Amniotic fluid (AF) volume assessment is an important component of antenatal testing of the fetus at risk for an adverse pregnancy outcome. Both the modified biophysical profile (nonstress test [NST] and amniotic fluid index [AFI]) 1 and the standard biophysical profile (movement, tone, breathing, NST, and presence of a 2 × 1 cm pocket of fluid) 2 include an ultrasound estimation of the adequacy of AF volume as an important component of fetal testing.
Pregnant patients with a low ultrasound estimation of AF volume obtained at term (37 weeks) are sometimes admitted to the hospital for induction of labor with intent to deliver. In preterm pregnancies (less than 37 weeks) with a low estimated AF volume by AFI, patients frequently undergo additional testing, hydration, and even administration of corticosteroids to enhance fetal lung maturity with subsequent early delivery. Oral hydration with hypotonic fluids has been reported to increase the AF volume as measured by the AFI 3–9 or measured by an increase in fetal urine production. 10,11 Intravenous (IV) hydration with hypotonic but not isotonic fluid is reported as increasing the AFI. 12 Other reports, however, have described an increase in the AFI with IV hydration using an isotonic solution. 13–15
A PubMed search was undertaken to determine whether dye-dilution techniques followed by IV hydration and subsequent direct measurement of the AF had been undertaken. The terms “dye dilution, hydration” and “dye dilution, hydration, amniotic” yielded no articles. This investigation was undertaken to determine, by using dye-determined and directly measured volumes, the influence of IV hydration with an isotonic solution on AF volume.
MATERIALS AND METHODS
Women with singleton pregnancies undergoing an amniocentesis for the assessment of fetal lung maturity before a planned cesarean delivery were eligible to participate in this investigation. Exclusion criteria were women who ruptured their membranes after the amniocentesis but before the planned cesarean delivery, women whose fetal maturity studies were immature, women with oligohydramnios or hydramnios, women in whom the AF volume could not be measured at repeat cesarean delivery, and women who declined to participate. Consecutive patients who satisfied the inclusion criteria and consented to participate were enrolled into the study. The Investigational Review Board approved this prospective investigation at the University of Mississippi Medical Center.
After signing the informed consent form, study participants underwent an ultrasound estimate of AF volume using the AFI. The AFI measurement was undertaken by dividing the uterus into four quadrants, with the linea nigra and umbilicus as landmarks. 16 The maximum vertical measurement in each quadrant without an aggregate of cord or fetal extremities was measured in cm; the sum of these measurements constitutes the AF index. Two methods of quantifying AFI measurements were used in the study: one based on AFI percentiles appropriate for gestational age 17 and one based on fixed thresholds constant for all gestational ages. 16 Definitions of low, normal, and high AFI were indicated by AFI less than the fifth percentile, AFI within the fifth to 95th percentiles, and AFI greater than the 95th percentile, respectively. Analogous definitions based on constant depths indicated low fluid (depth less than 5 cm), normal fluid (depths within 5.1–20 cm), and hydramnios (depth greater than 20 cm).
After completing the ultrasound measurement to estimate AF volume, study subjects underwent an ultrasound-directed amniocentesis with sterile techniques. After removal of 5 mL AF for fetal maturity studies and 3 mL AF as the baseline for the dye-dilution technique, 2 mL of a 20% aqueous solution of aminohippurate sodium (400 mg; Merck, West Point, PA) was injected into the amniotic cavity. The needle was left in place over the next 20 minutes, with continuous fetal monitoring of needle placement, fetal position, and fetal heart rate. Every 5 minutes the plunger of the syringe was withdrawn and depressed several times to promote rapid mixing of the aminohippurate with AF. Three milliliters of the AF–aminohippurate was withdrawn after 20 minutes and frozen at −20C until assayed for aminohippurate concentration and calculation of the AF volume. The AF volume was calculated using a dye-dilution spectrophotometric technique. 18 The current dye-dilution technique for calculating AF volume has been evaluated in our laboratory by placing dye into known amounts of AF and determining volumes. 19,20 In vitro this technique is accurate in measuring AF volumes. The dye-determined AF volumes were labeled as low (less than the fifth percentile), normal (fifth to 95th percentile), and high (greater than the 95th percentile), according to published normal volumes by gestational age. 21
All cesarean deliveries were undertaken within 6 hours of the amniocentesis in the pregnancies with evidence of fetal lung maturity. Just before cesarean delivery, study subjects were hydrated IV with 1000 mL of Ringers lactate. Thirty minutes after the IV hydration, the influence of that hydration on AF volume was appraised by a repeat ultrasound measurement of the AFI. Immediately after the AFI measurement, the cesarean delivery was started. The AF volume measurement at abdominal delivery was undertaken with the technique described by Horsager et al. 22 Plastic drapes with large plastic pockets were used on all patients to assist in the collection of the AF at delivery. After the bladder had been reflected away from the lower uterine segment, a 1-cm incision was made in the uterus, and the AF was aspirated into a suction collection device. This suction device used to collect the AF was a device that was in addition to the suction device used for the aspiration of blood or irrigating fluid from the operative field. The suctioning was continued until the AF no longer flowed freely. The fetus was then delivered, and any remaining AF in the uterus, operative field, and drape pockets was collected before delivery of the placenta. The AF volume was measured, and a 3-mL specimen was collected in a tube containing ethylenediaminetetraacetic acid. The hemoglobin concentration was measured in the AF specimen with a Sysmox NE-8000 automated hematology analyzer (Toa Medical Electronics, Los Alamitos, CA) to ascertain the volume of blood contamination. The patient's hemoglobin had been determined before the cesarean delivery and was used for the calculation of the blood volume in the AF. This value was then subtracted from the collected AF volume to determine the corrected true AF volume.
