Polyhydramnios

Etiology

In 50% to 60% of affected patients, polyhydramnios is idiopathic.[5] However, the idiopathic classification is one of exclusion and can only be made after ruling out other potential causes. Polyhydramnios may result from any pathology that impairs fetal swallowing, reduces fluid reabsorption from the gastrointestinal tract, or results in excessive urine production. One of the most common pathological causes of polyhydramnios is gestational diabetes, though chromosomal abnormalities are also relatively common. Less often, intrapartum transplacental infections lead to polyhydramnios.[1][6][7]

Impaired Fetal Swallowing and Gastrointestinal Absorption

Causes of impaired fetal swallowing include central nervous system lesions; neuromuscular dysfunction, such as myotonic dystrophy or arthrogryposis syndromes; craniofacial abnormalities, such as a cleft lip or palate; micrognathia; and obstructive neck masses.[1][6] In addition, obstruction in the fetal gastrointestinal tract due to duodenal atresia, tracheoesophageal fistula, esophageal atresia, a thoracic mass, or a diaphragmatic hernia can significantly limit amniotic fluid absorption and lead to polyhydramnios.

Excess Fetal Urine Production

Excessive fetal urine production is most often associated with maternal diabetes. In addition, macrosomic fetuses tend to produce more urine, even in non-diabetic pregnant individuals.

Less commonly, the fetus may have an abnormality that causes high-output cardiac failure, which can also lead to excessive urine production. These conditions include severe fetal anemia from maternal alloimmunization, parvovirus B19 infection, alpha-thalassemia, or other hemolytic disorders; fetal tachyarrhythmias, including supraventricular tachycardia; and arteriovenous shunting in conjunction with sacrococcygeal teratoma or chorioangioma.[1][2][6] Some renal and urologic conditions, such as Bartter syndrome, can also lead to the overproduction of fetal urine and polyhydramnios.[1][6]

Twin-twin transfusion syndrome is a serious complication affecting 8% to 10% of monochorionic twin pregnancies.[8][9] In twin-twin transfusion syndrome, vascular connections within the monochorionic placenta shunt blood from one fetus (the donor) to the other (the recipient). The result of this shunting can be severe volume depletion and oligohydramnios in the donor, whereas fluid overload, hydrops fetalis, and high-output cardiac failure in the recipient.[8][9][10]

Epidemiology

Polyhydramnios occurs in 1% to 2% of all pregnancies.[1][2][11][12][13] Of patients with polyhydramnios, approximately 65% to 70% have mild disease, 20% have moderate disease, and less than 15% have severe disease.[2][11][14] The condition is often identified incidentally in asymptomatic patients during ultrasonographic evaluation for other conditions in the third trimester.[2][7]

Chamberlin et al used ultrasonography to obtain qualitative amniotic fluid volumes to evaluate the perinatal mortality rate in 7562 patients with high-risk pregnancies.[15] The perinatal mortality rate of patients with normal fluid volumes was 1.97 deaths per 1000 patients but increased more than 2-fold to 4.12 deaths per 1000 patients with polyhydramnios.

Pathophysiology

Amniotic fluid regulation depends on a delicate balance between fluid production and absorption, which supports fetal development and protects the fetus. Polyhydramnios occurs when this balance is disrupted, leading to excessive amniotic fluid and potentially indicating underlying maternal or fetal conditions.

Physiology of Amniotic Fluid Regulation

Amniotic fluid is mainly produced from fetal urination and, to a lesser extent, from fetal lung fluid. Fetal urine is produced at a relatively steady rate, which increases as pregnancy progresses and the fetus grows. The estimated hourly fetal urine production rate for fetuses at 20, 30, and 40 weeks is 4.2, 22.7, and 52.2 mL/h, respectively, which amounts to approximately 100, 545, and 1250 mL/d.[16] This rate is typically higher in larger fetuses and lower in growth-restricted fetuses.[17]

