Several pathways for movement of amniotic fluid and solutes exist, including fetal swallowing, urination, pulmonary secretions, intramembranous movement between fetal blood and the placenta, and transmembranous movement across the amnion and chorion.30 To understand how variations in amniotic fluid volume can affect the fetus, we must first understand fluid dynamics. Amniotic fluid contains 98% to 99% water, with its solute composition changing throughout gestation. In early pregnancy the factors that affect amniotic fluid volume are not well known. What is known is that the osmolarity of amniotic fluid and maternal plasma are similar, suggesting that amniotic fluid is a transudate of maternal plasma originating from either placental surfaces or coming though fetal skin.4 The fetal skin remains nonkeratinized until week 22 to 25, allowing it to act as a membrane through which amniotic fluid can readily pass.61 As the fetal skin becomes keratinized and renal function matures, the hypotonic fetal urine causes the amniotic fluid osmolality to decline from 290 mOsm/kg in the first trimester to approximately 255 mOsm/kg near term.11 Conversely, concentrations of creatinine, urea, and uric acid from the fetal urine increase progressively in the amniotic fluid. Low concentrations of proteins (principally albumin) are found in late pregnancy and provide a minor source of nutrition for the developing fetus. Near term, the amniotic fluid contains increased particulate matter from desquamated fetal skin and gastrointestinal cells, hair, vernix caseosa, stem cells, and occasionally meconium. Surface exchange is the main component of fluid dynamics in early pregnancy before skin keratinization. Beyond 24 weeks, the surfaces in the mouth and nose can additionally act to exchange fluid, but this is not considered a major source of amniotic fluid volume regulation.12 A fundamental source of amniotic fluid, particularly in the second half of pregnancy, is the fetal renal system. This is evidenced by the almost complete lack of amniotic fluid in fetuses with renal agenesis or bladder outlet obstructions. Secretions of the respiratory tract, fetal swallowing, and transport within and across the fetal membranes also contribute to amniotic fluid volume (Figure 25-1). Confirmation of a functioning renal system first starts around 8 to 11 weeks, when urine is initially observed in the fetal bladder. The dilute urine that is produced is thought to cause the observed drop in osmolality and sodium concentration in the amniotic fluid that persists until delivery.4 As pregnancy advances, urinary byproducts are observed at two to three times the concentration found in fetal plasma.32 Estimates of fetal urine output have been made by three-dimensional (3D) measurements of bladder volume at timed intervals and have been found to range from 7 to 70 mL/hour from 24 weeks until delivery in two separate studies.43,77 Fetal urine production is characteristically decreased in pregnancies with abnormalities of placental function that result in intrauterine growth restriction (IUGR).97 However, no correlation is observed between fetal weight and urine production in normal pregnancies. In normal pregnancies, low fetal urine output is not associated with lower Apgar scores, pH less than 7.25, or late decelerations in labor.97 Fluid is excreted from the fetal pulmonary system. Approximately 300 to 400 mL of fluid is secreted per day, driven by chloride ion exchange across the pulmonary epithelium.11 It has been demonstrated in fetal sheep by Brace et al. that half of secreted lung fluid enters the amniotic fluid, and the other half is swallowed upon exiting the trachea.10 Amniotic fluid is prevented from entering the lungs by the closed larynx, producing a new efflux of fluid from the fetal lungs.28 This was confirmed in an investigation by Liley et al. that the intra-amniotic injection of contrast media resulted in few cases of detectable contrast found in the fetal or neonatal lung.2 The net amount of lung fluid entering the fetal amniotic fluid is approximately 150 to 200 mL per day. As further evidence of the entrance of secreted lung fluid into amniotic fluid, the phospholipids found in amniotic fluid are produced by pulmonary cells with one half of the pulmonary secretions going directly into the amniotic fluid and the other half being swallowed. Although meconium staining is not infrequent, with rates in the literature of 7% to 27% based on the population, meconium aspiration past the trachea is rare, less than 1% to 5%, and is usually associated with accompanying neonatal hypoxia.3,27 Rarely, the aspiration of amniotic fluid uncontaminated by meconium has been reported as a cause of neonatal death confirmed at autopsy.8,37 Analogous to renal agenesis being associated with low