The accuracy of the dye-dilution aminohippurate technique to reliably measure the AF volume has been evaluated in our laboratories and shown to accurately verify an actual AF volume. 23 The confirmation of the predelivery AF volume immediately before cesarean delivery by amniocentesis with the dye-dilution technique and the corroboration of the volume with direct measurement at cesarean delivery permits the impact of an IV bolus of a balanced salt solution to be evaluated.
Seventeen women were recruited into the study, which permitted us to detect an increase between the pre- and posthydration AF volume of 150 mL (against the null hypothesis of 40 mL increase purely owing to chance and using a hypothesized standard deviation of 140 mL) with 82% power while using a two-sided Wilcoxon signed rank test at a 5% significance level. This sample size also permitted us to detect a change in the AFI between the null hypothesis of 0.5–1.4 with 90% power (assumed standard deviation of 1.1). 7 Pre- and posthydration AF volume and AFI indices were compared with the Wilcoxon signed rank test, and median increases in the AF indices and their 95% confidence intervals (CIs) were obtained. 24 Data analysis was conducted using S-Plus statistical software (Mathsoft Inc., Seattle WA). All statistical tests performed were two-sided, and P values less than .05 were considered statistically significant.
Twenty-two women participated in this prospective study between January 2001 and June 2001. The fetal maturity studies on one of the women was immature, there were problems with fluid collection at the time of cesarean delivery on another patient, and three patients were excluded owing to AF volume outside of normal range (one case of oligohydramnios and two cases of polyhydramnios). None of the women who met the inclusion criteria refused study participation. Thus, there were 17 women with pre- and posthydration AF indices for analysis. There were no adverse effects from the amniocentesis or the IV hydration (premature rupture of the membranes or fetal distress) in the evaluated women. The maternal demographics of age, race, gravidity, parity, and gestational age at the time of delivery are presented in Table 1. More than 50% of study participants had a history of a prior cesarean delivery and either desired a repeat cesarean or had had a classical cesarean delivery; the remaining eight women (47%) had preeclampsia (five women) or diabetes mellitus (three women). Median age and gestational age were 26 years (range 17–37) and 36 weeks' pregnancy (range 34–39), respectively.
With the exception of a single patient, AFI indices, whether based on percentiles for gestational age or on constant depth values, reflected normal AF volume. Intravenous hydration resulted in an increase in the AF volume in 16 of 17 patients. In one patient the AF volume decreased from 436 mL to 325 mL despite an increase in the AFI from 5.8 to 6.3. For another patient, there was a reduction in pre- and post-AFI values from 10.3 cm to 10.1 cm, despite an increase in the AF volume from 625 mL to 650 mL. The observed AF indices are summarized in Table 2. The median prehydration AF indices were AF volume of 450 mL (range 250–953), and AFI of 8.6 (range 5.8–17.8). Statistically significant increases in the AF volume and in the AFI were found between the measurements taken before and after the IV hydration (P < .001 for AF volume and AFI changes; Table 2). Median increase in AF volume was 188 mL (95% CI 60, 254), and median increase in AFI was 1.7 cm (95% CI 1.1, 3.0). Comparison of changes in AF volume and AFI relative to the prehydration indices showed a median increase in AF volume of 43% (95% CI 21, 62), and a median increase of 25% (95% CI 15, 27) from the initial AFI.