Fluid absorption occurs mainly through fetal swallowing, though direct absorption through the fetal membranes also plays a role.[18][19] Similar to urine production, fetal swallowing increases throughout most of gestation as swallowing movements become progressively more coordinated.[20] The fetus swallows an estimated 500 to 1000 mL of amniotic fluid daily near term.[3][7][21] Animal evidence suggests that swallowing increases as amniotic fluid volume increases, which appears to be an important component of amniotic fluid volume regulation.[22] In addition, the hypotonic nature of amniotic fluid compared to the isotonic fetal plasma creates an osmotic gradient, enabling direct absorption of amniotic fluid into fetal vessels on the placental surface—a process known as intramembranous absorption.[23]  

Pathophysiology of Polyhydramnios

The pathophysiology of polyhydramnios is not fully understood. However, any imbalance in the complex regulatory mechanisms maintaining the amniotic fluid volume can result in polyhydramnios.[1][3][24]

Increased urine production: Given that glucose readily crosses the placenta, maternal hyperglycemia leads to fetal hyperglycemia and osmotic diuresis.[1][2][3] Fetal urine output also increases in high-output fetal cardiac states, such as severe anemia, arteriovenous shunts, and volume overload. Bartter syndrome is a rare autosomal recessive condition that affects fetal renal tubular function and results in sodium loss and polyuria, often leading to severe polyhydramnios.[25] 

Decreased amniotic fluid absorption: Swallowing requires complex coordination between cerebral and brainstem pathways, oral and pharyngeal sensorimotor function, and respiratory activity.[26] Many central nervous system and neuromuscular disorders and infections may prevent the fetus from swallowing effectively, decreasing amniotic fluid resorption and leading to polyhydramnios.[1][3] In addition, the gastrointestinal tract must be patent and functional for the fluid to be reabsorbed by the fetal vasculature. Therefore, polyhydramnios can also develop due to conditions that prevent the swallowed fluid from reaching the intestines, such as esophageal or duodenal atresia or gastrointestinal compression due to a neck or thoracic mass. Common aneuploidies such as trisomies 21, 18, and 13 can also be associated with polyhydramnios.[2][24]

History and Physical

Typically, polyhydramnios is detected either during an ultrasonographic evaluation performed for a symphysis-fundal height measurement greater than expected for the gestational age or is noted as an incidental finding when ultrasonography is performed for another indication. In these situations, the pregnant patient is often asymptomatic; a focused medical and prenatal history should be obtained to assess the patient for risk factors, signs, and symptoms related to potential underlying etiologies. The patient should be assessed for findings that may suggest impaired glucose tolerance, such as polyuria and polydipsia; congenital infections, such as recent sick contacts, rash, and fever; and risk factors for alloimmunization, such as Rh-negative blood type, history of bleeding in pregnancy, or blood transfusions. In addition, patients should asked about their perception of fetal movements, as limited fetal movement may suggest a fetal neuromuscular disorder.[1][2][4]

Polyhydramnios increases the risk of complications such as preterm labor, preterm prelabor rupture of membranes, and placental abruption. Therefore, these individuals should be asked about contractions, cramping, abdominal pain, loss of fluid, and vaginal bleeding. Any concerning symptoms should be further investigated with a pelvic examination and assessment of fetal well-being.

Patients with moderate-to-severe polyhydramnios may be symptomatic. These patients may present with clinically significant dyspnea secondary to excessive amniotic fluid restricting diaphragmatic movement. Lower extremity edema may also cause considerable discomfort.

A fundal height that is 3 cm above the gestational age in weeks or rapid uterine enlargement warrants a sonographic assessment of fetal growth and amniotic fluid volume to rule out macrosomia or polyhydramnios. In patients with severe polyhydramnios, the physical examination may also reveal a grossly distended abdomen, shallow breathing, and significant lower extremity edema.[1][2] Clinicians must also be aware that excessive amniotic fluid increases the risk of cord prolapse after membrane rupture, which may be appreciated as a pulsating purplish mass in the cervical canal or vagina.[6][7][27]

Evaluation

A thorough clinical assessment is required to evaluate polyhydramnios and identify its severity and potential underlying causes. This assessment includes ultrasonographic measurements of amniotic fluid volume, screening for maternal conditions, and assessing for possible fetal anomalies.

