|Year : 2014 | Volume
| Issue : 4 | Page : 429-434
Maternal hydration and L-arginine supplementation improves liquor volume in patients with decreased liquor and prolongs pregnancy
Shripad Hebbar, Lavanya Rai, Prashant Adiga
Department of Obstetrics and Gynaecology, KMC Manipal, Manipal University, Manipal, Karnataka, India
|Date of Web Publication||25-Jun-2014|
Shrigandha, 1-71C, Budnar, Opp. to MGM College, Kunjibettu, Udupi District - 576 102, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Oligohydramnios (reduced amniotic fluid) may be responsible for the problems of malpresentations, umbilical cord compression, meconium staining of amniotic fluid in the liquor, and difficult or failed external cephalic version. Simple intervention maternal hydration has been reported as a way of increasing amniotic fluid volume in order to reduce some of these problems. Objective: To assess the influence of maternal hydration and l-arginine supplementation in improving liquor volume in patients with decreased liquor. Study Design: Prospective nonrandomized interventional study. Materials and Methods: 50 patients remote from term, with decreased liquor [amniotic fluid index (AFI) < 8] were enrolled in the study. Before the proposed intervention, the antenatal risk factors were studied. Patients with hypertensive disorders of pregnancy were administered l-arginine (one sachet 3 g, two times daily) and others received both arginine and intravenous hydration (500 ml of fructodex which contains 5% dextrose and 5% fructose, and lactated Ringer's solution daily). The treatment was continued till the liquor improved significantly. However, patients were considered for delivery if the liquor remained less than 5. Mean increase in liquor, intervention delivery interval, and neonatal outcome were studied. Results: The mean gestational age at the time of recruitment was 33.4 1.9 weeks. The mean AFI at the time of enrolment was 6.9 (SD 0.8). These patients were delivered at 36.3 1.3 weeks, and thus, pregnancy could be prolonged by 2.9 weeks. The mean AFI at the end of therapeutic intervention was 9.3 (SD 1.7), and thus, an AFI increase of 2.4 could be obtained. There was no significant neonatal morbidity in these patients. Significant improvement in liquor volume was obtained in these patients after intervention with either or both l-arginine and fructodex infusion (P < 0.0001). The pregnancy could be prolonged from 33.4 weeks to 36.3 weeks. Conclusion: Treatment with l-arginine and fructodex resulted in significant improvement in liquor and prolongation of duration of pregnancy by around 3 weeks, which enabled us to administer steroids for lung maturation (in indicated cases). Thus, treatment with l-arginine and fructodex seems to be promising in improving fetal outcome in pregnancies complicated by decreased liquor.
Keywords: Amniotic fluid index, L-arginine, maternal hydration
|How to cite this article:|
Hebbar S, Rai L, Adiga P. Maternal hydration and L-arginine supplementation improves liquor volume in patients with decreased liquor and prolongs pregnancy. Med J DY Patil Univ 2014;7:429-34
|How to cite this URL:|
Hebbar S, Rai L, Adiga P. Maternal hydration and L-arginine supplementation improves liquor volume in patients with decreased liquor and prolongs pregnancy. Med J DY Patil Univ [serial online] 2014 [cited 2017 Apr 30];7:429-34. Available from: http://www.mjdrdypu.org/text.asp?2014/7/4/429/135255
| Introduction|| |
Amniotic fluid is one of the essential requirements for appropriate fetal growth and good fetal outcome. Decreased amniotic fluid (oligoamnios) is closely associated with chronic placental insufficiency, impaired lung development, and restricted space for the fetus to grow. Long-term oligoamnios may result in pressure-induced deformities, cord compression, fetal heart rate variation in labor, meconium aspiration, and increased operative delivery.
Amniotic fluid volume normally increases to about a litre between 32 and 34 weeks, but decreases thereafter till term to around 400 ml. Though there are no techniques to measure amniotic fluid quantitatively, four-quadrant assay (amniotic fluid index, i.e. AFI) by ultrasound, to some extent, can predict the amount of amniotic fluid. An AFI of 8 and above is considered normal, between 5 and 8 as low normal, and less than 5 is considered as oligoamnios. , When it is less than 3, the actual amount may be reduced to only a few millilitres of viscid fluid.
In chronic placental insufficiency, the fetus tries to acclimatize by redirecting blood flow to vital organs such as brain and heart at the cost of renal circulation. There is significant reduction in urine output, which results in reduction of available intrauterine space for adequate fetal growth. Subjected to pressure from all sides, the fetus assumes a peculiar appearance and musculoskeletal deformities such as club foot, talipes, and wry neck may be seen. Lack of movement of amniotic fluid within the tracheobronchial tree results in pulmonary hypoplasia.
