Is Fetal Hydrops in Turner Syndrome a Risk Factor for the Development of Maternal Mirror Syndrome?

Mirror syndrome is a rare and serious maternal condition associated with immune and non-immune fetal hydrops after 16 weeks of gestational age. Subjacent conditions associated with fetal hydrops may carry different risks for Mirror syndrome. Fetuses with Turner syndrome are frequently found to be hydropic on ultrasound. We designed a retrospective multicenter study to evaluate the risk for Mirror syndrome among pregnancies complicated with Turner syndrome and fetal hydrops. Data were extracted from a questionnaire sent to specialists in maternal fetal medicine in Germany. Out of 758 cases, 138 fulfilled our inclusion criteria and were included in the analysis. Of the included 138, 66 presented with persisting hydrops at or after 16 weeks. The frequency of placental hydrops/placentomegaly was rather low (8.1%). Of note, no Mirror syndrome was observed in our study cohort. We propose that the risk of this pregnancy complication varies according to the subjacent cause of fetal hydrops. In Turner syndrome, the risk for Mirror syndrome is lower than that reported in the literature. Our observations are relevant for clinical management and parental counseling.

SIMPSON-GOLABI-BEHMEL syndrome type 1: How placental immunohistochemistry can rapidly Predict the diagnosis.

INTRODUCTION: Glypican-3 (GPC3) is an oncofetal protein involved in cellular signaling, strongly expressed in the placenta, absent or diminished in postnatal life, but often increased in human malignancies. Germline loss-of-function variants of GPC3 gene are associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1), a rare recessive X-linked overgrowth disease characterized by typical facial features, congenital abnormalities, and an increased risk of developing childhood cancers. METHODS: A clinical suspicion of SGBS1 was postulated for a newborn with prenatal history of overgrowth and polyhydramnios, presenting with neonatal weight and length >99th percentile, coarse facies, iris and retinal coloboma, supernumerary nipples, and splenomegaly. While waiting for whole-genome sequencing (WGS) results, we investigated placental GPC3 immunohistochemical expression in the proband, in three additional cases of SGBS1, and disorders commonly associated with fetal macrosomia and/or placentomegaly. RESULTS: WGS in the proband identified a likely pathogenic maternally inherited missense variant in GPC3: c.1645A > G, (p.Ile549Val), and GPC3 immunohistochemistry demonstrated full-thickness loss of stain of the placental parenchyma. The same pattern ("null") was also present in the placentas of three additional cases of SGBS1, but not in those of unaffected controls. DISCUSSION: Immunohistochemical expression of GPC3 in the placenta is highly reproducible. Our findings showed that a "null pattern" of staining is predictive of SGBS1 and represents a valuable aid in the differential diagnosis of fetal macrosomias, allowing targeted genetic testing and earlier diagnosis.

Insights into the role of placenta thickness as a predictive marker of perinatal outcome.

The placenta is a transitory organ indispensable for normal fetal maturation and growth. Recognition of abnormal placental variants is important in clinical practice, and a broader understanding of the significance of placental variants would help clinicians better manage affected pregnancies. Increased thickness of the placenta is reported to be a nonspecific finding but it is associated with many maternal and fetal abnormalities, including preeclampsia and abnormal fetal growth. In this review, we address the questions regarding the characteristics of placenta thickness and the relationship between thickened placenta and poor pregnancy outcomes.

Placental infection by Zika virus in French Guiana.