amniotic fluid, disruption in fetal swallowing is associated with excess amniotic fluid volume. The human fetus demonstrates swallowing around the same time that urine production begins, at 8 to 11 weeks,68 and the swallowed volume increases with gestational age. The ovine model has been used historically to approximate human fetal development.4 Studies evaluating the volume of amniotic fluid swallowed by the fetus were done primarily in sheep models, and found to range between 210 and 1085 mL/day.80,93 Ovine studies have also shown that the amount of amniotic fluid swallowed daily in late gestation is correlated with the amniotic fluid volume, suggesting that the fetus can react and attempt to regulate its amniotic fluid surroundings. This attempted regulation is not thought to be a major controller of volume,9 although the fetus is able to modulate its swallowing. In primate studies, esophageal ligation initially resulted in polyhydramnios, but the polyhydramnios did not persist across gestation and at the time of delivery the amniotic fluid volume was normal.67 Observations of swallowed amniotic fluid volume in near-term fetuses range from 210 to 840 mL per day (average 565 mL). This volume is equivalent to 5% to 10% of the fetal body weight.31 Excess fluid not removed by fetal swallowing is reabsorbed via an intramembranous pathway. More specifically, this is the reabsorption of fluid and solutes from the amniotic compartment to the fetal blood via the amnion.5 This pathway is capable of absorbing large quantities of fluid. As the fluid requirements of the fetus increase with increasing gestation, water flow from the amniotic cavity to the fetal circulation via the fetal membranes increases up to 400 mL/day.65 This is thought to be regulated at least partially by aquaporins found in the human chorioamniotic membranes and the placenta. Aquaporins are small (26- to 34-kDa) cell membrane proteins, which regulate water flux across the cell membranes, have been found to be adaptive to abnormal amniotic fluid levels, and may represent a possible future therapeutic target for abnormal amniotic fluid volume regulation.22,39,99 The osmotic gradient between the amniotic fluid and fetal blood also drives fluids and solutes from the amniotic fluid into the fetal blood.32 The flow of solutes and fluid, although bidirectional, is not necessarily equal.4,26 Vascular endothelial growth factor (VEGF) may also have an impact on intramembranous absorption of fluid. Transmembranous movement of amniotic fluid describes the transport of water and solutes from the maternal circulation to the amniotic compartment via the placenta.5 Overall this has been found to be an insignificant contribution to amniotic fluid dynamics.30 The evaluation of amniotic fluid volume is important during the routine ultrasound evaluation of the fetus because variation above or below normal is associated with increased perinatal morbidity and mortality.18,19 Direct measurement of amniotic fluid volume must be done at the time of hysterotomy with corrections then made for any blood present.35 This, understandably, can only be done at the time of delivery and thus is an impractical technique for serial assessment of amniotic fluid volume across gestation. An indirect measurement can be performed via amniocentesis with subsequent dye-dilution calculation of the amniotic fluid volume.58,81 The relative accuracy of this indicator dilution technique has been validated by comparing the actual amniotic fluid volume at time of cesarean delivery with that predicted immediately before by dye dilution with only a 7% difference between the dye-determined and direct-measurement volumes (r = .99, P < .001).56,63 This method, however, is invasive and requires laboratory support. Magnetic resonance imaging has also been evaluated as a means for estimating amniotic fluid volume;98 however, this is an impractical approach to everyday screening. Because the aforementioned techniques to measure amniotic fluid volume are time consuming, cumbersome, and may require laboratory support, volumes are usually estimated by ultrasound. Sonographic techniques to estimate amniotic fluid volume include subjective (qualitative) estimation and semiquantitative methods: measurement of a two-diameter pocket (2 × 2), maximum vertical or single deepest pocket (SDP), and the amniotic fluid index (AFI). Advantages of sonographic estimates include that they are simple to perform, easy to teach to residents, midwives, and nurses, and are reproducible. In a study comparing all four measurements in singleton pregnancies with dye-dilution technique across different operator experiences, the accuracy of subjective and objective (sonographic) estimates was not affected by operator experience and was similarly accurate in identifying normal