Different medical and interventional methods have been tried to treat oligohydramnios. The present study was performed to find the effect of maternal intravenous hydration and l-arginine supplementation on AFI, the mode of delivery, and fetal outcome.
| Materials and Methods|| |
This was a prospective interventional study done in the Department of Obstetrics and Gynaecology, KMC Manipal, after getting approval from the institutional research ethics committee. Our ethical committee did not approve enrolling the control group, as the subjects in the control group will be deprived of the benefit. Fifty cases were selected after taking detailed history of present pregnancy and past medical and obstetrical history. The inclusion criteria were gestational age between 28 and 35 weeks, a singleton pregnancy, presence of intact membranes, and initial AFI between 4 and 8. Pregnancies with anomalies, diabetes mellitus, renal disease, prelabor preterm rupture of membranes (PROM), severe preeclampsia, and severe intrauterine growth restriction (where urgent delivery was required) were excluded from the study. Fetal congenital anomalies are known to interfere with production or absorption of amniotic fluid. Diabetes and renal disease may alter the maternal and fetal plasma and urine osmolality. PROM is known to produce decrease in liquor due to constant leak.
The amniotic fluid volume was estimated as AFI in accordance with the four-quadrant technique. The AFI was calculated by summing up the maximum vertical fluid pockets (measured in cm) in each of the four quadrants, as described by Phelan et al.  The examinations were performed with a convex 3.5-MHz probe (Toshiba Medical Systems Corporation, Shimoishigami, Japan). All the AFI estimates were done either by the first or the third author.
We had 11 patients who had gestational hypertension. Though mild preeclampsia was not an exclusion criterion, our series did not have it. Patients with gestational hypertension were administered only l-arginine (one sachet 3 g, two times daily). It is well known that in hypertensive disorders of pregnancy, there is intravenous volume restriction, and hence, the patients may not tolerate fluid challenge. Others received both l-arginine and intravenous hydration (500 ml of fructodex 10% which contains 5% dextrose and 5% fructose and 500 ml of Ringer Lactate) daily. Patients were closely monitored for hemodynamic alterations such as febrile episode, and fluid overload during intravenous infusion. All women complied with the protocol and no maternal complications due to therapeutic intervention were found. No patients were discontinued from the study because of any adverse effects. The treatment was continued till the liquor improved significantly. Whenever there were additional risk factors [Table 2], appropriate management measures as per the standard protocol were taken in addition to the above-mentioned intervention. All patients were monitored regularly with serial nonstress test (NST) and biophysical profile (BPP) till delivery. However, patients were considered for delivery if the liquor remained less than 5 irrespective of the gestational age or when the liquor remained low normal (in the range of 5-8 beyond 36 weeks). Mean increase in liquor, intervention delivery interval, and neonatal outcome were studied.
Data were analyzed using Statistical Package for Social Sciences (SPSS) version 14, and statistical comparisons were made before and after intervention. Student's t-test was used to find the statistical significance of the observations. The differences were considered significant if the P value was less than 0.05 and highly significant if it was <0.01.
| Results|| |
Data for patients' age, parity, gestational age at recruitment, and mean liquor volume are summarized in [Table 1].
The majority of cases were primigravidae (74%). They were detected to have low liquor during their third trimester (range 29-35 weeks) scan for fetal growth and amniotic fluid estimation. We defined low normal liquor as AFI in the range of 5.1-8 cm and oligoamnios as AFI <5 cm. The mean value of AFI was 6.9 cm around 34 weeks in the population we studied.
[Table 2] shows the antenatal risk factors.
Mild intrauterine growth restriction (IUGR) was detected in 34% of patients. Mild IUGR was experienced by those fetuses with biometric parameters (mainly abdominal circumference) falling below 10 th percentile, but with no Doppler changes such as absent or reversed diastolic flow in umbilical arteries, cerebroplacental ratio >1.08, and no venous Doppler changes. We did not include those patients with severe IUGR where urgent delivery was required. Mild elevation of umbilical S/D ratio was not considered as the indicator of severe IUGR in our study. The other major antenatal risk factors included threatened preterm labor and gestational hypertension.
