Magnetic resonance imaging of intracranial anomalies in pregnancies complicated by twin anemia-polycythemia sequence.

PURPOSE: To describe fetal brain Magnetic Resonance Imaging (MRI) findings in a large series of monochorionic (MC) pregnancies complicated by Twin Anemia-Polycythemia Sequence (TAPS) prenatally diagnosed, so to characterize the potential intracranial complications associated with this condition, their frequency and potential treatment options. METHODS: This is a retrospective study of MC twin pregnancies complicated by TAPS and undergone fetal MRI in a single institution from 2006 to 2023. MRI control was performed and post-natal ultrasound (US) or MRI were available. RESULTS: 1250 MC pregnancies were evaluated in our institution. 50 pregnancies (4%) were diagnosed with TAPS, 29 underwent a fetal brain MRI. 13/29 pregnancies (44.8%) demonstrated brain findings at MRI in at least a twin. Neuroradiological findings were detected in 14/57 twins (24.6%). We detected four main categories of findings: hemorrhagic lesions, T2-weighted white-matter hyperintensities (WMH), brain edema-swelling and venous congestion. Nineteen findings were present in the anemic and three in the polycythemic twins, with a statistically significant ratio between the two groups (p-value = 0.01). Intrauterine MRI follow-up demonstrated the sequalae of hemorrhagic lesions. A complete regression of brain swelling, veins prominence and T2-WMHs was demonstrated after treatment. Postnatal imaging confirmed prenatal features. CONCLUSIONS: Our work demonstrates that TAPS-related MRI anomalies consisted in edematous/hemorrhagic lesions that occur mostly in anemic rather than in polycythemic twins. Fetoscopic laser surgery could have a potential decongestant role. Therefore, prenatal MRI may help in counselling and management in TAPS pregnancies, especially for the planning of therapy and the monitoring of its efficacy.

Amnioreduction for Polyhydramnios in a Consecutive Series at a Single Center: Indications, Risks and Perinatal Outcomes.

Pregnancies complicated by severe polyhydramnios are associated with a high rate of underlying fetal anomaly. Amnioreduction may be offered to alleviate maternal symptoms. This is a retrospective study of amnioreductions performed on singleton and twin gestations complicated by symptomatic polyhydramnios between 2010 and 2023 at our tertiary referral center. The indications, procedural techniques and pregnancy and neonatal outcomes were retrieved from an archive database and reviewed with the use of the maternal and child medical record chart, the hospital electronic clinical discharge report and telephone recalls. Our study comprised 86 pregnancies, 65 singletons and 21 twin pregnancies. Fetal anomalies were identified in 79% of cases, mainly gastrointestinal obstructive anomalies; 9.3% of cases were idiopathic. The median gestational age at first amnioreduction was 32.5 weeks, and peri-procedural complications were rare (1 case of placental abruption and 2 cases of preterm delivery). The median gestational age at delivery was 36.5 weeks, with a median prolongation of the pregnancy from the time of first drain until birth of 30 days. Preterm labor < 37 weeks occurred in 48.8% of procedures, with 26.7% of patients delivering before 34 weeks and pPROM < 36 weeks recorded in 23.2% of cases. In conclusion, amnioreduction offered to alleviate maternal symptoms is a reasonably safe procedure with a low complication rate. These pregnancies necessitate management in a tertiary referral center because of their need for a multidisciplinary approach both prenatally and postnatally.

Fetal Myocarditis Associated With Maternal SARS-CoV-2 Infection.

We report the first case of significant fetal myocardial involvement associated with maternal SARS-CoV-2 infection, in which restoration of cardiac function at birth was noted. The demonstration of previous infection was supported by the quantification of humoral response in child and mother, in particular the presence of anti-N antibodies and through the detection of specific antibodies against the BA.4/5 variant.

Maternal hemodynamic evaluation in monochorionic twin pregnancy complicated by twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.