OBJECTIVES: To describe placental findings on prenatal ultrasound and anatomopathological examination in women with Zika virus (ZIKV) infection, and to assess their association with congenital ZIKV infection and severe adverse outcome, defined as fetal loss or congenital Zika syndrome (CZS). METHODS: This was a prospective study of pregnancies undergoing testing for maternal ZIKV infection at a center in French Guiana during the ZIKV epidemic. In ZIKV-positive women, congenital infection was defined as either a positive reverse transcription polymerase chain reaction result or identification of ZIKV-specific immunoglobulin-M in at least one placental, fetal or neonatal sample. Placental ZIKV-infection status was classified as non-exposed (placentae from non-infected women), exposed (placentae from ZIKV-infected women without congenital infection) or infected (placentae from ZIKV-infected women with proven congenital infection). Placentae were assessed by monthly prenatal ultrasound examinations, measuring placental thickness and umbilical artery Doppler parameters, and by anatomopathological examination after live birth or intrauterine death in women with ZIKV infection. The association of placental thickness during pregnancy and anatomopathological findings with the ZIKV status of the placenta was assessed. The association between placental findings and severe adverse outcome (CZS or fetal loss) in the infected group was also assessed. RESULTS: Among 291 fetuses/neonates/placentae from women with proven ZIKV infection, congenital infection was confirmed in 76 cases, of which 16 resulted in CZS and 11 resulted in fetal loss. The 215 remaining placentae from ZIKV-positive women without evidence of congenital ZIKV infection represented the exposed group. A total of 334 placentae from ZIKV-negative pregnant women represented the non-exposed control group. Placentomegaly (placental thickness > 40 mm) was observed more frequently in infected placentae (39.5%) than in exposed placentae (17.2%) or controls (7.2%), even when adjusting for gestational age at diagnosis and comorbidities (adjusted hazard ratio (aHR), 2.02 (95% CI, 1.22-3.36) and aHR, 3.23 (95% CI, 1.86-5.61), respectively), and appeared earlier in infected placentae. In the infected group, placentomegaly was observed more frequently in cases of CZS (62.5%) or fetal loss (45.5%) than in those with asymptomatic congenital infection (30.6%) (aHR, 5.43 (95% CI, 2.17-13.56) and aHR, 4.95 (95% CI, 1.65-14.83), respectively). Abnormal umbilical artery Doppler was observed more frequently in cases of congenital infection resulting in fetal loss than in those with asymptomatic congenital infection (30.0% vs 6.1%; adjusted relative risk (aRR), 4.83 (95% CI, 1.09-20.64)). Infected placentae also exhibited a higher risk for any pathological anomaly than did exposed placentae (62.8% vs 21.6%; aRR, 2.60 (95% CI, 1.40-4.83)). CONCLUSIONS: Early placentomegaly may represent the first sign of congenital infection in ZIKV-infected women, and should prompt enhanced follow-up of these pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Proteomic analysis of Nrk gene-disrupted placental tissue cells explains physiological significance of NRK.

OBJECTIVE: NRK is a unique X chromosome-linked protein kinase expressed predominantly in placenta. The gene knockout causes placental overgrowth and delayed labor of Nrk-null fetuses from dams in mouse. To clarify unknown mechanisms behind the Nrk-null phenotypes, protein expression profiles were analyzed in the Nrk-null placenta using a high-performance two-dimensional electrophoresis methodology. RESULTS: Among around 1800 spots detected, we characterized a dozen protein spots whose expression levels were significantly altered in the Nrk-null placenta compared to wild-type. Analyzing these data sets is expected to reflect the difference physiologically in the presence or absence of NRK, facilitating the development of therapeutic strategies.

Massive subchorionic hematoma (Breus' mole) presents a variety of ultrasonic appearances: A case report and literature review.

Massive subchorionic hematoma (MSH) presents a variety of ultrasonic appearances. Placentomegaly with fetal growth restriction should be included as one of the differential diagnoses for intraplacental MSH. Care management of MSH requires to be tailored to each individual's responses while taking the NICU's capabilities and the patient's wishes into consideration.

Placental mesenchymal dysplasia: An underdiagnosed placental pathology with various clinical outcomes.