The overall improvement in AFI according to the type of intervention is shown in [Table 3]. Thirty-nine patients received both intravenous fluid therapy and oral l-arginine supplementation (mean duration of treatment: 18.4 days, minimum: 11 days, maximum: 24 days). Eleven patients received l-arginine supplementation (mean duration of treatment: 21.6 days, minimum: 14 days, maximum: 35 days). Those who received only l-arginine supplementation showed an increase of 1.8 cm in AFI and those who received combined intervention improved their AFI score by 2.5 cm. The overall increase in liquor was found to be 2.4 cm [pre-treatment AFI 6.9 (SD 0.8), post-treatment AFI 9.3 (SD 1.7); P < 0.05]. The increase was statistically significant in all the classes.
The end point of the intervention was to achieve reasonable gestational age of 36-37 weeks in our study. The average gestational age at the time of delivery was 36.3 ± 1.3 weeks, and thus, pregnancy could be prolonged by 2.9 weeks. The prolongation of gestation was beneficial for the fetus as it improved their intrauterine stay and growth. There was no significant neonatal morbidity in the babies born.
The obstetric outcome of these patients has been detailed in [Table 4]. It can be seen that 62% of patients had caesarean delivery, the main indication being fetal distress (51.6%). This can be attributed to the fact that foetuses with low liquor are likely to experience cord compression and variable deceleration.
[Table 5] shows the neonatal outcome in these 50 singleton pregnancies. There were no perinatal deaths. There were three neonates who had 5-min APGAR score between 4 and 6. Two of them recovered in neonatal intensive care unit (NICU) with continuous positive airway pressure (CPAP) ventilation. One baby developed respiratory distress and required invasive mechanical ventilation; however, the baby recovered completely. There was no incidence of necrotizing enterocolitis, hypoxic ischemic encephalopathy, or sepsis in any of the babies.
| Discussion|| |
Amniotic fluid has multiple functions. Its main role is to permit fetal lung development by two-way movement of fluid into fetal bronchioles, and early severe oligoamnios is associated with pulmonary hypoplasia in the neonate. Amniotic fluid allows free movements of growing fetus and prevents limb contractures. It prevents adhesions between fetus and amnion and protects the fetus from mechanical injury. Reduction in amniotic fluid in labor is associated with variable amount of umbilical cord compression and fetal hypoxia.
Transabdominal ultrasound has helped obstetricians significantly in the antenatal assessment of amniotic fluid. Though traditionally oligoamnios , is defined as AFI <5 cm and low normal liquor as 5.1-8, there are other accepted definitions of an abnormal amniotic fluid volume. A low amniotic fluid volume has been defined as the following: less than 200 ml,  less than 500 ml,  below 3rd percentile (which is equal to AFI of 4) for gestational age, or a single deepest pocket of less than 2 cm.  Nabhan and Abdelmoula, in their Cochrane review which included five randomized controlled trials comprising 3226 women, found that with AFI of <5 cm, there were more induction rates, higher induction failures without failure to respond to inductions, more cesarean deliveries for fetal distress without much difference in NICU admission rates, and improved perinatal outcome.  They opined that lower cut offs such as 3rd percentile (equal to AFI of 4) or single deepest vertical pocket (less than 2 cm) used for definition of oligoamnios may be of more end benefits. Keeping these facts into consideration, we have used AFI range of 4-8 cm as the inclusion criterion in our study.
Maternal hydration is a well-known therapeutic intervention to improve the placental fluid transfer. With respect to the physiological principles, water transfer between mother and fetus is regulated by osmotic forces, in which electrolyte gradients determine net transplacental water exchange. In an ovine study with maternal fluid overloading, it was reported that a reduction of maternal fetal osmotic gradient facilitated water transfer to the fetus, leading to an increase in fetal urine production. 
Nitric oxide (NO) is an important regulator of placental perfusion, as it plays a role in placental vascular endothelial function. NO is synthesized from the physiologic precursor l-arginine by the stereospecific enzyme NO synthase in what is called the l-arginine/NO pathway, and l-arginine is the only substrate for the production of NO.  NO diffuses into the underlying vascular smooth muscle cells and mediates vasodilatation and platelet stabilization by a cyclic GMP-dependent process.  It is not known whether an improvement of endogenous NO production could enhance fetal growth. NO-induced vasodilation in renal vessels may improve glomerular filtration rate (GFR) and thereby enhance fetal urine production.
Fructodex solution is a combination of dextrose 5% and fructose 5%. Dextrose and fructose molecules readily pass the placental barrier and act as an energy source for the growing fetus and, hence, may be useful in growth-restricted fetuses. They are also readily oxidized to carbon dioxide and water at the end of energy production. Carbon dioxide is readily excreted by maternal lungs and the remaining intravenous fluid acts like hypotonic solution which induces osmotic diuresis in even otherwise normal fetus and improves liquor.