Diagnosis

Polyhydramnios should be diagnosed based on a quantitative sonographic assessment of amniotic fluid volume.[28] Amniotic fluid is best evaluated using one of two methods—by measuring the single deepest vertical pocket of amniotic fluid, which is also referred to as the maximal vertical pocket or single deepest pocket, or by calculating the amniotic fluid index, which represents the quantitative sum of the deepest vertical pocket measurements obtained in each of the 4 abdominal quadrants. These same values can also be used to determine the severity of polyhydramnios.[2][29] Both amniotic fluid index and deepest vertical pocket correlate relatively poorly with actual amniotic fluid volume, as determined by dye dilution techniques.[30] However, similar to dye dilution tests, abnormal amniotic fluid indexes and deepest vertical pockets are associated with adverse outcomes, and therefore, the noninvasive assessments of amniotic fluid volume are preferred for diagnosing and monitoring polyhydramnios.[2]

A normal deepest vertical pocket is ≥2 and <8 cm. Measurements ≥8 cm indicate polyhydramnios, with mild polyhydramnios defined as a deepest vertical pocket of 8 to 11.9 cm, moderate polyhydramnios as a deepest vertical pocket of 12 to 15.9 cm, and severe polyhydramnios as a deepest vertical pocket ≥16 cm. Historically, polyhydramnios was defined as an amniotic fluid index ≥25 cm. However, more recent data suggest an amniotic fluid index of 24 cm exceeds the 97.5th percentile at all gestational ages after 20 weeks. For this reason, the Society for Maternal-Fetal Medicine (SMFM) recommends defining polyhydramnios as an amniotic fluid index of ≥24 cm when using the amniotic fluid index.[11] The amniotic fluid index can further classify polyhydramnios as mild (≥24 to <30 cm), moderate (≥30 to <35 cm), or severe (≥35 cm) (see Table. Definitions of Mild, Moderate, and Severe Polyhydramnios). The amniotic fluid index can only be used in singleton pregnancies, whereas the deepest vertical pocket can be used in singleton and multiple gestations.

Table. Definitions of Mild, Moderate, and Severe Polyhydramnios

DVP, deepest vertical pocket; AFI, amniotic fluid index.

To accurately measure a pocket of amniotic fluid, the ultrasound transducer should be placed perpendicular to the floor while scanning in the sagittal plane parallel to the spine.[2][5] According to a major 2014 multi-disciplinary workshop by the United States National Institute of Child Health and Human Development (NICHD) and various coordinating professional organizations, including the SMFM, measured pockets must be at least 1 cm wide and free of umbilical cord and fetal parts.[31] Color Doppler can aid in detecting the umbilical cord and fetal parts present within a fluid pocket. Studies have shown that color Doppler can reduce the amniotic fluid index and deepest vertical pocket measurements by approximately 20%.[32][33] A prospective study found that in 27 patients diagnosed with polyhydramnios using deepest vertical pocket criteria, only 2 had a deepest vertical pocket ≥8 cm using color Doppler. Importantly, in this study, color Doppler did not change outcomes.[34]

Although the deepest vertical pocket and amniotic fluid index can be used to diagnose polyhydramnios, the deepest vertical pocket is often performed due to its simplicity and its use associated with fewer obstetric interventions and comparable outcomes in patients with oligohydramnios.[31][35][36] However, evidence suggests that the deepest vertical pocket tends to overestimate the amniotic fluid volume, whereas the amniotic fluid index may underestimate it.[34][37] Therefore, the SMFM cautions that using the deepest vertical pocket alone may lead to overdiagnosing polyhydramnios.[2][35]

Evaluation After Diagnosis

Once polyhydramnios is diagnosed, an evaluation should attempt to identify an underlying cause. This process begins with reviewing the prenatal record and obtaining a detailed medical history and obstetric ultrasound.