BACKGROUND: Placental mesenchymal dysplasia (PMD) is a rare vascular and connective placental anomaly, which is often associated with severe fetal and/or maternal complications. The diversity of presentation of PMD challenges diagnosis and effective pregnancy management. OBJECTIVE: We aimed to review cases presenting at 7 tertiary centers worldwide over the last decade and to study the occurrence of obstetric and neonatal complications. STUDY DESIGN: Pathology databases from 7 tertiary hospitals were screened for cases of PMD (between 2007-2017). Pregnancy history, outcomes and ultrasound images were then reviewed for each case. RESULTS: Twenty-two cases of PMD were identified. Mean gestational age at diagnosis was 23 weeks (16-39 weeks). Prenatal biochemical screening was abnormal in 8 cases (36%). Of the 12 cases that underwent invasive genetic testing, 4 were abnormal. Six patients (27%) developed maternal complications (preeclampsia/gestational hypertension). Fetal growth restriction was identified in 11 cases (50%) and fetal death in 4 (18%). Four (18%) pregnancies were terminated, 9/14 (64%) delivered preterm and only three (14%) progressed normally. Fourteen babies were born alive; 5 (35%) died in the first sixty-one days after birth, 5 (35%) had transient thrombopenia and 1 (7%) had developmental delay at last follow-up. Our series identified four potential new associations with PMD: placental triploidy mosaicism, CHARGE syndrome, fetal pleuropulmonary blastoma and fetal skeletal dysplasia. CONCLUSIONS: PMD was substantially under-diagnosed before delivery in this cohort. Sonographers, fetal medicine specialists, obstetricians and pathologists should all suspect PMD in cases of an enlarged placenta and should look for fetal abnormalities. Diagnostic genetic testing should be discussed to exclude partial molar pregnancy. Close pregnancy follow-up is indicated due to the high risk of associated fetal or maternal adverse outcomes.

Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a complex imprinting disorder involving fetal overgrowth and placentomegaly, and is associated with a variety of genetic and epigenetic mutations affecting the expression of imprinted genes on human chromosome 11p15.5. Most BWS cases are linked to loss of methylation at the imprint control region 2 (ICR2) within this domain, which in mice regulates the silencing of several maternally expressed imprinted genes. Modelling this disorder in mice is confounded by the unique embryonic requirement for Ascl2, which is imprinted in mice but not in humans. To overcome this issue, we generated a novel model combining a truncation of distal chromosome 7 allele (DelTel7) with transgenic rescue of Ascl2 expression. This novel model recapitulated placentomegaly associated with BWS, but did not lead to fetal overgrowth.

Non-Immune Hydrops Fetalis: Do Placentomegaly and Polyhydramnios Matter?

OBJECTIVES: Polyhydramnios and placentomegaly are commonly observed in nonimmune hydrops fetalis (NIHF); however, whether their ultrasonographic identification is relevant for prognosis is controversial. We evaluated outcomes of fetal or neonatal death and preterm birth (PTB) in cases of NIHF alone and in those with polyhydramnios and/or placentomegaly (P/PM). METHODS: We conducted a retrospective cohort of singletons with NIHF evaluated between 1994 and 2013. Nonimmune hydrops fetalis was defined as 2 or more abnormal fluid collections, including ascites, pericardial effusion, pleural effusion, and skin edema. Primary outcomes were intrauterine fetal demise (IUFD) and neonatal death. Secondary outcomes were PTB (<37, < 34, and <28 weeks) and spontaneous PTB. Outcomes were compared between cases of NIHF alone and NIHF with P/PM. RESULTS: A total of 153 cases were included; 21% (32 of 153) had NIHF alone, and 79% (121 of 153) had NIHF with P/PM. There was no significant difference in neonatal death (38.1% versus 43.0%; P = .809) between the groups. Intrauterine fetal demise was seen more frequently in NIHF alone (34.4% versus 17.4%; P = .049). Nonimmune hydrops fetalis-with-P/PM cases were more likely to deliver before 37 weeks (80.0% versus 57.1%; P = .045) and before 34 weeks (60.0% versus 28.6%; P = .015) and to have spontaneous PTB (64.4% versus 33.3%; P = .042). Adjusted odds ratios accounting for the etiology of NIHF supported these findings, with the exception of IUFD. CONCLUSIONS: Compared to NIHF alone, pregnancies with NIHF and P/PM had a lower risk of IUFD and were at increased risk of PTB (<37 and <34 weeks) and spontaneous PTB. This information may help providers in counseling patients with NIHF and supports the need for close antenatal surveillance.

Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review.

