The role of fetal therapy in the management of mirror syndrome: a narrative review.

OBJECTIVES: Mirror syndrome (MS) is a condition characterized by the presence of maternal, fetal, and placental edema and is reversible through delivery or pregnancy termination. As fetal hydrops itself may be amenable to treatment, we sought to determine outcomes for MS primarily managed by fetal therapy through a narrative review of the literature and cases managed at our fetal center. STUDY DESIGN: PubMed, Embase, Web of Science, Scopus, and Google Scholar databases were searched through January 2024 using key words: mirror syndrome, Ballantyne's syndrome, fetal hydrops, maternal hydrops, pseudotoxemia, triple edema, maternal recovery, fetal therapy, and resolution. Manuscripts describing primary management by fetal therapy that included maternal and fetal outcomes were identified. Clinical details of MS patients managed with fetal therapy at our center were also included for descriptive analysis. RESULTS: 16 of 517 manuscripts (3.1%) described fetal therapy as the primary intended treatment in 17 patients. 3 patients managed at our center were included in the analysis. Among 20 patients undergoing primary fetal therapy for management of mirror syndrome, median gestational age of presentation was 24 weeks and 5 days gestation; predominant clinical findings were maternal edema (15/20), proteinuria (10/20), pulmonary edema (8/20), and hypertension (8/20); the primary laboratory abnormalities were anemia (8/20) and elevated creatinine or transaminases (5/20). Condition-specific fetal therapies led to resolution of hydrops in 17 (85%) cases and MS in 19 (95%) cases. The median time to hydrops resolution was 7.5 days and to resolution of mirror syndrome was 10 days. Fetal therapy prolonged pregnancy by a median of 10 weeks with a median gestational age of 35 weeks and 5 days at delivery. All women delivered for indications other than mirror syndrome and 19/20 fetuses survived. CONCLUSION: In appropriately selected cases, MS often resolves after fetal therapy of hydrops allowing for safe pregnancy prolongation with good maternal and infant outcomes.

Clinical presentation and maternal-fetal outcomes of Mirror Syndrome: A case series of 10 affected pregnancies.

Background: Mirror Syndrome, also known as Ballantyne syndrome, is a rare condition with fewer than 120 cases described in the literature. A simultaneous edematous state of the mother, fetus and placenta is pathognomonic, with the maternal condition frequently presenting with signs and symptoms similar to that of preeclampsia. Objective: Our aim was to add to the international body of literature through identification of all cases of Mirror Syndrome at two Canadian tertiary obstetric centres and characterize the maternal presentation, laboratory findings, and perinatal outcomes. Methodology: We performed a retrospective chart review of all cases of fetal hydrops from two tertiary centres in Winnipeg (Manitoba, Canada) between 2000 and 2019. There were 276 cases of fetal hydrops during this period, of which 10 cases satisfied the diagnostic criteria for Mirror Syndrome where maternal and perinatal outcomes were analysed. Results: The median gestational age at diagnosis with Mirror Syndrome was 23 weeks and 3 days of gestation and at birth was 25 weeks and 0 days of gestation. The majority of women were multiparous (80%) and had elevated maternal body mass index (median 33 kg/m2). The most common maternal clinical findings included weight gain (100%) and hypertension (90%). The most common laboratory findings included low hematocrit (100%), hypoalbuminemia (80%), anemia (70%) and hyperuricemia (70%). Structural anomalies were observed in 50% of cases, over half of the fetuses were stillborn (66.7%) and one quarter of pregnancies resulted in neonatal deaths (25%). The median time until maternal improvement of Mirror Syndrome was 2 days postpartum. Conclusion: Mirror Syndrome affected 3.6% of all cases of fetal hydrops in our cohort, and showed associations with multiparity, elevated BMI, hemodilution, hypoalbuminemia, anemia and hyperuricemia. Delivery is frequently required for fetal and/or maternal indications and symptoms usually improved rapidly after delivery.

Mirror syndrome in monochorionic diamniotic twins presenting as maternal hyponatremia: A case report.

