Isolated Transient Neonatal Ascites in a Preterm Infant Born to a Mother with Mirror Syndrome: A Case Report

Introduction

Isolated neonatal ascites, defined as fluid accumulation within the peritoneal cavity without associated systemic or structural anomalies, is a rare but important finding in neonatology. Although it may be associated with chromosomal abnormalities, congenital infections, or structural malformations [1], isolated cases pose distinct diagnostic challenges. The prevalence of isolated fetal ascites remains uncertain; a tertiary-center series revealed detection in approximately 0.05% of prenatal scans (about 1 in 2,000), but this rate may be inflated due to referral bias [2]. Advanced imaging, fluid analysis, and genetic testing are often necessary to determine the underlying cause, which may range from transient idiopathic ascites to genetic abnormalities [3].

When fetal ascites occurs in isolation, without additional features of hydrops or maternal illness, it usually reflects intra-abdominal causes (eg, genitourinary or gastrointestinal anomalies) and is associated with relatively favorable neonatal outcomes [4]. In contrast, fetal ascites accompanied by maternal mirror syndrome generally indicates underlying hydrops fetalis from more severe etiologies and is correlated with worse maternal and fetal prognoses [5]. We encountered an unusual case in which mirror syndrome developed in the presence of isolated fetal ascites alone, without other signs of hydrops.

The differential diagnosis of isolated neonatal ascites is broad [1]. In some instances, no definitive cause is identified, as in benign idiopathic neonatal ascites, in which fluid accumulation resolves spontaneously [6,7]. The introduction of advanced diagnostic methods such as whole-exome sequencing (WES) has enhanced the capacity to detect rare genetic causes.

Mirror syndrome, or Ballantyne syndrome, is a sporadic disorder in which generalized maternal edema “mirrors” that of the hydropic fetus and placenta. Although its pathogenesis remains unclear, it has been proposed that the hydropic placenta increases production of soluble fms-like tyrosine kinase 1 (sFlt1-a), a mediator of preeclampsia, leading to maternal endothelial and vascular dysfunction [8]. The prevalence of mirror syndrome has not been well established, partly due to variability in diagnostic criteria among studies. This rare complication is often difficult to recognize because of its clinical overlap with other pregnancy-related conditions. Common manifestations include rapid weight gain, progressive peripheral edema, dyspnea, and signs of preeclampsia with severe features such as hypertension and proteinuria [9,10]. Diagnosis is typically based on a combination of clinical presentation, evidence of maternal and fetal edema, and exclusion of other potential etiologies [9].

Management strategies are generally directed toward the underlying cause, whether related to fetal hydrops or other maternal complications. These measures may include close surveillance, blood pressure control, and, in severe cases, delivery of the fetus. The timing of delivery depends on gestational age, maternal condition, and fetal status [10]. Because of the rarity and complexity of mirror syndrome, management requires an individualized, multidisciplinary approach [5,10,11].

This report describes a case of transient isolated neonatal ascites in a preterm neonate born to a mother with generalized edema and progressive weight gain, in whom an extensive diagnostic evaluation, including genetic testing, failed to identify a definitive cause.

It constitutes a rare instance in which isolated neonatal ascites occurred in association with maternal mirror syndrome in the absence of generalized fetal hydrops. This atypical presentation underscores the diagnostic challenges involved and demonstrates that favorable maternal and neonatal outcomes can be achieved even in uncommon clinical contexts.

Case Report

A female neonate was delivered at 32 weeks of gestation, weighing 3000 g, by cesarean section due to maternal mirror syndrome. The pregnancy was conceived through in vitro fertilization for a 27-year-old gravida 2, para 0, abortus 1 woman married to her first cousin. The couple had a 10-year history of infertility attributed to male factors, including oligospermia and decreased sperm motility. The pregnancy was closely monitored with routine antenatal care and recommended supplements; no maternal complications were observed. There was no history of chronic hypertension, preexisting diabetes, renal or cardiac disease, or autoimmune disorders. Both the mother and the neonate had blood type O positive. The mother’s indirect Coombs test titers were negative.

Targeted prenatal ultrasound at 25 weeks of gestation identified moderate fetal ascites without associated structural abnormalities. The examination included a comprehensive evaluation of fetal anatomy, focusing on major organ systems to detect potential anomalies. By 30 weeks of gestation, follow-up imaging demonstrated progression of fetal ascites along with maternal peripheral edema and shortness of breath. Maternal blood pressure remained normal at 112/78 mmHg, and urine testing showed no proteinuria. The presence of worsening maternal edema and respiratory distress, despite normal blood pressure, absence of proteinuria, and unremarkable laboratory findings, raised suspicion for mirror syndrome and guided subsequent management. Amniocentesis at 31 weeks revealed a normal female karyotype (46,XX), and TORCH [toxoplasmosis, other agents, rubella, cytomegalovirus, herpes simplex] screening for congenital infections was negative. Repeat targeted ultrasound performed at a tertiary referral center confirmed the absence of structural abnormalities.

