Key words
polyhydramnios - amniotic fluid - high risk pregnancy
Schlüsselwörter
Polyhydramnion - Fruchtwasser - Risikoschwangerschaft
Introduction
Polyhydramnios is the term used to describe an excess accumulation of amniotic fluid.
This clinical condition is associated with a high risk of poor pregnancy outcomes
[1], [2], [3]. The reported prevalence of polyhydramnios ranges from
0.2 to 1.6 % of all pregnancies [4], [5], [6], [7].
Under physiological conditions there is a dynamic equilibrium between the production
and resorption of amniotic fluid. Fluid levels are influenced by fetal urination and
fetal lung liquid production. Amniotic fluid is reabsorbed by fetal swallowing and
intramembranous and intravascular absorption. The relative attribution of each of
these mechanisms varies over the course of the pregnancy. A disturbed equilibrium
can be the result of compromised swallowing function or increased urination and can
lead to polyhydramnios [8], [9], [10], [11].
A fetus close to term will produce between 500–1200 ml urine and swallow between
210–760 ml of amniotic fluid per day. Even small changes in this equilibrium can
result in significant changes in amniotic fluid volumes [9], [10], [11].
Etiology
An underlying disease is only found in 17 % of cases in mild polyhydramnios. In
contrast, an underlying disease is detected in 91 % of cases in moderate to severe
polyhydramnios [5]. The literature lists the following
potential etiologies [5], [7], [12], [13], [14], [15], [16], [17], [18], [19]:
-
fetal malformations and genetic anomalies (8–45 %)
-
maternal diabetes mellitus (5–26 %)
-
multiple pregnancies (8–10 %)
-
fetal anemia (1–11 %)
-
other causes, e.g. viral infections, Bartter syndrome, neuromuscular
disorders, maternal hypercalcemia. Viral infections which can lead to
polyhydramnios include parvovirus B19, rubella, and cytomegalovirus. Other
infections, e.g. toxoplasmosis and syphilis, can also cause polyhydramnios
[80], [81], [82].
Advances in detailed ultrasound scanning and the prevention of Rhesus isoimmunization
in the last decades have changed the relative frequency of these etiologies and
significantly reduced the number of idiopathic cases [12], [13], [14], [15], [16], [17], [18], [19].
Well-known malformations which impair the swallowing reflex include esophageal
atresia, duodenal atresia [16], [17] and neuromuscular disorders such as myotonic dystrophy. Increased
urine production, as occurs with increased cardiac output associated with fetal
anemia, can also result in increased production of amniotic fluid [20], [21]. These changes can
also occur in the context of chromosomal disorders such as trisomy 21 and different
syndromes. Duodenal atresia is the most important etiology in cases with trisomy 21
[79].
Poorly managed gestational diabetes is associated with fetal macrosomia and
polyhydramnios but the pathogenesis has not been elucidated yet [22]. One possible explanation is fetal hyperglycemia
resulting in increased osmotic diuresis which subsequently leads to polyuria. This
theory is supported by evidence of a strong association with high glycosylated
hemoglobin values (HBA1c) in cases with polyhydramnios [22], [23]. According to the
AWMF S3-guideline, polyhydramnios can be an indication of diabetogenic fetopathy.
However, due to the wide range in amniotic fluid volumes, polyhydramnios does not
play an important role in monitoring gestational diabetes [68]. The prevalence of polyhydramnios in maternal cases with diabetes
mellitus is 18.8 % [23]. As the cause could also be fetal
metabolic syndrome, children born after pregnancy complicated by polyhydramnios
should be followed up by a pediatrician [24], [25].
Ultrasound Assessment of Amniotic Fluid Volume
Ultrasound Assessment of Amniotic Fluid Volume
Ultrasound and subjective or semi-quantitative assessment is used to evaluate
amniotic fluid volumes. With the subjective method, the examiner estimates the
volume of amniotic fluid based on personal impressions of the amniotic fluid depot.
The sonographerʼs experience plays an important role here [26]. When evaluating cases of oligo- or polyhydramnios, the use of
biometric measurements and references is more accurate when examiners are less
experienced, while evaluation based solely on subjective assessment is associated
with good results if done by an experienced examiner [27].
Various semi-quantitative methods to measure amniotic fluid volumes have been
described. But these methods also have their limitations which must be taken into
account [28].