amniotic fluid volume. The disadvantage is that they are two-dimensional (2D) representations of a complex, 3D structure with limited significance relative to clinical outcome. Although each has been studied extensively, no technique is universally considered superior at predicting perinatal outcome. In the same study, the accuracy of estimates of all four techniques ranged from 65% to 70%, and the three sonographic estimates were similar, ranging from 59% to 67%. Alarmingly, none of the techniques was accurate in the identification of abnormal volumes (oligohydramnios, or low amniotic fluid, and polyhydramnios, or high amniotic fluid). The accuracy in the identification of normal volumes in twin pregnancies was dismal, ranging from 7% to 29%.53 Amniotic fluid index is the summation of the vertical diameter of the largest pocket in each of the four quadrants, as proposed by Phelan and Rutherford.79 It uses the maternal umbilicus as the central reference point and requires the transducer to be oriented in the longitudinal axis of the maternal abdomen and be kept perpendicular to the floor during scanning. The AFI correlates closely with actual amniotic fluid volume as determined by dye dilution techniques for normal fluid volume, although it loses its predictive value at the upper and lower ends of the extreme. Moore and Cayle established the mean and outer boundaries (5th and 95th percentiles, respectively) for the AFI from 16 to 42 weeks’ gestation in a study of 791 normal pregnancies.69 Magann et al. also established 5th to 95th percentiles, respectively, as 4.2 to 14.9 cm for AFI at gestational age 37 to 41 weeks.48,60 Both can be seen in Figure 25-2. The mean AFI is approximately 12 to 14 cm throughout most of pregnancy, declining after 33 weeks. Above the 95th percentile is approximately 20 cm and below the 5th percentile is approximately 7 cm. The absolute maximum normal AFI is less than 24 or 25 cm. Typical limits for amniotic fluid assessment by AFI are defined in Table 25-1. TABLE 25-1 Diagnostic Categories by Measurement of the Amniotic Fluid Index Data from Moore TR. Oligohydramnios. Contemp Obstet Gynecol. 1996;41:15. The single deepest vertical pocket, as originally described by Chamberlain,40 is simply found by identifying the largest pocket of amniotic fluid after a global assessment and taking the largest vertical measurement with a horizontal measurement of 1 cm. At gestational age 37 to 41 weeks, the 5th to 95th percentile was 2.3 to 6 cm for SDP, and 4.6 to 38.3 cm for a 2D pocket 3.9 to 34.6 cm according to nomograms by Magann et al.60 Typical limits for amniotic fluid assessment by SDP are shown in Table 25-2. TABLE 25-2 Diagnostic Categories by Measurement of the Maximum Vertical Pocket Data from Chamberlain PF, et al. Ultrasound evaluation of amniotic fluid volume: I. The relationship of marginal and decreased amniotic fluid volumes to perinatal outcomes. Am J Obstet Gynecol. 1984;150:245. As stated, the ideal test for sonographic assessment of amniotic fluid volume has not been firmly established. The ideal semiquantitative sonographic technique should be one that correctly identifies the patients at risk for adverse outcome. Amniotic fluid index, SDP, and a two-diameter pocket were compared in a study of 50 normal pregnancies between the gestational ages of 14 and 41 weeks. The prevalence of oligohydramnios as defined by AFI less than or equal to 5 cm, SDP less than 2 cm, or two-diameter pocket less than 15 cm2 were significantly different (P < .0001) for the three techniques (8%, 1%, and 30%, respectively). The prevalence of polyhydramnios as defined by AFI greater than 24 cm, SDP greater than 8 cm, or two-diameter pocket greater than 50 cm2 was also diagnosed with significantly different frequencies (P < .0001) (0%, 0.7%, and 3%, respectively).60 Outcome was not assessed in this study. Subsequently, two prospective randomized trials comparing the use of SDP versus AFI during modified biophysical profiles in complicated pregnancies were performed. Chauhan and colleagues20 studied 1080 women and found that AFI identified oligohydramnios in 17% of pregnancies compared with 10% identified in SDP-assessed pregnancies (P = .002). However, there was no difference in delivery mode, NICU admission, umbilical artery pH, or Apgar score. Magann and colleagues57 had similar findings, showing oligohydramnios was identified in twice as many patients using AFI as compared with SDP in 537 pregnancies (38% vs. 17%, P < .001), resulting in a doubling of inductions of labor (30% vs. 15%, P < .001) and cesarean sections for fetal distress (13% vs. 7%, P < .05). There was, however, no improvement of perinatal outcome. This was confirmed in two meta-analyses51,72 comparing the measurement of AFI to SDP. Neither sonographic test was superior to