoelastography in predicting the onset of spontaneous delivery in singleton pregnancies at term and to compare its diagnostic performance with that provided by the cervical length (CL) and posterior cervical angle (PCA). METHODS: This work was a prospective study including nulliparous singleton pregnancies at gestational ages of 37 weeks to 38 weeks 6 days. The CL, PCA, hardness ratio (HR), and mean strain from the internal os and external os were obtained by a transvaginal ultrasound approach using semiautomatic software (E-Cervix; Samsung Medison Co, Ltd, Seoul, Korea). Multivariate logistic regression and area under the curve analyses were used to test the strength of the association and the diagnostic performance of the variables considered in predicting delivery within 7 days. RESULTS: A total of 398 women were included, and 24.6% delivered within 7 days. The CL was shorter (19.5 versus 2 7 mm; P = .0001), PCA narrower (99° versus 102°; P = .02) HR lower (35.3 versus 40.7; P = .0001), mean strain from the external os higher (0.41 versus 0.35; P = .0001), and mean strain from the internal os higher (0.38 versus 0.33; P = .0001) higher in women who delivered within 7 days from the assessment. At the multivariable logistic regression analysis, the CL (adjusted odds ratio, 1.307) and HR (adjusted odds ratio, 1.227) were the only variables independently associated with delivery within 1 week. A model combining the CL and HR showed an area under the curve of 0.873 in predicting delivery within 7 days, higher than that obtained by using the CL and HR singularly (P ≤ .0001). CONCLUSIONS: The HR assessed by sonoelastography improves the efficacy of the CL in predicting imminent delivery in nulliparous women close to term.

Fetal Cardiac Remodeling Is Affected by the Type of Embryo Transfer in Pregnancies Conceived by in vitro Fertilization: A Prospective Cohort Study.

OBJECTIVE: Pregnancies conceived via intracytoplasmic sperm injection (ICSI) are associated with a higher risk of fetal cardiac remodeling. The aim of this study was to evaluate whether the type of embryo transfer may affect the magnitude of fetal cardiac remodeling in pregnancies conceived via ICSI. METHODS: Prospective cross-sectional study including 212 pregnancies conceived by ICSI (111 with frozen and 101 with fresh embryos) and 120 spontaneously conceived gestations. All women underwent ultrasound biometric evaluation, Doppler, and echocardiographic assessment, including evaluation of left and right atrial areas and sphericity index (SI), at 20-24 weeks of gestation. The χ2 and Kruskal-Wallis H tests were used to analyze the data. RESULTS: There was no difference in maternal characteristics, gestational age at ultrasound, Doppler, and fetal weight among the study groups. In pregnancies conceived by ICSI, left and right atrial areas were higher (p < 0.0001) and SI was lower (p < 0.0001) compared to spontaneously conceived pregnancies. Left (p = 0.004) and right (p = 0.023) atrial areas and left (p = 0.036) and right (p = 0.002) SIs were more affected in ICSI pregnancies conceived by fresh embryos. CONCLUSION: The risk of fetal cardiac remodeling is higher in pregnancies conceived by ICSI and independent from fetal size and Doppler. The magnitude of these changes is affected by the type of ICSI technique and is higher in pregnancies conceived by fresh embryos.

5D CNS+ Software for Automatically Imaging Axial, Sagittal, and Coronal Planes of Normal and Abnormal Second-Trimester Fetal Brains.

The purpose of this study was to test new 5D CNS+ software (Samsung Medison Co, Ltd, Seoul, Korea), which is designed to image axial, sagittal, and coronal planes of the fetal brain from volumes obtained by 3-dimensional sonography. The study consisted of 2 different steps. First in a prospective study, 3-dimensional fetal brain volumes were acquired in 183 normal consecutive singleton pregnancies undergoing routine sonographic examinations at 18 to 24 weeks' gestation. The 5D CNS+ software was applied, and the percentage of adequate visualization of brain diagnostic planes was evaluated by 2 independent observers. In the second step, the software was also tested in 22 fetuses with cerebral anomalies. In 180 of 183 fetuses (98.4%), 5D CNS+ successfully reconstructed all of the diagnostic planes. Using the software on healthy fetuses, the observers acknowledged the presence of diagnostic images with visualization rates ranging from 97.7% to 99.4% for axial planes, 94.4% to 97.7% for sagittal planes, and 92.2% to 97.2% for coronal planes. The Cohen κ coefficient was analyzed to evaluate the agreement rates between the observers and resulted in values of 0.96 or greater for axial planes, 0.90 or greater for sagittal planes, and 0.89 or greater for coronal planes. All 22 fetuses with brain anomalies were identified among a series that also included healthy fetuses, and in 21 of the 22 cases, a correct diagnosis was made. 5D CNS+ was efficient in successfully imaging standard axial, sagittal, and coronal planes of the fetal brain. This approach may simplify the examination of the fetal central nervous system and reduce operator dependency.