BACKGROUND: Maternal cardiovascular adaptations are amplified in twin pregnancies to support the metabolic request of the feto-placental unit. Few studies have evaluated the maternal hemodynamics changes after routine use of laser surgery in the treatment of twin-twin transfusion syndrome. OBJECTIVE: The aim of our study was to evaluate hemodynamic changes in monochorionic twin pregnancies complicated by twin-twin transfusion syndrome before and after treatment with fetoscopic laser surgery. STUDY DESIGN: A prospective observational study from 2020 to 2022, included monochorionic twin pregnancies complicated with twin-twin transfusion syndrome undergoing laser surgery between 16 and 26 weeks of gestation. To assess placental function and perfusion, uterine artery pulsatility index, hemoglobin, hematocrit, and soluble fms-like tyrosine kinase-1/placental growth factor ratio sampling prelaser and 24 hours postlaser were measured. Echocardiography by a single cardiologist evaluated maternal hemodynamics at presurgery, 24 hours, and 1 week postlaser. Those data were crosswise compared with cardiovascular indices of uncomplicated monochorionic pregnancies recruited at the same gestational age using nonparametric tests. Moreover, we fitted random-intercept linear regression models to investigate maternal hemodynamic changes according to the amount of amniotic fluid drained during laser surgery. RESULTS: Forty-two twin-twin transfusion syndrome pregnancies with a median gestational age of 19.1 (17.4-20.9) weeks and 15 uncomplicated monochorionic pregnancies at the same gestational age were enrolled. Overall survival rate after laser was 72% with delivery at a median gestational age of 31.5 (27-34) weeks. Significant changes in blood chemistry and placental function were observed in the twin-twin transfusion syndrome group, along with alterations in arterial pressure, heart rate, cardiac output, and ventricular strain, eventually aligning with the uncomplicated group's values by 1 week postlaser. The amount of amniodrainage, with a 1000 ml cut-off, did not significantly impact hemodynamic parameters. Lastly, we detected a percentage of laser surgery complications in agreement with international literature and we did not record any maternal procedure-related problems. CONCLUSION: Our analysis highlighted that maternal cardiovascular status in monochorionic twin pregnancy complicated by twin-twin transfusion syndrome was more dynamic and; 1 week after fetoscopic laser ablation of placental anastomosis completed by amniodrainage, maternal hemodynamic parameters restored to values similar to uncomplicated monochorionic twin pregnancies.

The "cortical invagination sign": a midtrimester sonographic marker of unilateral cortical focal dysgyria in fetuses with complete agenesis of the corpus callosum.

BACKGROUND: Agenesis of the corpus callosum is associated with several malformations of cortical development. Recently, features of focal cortical dysgyria have been described in fetuses with agenesis of the corpus callosum. OBJECTIVE: This study aimed to describe the "cortical invagination sign," a specific sonographic feature of focal cortical dysgyria, which is consistently seen at midtrimester axial brain ultrasound in fetuses with complete agenesis of the corpus callosum. STUDY DESIGN: This was a retrospective analysis of prospectively collected data from 2018 to 2021, including patients referred to 5 fetal medicine centers in the second trimester of pregnancy (19 0/7 to 22 0/7 weeks of gestation) with suspected complete agenesis of the corpus callosum. All cases with the diagnosis of complete agenesis of the corpus callosum were submitted to an axial sonographic assessment of the fetal brain on the transventricular plane. In this scanning section, the mesial profile of both cerebral hemispheres at the level of the frontal-parietal cortex was investigated. In this area, the operator looked for an abnormal invagination of the cortical surface along the widened interhemispheric fissure, which was referred to as the "cortical invagination sign." All fetuses were submitted to dedicated antenatal magnetic resonance imaging to reassess the ultrasound findings. Cases with additional brain anomalies, which did not involve the cortex, were excluded. The final diagnosis was confirmed at postnatal brain magnetic resonance imaging or postmortem examination, for cases undergoing termination of pregnancy. The primary outcome of this study was to evaluate the presence and laterality of the "cortical invagination sign" in fetuses with complete agenesis of the corpus callosum at antenatal ultrasound and magnetic resonance imaging. RESULTS: During the study period, 64 cases of complete agenesis of the corpus callosum were included; of those cases, 50 (78.1%) resulted in termination of pregnancy, and 14 (21.9%) resulted in a live birth. The "cortical invagination sign" was detected at ultrasound in 13 of 64 cases (20.3%) and at targeted brain magnetic resonance imaging in 2 additional cases (23.4%), all of which were electively terminated. Moreover, the "cortical invagination sign" was found to be exclusively unilateral and on the left cerebral hemisphere in all the cases. There was a predominant number, although nonsignificant, of male fetuses (80.0% of cases; P=.06) in the group of complete agenesis of the corpus callosum with the "cortical invagination sign." CONCLUSION: The "cortical invagination sign" is a specific marker of focal cortical dysgyria, which seems to characterize at midtrimester of pregnancy in a large group of fetuses with complete agenesis of the corpus callosum. The etiology, pathophysiology, and prognostic significance of this finding remain to be elucidated.