Routine screening tests: Routine prenatal care includes screening for various potential underlying etiologies, including alloimmunization, aneuploidy, congenital anomalies using a mid-trimester ultrasound, gestational diabetes, and syphilis; appropriate testing should be ordered if not yet completed. Because gestational diabetes is a prevalent cause of polyhydramnios, the SMFM advises that rescreening for gestational diabetes may be considered if it has been at least 1 month since the initial screening was completed.[2] In monochorionic twin gestations, the SMFM recommends screening for twin-twin transfusion syndrome every 2 weeks, starting at 16 weeks of gestation and continuing through delivery.[38]

Targeted obstetric ultrasound: A targeted obstetric ultrasound should be performed as part of the initial assessment of polyhydramnios to evaluate the fetus for common structural causes of excess amniotic fluid. Although congenital anomalies are relatively uncommon in patients with mild disease, the rate of anomalies is approximately 30% to 40% in patients with severe polyhydramnios.[11][14][39][40] According to the SMFM, this targeted ultrasound should assess the fetus for the conditions associated with polyhydramnios, including:

• Fetal growth abnormalities, including both macrosomia and growth restriction
• Fetal hydrops

• Specific structural anomalies
  • Face and palate anomalies
  • Obstructive neck masses
  • Cardiac defects
  • Tracheoesophageal fistula or esophageal atresia, by assessing the presence and size of the stomach
  • Arthrogryposis syndromes, by assessing the positions of the hands and feet
  • Ureteropelvic junction obstructions

• Arteriovenous shunts leading to high-output cardiac failure
  • Sacrococcygeal teratoma, by assessing the lower spine and pelvis
  • Chorioangioma, by assessing the placenta
  • Twin-twin transfusion syndrome in monochorionic twins

• Neurologic dysfunction, by assessing fetal movement and major CNS structures [2]

Other areas that experts often assess include the thoracic cavity for a large compressive mass, the diaphragm for a diaphragmatic hernia, the abdomen for signs of intestinal atresia such as the double bubble sign, and markers of aneuploidy. Middle cerebral artery-peak systolic velocity (MCA-PSV) is indicated in all patients with fetal hydrops to screen for severe fetal anemia; some experts determine the MCA-PSV in all patients undergoing a targeted ultrasound for polyhydramnios.[1][4]

Serum testing for congenital infections: If risk factors such as recent sick contacts or a suspicious rash are present, serum testing for congenital infections may also be appropriate, such as screening or rescreening for syphilis, rubella, parvovirus B19, HIV, hepatitis, cytomegalovirus, and toxoplasmosis. 

Genetic testing: Referral to a genetic counselor and relevant genetic testing is indicated when the history or second-trimester ultrasound suggests a possible genetic abnormality. Amniocentesis and karyotyping can confirm aneuploidy, including trisomies 21, 18, and 13.[1][2][4] Although amniocentesis is generally not indicated specifically for idiopathic polyhydramnios, it should be offered to all pregnant individuals who may elect to undergo the procedure after appropriate counseling.[2] For patients with severe polyhydramnios or when a congenital anomaly is identified, it is appropriate to offer chromosomal microarray analysis or whole genome sequencing, as several conditions, including Bartter, Noonan, Prader-Willi, and Beckwith-Wiedemann syndromes, may be associated with polyhydramnios.[41][42][43] A study found that approximately 5.5% of patients with moderate or severe polyhydramnios had a fetus with a clinically significant genetic anomaly.[42]

When no cause is identified antenatally, the patient is diagnosed with idiopathic polyhydramnios. Occasionally, a cause for the increased amniotic fluid volume is discovered after birth.[2][11] 

Treatment / Management

The management of polyhydramnios depends on its severity and underlying cause. Mild idiopathic polyhydramnios rarely require treatment, whereas those with severe disease are more likely to experience uterine irritability, abdominal pain, or dyspnea that could benefit from treatment.[1][2]

Antepartum Monitoring

Antepartum fetal surveillance: Antepartum fetal surveillance is recommended for patients with moderate-to-severe polyhydramnios starting between 32 and 34 weeks of gestation due to the increased risk of perinatal morbidity and mortality. The SMFM suggests that antepartum fetal surveillance is not required to indicate mild idiopathic polyhydramnios.[2] When performed, antepartum fetal surveillance typically consists of a complete or modified biophysical profile.

