What are the causes of polyhydramnios (excessive amniotic fluid) in pregnant women, particularly those with a history of diabetes (diabetes mellitus) or carrying multiple fetuses (e.g. twins or triplets)?

Causes of Polyhydramnios

Polyhydramnios results from maternal diabetes mellitus, fetal anomalies affecting swallowing, multiple gestations (particularly twin-twin transfusion syndrome), congenital infections, and idiopathic causes, with maternal diabetes and fetal structural abnormalities being the two most common pathologic etiologies. 1

Major Etiologic Categories

Maternal Causes

• Gestational diabetes mellitus is one of the two most common pathologic causes of polyhydramnios and is frequently associated with fetal macrosomia 2, 1
• Maternal diabetes can cause transient polyhydramnios that may resolve with glycemic control, though it can recur later in pregnancy 3

Fetal Causes

Structural and Genetic Abnormalities

• Fetal anomalies that disturb swallowing of amniotic fluid represent the other most common pathologic cause, with up to 20% of early-onset cases having structural or chromosomal abnormalities 4, 2, 1
• Chromosomal disorders are a recognized major cause requiring genetic evaluation 5

Rare Tubular Disorders

• Bartter syndrome (BS) is virtually always the cause when polyhydramnios results from excessive fetal polyuria, with severe polyhydramnios occurring in types 1,2, 4a, and 4b, and very severe polyhydramnios in type 4b 6
• No other inherited tubular disorders cause severe polyhydramnios; notably, polyhydramnios is not a feature of severe proximal tubulopathies or nephrogenic diabetes insipidus 6

Multiple Gestations

• Twin-twin transfusion syndrome (TTTS) affects 10-20% of monochorionic twins, with the recipient twin developing polyhydramnios (MVP >8 cm) while the donor develops oligohydramnios (MVP <2 cm) 4
• Multiple gestations in general are a recognized major cause of polyhydramnios 5

Infections and Immunologic

• Congenital fetal infections are an established cause requiring evaluation 1
• Isoimmunologic disease (alloimmunization) can lead to polyhydramnios 1, 5

Idiopathic

• Most cases of mild polyhydramnios are idiopathic, though even these carry increased stillbirth risk 4, 1

Clinical Significance and Risk Stratification

Mortality Risk

• Polyhydramnios independently increases stillbirth risk with odds ratios ranging from 1.8 to 5.8 depending on severity and presence of other anomalies 4
• In a large cohort of over 200,000 singleton births, polyhydramnios was independently associated with stillbirth (OR 1.8; 95% CI 1.4-2.2) 4
• Isolated polyhydramnios without fetal anomalies has lower perinatal mortality than cases with additional abnormalities, but risk remains elevated 4

Associated Complications

• Typical complications include maternal dyspnea, preterm labor, premature rupture of membranes (PPROM), abnormal fetal presentation, cord prolapse, and postpartum hemorrhage 2
• Perinatal morbidity and mortality is high, and maternal complications are frequent 5

Critical Diagnostic Pitfalls

Twin Pregnancies

• Any polyhydramnios in twin pregnancies requires immediate assessment for TTTS, which has stage-dependent prognosis and may require specialized fetoscopic laser photocoagulation 4
• TTTS requires monitoring at least every 2 weeks starting at 16 weeks, with more frequent monitoring if pathology develops 4

Transient Cases

• Polyhydramnios may be transient, particularly in gestational diabetes, but even mild cases carry increased stillbirth risk 4, 3
• In one case report, polyhydramnios normalized within 4 days but recurred at 38 weeks with severe fetal bradycardia requiring emergency cesarean section 3

Misdiagnosis Concerns

• Cases initially misdiagnosed as pseudohypoaldosteronism type I with polyhydramnios have later been shown to harbor KCNJ1 mutations underlying Bartter syndrome type 2 6