Single deepest pocket measurement
For this type of measurement the uterus is divided into four quadrants. The
amniotic fluid volume is measured vertically in the deepest amniotic fluid
pocket. Values below 2 cm indicate oligohydramnios, values over 8 cm indicate
polyhydramnios [30]. The advantage of this method is
its simplicity, making it the most commonly used method in practice. It is also
the method of choice in multiple gestation. In cases with multiple gestation, a
range of 3–8 cm is defined as normal. With this method, polyhydramnios is
classified as mild, moderate or severe. Mild polyhydramnios is characterized by
a value of 8–11 cm, moderate polyhydramnios by a value between 12–15 cm and
severe polyhydramnios by values above 16 cm [86].
The 4-quadrant method (AFI – Amniotic Fluid Index)
With this method, the deepest amniotic pocket in each of the four quadrants is
measured vertically and the values added together. The uterus is divided
vertically into two halves by an imaginary line along the linea nigra. An
imaginary horizontal line through the umbilicus divides the uterus into an upper
and a lower half. During measurement the transducer is held at right angles to
the sagittal plane of the patientʼs abdomen. The transducer should not be tilted
along the maternal abdomen, i.e. it must be kept at a right angle. The measured
amniotic fluid pockets must be free of fetal extremities and the umbilical cord
and must be at least 0.5 cm wide. The Amniotic Fluid Index (AFI) is the sum of
measurements of all four quadrants. According to one study group, AFI values
between 8.1 and 18 cm are normal, values between 5.1 und 8.0 cm indicate
oligohydramnios, an AFI value of less than 5.0 cm indicates severe
oligohydramnios and a value above 18 cm is classified as polyhydramnios [31].
Based on AFI values obtained during prenatal screening, some clinicians
categorize polyhydramnios into three groups according to severity: mild
polyhydramnios (AFI of 25–30 cm), moderate polyhydramnios (30.1–35 cm) and
severe polyhydramnios (≥ 35.1 cm) [87].
Moore und Cayle [32] investigated the distribution of
AFI measurements in a population with normal pregnancies. In contrast to the
definition of oligohydramnios proposed by Phelan et al. (AFI less than 5 cm
[31]) they found that an AFI of 5 cm was only
found in 1 % of normal pregnancies. Intraobserver variation ranged between 0.5
and 1 cm, and interobserver variation was between 1 and 2 cm. Taking the
calculated average of three measurements is recommended to achieve the greatest
accuracy, particularly when the AFI is less than 10 cm [32]. The use of color flow Doppler has the advantage that umbilical
cord loops are detected more easily. But, according to a retrospective study by
Zlatnik et al. [34], AFI measured with color flow
Doppler overestimated oligohydramnios and underestimated polyhydramnios if
standard AFI tables (obtained without color flow Doppler) were used [33], [34].
It should be noted that the pressure exerted by the transducer can change AFI and
single deepest pocket measurements. If the pressure is minimal, AFI increases by
13 %, while if strong pressure is exerted, AFI is underestimated by 21 % [35], [36], [37], [38].
Amniotic fluid quantification in the German Maternity Guidelines
In the German Maternity Guidelines, assessment of amniotic fluid is a standard
examination in prenatal care. Oligohydramnios and polyhydramnios are considered
indicative of a developmental disorder. If there is a suspicion of a
developmental disorder, regular follow-up examinations and further diagnostic
tests are recommended [69]. The diagnosis of
polyhydramnios appears to be independent of gestational week. An enlarged amnion
at the first ultrasound scan in the 7th week of gestation is associated with
early embryonic death [70], [71]. However different constellations can affect prognosis.
Polyhydramnios combined with a small for gestational age (SGA) fetus has a
particularly poor prognosis as this combination is associated with a high
incidence of malformations. Typically, trisomy 18 is a suspected diagnosis [72], [73]. In a
monochoriotic diamniotic twin pregnancy with polyhydramnios in the amniotic sac
of one fetus and oligohydramnios in the amniotic sac of the other, the cause is
often feto-fetal transfusion syndrome [74], [75], [76], [77].
Comparison of the two methods (AFI and SDP)
The goal of amniotic fluid volume quantification is to detect amniotic fluid
pathologies associated with poor outcomes rather than to determine the actual
amniotic fluid volume [29]. A systematic review of
randomized studies found no evidence that one method was superior to another
[39], [40], [41], [89]. Significantly
more cases of oligohydramnios were diagnosed using the AFI method. But there
were no significant differences between methods with regard to prognosis of
perinatal outcome in post-term pregnancies. However, single deepest pocket (SDP)
measurement is the method of choice in multiple pregnancies as it is simpler to
perform and equally effective [90], [91], [92], [93], [94], [95], [96], [97], [98].