Obstetric ultrasound: A repeat ultrasound is appropriate if the patient develops new signs or symptoms indicating their condition is worsening. However, there is no consensus regarding the frequency and interval of follow-up ultrasonography in asymptomatic patients with idiopathic polyhydramnios. These ultrasounds may be used to monitor patients for worsening polyhydramnios or to assess fetal growth, as growth abnormalities are more common with polyhydramnios. Specifically, macrosomia, typically defined as a birth weight >4000 g, can be observed in 15% to 30% of patients with isolated mild polyhydramnios, as larger fetuses have increased urine output. On the other hand, fetal growth restriction in the setting of polyhydramnios is typically associated with underlying pathology, and closer monitoring is warranted.[2] 

Amnioreduction

For symptomatic patients with severe polyhydramnios, amnioreduction can be considered.[2] Amnioreduction is an ultrasound-guided procedure that removes amniotic fluid through a large transabdominal needle, typically a 15-cm 20-gauge needle.[43] Typically, 1.5 and 3 L of fluid are removed during the procedure. However, amnioreduction does not address the underlying cause of excess amniotic fluid, so fluid frequently reaccumulates, limiting the procedure's efficacy. More than one procedure is required in 42% to 46% of individuals.[43][44] Amnioreduction is generally not appropriate for asymptomatic patients or those with non-severe disease.[2] (B2)

In twin gestations complicated by twin-twin transfusion syndrome, amnioreduction was historically the mainstay of treatment. However, most experts now believe that selective fetoscopic laser photocoagulation (SFLP) is a superior treatment for patients with more severe diseases; SFLP treats the root cause of twin-twin transfusion syndrome and appears to be associated with superior outcomes in some studies.[2][45] The SMFM now recommends SFLP for patients with stages II through IV twin-twin transfusion syndrome who are less than 26 weeks of gestation.[2]

Significant adverse events within 48 hours of the procedure are uncommon; if events occur, they may include preterm labor, preterm prelabor rupture of membranes, intrauterine infection, and placental abruption.[43][44][46] However, preterm birth, in general, is relatively common in patients requiring amnioreduction, with individuals delivering on average 3.7 weeks following their first amnioreduction and at an average gestational age of approximately 36 weeks.[43][44] (B2)

Indomethacin

Indomethacin is a prostaglandin synthetase inhibitor that decreases fetal urine output and amniotic fluid volume, in addition to reducing uterine irritability in preterm patients.[47][48][49] However, indomethacin is associated with adverse fetal and neonatal outcomes, such as periventricular leukomalacia, severe intraventricular hemorrhage, and necrotizing enterocolitis, when administered after 32 weeks of gestation.[50] Furthermore, no evidence suggests that indomethacin improves maternal or neonatal outcomes when used specifically for polyhydramnios. Therefore, the SMFM recommends against the use of indomethacin for the sole indication of decreasing amniotic fluid volume.[2] (A1)

However, due to its ability to reduce uterine irritability, a 48-hour course of indomethacin can be a good choice for patients less than 32 weeks gestation with preterm labor contractions related to uterine overdistention from polyhydramnios. For patients less than 32 weeks, a short course of indomethacin before or after amnioreduction is also appropriate for its tocolytic and therapeutic effects. Indomethacin is contraindicated in patients ≥32 weeks; nifedipine or terbutaline are preferred if a tocolytic agent is needed in this population.

Delivery

The delivery timing depends on the severity of polyhydramnios and the presence and severity of any underlying conditions or complications, such as congenital anomalies, preterm prelabor rupture of membranes, and placental abruption. Patients with underlying pathology should be treated according to recommendations specific to the pathology, and those with severe polyhydramnios should be delivered at a tertiary facility due to significant potential increases in maternal and neonatal morbidity and mortality.[1][2] In patients with mild idiopathic polyhydramnios, labor should be allowed to occur spontaneously at term. When induction of labor is planned, it should not occur before 39 weeks in the absence of other indications.[2][51] 

The mode of delivery is based on typical obstetric indications. Even in the absence of diabetes, macrosomia is present in 15% to 30% of patients with idiopathic polyhydramnios, and these patients are significantly more likely to require cesarean delivery.