Upon delivery, the neonate exhibited bradycardia and cyanosis, requiring resuscitation and intubation for clinically significant respiratory distress. The infant produced a weak cry immediately after birth and required ventilatory support. Apgar scores were 5 and 8 at 1 and 5 min, respectively. After stabilization, she was transferred to the neonatal intensive care unit and maintained on mechanical ventilation through an endotracheal tube. Gross examination of the placenta showed a single discoid organ measuring approximately 14×16×2 cm and weighing 288 g, with intact membranes and a 3-vessel umbilical cord of normal length and central insertion.

At admission, the neonate had an abdominal circumference of 36 cm (>95th percentile), consistent with significant ascites, a head circumference of 29.5 cm (approximately 50th percentile), and a length of 40.5 cm (approximately 25th percentile). On physical examination, the neonate was on mechanical ventilation and appeared pink, without dysmorphic features, cyanosis, or jaundice. Cardiovascular assessment revealed a regular heart rate without murmurs, cyanosis, or pallor. Gastrointestinal examination showed a greatly distended, tense abdomen without palpable masses; external genitalia were normal for a female neonate (Figure 1).

Initial routine hematologic and biochemical investigations were unremarkable, including thyroid function tests, comprehensive metabolic panel, ammonia levels, direct Coombs test, and arterial blood gases (Table 1). Postnatal ultrasound and X-ray confirmed clinically significant ascites without thoracic effusion or evidence of structural gastrointestinal or genitourinary anomalies. Although ultrasound images would have been more illustrative, only radiologist reports were available in this setting; these accurately documented the presence of ascitic fluid before and after therapeutic paracentesis (Figure 2). Echocardiography revealed a moderate patent foramen ovale with left-to-right shunting and trace tricuspid regurgitation, without pulmonary hypertension. Brain ultrasound findings were normal.

A complete skeletal survey showed no abnormalities. The skull, spine, thoracic cage, pelvis, long bones, hands, and feet all demonstrated normal morphology, alignment, and ossification patterns, without evidence of fractures, dysplasia, lytic or sclerotic lesions, or deformities (Figure 3).

A blood sample was sent for WES to evaluate a possible genetic etiology. The analysis revealed no relevant findings consistent with the clinical phenotype of isolated fetal ascites. No pathogenic or likely pathogenic variants, structural abnormalities, or copy number variations were detected. The report recommended trio analysis for a more comprehensive genetic assessment; however, this was not performed because of financial concerns.

Initial management was supportive; it included mechanical ventilation for respiratory compromise and ultrasound-guided abdominal paracentesis, which drained 450 mL of yellow ascitic fluid. Analysis of the fluid showed 28 cells/mL (15% lymphocytes and 85% granulocytes), protein 0.3 g/dL, albumin 0.16 g/dL, lactate dehydrogenase 169 IU/L, triglycerides 8 mg/dL, pH 8, and glucose 68 mg/dL. Cytologic examination showed no abnormal cells, and bacterial culture findings were negative.

Post-procedure, the neonate developed transient hypotension, which was effectively managed with crystalloid and colloid boluses. Empirical antibiotic therapy was initiated after obtaining a blood culture, which later returned negative results. The neonate was successfully extubated on the second day without residual respiratory distress. On admission, the abdominal circumference measured 36 cm; after therapeutic paracentesis, it decreased to 31 cm and remained stable on subsequent evaluations. Daily monitoring of abdominal circumference and repeat ultrasonography showed no recurrence of free fluid accumulation. Orogastric feeding began on the third day of admission and was well tolerated. Oral feeding by sucking was introduced when the infant reached a corrected gestational age of 34+1 weeks. The infant was discharged home after completion of treatment, with clear follow-up instructions and referrals to a neonatologist and genetic specialist for continued evaluation and counseling.

Discussion

Fetal ascites refers to abnormal fluid accumulation within the peritoneal cavity and is frequently associated with hydrops fetalis. It may be classified as immune or nonimmune; nonimmune cases represent approximately 90% of occurrences after the introduction of Rhesus isoimmunization prophylaxis [12]. Isolated fetal ascites, defined as peritoneal fluid collection without involvement of other compartments, generally carries a more favorable prognosis than hydrops fetalis [11].