Further Diagnostic Tests when Polyhydramnios is Present
Further Diagnostic Tests when Polyhydramnios is Present
Ultrasound investigation
The fetus should be examined carefully during fetal organ screening. The
anomalies most commonly missed at screening are tracheoesophageal fistula,
cardiac septal defects and cleft palate [7]. If a
fetal malformation or several soft markers are present, fetal karyotyping is
recommended after obtaining informed parental consent in accordance with the
German Genetic Diagnosis Act [42], [43], [44], [45]. In a large study, the prevalence of aneuploidy in
fetal anomalies was found to be 10 % (95 % CI: 5–19 %) [7]. The risk of fetal malformation in cases with severe
polyhydramnios has been reported to increase to 11 %, but this figure is still
discussed controversially. The risk of fetal anomalies is 1 % with mild
polyhydramnios and 2 % with moderate polyhydramnios 2 % [99].
In Germany, a detailed ultrasound scan done in an experienced prenatal center
(DEGUM II/III [German Society for Ultrasound Medicine]) is recommended if there
is a high degree of suspicion of fetal malformation.
Some causes, e.g. swallowing disorders and tracheoesophogeal fistula or atresia
can be completely overlooked by ultrasound. In this case, fetal MRI can offer a
better alternative in the diagnosis of tracheoesophogeal fistula or atresia in
utero [82], [83], [84], [85].
Laboratory tests
Laboratory tests to identify causes of polyhydramnios should include:
-
75 g oral glucose tolerance test (OGTT) to exclude gestational
diabetes
-
maternal diagnostic testing for infection (ToRCH serology)
-
if there is a suspicion of fetal anemia or fetal hydrops, tests to
exclude immunological causes (maternal blood group, Rhesus factor,
screening for antibodies) and hematological disorders (possibly
Kleihauer-Betke test to exclude fetomaternal hemorrhage) are indicated.
The literature also lists certain drugs, e.g. lithium, which are
associated with a higher incidence of polyhydramnios. Lithium is a
psychotropic drug prescribed prenatally, e.g. to treat bipolar disorders
[100].
Severe fetal anemia is frequently associated with pleural and pericardial
effusion, ascites and/or skin edema. Measurement of middle cerebral artery peak
systolic velocity is a useful method to diagnose fetal anemia; fetuses with a
peak systolic velocity > 1.5 MoM have a strong risk of anemia.
Intrauterine infection may be suspected based on maternal symptoms or fetal
abnormalities such as hydrocephalus due to toxoplasmosis.
Prognosis
The risk of the following obstetric complications is increased when polyhydramnios
is
present due to over-expansion of the uterus [1], [46], [47]:
-
maternal dyspnea
-
preterm labor
-
premature rupture of membranes
-
abnormal fetal presentation
-
umbilical cord prolapse
-
postpartum hemorrhage
-
fetal macrosomia due to maternal diabetes mellitus
-
hypertensive disorders of pregnancy
-
urinary tract infections
These risks vary depending on the severity and etiology of the polyhydramnios [1], [2], [3]. Perinatal mortality increased 13-fold when the single deepest pocket
was less than 2 cm; when the SDP was less than 1 cm, perinatal mortality increased
47-fold [26].
A prospective longitudinal study of normal singleton pregnancies lists the following
potential complications [34]:
-
higher rates of cesarean sections for fetal indications
-
higher rates of admission to neonatal intensive care units
-
higher birth weight
-
lower 5-minute Apgar scores
In a large study of 85 000 pregnancies, of which 3900 pregnancies had an increased
AFI, it was found that polyhydramnios was an independent risk factor for perinatal
mortality [48]. Small for gestational age (SGA) fetuses
with polyhydramnios had the poorest prognosis [78].
Treatment Options to Reduce Amniotic Fluid Volume
Treatment Options to Reduce Amniotic Fluid Volume
Treatment consists of reducing the volume of amniotic fluid to improve maternal
well-being and prolong the pregnancy. The following methods are used to reduce
amniotic fluid volumes:
-
amnioreduction (therapeutic amniocentesis) [53], [54], [55]
-
pharmacological treatment [49], [50], [51], [52]
Amnioreduction
To date, this method has not been evaluated in randomized or controlled studies,
but it offers a clear clinical benefit if done after careful diagnostic
evaluation. However, there is no consensus regarding the volume of aspirated
amniotic fluid, the speed of aspiration and the use of tocolytics or
antibiotics. The intervention is usually concluded when ultrasound examination
shows an AFI of 15 to 20 cm or if intra-amniotic pressure drops to < 20 mmHg
[53], [66]. In some
cases, the intervention had to be terminated due to maternal discomfort or
premature placental abruption. Tocolytics are routinely used as prophylaxis to
prevent onset of preterm labor.