A partial molar pregnancy almost always ends in miscarriage due to a triploid fetus. We describe a rare case of a singleton, partial molar pregnancy with a seemingly huge placenta, which continued to delivery of a live-born diploid baby. A 27-year-old primigravida suffered from severe pre-eclampsia and progressive anemia. The uterus was enormously enlarged for the gestational age. A cesarean section was performed because of deterioration of maternal status at 25 weeks' gestation, when more than 3000 mL blood spouted concurrently with the delivery of the placenta. The histological examination showed congestion in the decidua, which indicated disturbance of maternal venous return from the intervillous space. The chromosome complement of the placenta and the neonate were 69,XXX and 46,XX, respectively. We also reviewed all published cases of a singleton, partial molar pregnancy. A literature search yielded 18 cases of a singleton, diploid fetus with partial molar pregnancy. The mean gestational age at delivery was 24.5 ± 6.2 weeks, and fetuses survived outside the uterus in only four cases (22.2%). Intriguingly, previous reports numbered 10 cases with diploid placenta as well as five cases with no karyotyping of the placenta, indicating that they may have included a complete mole in a twin pregnancy or placental mesenchymal dysplasia. In conclusion, this was the first case of placentomegaly that presented manifestations of excessive abdominal distension and maternal severe anemia, and the second case of a singleton, partial molar pregnancy confirmed by chromosome analysis resulting in a diploid living baby.

[Disproportion between placenta weight and birth weight: Physiologic or pathologic]. / Disproportion fœto-placentaire à terme : physiologique ou pathologique.

OBJECTIVES: To study risk factors, maternal and neonatal outcome with a high placental weight to birth weight ratio (PW/BW). MATERIALS AND METHODS: Two groups of full term singleton pregnancies were created in this single centre retrospective population-based study (a high PW/BW above 0.25 and group control with normal PW/BW between 0.15 and 0.25). Maternal and neonatal outcomes were compared. RESULTS: Compared with the group with normal PW/BW ratios, the high PW/BW ratio group was associated with increased rates of pre-eclampsia (15.5% versus 1.7%, P<0.05) and small for gestational age (8% versus 0%, P<0.05). Neither maternal risk factors nor neonatal outcome difference were shown after adjusting confounding factors. CONCLUSION: High PW/BW with placentomegaly is associated with increased risk of pre-eclampsia at term underlying a mixture of condition in its pathogenesis.

Intrauterine Growth Restriction Associated with Hematologic Abnormalities: Probable Manifestations of Placental Mesenchymal Dysplasia.

Introduction Placental mesenchymal dysplasia is a rare vascular disease associated with intrauterine growth restriction, fetal demise as well as Beckwith-Wiedemann syndrome. Some neonates present hematologic abnormalities possibly related to consumptive coagulopathy and hemolytic anemia in the placental circulation. Case report We present a case of placental mesenchymal dysplasia in a fetus with intrauterine growth restriction and cerebellar hemorrhagic injury diagnosed in the 20th week of pregnancy. During 26th week, our patient had an intrauterine fetal demise in the context of gestational hypertension. We have detailed the ultrasound findings that made us suspect the presence of hematologic disorders during 20th week. Discussion We believe that the cerebellar hematoma could be the consequence of thrombocytopenia accompanied by anemia. If hemorrhagic damage during fetal life is found, above all associates with an anomalous placental appearance and with intrauterine growth restriction, PMD should be suspected along other etiologies.

The riddle of Ballantyne's syndrome in the aspect of hydrops fetalis.

Ballantyne's syndrome, the combination of maternal generalized edema and fetal ascites, is rare and alarming in gestation. Early diagnosis might be useful in providing proper management of the fetus and aiming at an improved clinical result. The syndrome is an indication that HF is there, it has already started expanding the fetal torso and endangering the child-bearer's life. Despite the detailed investigation, no apparent cause for the emergence of the hydrops was identified.

Unusual markedly-dilated chorionic vessels with placentomegaly.