This is a case report of a 39-year-old patient, G5P1031, with monochorionic diamniotic twins at 30 weeks and 1 day of gestation, who developed mirror syndrome without twin-to-twin transfusion syndrome (TTTS) with a unique presentation of maternal and neonatal hyponatremia. Coinciding with severe hyponatremia were maternal symptoms of edema, nausea and vomiting, hypoalbuminemia, elevated uric acid, as well as fetal selective growth restriction, polyhydramnios, umbilical artery absent end diastolic flow and prolonged bradycardia of twin B. Given the poor status of twin B and the risks to twin A, the patient underwent emergent cesarean delivery. Hyponatremia in all three patients resolved in the following 48-72 h. Mirror syndrome is associated with significant maternal and fetal morbidity and mortality. In this case, severe hyponatremia posed additional risks. Therefore, electrolyte monitoring should be considered in both mother and neonate(s).

Síndrome de Ballantyne: segundo episodio en una embarazada. Reporte de caso y revisión de la bibliografía / Ballantyne syndrome: Second episode in a pregnant woman. Case report and literature review

Resumen ANTECEDENTES: El síndrome de Ballantyne es un cuadro poco frecuente asociado con hidrops fetal, en el que la madre refleja los síntomas fetales. Es decisivo diferenciarlo de la preeclampsia porque comparten signos de hipertensión y proteinuria. Su etiopatogenia se desconoce pero se han propuesto teorías asociadas con el desequilibrio entre factores angiogénicos y antiangiogénicos. CASO CLÍNICO: Paciente de 29 años, controlada en la consulta de Medicina Materno-Fetal debido al antecedente de síndrome de Ballantyne en el embarazo previo. En la ecografía de control a las 26 semanas se detectaron placentomegalia, ascitis fetal e incremento del líquido amniótico. Las ecografías posteriores demostraron polihidramnios e hidrops a las 28 semanas. Enseguida de la aparición del edema se estableció el diagnóstico de síndrome del espejo recidivante e hidrops no inmunitario. Se hospitalizó para drenaje del líquido. La amniorrexis se produjo a las 29 + 6 semanas. Una semana después se inició la dinámica uterina y el embarazo finalizó a las 31 semanas, después de la ruptura prematura de membranas. El neonato fue un varón de 3200 g, Apgar 2-6-8 al minuto, 5 y 10 minutos, respectivamente. Después del estudio postnatal se estableció el diagnóstico de perforación ileal múltiple. El recién nacido requirió 5 intervenciones quirúrgicas, con posoperatorio tórpido y se dio de alta a los 3 meses de vida. CONCLUSIONES: El síndrome del espejo es infradiagnosticado, a pesar de su potencial para complicar gravemente el embarazo asociado con hidrops. La recuperación de la madre suele ser favorable a los pocos días de posparto aunque la morbilidad y la mortalidad fetal son elevadas.

Abstract BACKGROUND: Ballantyne syndrome is characterized by the triad: fetal, placental and maternal edema. It is an uncommon condition associated with fetal hydrops, in which mother reflects fetal symptoms. It is essential to differentiate from preeclampsia, since there are common signs such as hypertension and proteinuria. Etiopathogenesis is unknown, although theories associated with an imbalance between angiogenic and antiangiogenic factors have been postulated. Treatment consists of ending the pregnancy or improving the fetal situation. CLINICAL CASE: We present the case of a 29-years pregnant woman controlled in the Maternal-Fetal Medicine Unit due to the history of Ballantyne Syndrome in the previous gestation. In the follow-up ultrasound performed at 26-weeks, placentomegaly, fetal ascites and increased amniotic fluid were detected. Subsequent ultrasounds showed polyhydramnios and fetal hydrops at 28-weeks. After maternal edema began, she was diagnosed with recurrent Mirror Syndrome and non-immune hydrops. Admission was indicated and amniodrainage was performed due to symptomatic polyhydramnios. Finally, premature rupture of membranes occurred at 29+6-weeks. She started uterine dynamic after one week, ending in a preterm delivery at 31-weeks after premature rupture of membranes. A 3200gr male was born with Apgar Scores 2-6-8 at 1, 5 and 10min respectively and, after postnatal study, he was diagnosed with multiple ileal perforation. Five surgical interventions were necessary, with a complicated postoperative period and could be discharged at 3 months of age. CONCLUSIONS: Mirror syndrome is an underdiagnosed pathology of unknown incidence that can seriously complicate gestation associated with fetal hydrops. Maternal recovery is favorable few days after delivery, but it leads to high fetal morbi-mortality.