Complications occur in 1–3 % of cases and can include premature labor, placental
abruption, premature rupture of membranes, hyperproteinemia and amniotic
infection syndrome [52], [54]. After the procedure, regular monitoring of amniotic fluid
volumes is recommended, with monitoring done every 1 to 3 weeks.
Prostaglandin synthetase inhibitor
Prostaglandin synthetase inhibitors stimulate fetal secretion of arginine
vasopressin, resulting in vasopressin-induced antidiuresis [49], [57], [58], [62]. Reduced renal blood flow
reduces fetal urine production. These substances can also inhibit fetal lung
liquid production or increase reabsorption rates [56].
However, prostaglandin synthetase inhibitors have not been approved for this
indication in pregnancy in Germany.
While these substances are used as an analgesic or in anti-inflammatory therapy
in the 1st and 2nd trimesters of pregnancy, patients are advised against using
these substances after the 28th week of gestation [88]. It should be noted that the use of these drugs is not generally
approved in pregnancy.
Sulindac
Sulindac is a non-steroidal anti-inflammatory drug; use of sulindac can also lead
to a reduction of amniotic fluid volume. There are some reports that sulindac
decreases pulsatility in fetal ductus arteriosus less than indomethacin [58], [59], [60], [61]. However, the
efficacy of sulindac has not been confirmed by further studies yet.
Potential Future Experimental Therapies
Potential Future Experimental Therapies
As fetal urine production constitutes the main source of amniotic fluid and changes
in urine production can significantly change the dynamics of amniotic fluid volumes,
the effect of intra-amniotic administration of arginine vasopressin was
investigated. Arginine vasopressin is absorbed into fetal plasma from the
intra-amniotic fluid. The effects of a V2 receptor agonist,
deamino(D-Arg8)-vasopressin, on fetal plasma arginine vasopressin immunoreactivity,
fetal urine production and swallowing was investigated in 6 individual ovine
pregnancies. It was demonstrated that intra-amniotic administration of
deamino(D-Arg8)-vasopressin resulted in persistent fetal antidiuresis with no
cardiovascular effects and no changes in fetal swallowing. Even though the data do
not permit a general conclusion to be drawn, these results indicate this could be
a
potential therapy for polyhydramnios [63].
Another potential therapy is based on mRNA expression in chorion and amnion cells
of
aquaporin (AQP) 1, 8 und 9 in amniotic fluid, which is increased in polyhydramnios.
Aquaporins are water channel proteins which regulate the flow of water across
cellular membranes. AQP1 expression could represent a compensatory response to
polyhydramnios. The effect of reducing this protein on polyhydramnios requires
further study [64], [65]. The
efficacy and safety of these experimental therapeutic approaches should be
investigated in prospective randomized studies.
Monitoring of Pregnancies with Polyhydramnios
Monitoring of Pregnancies with Polyhydramnios
In view of the increased perinatal mortality and morbidity associated with
pregnancies with polyhydramnios, careful monitoring is recommended [46].
Expectant management vs. intervention
There are no prospective randomized studies comparing expectant management to
active intervention in idiopathic polyhydramnios [1].
Intervention is generally recommended in cases with severe maternal discomfort
or obstetric complications, e.g. premature labor.
Delivery
Fetal head presentation should be checked several times during labor, as fetal
position change to breech presentation or transverse lie can occur
intrapartum.
Spontaneous rupture of membranes can lead to acute uterine decompression with the
risk of cord prolapse or placental abruption. Artificial rupture of membranes
should therefore only be done under controlled conditions.
Although polyhydramnios does not constitute a contraindication for the
application of oxytocin or prostaglandins, these substances should be
administered with care. There is an increased risk of atonic bleeding and
amniotic-fluid embolism postpartum [57], [67].
Conclusion
Polyhydramnios diagnosed on ultrasound requires further maternal and fetal diagnostic
tests. Maternal gestational diabetes should be excluded and maternal ToRCH screening
is recommended. Detailed morphological testing should be planned for the fetus.
Delivery in a perinatal center is recommended.