The etiologies of isolated fetal ascites are diverse. The most common causes include genitourinary anomalies (24%), gastrointestinal malformations (20%), viral or bacterial infections (9%), and cardiac conditions (9%) [13]. Idiopathic cases, in which no definitive cause is identified, comprise approximately 13% of all cases [13]. The most frequently reported gastrointestinal cause is meconium peritonitis secondary to bowel perforation, whereas obstructive uropathy is the predominant genitourinary etiology. Infectious causes such as cytomegalovirus, toxoplasmosis, and syphilis have also been implicated [14]. In the present case, serial fetal imaging and postnatal ultrasound clearly excluded obstructive uropathy, meconium peritonitis, structural abnormalities, and cardiac dysfunction other than a moderate patent foramen ovale, indicating a nonstructural, idiopathic origin.

Biochemical analysis of ascitic fluid aids in distinguishing exudative from transudative causes. High-protein exudates suggest inflammatory or neoplastic processes, whereas low-protein transudates imply lymphatic or vascular etiologies [15]. In the present case, paracentesis yielded fluid with low protein (0.3 g/dL), low triglycerides, and minimal cellularity, findings consistent with a transudative process and indicative of transient lymphatic imbalance as the probable mechanism. The sterile, acellular nature of the fluid further excluded intra-abdominal infection or perforation.

Genetic testing, including karyotyping and WES, is recommended when structural anomalies or syndromic patterns are suspected, because such testing can identify genetic mutations in approximately 31% of acutely ill infants with presumed genetic diseases [16]. The normal karyotype and negative WES findings in our patient support the idiopathic classification, consistent with literature indicating that no definitive etiology is determined in up to 13% of cases [13].

Management of fetal ascites depends on its severity and underlying cause. In utero, close monitoring of ascitic fluid volume and related complications is essential to guide intervention. When severe ascites occurs with obstetric complications such as mirror syndrome, preterm delivery is recommended [17]. In the present case, maternal mirror syndrome led to clinically significant symptoms, including edema and shortness of breath, prompting delivery at 32 weeks to preserve both maternal and fetal health. Postnatal management typically includes respiratory support, paracentesis, and targeted therapy based on the underlying etiology.

Several published case reports have described fetal ascites associated with maternal mirror syndrome. Rustamov et al. reported a case of fetal ascites and mirror syndrome without generalized hydrops, in which the neonate had a poor outcome despite postnatal intervention [18]. In contrast, Tanimura et al. described idiopathic fetal ascites associated with maternal mirror syndrome that resolved after delivery, a scenario consistent with the present case, emphasizing that timely delivery and supportive care can lead to favorable outcomes when high-risk causes are excluded. Other reports have cited differing etiologies, such as fetal cardiomyopathy resulting in mirror syndrome and stillbirth [19], or obstructive uropathy managed by intrauterine shunting with resolution of maternal symptoms [20]. These comparisons highlight both the diagnostic complexity and variable prognosis of fetal ascites. The present case adds to the limited literature by demonstrating that, even in the presence of mirror syndrome, isolated idiopathic ascites can completely resolve with conservative neonatal care.

The prognosis of isolated fetal ascites largely depends on the underlying etiology. The most favorable outcomes are observed in cases of chylous ascites (100%) and idiopathic ascites (90%), whereas cases related to gastrointestinal or genitourinary causes have survival rates of approximately 77%. The prognosis substantially declines in cases associated with structural, cardiac, or metabolic abnormalities, where survival rates fall below 35%. Finally, approximately 6.6% of cases progress to fetal hydrops [4,13].

Given the comprehensive negative findings in our patient and the complete resolution of symptoms, idiopathic ascites remains the most likely diagnosis. The clinical course further supports this, given that ascites resolved promptly after paracentesis, without recurrence or complications during neonatal intensive care unit admission.

Conclusions

This report presents a rare case of transient isolated neonatal ascites occurring in the context of maternal mirror syndrome. Extensive postnatal evaluation identified no structural, infectious, metabolic, or genetic cause. The patient responded favorably to supportive management, with complete resolution of ascites and no recurrence during hospitalization. The absence of recurrent fluid accumulation, normal genetic testing, and resolution with minimal intervention collectively support an idiopathic diagnosis. Isolated neonatal ascites may resolve spontaneously, even in the presence of maternal complications. Advanced genetic testing remains essential to exclude rare etiologies. Conservative neonatal management, including supportive measures and close monitoring, can achieve favorable outcomes in select idiopathic cases.