Long-Term Postnatal Follow-Up in Monochorionic TTTS Twin Pregnancies Treated with Fetoscopic Laser Surgery and Complicated by Right Ventricular Outflow Tract Anomalies.

Right ventricular outflow tract anomalies (RVOTAs), such as pulmonary stenosis (PS), pulmonary atresia (PA), and pulmonary insufficiency (PI), are typical cardiac anomalies in monochorionic twins, and they are complicated by twin-to-twin transfusion syndrome (TTTS). The aim of this study was to conduct a long-term postnatal cardiological evaluation of prenatal RVOTAs in monochorionic diamniotic twin pregnancies complicated by TTTS and treated with fetoscopic laser surgery (FLS) and to analyze possible prenatal predictors of congenital heart disease (CHD). Prenatal RVOTAs were retrospectively retrieved from all TTTS cases treated with FLS in our unit between 2009 and 2019. Twenty-eight prenatal cases of RVOTAs (16 PI, 10 PS, 2 PA) were observed out of 335 cases of TTTS. Four cases did not reach the postnatal period. CHD was present in 17 of the remaining 24 cases (70.8%), with 10 being severe (58.8%; 10/17); nine cases of PS required balloon valvuloplasty, and one case required biventricular non-compaction cardiomyopathy. The risk of major CHD increased with prenatal evidence of PS and decreased with the gestational age at the time of TTTS and with the prenatal normalization of blood flow across the pulmonary valve. Despite treatment with FLS, the majority of monochorionic diamniotic twin pregnancies complicated by TTTS with prenatal RVOTAs had CHD at long-term follow-up.

Fetal oxygen and glucose utilization of uncomplicated monochorionic twins: Adapting to the intrauterine environment.

INTRODUCTION: Monochorionic twins (MC) develop under unique intrauterine conditions and show a high risk of compromise during fetal life. Here we describe umbilical vein blood flow (UVBF) and fetal oxygen and glucose utilization in uncomplicated MC twins and investigate possible differences within twin-pairs according to birth-order. METHODS: Prospective single-center study on 48 uncomplicated MC twins enrolled at the time of elective cesarean delivery. Ultrasound measurements of UVBF for Twin 1 and Twin 2 labelled according to birth-order were performed before spinal anesthesia. Umbilical arterial and venous blood samples were collected for each twin after fetal delivery, and fetal oxygen and glucose deliveries and uptakes were computed. RESULTS: All twins were delivered within 2 min from one-another under steady-state conditions at 36.4 weeks of median gestational age (IQR 36.0-37.0). Birthweight and umbilical cord gas analyses were within physiological ranges for all twins. Second-born twins showed significantly lower UVBF, measured before delivery, and lower median birthweight compared to first-borns. Moreover, median values of estimated fetal oxygen and glucose consumption were lower in second compared to first MC twins. DISCUSSION: Uncomplicated MC twins show different birthweight, oxygenation and metabolic rates based on their position in utero, hinting at pre-existing conditions possibly deriving by uneven vascular and metabolic distribution of the two placental territories. The innovative findings of this study emphasize the biological uniqueness of these pregnancies and prompt further physiological studies on MC twins and placenta metabolism.

Fetal Hydrothorax Treated with Pleuro-Amniotic Shunting: Fetal and Maternal Complications and Long-Term Outcomes.

INTRODUCTION: We aimed to identify maternal and fetal complications and investigate postnatal and long-term outcomes of fetal hydrothorax (FHT) treated with pleuro-amniotic shunting (shunt). METHODS: Single-center retrospective observational cohort of shunt cases performed from 2000 to 2021. Risk factors for maternal complications, fetal demise, neonatal death (NND), and postnatal outcomes were identified. RESULTS: Out of 88 cases, 70 (79.5%) were complicated by hydrops, with an average gestational age (GA) at diagnosis of 27 weeks (range 16-34). In 16 cases, definitive etiology of FHT was identified; five cases of Noonan syndrome and three cases of monogenic disorders diagnosed by whole-exome sequencing (EPHB4, VEGFR3, RASA1). Shunt was performed at an average GA of 28 weeks (20-34), with a dislodgement in 10 cases (11.4%). Maternal: Complications occurred in three cases; survival rate was 76.1% (67/88). Follow-up data were available for 57/67 (85.1%) children. Incidence of severe neurodevelopmental impairment and pneumopathy (broncho dysplasia, persistent pulmonary hypertension of newborn, and asthma) was 5.3% and 8.8%, respectively. Post-treatment persistence of hydrops, FHT associated with genetic syndromes, and GA at birth were risk factors for fetal demise, NND, and postnatal complications. CONCLUSION: In truly isolated FHT, whenever indicated, pleuro-amniotic shunting is a safe procedure associated with good survival rate and long-term outcome.