the other. Both poorly identified abnormal volumes when compared with dye-determined or directly measured amniotic fluid volume. However, AFI overdiagnosed clinically insignificant oligohydramnios, leading to more intervention without a difference in outcome, suggesting that the single deepest pocket may be a superior sonographic assessment for antenatal testing of the at-risk pregnancy.72 Use of color Doppler has not been shown to aid in identification of pregnancies with adverse outcomes. Using dye-determined volume as the benchmark, Magann et al.49 compared gray-scale ultrasonography to Doppler color ultrasonography and found that Doppler not only overdiagnosed oligohydramnios, but labeled 37% of women with normal AFV as having oligohydramnios. Sahin et al.83 attempted to apply the Cavalieri method, a mathematical approximation of volumes, to estimate amniotic fluid volume. Their results correlated with concurrent AFI measurements, and although this is a promising theory, it is complicated to perform and has not been correlated with pregnancy outcome or a directly measured volume. Three-dimensional ultrasound technology has found relevance in the evaluation of the fetus; however, it has not yet found application in the assessment of amniotic fluid. There has been only one attempt to assess third-trimester amniotic fluid volume with 3D ultrasonography. The authors conclude that 3D volume datasets are reliable for determining volume; however, it was determined subjectively by the sonographer based on five volume acquisitions and compared with the value obtained during the 2D ultrasound; there was no attempt at calculating a volume based on a gold standard.15 Interestingly, in the first trimester, growth charts have been developed for gestational sac volume and embryonic volume, the ratio of which correlates positively with gestational age.82 Clinical applications for this data have not yet been developed, but normal versus abnormal early pregnancies are being investigated to determine if these parameters can help predict early adverse outcomes such as miscarriage. Gravid women accumulate approximately 6 L of additional fluid volume during pregnancy. Most of this fluid is associated with the conceptus: 2800 mL in the fetus, 400 mL in the placenta, and 700 to 800 mL of amniotic fluid.84 The remainder of the fluid is associated with the maternal uterus (800 mL), breasts (500 mL), and maternal blood volume expansion (850 mL).84 Throughout gestation, amniotic fluid volume is highly regulated, gradually increasing in the first trimester, stabilizing in the second trimester, and decreasing late in the third trimester while remaining in a relatively narrow range of volumes. Amniotic fluid volume has been defined in both these manners. The 5th and 95th percentiles have been defined for AFI, SDP, the two-diameter pocket, and dye-directed techniques across gestational ages, as fluid has been found to vary significantly throughout pregnancy. Nomograms for amniotic fluid in normal pregnancies were developed by Queenan et al. in 1972 by dye-determined methods,81 Moore and Cayle by AFI,69 Brace and Wolfe by dye-dilution and direct measurement,11 Magann et al. by dye-dilution, direct measurement, and sonographic estimate (Figure 25-3).48,60 Two of these studies showed that amniotic fluid volume increases steadily in early gestation and remains relatively stable between 22 and 38 weeks, averaging 750 to 800 mL. Thereafter, amniotic fluid declines by 8% per week, with a mean volume of approximately 500 mL at 40 to 42 weeks. The third nomogram found that amniotic fluid volume continues to increase throughout gestation, confirming a mean volume of approximately 800 mL at term.48 A study of more than 15,000 patients done by Shanks et al.86 showed that AFI less than the 5th percentile versus a cutoff of 5 cm better predicts fetuses at risk for newborn intensive care (NICU) admission, although this study has been criticized for its retrospective design and the variable intervals between the time the measurement was obtained and the time of delivery. Additionally, an investigation of 291 pregnancies with dye-determined volumes in which the third and fifth percentiles of the AFI were assessed to determine if either of these percentiles was superior to the fixed cutoff of less than 5 for the AFI to detect the 75 pregnancies with oligohydramnios, discovered that both the percentiles (third and fifth) and the fixed cutoff (<5) poorly identified oligohydramnios, but neither was superior to the other.55 Multifetal pregnancies are at a higher risk of perinatal morbidity and mortality than singleton pregnancies. When evaluating the health of the amniotic fluid in twin pregnancies, singleton growth curves currently provide the best predictors of adverse outcomes, and the evaluation