Characteristics and management of mirror syndrome: a systematic review (1956-2016).

OBJECTIVES: To describe the clinical features of mirror syndrome and to correlate the effects of different treatments with the fetal outcomes. DATA SOURCES: Online search up to May 2016 was conducted in the PubMed, Embase (Ovid platform) and clinicalTrials.gov without restrictions of language, date or journal. Only papers providing both fetal and maternal presentations and outcomes were included. RESULTS: The study included 74 papers (n=111), with an additional two patients diagnosed at our center (n=113). The mean gestational age at diagnosis was 27 weeks±30 days (16-39 weeks). Whether early or late gestational age at diagnosis, and whether mother and fetus show symptoms simultaneously or on different dates, has insignificant impact on fetal outcome (P=0.06 and P=0.46, respectively). Edema (84%) followed by hypertension (60.1%) were the leading maternal findings. Fetal hydrops (94.7%) and placental edema (62.8%) were the commonest sonographic features. Procedures correcting fetal hydrops/anemia in utero as well as labor induction were the only treatment options correlated with improved fetal survival (χ2 analysis, P=0.01 and Fisher's exact test, P=0.02; respectively). The overall rate of fetal/neonatal mortality was 67.26%. CONCLUSION: The gestational age at diagnosis and sequence of presentation have insignificant impact on fetal outcome. Improved fetal survival was associated with procedural interventions that correct fetal hydrops as well as labor induction.

Echocardiography findings in a case with Ballantyne syndrome.

Marked fluid retention occurs in Ballantyne syndrome, but few reports are available on changes in cardiac morphology in this syndrome. A woman with generalized edema, dyspnea, fetal hydrops (skin edema and ascites), thickened placenta, and elevated plasma B-type natriuretic peptide level (344 pg/mL) was admitted to our hospital at gestational week (GW) 20+3 . Blood pressure remained within the normal range. However, acute increases in left atrial volume index, pulmonary artery systolic pressure, and hyperdynamic left ventricular function (as evidenced by increased left ventricular ejection fraction to 74% with cardiac index of 5.1 L/min/m2 ) occurred preceding fetal death at GW 21+4 in the presence of increased inferior vena cava diameter (23 mm) and relatively low systemic vascular resistance of 752 dyn·s/cm5 . These findings suggested life-threatening heart failure and required cesarean delivery at GW 21+5 resulting in complete recovery. The placenta suggested cytomegalovirus infection.

Síndrome de Ballantyne / Ballantyne syndrome

Ballantyne syndrome (triple edema syndrome or mirror syndrome) is characterized by maternal edema, placental edema and fetal hydrops, associated to hypertensive syndrome as a variant of preeclampsia. We report a case of prenatal diagnosis of Ballantyne syndrome. A patient diagnosed with anemia, edema and abdominal pain was hospitalized at 26 weeks of gestation. Serial obstetric ultrasound tomography imaging showed placental edema, severe oligohydroamnios, fetal hydrops, abnormal fetal umbilical Doppler measurements, and ultrasonographic signs of anemia. The patient developed hypertensive disorders of pregnancy, a cesarean section was performed and an 840 g male infant was born, Apgar 2-8, with sepsis and fetal anemia, who died two days after cesarean delivery. A literature review of Ballantyne Syndrome, its physiopathology and diagnosis is performed.

El síndrome de Ballantyne (o de triple edema o síndrome en espejo), se caracteriza por edema materno, edema placentario e hidrops fetal, asociadoun síndrome hipertensivo variante de la preeclampsia. Se presenta un caso clínico de diagnóstico prenatal de síndrome de Ballantyne. A las 26 semanas de gestación se hospitaliza paciente con diagnóstico de anemia, edema y dolor abdominal. Las ecotomografias obstétricas seriadas demuestran edema placentario, oligohidroamnios severo, hidrops fetal, alteración del Doppler umbilical fetal, y signos ultrasonográficos de anemia.La paciente evoluciona con sindrome hipertensivo del embarazo, se realiza cesárea y se obtiene un recién nacido de 840 g, sexo masculino, Apgar 2-8, con sepsis y anemia fetal que fallece al segundo día. Se realiza una revisión de la literatura, de la fisiopatología y diagnóstico del síndrome de Ballantyne.