TSEN54 Gene-Related Pontocerebellar-Hypoplasia and Role of Prenatal MR Imaging: Besides the Common Posterior Fossa Cystic Malformations.

Pontocerebellar-hypoplasia (PCH) related to TSEN54-gene mutation, a rare autosomal recessive disorder, can be associated with three different phenotypes: PCH2A, PCH4 and PCH5. Prenatal imaging features are very scant, in particular for PCH4 and PCH5. The aim of this letter is to illustrate key role of prenatal MR imaging in better evaluation of the cerebellar vermis-hemispheres and pons, which may lead to the differential diagnosis between three PCH TSEN54-related phenotypes already at mid-gestation based on the pattern of the degree of involvement of the vermis and the cerebellar cortex respectively.

Cerebro-placental and umbilico-cerebral ratios in uncomplicated monochorionic twins: Longitudinal references and comparison with singletons.

OBJECTIVES: Monochorionic twins (MC) are at high risk of adverse outcomes and Doppler investigation of umbilical and cerebral flows is mandatory for their surveillance. The cerebro-placental (CPR) and umbilico-cerebral (UCR) ratios are considered non-invasive measures of fetal adaptation to hypoxemia. We aimed to provide longitudinal references for CPR and UCR from 16 to 37 weeks of gestation that are specific for MC twins, and compare these with singleton charts. METHODS: Longitudinal study of a cohort of consecutive uncomplicated MC twin pregnancies monitored at our unit from 2010 to 2018. The estimated centile curves were obtained estimating the median with fractional polynomials by a multilevel model and the external centiles through the residuals. The comparison with singletons references was made through graphic evaluation. RESULTS: One-hundred-fifty-two MC pregnancies were included with a median of 10 longitudinal ultrasounds each. References for CPR and UCR in function of gestational age are presented. Compared to singletons, MC twins showed an earlier and greater circulatory redistribution with lower CPR and higher UCR median values. CONCLUSIONS: MC twin-specific references for CPR and UCR suitable for serial monitoring are presented. The comparison with singleton references demonstrates substantial differences in the hemodynamic balance that must be considered when interpreting findings in MC twins.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

Severe Fetal Symptomatic Infection from Human Cytomegalovirus following Nonprimary Maternal Infection: Report of Two Cases.

INTRODUCTION: Human cytomegalovirus (HCMV) is the most common congenital infection, especially severe after a maternal primary infection; sequelae in neonates born to mothers experiencing a nonprimary infection have been already reported. Hereby, two cases of severe fetal HCMV disease in seroimmune gravidas referred to our Unit are described. CASES PRESENTATION: Case 1: A fetus at 21 weeks' gestation with signs of anemia and brain abnormalities at ultrasound, described at magnetic resonance (MR) imaging as ependymal irregularity and bilateral asymmetric parenchymal thinning; amniotic fluid sample was positive for HCMV although the woman had a previous immunity; after termination of pregnancy, autopsy demonstrated a thicken layer of disorganized neurons on the right cortical plate, while on the left, there was a morphological pattern coherent with polymicrogyria. Case 2: A fetus at 20 weeks' gestation with anemia, moderate atrioventricular insufficiency, hepatosplenomegaly but no major cerebral lesions. Fetal blood was positive for HCMV, although unexpected for prepregnancy maternal immunity, and intrauterine transfusion was needed. A cesarean section at 34 weeks' gestation was performed due to worsening condition of the fetus, who had a birthweight of 2,210 g and needed platelet transfusions, but MR examination and clinical evaluation were normal. CONCLUSION: The impact of nonprimary maternal infection on pregnancy outcome is unknown and fetal brain damage in HCMV seroimmune transmitter-mothers can occur as a consequence of maternal reinfection or reactivation for a hypotetic different role of HCMV-primed CD4+ or CD8+ T-cells in fetal brain, with progressive brain lesions coexistent in the first case and with severe unexpected anemia in the second case. A previous maternal HCMV immunity should not exempt to test anemic fetuses for such infection, nor to consider a potential transplacental transmission.