Upon admission for delivery, the fetal presentation should be sonographically confirmed due to the increased risk of malpresentation, and an external cephalic version may be performed for noncephalic presentations if no contraindications are present.[2] Continuous electronic fetal monitoring is recommended during labor due to studies that show increased rates of nonreassuring fetal heart rate tracings, dysfunctional labor, and complications after membrane rupture, including cord prolapse and placental abruption, in the setting of polyhydramnios.[2]

At delivery, the healthcare team should be prepared for potential complications. Shoulder dystocia is more common with fetal macrosomia and gestational diabetes. Postpartum hemorrhage related to uterine atony is more common following gestations complicated by chronic uterine overdistension, and transient tachypnea of the newborn is encountered in neonates related to persistent fluid in the fetal lungs. Due to the increased risk of transient tachypnea of the newborn, neonatal support should be available for all patients with polyhydramnios.[1][2]

Differential Diagnosis

In patients presenting with abdominal enlargement beyond what is expected for their gestational age, the differential diagnosis includes:

• Macrosomia
• Multiple gestations
• Maternal volume overload due to cirrhosis, ascites, heart failure, end-stage renal disease, or pre-eclampsia
• Tumors, including chorioangioma
• Hematoma in placental abruption

Patients with polyhydramnios may also present with dyspnea or other respiratory difficulties related to compression of the thoracic cavity by the overdistended uterus. In these situations, the differential diagnosis includes:

• Pre-eclampsia spectrum disorders
• Venous thromboembolic events
• Reactive airway disease or exacerbation of a chronic pulmonary condition
• Cardiac arrhythmia or pregnancy-induced cardiomyopathy
• Infection
• Normal discomforts of pregnancy

Prognosis

The prognosis for mild idiopathic polyhydramnios is excellent, though the maternal and fetal prognosis worsens as the severity of polyhydramnios increases. Patients with mild idiopathic polyhydramnios frequently have a self-limited disease that resolves without any intervention.[52] A 2016 study found that polyhydramnios resolved in 37% of patients, all with mild disease.[53] 

In patients with normal antenatal anatomy ultrasound results and mild-to-moderate polyhydramnios, the chance of a significant congenital anomaly being first identified postnatally is 1% to 2%; this risk increases to 11% in patients with severe polyhydramnios.[11] Idiopathic polyhydramnios is also associated with a 3-fold increase in 5-minute APGAR scores less than 7.

For the fetus, the prognosis directly correlates with the underlying cause of polyhydramnios.[1][2] Growth-restricted fetuses with polyhydramnios frequently have significant underlying pathology and, therefore, tend to have the poorest prognosis. In addition, multiple studies suggest that even isolated polyhydramnios is associated with increased rates of intrauterine fetal demise or perinatal fetal mortality.[54][55] Severe and rapidly progressing polyhydramnios is an independent risk factor for perinatal mortality.

Complications

Perinatal and maternal morbidity and mortality increase as the severity of polyhydramnios increases. Polyhydramnios is associated with a higher incidence of fetal macrosomia, malpresentation, placental abruption, cord prolapse, cesarean birth, neonatal respiratory distress, low 5-minute APGAR scores, postpartum hemorrhage, and perinatal mortality.[6][7][27][56][57][58] Rates of preterm labor and preterm prelabor rupture of membranes are also both increased in patients with more severe polyhydramnios compared to the general obstetric population.[54]

Excess amniotic fluid increases the risk of a non-engaged fetal vertex. Therefore, polyhydramnios is a risk factor for fetal malpresentation, umbilical cord prolapse after membrane rupture, labor dystocia, and, as a result of these complications, cesarean birth.[54][57] In addition, uterine overdistention and the rapid uterine decompression that occurs following membrane rupture in patients with polyhydramnios increase the risk of placental abruption. Similarly, chronic uterine overdistention increases the risk of postpartum hemorrhage due to uterine atony.[54][57][59][60]

As mentioned previously, larger fetuses produce larger volumes of urine, and, therefore, rates of fetal macrosomia are higher in patients with polyhydramnios, even in the absence of gestational diabetes. Notably, both isolated polyhydramnios and fetal macrosomia appear to increase rates of shoulder dystocia.[57] 

The neonate is also at risk of numerous potential complications if underlying pathology is present. A large cohort study found rates of major congenital anomalies to be 8%, 12%, and 31% in patients with mild, moderate, and severe polyhydramnios, respectively.[11] Respiratory morbidity in term neonates is also 4.8 times more likely when the pregnancy is complicated by idiopathic polyhydramnios.[56]