of fluid with singleton nomograms is frequently being used. This approach appears reasonable because in the only evaluation of volume in third-trimester diamniotic twin pregnancies, the amniotic fluid volume, or each sac, was similar to that of normal singleton pregnancies.62 Morin and Lim70 performed a literature review with the Diagnostic Imaging Committee of the Society of Obstetricians and Gynaecologists of Canada and suggest that the SDP should be used in each sac with standard definitions for singleton pregnancies, although they state that there is not enough evidence to suggest that one method is more predictive than the others of adverse pregnancy outcome. The AFI has been used to estimate amniotic fluid volume in twins; however, when using the summated AFI (measurement of all four quadrants as is done in singletons but without taking membrane placement into consideration), the measurement poorly predicts dye-determined oligohydramnios and polyhydramnios.1 In a single prospective observational study of 299 diamniotic twin pregnancies, SDP was found to be constant between 17 and 37 weeks, with an increase in fetal labor intolerance and neonatal morbidity in twin pregnancies with polyhydramnios. Alternate fixed cutoffs of less than 2.2 cm for a low amniotic fluid volume and greater than 7.5 cm for a high amniotic fluid volume were suggested in diamniotic twin pregnancies to identify pregnancies at risk for adverse intrapartum and neonatal outcomes (Table 25-3).56 TABLE 25-3 Estimated SDP Percentile Distributions for Each Gestational Age (299 diamniotic twin pregnancies) EGA, Estimated gestational age; SDP, single deepest pocket. Data from Magann EF, Doherty DA, Ennen CS, et al. The ultrasound estimation of amniotic fluid volume in diamniotic twin pregnancies and prediction of peripartum outcomes. Am J Obstet Gynecol. 2007;196(6):570. Hernandez et al.33 performed a retrospective review of 1951 twin pregnancies, both dichorionic and monochorionic, with twin-twin transfusion syndrome excluded. Polyhydramnios was identified in 18% of pregnancies, defined as mild (SDP 8-9.9 cm), moderate (SDP 10-11.9 cm), and severe (SDP ≥12 cm). Pregnancy outcomes were reviewed, and polyhydramnios was not associated with preterm delivery, fetal growth restriction, NICU admission, or neonatal death in either twin. The incidence of major anomalies became more common in increasing polyhydramnios in both monochorionic and dichorionic pregnancies with a prevalence of almost 20% in severe polyhydramnios. Severe polyhydramnios was significantly associated with stillbirth in monochorionic pregnancies (27%, P < .001). Assessing relative amniotic fluid volume in twin pregnancies is also important because disparity in amniotic fluid volume is a significant component of twin oligohydramnios-polyhydramnios sequence (TOPS), of which twin-twin transfusion syndrome (TTTS) is the extreme endpoint. Twin-twin transfusion syndrome carries with it a three- to fivefold increase in mortality and morbidity.90 It is often uncovered with ultrasound evidence of discordant fetal weights and amniotic fluid in monochorionic/diamniotic twins, although it has been documented in monochorionic/monoamniotic pregnancies.89 It may also present sonographically as a “stuck twin,” with the fetus appearing to be suspended to the uterine wall with no intervening membrane visible, or there may be tightly adhered membranes that make a fetus appear wrapped in plastic wrap (Figure 25-4). It is recommended that evaluation for twin-twin transfusion in these pregnancies should begin in the second trimester with weekly surveillance if discordant, and evaluation every 2 weeks for concordant pregnancies.17
Amniotic Fluid Volume
Amniotic Fluid Dynamics
Composition
Production and Regulation
Measurement of Amniotic Fluid Volume
Amniotic Fluid Index Measurement
Amniotic Fluid Volume
AFI Value
Patients
Polyhydramnios
≥25 cm
2%
Normal
>8 to <25 cm
76%
Moderate oligohydramnios
≥5 to ≤8 cm
20%
Severe oligohydramnios
<5 cm
2%
Single Deepest Pocket or Maximal Vertical Pocket
Amniotic Fluid Volume
MVP Value
Patients
Polyhydramnios
≥8.0 cm
3%
Normal
>2 to <8 cm
94%
Moderate oligohydramnios
≥1 to ≤2 cm
2%
Severe oligohydramnios
<1 cm
1%
Comparing Amniotic Fluid Assessment Techniques
Other Techniques
Normal Volume and the Singleton Pregnancy
Twins and Amniotic Fluid
EGA (weeks)
2.5th
5th
10th
50th
90th
95th
97.5th
Twin Sacs
<17
2.02
2.11
2.54
3.96
6.48
6.86
6.88
22
17-19
2.13
2.14
2.64
4.07
6.56
6.97
7.02
143
20-22
2.22
2.23
2.79
4.22
6.6
7.04
7.21
276
23-25
2.23
2.28
2.93
4.38
6.67
7.19
7.45
322
26-28
2.29
2.37
3.06
4.53
6.8
7.44
7.79
390
29-31
2.43
2.46
3.2
4.67
6.91
7.69
8.09
323
32-34
2.44
2.51
3.32
4.8
6.98
7.76
8.27
283
35-37
2.41
2.54
3.39
4.9
7.01
7.81
8.39
129
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