Prenatal Diagnosis and Neurodevelopmental Outcome in Isolated Cerebellar Hypoplasia of Suspected Hemorrhagic Etiology: a Retrospective Cohort Study.

Data about the neurological prognosis of isolated cerebellar hypoplasia in utero are scant and inconsistent. In this monocentric retrospective study, we describe the neurodevelopmental outcomes in a series of children with isolated cerebellar hypoplasia of presumably hemorrhagic origin prenatally detected with fetal magnetic resonance imaging (fMRI). We retrospectively reviewed the charts of all the pregnant women who were referred for a neurological consultation, diagnosed with fetal encephalic malformation/disruption between 2010 and 2020 in the Fetal Therapy Unit of our institution. Fetal MRI (fMRI) was performed in all the pregnancies. Fetuses with cerebellar hypoplasia presumably of hemorrhagic origin were selected for the study. Fetuses exposed to alcohol or with additional malformations in other cerebral or body areas were excluded. All the infants received the postpartum follow-up care adopted in our center, including post-natal MRI, serial neurological examinations, standardized neurodevelopmental tests, and regular parental interviews. Cognitive functions were tested with GRIFFITHS II, WPPSI-III, and WISC-IV according to the child's age. A total of 14 pregnant women out of 479 fetal consultations were eligible and included in the study group. In 57% of cases, the etiology of the hemorrhage was unknown. In 21% of cases, it was attributed to a blood transfusion, while in the remaining ones, it was attributed to maternal predisposing factors. Among the survivors, two infants were excluded for prematurity, and two were lost to follow-up. Ten patients were thus included in the study. Six patients had normal neurodevelopment and cognition, and three presented mild-moderate neurological signs, i.e., mild dyspraxia and visuoperceptual impairment. Only one child had a severe outcome, i.e., autism spectrum disorder. The cerebellum is particularly vulnerable to disruptions throughout its prolonged development. Extreme caution must be used in prenatal counseling considering that in the acute phase, lesion extension and vermis involvement can be overestimated with fMRI. In cases of uncertainty, performing an additional fMRI could be advisable after 4-8 weeks. However, in our series, infants with isolated cerebellar hypoplasia tended to have a favorable prognosis. Nevertheless, a long-term follow-up is needed and should include a postnatal brain MRI, serial neurological examinations, and neurodevelopmental tests at least up to school age.

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 (

Right ventricular outflow tract abnormalities in monochorionic twin pregnancies without twin-to-twin transfusion syndrome: Prenatal course and postnatal long-term outcomes.

OBJECTIVES: Right ventricular outflow tract abnormalities (RVOTA) have been mostly reported in recipient twins (RT) of monochorionic/diamniotic (MC/DA) twin pregnancies with twin-to-twin transfusion syndrome (TTTS). Aim of the study was to describe RVOTA detected in MC/DA pregnancies without TTTS. METHODS: Cases of RVOTA were retrieved from our database among all MC/DA pregnancies without TTTS from 2009 to 2018. RESULTS: Out of 891 MC/DA twin pregnancies without TTTS, 14 (1.6%) were associated with RVOTA: 10 pulmonary stenosis (PS), one steno-insufficiency, one insufficiency and two atresia (PA). In 93% of cases (13/14), pregnancy was complicated either by amniotic fluid discrepancy (AFD) or by TAPS or mostly by selective fetal growth restriction (sFGR) (11/13: 85%), involving predominantly (10/11: 91%) the large twin, with high incidence (9/11: 82%) of sFGR and AFD coexistence. Eight out of 14 (57%) survived after the perinatal period (7 PS, 1 PA). Five (62%) underwent pulmonary balloon valvuloplasty, whereas 3 children still showed persistent mild PS at cardiac follow up after 1 year of life. CONCLUSIONS: RVOTA can occur in MC/DA pregnancies without TTTS, particularly when other complications coexist. In complicated cases specialized fetal echocardiographic evaluation is recommended during pregnancy; RVOTA cases should be delivered in a tertiary level center, where cardiologists are available.

A closer look at discordant placental echogenicity: two cases under the microscope.

Discordant placental echogenicity is observed in MC pregnancies complicated with twin anemia-polycythemia sequence, but could also belong to complicated singleton gestation.

Fetal thick corpus callosum: new insights from neuroimaging and neuropathology in two cases and literature review.