We reported a very rare case with placentomegaly and markedly-dilated chorionic vessels. A 23-year-old Japanese pregnant woman was referred to our hospital at 32 weeks of gestation because of suspected dilatation of the umbilical vein. Ultrasound revealed fetal growth restriction with no fetal anomalies. The placenta was thick. The umbilical cord had two arteries and one vein, and marginal insertion of the umbilical cord in the placenta was suspected. A lot of remarkably tortuous tubular structures were observed on the surface of the placenta. Slow blood flow, indemonstrable with color Doppler, was observed within them. Labor started suddenly and progressed very rapidly at 33 weeks of gestation. A female infant weighing 1524 g was delivered. The infant had no malformations. However, she showed hypotension, anemia and DIC and required blood transfusion. The placenta was very large, weighing 1416 g. On the fetal surface, numerous dilated and tortuous vessels were observed, arising from a vein that was connected to the umbilical vein. These venous channels were dilated and tortuous and led into the placenta. In conclusion, prenatal diagnosis of placentomegaly and markedly-dilated chorionic vessels requires assessment of growth, anemia and DIC of the fetus and the newborn infant.

Displasia mesenquimal placentaria: caso clínico / Placental mesenchymal dysplasia: a case report

La displasia mesenquimal placentaria es una entidad poco conocida, de etiología incierta y subdiagnosticada. Frecuentemente, es confundida con enfermedad trofoblástica gestacional debido a que se presenta con hallazgos ultrasonográficos caracterizados por una placenta engrosada, con quistes e imágenes hipoecogénicas y niveles de gonadotrofina coriónica humana normales o levemente aumentados. El feto es frecuentemente viable y puede manifestar retraso del crecimiento intrauterino, prematurez o asociarse al síndrome de Beckwith-Wiedemann. Se presenta el caso de una mujer joven con un parto pretérmino con placentomegalia, sospecha de mola hidatidiforme parcial y un recién nacido pequeño para la edad gestacional.

The placental mesenchymal dysplasia is a not well known entity, with an uncertain etiology and under diagnosed. It is frequently confused with gestational trophoblastic disease because of its ultrasonographic features of a thick placenta, cysts and hypoechogenic images, with normal or slightly increased levels of human chorionic gonadotrophic hormone. The fetus is often viable and can manifest intrauterine growth restriction, prematurity or be associated with Beckwith-Wiedemann syndrome. We present a case report of a young woman with a preterm delivery, placentomegaly, suspicious of a partial hydatidiform mole and a low growth newborn.

Hyperimmunoglobulin for prevention of congenital cytomegalovirus disease.

Primary cytomegalovirus (CMV) infection during the first half of pregnancy is responsible for the majority of symptomatic congenital infections. Between one-third and one-half of fetuses become infected, and up to one-half of infected fetuses will have neurologic or sensorineural sequelae at birth or later in life. Following favorable results obtained in animal experiments, observational studies have shown beneficial effects after administration of high-titer CMV hyperimmunoglobulin to pregnant women with fetal infection or disease subsequent to primary CMV infection. The mechanisms of action of hyperimmunoglobulin are multiple and not yet fully understood. However, they could reside in 2 major properties: (1) antiviral activities due to high-avidity neutralizing antibodies and (2) immunomodulating activities mostly including downregulation of cytokine-mediated cellular immune responses. A decreased viral pathogenicity occurs as an immediate consequence, whereas reduced placental inflammation and restored function are the long-term effects.

Autosomal recessive polycystic kidney disease: antenatal diagnosis and histopathological correlation.

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common inheritable disease manifesting in infancy and childhood with a frequency of 1:6,000 to 1:55,000 births. The patient in her second trimester presented with a history of amenorrhea. Ultrasound examination revealed bilateral, enlarged, hyperechogenic kidneys, placentomegaly, and severe oligohydramnios. The pregnancy was terminated. An autopsy was performed on the fetus. Both the kidneys were found to be enlarged and the cut surface showed numerous cysts. The liver sections showed changes due to fibrosis. The final diagnosis of autosomal recessive polycystic kidney disease was made based on these findings. In this article, we correlate the ante-natal ultrasound and histopathological findings in autosomal recessive polycystic kidney disease.