Low ultrasound estimates of AF volume have been correlated with variable decelerations developing during labor, cesarean deliveries for suspected fetal compromise, and low Apgar scores at delivery. 16 This purported relationship between a low estimation of AF volume and some degree of adverse pregnancy outcome has motivated health care providers to consider delivery of the term pregnant patient with low estimates of AF volume. Based primarily on this single parameter, providers have been known to aggressively pursue delivery in preterm pregnancies despite other assessments of fetal health that are reassuring of fetal well-being. If the ultrasound estimate of AF volume could be increased from a low estimate by some intervention, then additional time for in utero fetal maturity could be realized.
The methodology used to document an increase in AF volume is concerning, because that approach makes use of the AFI that is an ultrasound estimate of the AF volume. The poor correlation between ultrasound estimates of AF volume and dye-determined or directly measured AF volumes 19,20,22 makes the findings using that technique less than reliable. The question remains whether oral or IV hydration truly increases the actual volume of fluid or just changes the ultrasound estimate of that AF volume. The results from the present investigation suggest that the maternal administration of IV fluids can produce not only a modest increase in the AFI of 1.7 cm, as has been demonstrated by other investigations, but an increase in the actual AF volume of 188 mL or, alternatively, a median increase of 43% of the prehydration volume. In the two studies of normal AF volume across gestation, 21,25 AF volume has been observed to remain relatively constant from 22 weeks until late in the third trimester of pregnancy. The stability of the AFI at an 8-hour interval after initiation of treatment with oral water and 1-deamino-[8-D-arginine] vasopressin is suggestive of the length of time that the AF volume may remain increased. 26 The short period between the dye-determined and directly measured AF volume at cesarean delivery (6 hours) and the consistent volumes in the third trimester of pregnancy assist in validating the observed increase in AF volume by IV hydration that was recorded in this study. The technique of determining the AF volume by dye-determination and the confirmation of that volume by direct measurement at cesarean delivery adds corroboration to our conclusions. 23
The effect of oral hydration on the AF volume, as estimated by an increase in the AFI or an increase in fetal urine production has been well documented in a number of investigations. 3–11 The effects of an IV infusion of an isotonic solution into the mother and the effects on the AF volume are less certain. In an investigation comparing an IV infusion of an isotonic fluid, hypotonic fluid, and oral hydration a significant increase in the AFI took place in the oral hydration group and the group infused IV with a hypotonic fluid, but not in the isotonic fluid group. 12 A case report of a women with acute hypovolemia treated with an isotonic infusion administered IV, 13 a retrospective review of women treated with oral hydration or an IV infusion with an isotonic solution, 15 and a study of IV infusion of an isotonic solution in women with preterm ruptured membranes 14 all documented an increasing AF volume as estimated by ultrasound. The complex interactions of fetal production of fluid by the lungs and kidneys, the reabsorption of the fluid by swallowing and the poorly understood intramembranous flow make the understanding of these physiologic processes incomplete. 27
There are limitations to this study. All pregnancies had an AFI less than 5 and a normal AF volume by gestational age at the time of the dye-determined volume. Therefore, the influence of IV hydration on women with an AFI greater than 5 and a low volume of AF by a directly measured or, conversely, a high volume by dye-determined technique or ultrasound estimation remains uncertain. The increase in the AFI with maternal hydration is also a limitation of this study, because the assessor reevaluating the AFI was unblinded, and there is no control group. Nevertheless, the increase in the AFI is consistent with other investigations that have shown an increased AFI with maternal hydration in pregnancies with a low AFI. 3–15 The small sample size is acknowledged. Challenges to performance of such a study as this include the difficulty of enrolling women, the technical challenges of dye-dilution methods, and the difficulty directly measuring AF volume at cesarean delivery. Given these limitations of study design and size, we believe that our conclusions are well founded.
By using the actual AF volume measurements and combining this data with the typically used AFI indices, we confirmed that the increases in AFI indices observed in hydration studies do reflect the increases in the actual AF volume. Further investigations are needed into the length of time that the AF volume remains increased and whether different types of IV solutions could have a variable or greater impact on increasing AF volume. The overall complex dynamics of AF volume and its regulation will need further study to understand the relationship between IV maternal fluid administration and expansion of AF volume.
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