PURPOSE: To describe the correlation between fetal imaging (in vivo and ex vivo) and neuropathology in two fetuses at early gestational age (GA) with isolated thick corpus callosum (CC), a rare finding whose pathological significance and neuropathology data are scarce. METHODS: Two fetuses at 21-week GA underwent fetal MRI (fMRI) for suspected callosal anomalies at ultrasound (US). After fMRI results, termination of pregnancy (TOP) was carried out and post-mortem MRI (pmMRI) was performed. Neuropathology correlation consisted in macro and microscopic evaluation with sections prepared for hematoxylin-eosin and immunohistochemistry staining. RESULTS: Fetal imaging confirmed in both cases the presence of a shorter and thicker CC with respect to the reference standard at the same GA, without a clear distinction between its different parts. Moreover, on pmMRI, an abnormal slightly T2-weighted hyperintense layer along the superior and inferior surface of CC was noted in both cases. At histopathology, these findings corresponded to an increased amount of white matter tracts but also to an abnormal representation of embryological structures that contribute to CC development, naming induseum griseum (IG) and the glioepithelial layer (GL) of the "callosal sling." After reviewing the literature data, we confirmed the recent embryological theory regarding the CC development and provide new insights into the pathophysiology of the abnormal cases. CONCLUSIONS: An abnormally thick CC at the early fetal period could be associated to an abnormal representation of the midline glia structures, so to result in potential disturbance of the axon guidance mechanism of callosal formation and eventually in CC dysgenesis.

Recommendations for neonatologists and pediatricians working in first level birthing centers on the first communication of genetic disease and malformation syndrome diagnosis: consensus issued by 6 Italian scientific societies and 4 parents' associations.

BACKGROUND: Genetic diseases are chronic conditions with relevant impact on the lives of patients and their families. In USA and Europe it is estimated a prevalence of 60 million affected subjects, 75% of whom are in developmental age. A significant number of newborns are admitted in the Neonatal Intensive Care Units (NICU) for reasons different from prematurity, although the prevalence of those with genetic diseases is unknown. It is, then, common for the neonatologist to start a diagnostic process on suspicion of a genetic disease or malformation syndrome, or to make and communicate these diagnoses. Many surveys showed that the degree of parental satisfaction with the methods of communication of diagnosis is low. Poor communication may have short and long-term negative effects on health and psychological and social development of the child and his family. We draw up recommendations on this issue, shared by 6 Italian Scientific Societies and 4 Parents' Associations, aimed at making the neonatologist's task easier at the difficult time of communication to parents of a genetic disease/malformation syndrome diagnosis for their child. METHODS: We used the method of the consensus paper. A multidisciplinary panel of experts was first established, based on the clinical and scientific sharing of the thematic area of present recommendations. They were suggested by the Boards of the six Scientific Societies that joined the initiative: Italian Societies of Pediatrics, Neonatology, Human Genetics, Perinatal Medicine, Obstetric and Gynecological Ultrasound and Biophysical Methodologies, and Pediatric Genetic Diseases and Congenital Disabilities. To obtain a deeper and global vision of the communication process, and to reach a better clinical management of patients and their families, representatives of four Parents' Associations were also recruited: Italian Association of Down People, Cornelia de Lange National Volunteer Association, Italian Federation of Rare Diseases, and Williams Syndrome People Association. They worked from September 2019 to November 2020 to achieve a consensus on the recommendations for the communication of a new diagnosis of genetic disease. RESULTS: The consensus of experts drafted a final document defining the recommendations, for the neonatologist and/or the pediatrician working in a fist level birthing center, on the first communication of genetic disease or malformation syndrome diagnosis. Although there is no universal communication technique to make the informative process effective, we tried to identify a few relevant strategic principles that the neonatologist/pediatrician may use in the relationship with the family. We also summarized basic principles and significant aspects relating to the modalities of interaction with families in a table, in order to create an easy tool for the neonatologist to be applied in the daily care practice. We finally obtained an intersociety document, now published on the websites of the Scientific Societies involved. CONCLUSIONS: The neonatologist/pediatrician is often the first to observe complex syndromic pictures, not always identified before birth, although today more frequently prenatally diagnosed. It is necessary for him to know the aspects of genetic diseases related to communication and bioethics, as well as the biological and clinical ones, which together outline the cornerstones of the multidisciplinary care of these patients. This consensus provide practical recommendations on how to make the first communication of a genetic disease /malformation syndrome diagnosis. The proposed goal is to make easier the informative process, and to implement the best practices in the relationship with the family. A better doctor-patient/family interaction may improve health outcomes of the child and his family, as well as reduce legal disputes with parents and the phenomenon of defensive medicine.

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.