In [Table 6] we have compared the change in AFI in the present study with a few earlier studies. Doi et al. studied the effect of three methods of volume expansion (intravenous hypotonic fluid, intravenous isotonic fluid, and oral rehydration) in Japanese women.  They found significant decrease in maternal hematocrit and plasma osmolality after fluid administration, and these changes were closely correlated with the resultant increase in AFI.
|Table 6: Comparison of results of the present study and previous studies|
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Magann et al. studied 17 women who were undergoing amniocentesis for the evaluation of fetal lung maturity before an elective cesarean delivery.  AFI was obtained before the amniocentesis, and at the time of the amniocentesis, the amniotic fluid (AF) volume was determined by diazo-dye reaction with subsequent spectrophotometric analysis of amniotic fluid samples. Amniotic fluid volume was subsequently estimated after the hydration by a repeat AFI. Amniotic fluid volume was directly measured at cesarean delivery and compared with the dye-determined volume. The prehydration median AF volume was 450 ml (range 250-953), and the median increase in AF volume was 188 ml [95% confidence interval (CI) 60, 254 ml; P < 0.001]. Median AFI was 8.6 (range 5.8-17.8) with a median change in AFI of 1.7 cm (95% CI 1.1, 3.0; P < 0.001). They opined that maternal intravenous hydration increased both the actual and ultrasound-estimated AF volumes in normal third-trimester pregnancies.
Malhotra and Deka evaluated AFI of 25 pregnant women at 3, 24, and 48 h after maternal oral hydration with 2 l of water over 1 h.  Post-hydration AFI at 3 h was significantly greater than pre-hydration AFI. However, AFI values at 24 and 48 h were not significantly different from pre-hydration AFI. Maternal hydration increased the AFI in women with normal and decreased amniotic fluid, but the increase in AFI lasted for less than 24 h.
Fait et al. evaluated the effect of long-term (1 week) oral hydration on amniotic fluid volume in 30 women with an AFI <10th percentile.  The women were instructed to drink at least 2 l of water daily; their AFI was evaluated before and 1 week after the initiation of oral hydration. One week later, the AFI increased from 8.1 ± 0.73 (mean ± SD) to 11.8 ± 2.4 (P < 0.01) in 25 (83%) of the study subjects. They concluded that long-term maternal oral hydration seems to significantly increase the AFI in selected women with reduced fluid and possibly prevents oligohydramnios.
Abida Ahmad studied the effect of intravenous infusion of 200 ml of aminoacids and 500 ml of 10% fructodex on alternate day basis in 20 clinically and sonographically proven cases of oligoamnios.  Significant improvement in amniotic index was observed at the time of delivery.
Sreedharan et al. studied the effect of l-arginine in 100 women diagnosed to have oligoamnios between 28 and 36 weeks of gestation.  The expectant mothers were prescribed sachets of l-arginine containing 3 g of the active ingredient for periods varying between 1 and 4 weeks. There was significant improvement in AFI (by 2.03 ± 0.39 cm), and they opined that l-arginine can be used as a cheaper alternative to ultrasound-guided amnioinfusion in pregnancy complicated by low liquor remote from term.
In a controlled randomized institutional trial, Patrelli et al. recruited 66 women with oligoamnios (AFI < 5) for intravenous infusion of 1500 ml of isotonic solution on a daily basis.  The mean AFI ± SD at recruitment was 3.9 ± 1.1 mm and, at the end of 7 days, AFI increased to 7.7 ± 1.5 mm. They recommended intravenous hydration for all idiopathic oligoamnios as this therapy is simple and free from adverse effects and no special monitoring is required.
Increase in amniotic fluid following maternal hydration (both oral and parenteral) has been shown to improve amniotic fluid volume. [Table 6] compares improvement in AFI in the present study with 3 other studies. In our study, the mean AFI at the time of recruitment was 6.9 cm and the mean gestational age was 33.4 weeks. Prior to delivery, the mean AFI was 9.3, and thus, an AFI increase of 2.4 could be obtained which we presume was definitely helpful for the fetus. These patients were delivered at 36.3 ± 1.3 weeks, and thus, pregnancy could be prolonged by 2.9 weeks.
| Conclusion|| |
Management of pregnant women less than 34 weeks of gestational age with oligoamnios is a challenging situation. To avoid preterm labor induction and to prevent its serious consequences for the mother and newborn, therapeutic intervention is desirable to prolong the pregnancy, so that risks of prematurity are minimized and the obstetrician buys time to administer steroid prophylaxis. Keeping in mind the cost of rearing preterm baby in NICU, intravenous infusion of fructodex and oral l-arginine can be used a cheap and feasible method in resource-poor countries.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]