Comparison of the Effects of L-Arginine and Fluid Therapy in Pregnant Women with Oligohydramnios
The Role of Amniotic Fluid
Amniotic fluid plays various roles in fetal development, including promoting proper growth, lung maturation, and preventing physical injuries during pregnancy. Naturally, amniotic fluid increases between weeks 32 and 34 of pregnancy, reaching approximately one liter. However, it gradually decreases, reaching about 400 cc at the time of delivery.
Determining Amniotic Fluid Levels
Accurately measuring amniotic fluid volume is challenging. However, the Amniotic Fluid Index (AFI), measured through ultrasound by summing the vertical depths of the largest amniotic fluid pockets in each of the four quadrants of the uterus, is considered a reliable method. Oligohydramnios refers to a lower-than-normal amniotic fluid volume relative to gestational age. This condition can lead to fetal deformities, fetal distress, abnormal presentation, the need for cesarean section, umbilical cord compression, and, in severe cases, fetal death. Based on available sources, an AFI of 8 or above is considered normal, between 5 and 8 is borderline, and below 5 is classified as oligohydramnios.
Benefits of Early Diagnosis
Timely and accurate diagnosis of oligohydramnios, along with proper management, is associated with better pregnancy outcomes. The prevalence of oligohydramnios varies due to differences in diagnostic criteria, study populations (low-risk, high-risk, screening groups), and gestational age. The etiology of oligohydramnios differs based on pregnancy trimester. In the third trimester, the most common causes include premature rupture of membranes, fetal kidney abnormalities, and placental insufficiency, which can lead to intrauterine growth restriction (IUGR).
Prognostic Factors
The prognosis of oligohydramnios depends on various factors such as etiology, severity, gestational age, and the duration of the condition. Studies indicate that patients with this condition generally have a poorer prognosis compared to the control group. While modern diagnostic methods have made detection easier, a highly effective, cost-efficient, and widely accessible treatment remains unavailable. Several therapeutic approaches have been proposed, including fluid therapy.
Mechanism of Fluid Therapy
Fluid therapy works by reducing maternal plasma osmolality, which in turn increases the amniotic fluid index. Another recently introduced treatment for these patients is L-Arginine supplementation. L-Arginine is a semi-essential amino acid utilized by all body cells. It serves as a precursor for nitric oxide, a known vasodilator. Consequently, L-Arginine helps regulate placental perfusion and increases umbilical artery blood flow, which may alleviate fetal growth restrictions.
Study Methodology
In this study, 64 patients were initially assessed. Pregnant women between 28 and 36 weeks of gestation, diagnosed with oligohydramnios based on ultrasound and clinical examination, were included. Before participation, written informed consent was obtained. Inclusion criteria included a singleton pregnancy with an intact amniotic sac and an AFI below 8 cm. Exclusion criteria encompassed pregnancies with fetal anomalies, maternal conditions such as diabetes, severe preeclampsia, lupus, kidney, cardiac, or pulmonary disease, and pre-labor rupture of membranes.
The intervention group received 3 grams of L-Arginine twice daily along with oral or intravenous (IV) fluid therapy. If the patient did not have gestational hypertension, IV Ringer’s lactate was administered at a rate of 3 liters per 24 hours, depending on gestational age and AFI. The control group received only oral (2 liters over 2 hours) or IV (3 liters per 24 hours) fluid therapy.
Study Design
Amniotic fluid levels were measured using ultrasound. The uterus was divided into four quadrants, and the largest vertical fluid pocket in each region was measured and summed to calculate the AFI in centimeters. An AFI below 5 cm was classified as oligohydramnios, between 5 and 8 cm as borderline, and above 8 cm as normal. During IV fluid therapy, patients were monitored for signs of vascular overload. The procedure was carried out under the supervision of high-risk pregnancy nurses, with vital signs checked throughout. Patients were followed weekly via ultrasound until delivery to assess changes in AFI.
Outcome Measures
Primary outcomes included changes in amniotic fluid volume and its effect on gestational age at delivery. Secondary outcomes included Apgar scores at 1 and 5 minutes post-birth, birth weight, gestational age at delivery, delivery method (vaginal or cesarean), small-for-gestational-age (SGA) status (defined as birth weight below the 10th percentile for gestational age), and abnormal fetal presentation.
The sample size was calculated based on a study by Iqbal et al., with a power of 90% and an alpha error of 0.01. Allowing for potential dropout, 25 patients per group were required, totaling 50 participants. A four-block randomization method was used.
Study Findings
The findings of this study suggest that both L-Arginine combined with fluid therapy and fluid therapy alone can effectively increase amniotic fluid volume in pregnant women with oligohydramnios, thereby reducing pregnancy complications. However, L-Arginine with fluid therapy resulted in a greater increase in AFI and a reduction in pregnancy complications compared to fluid therapy alone, making it a potentially superior choice for these patients.
Ultrasound in the Diagnosis of Oligohydramnios
Today, with the use of ultrasound, the diagnosis of oligo-hydramnios has become easier than before. Therefore, it is now possible to easily and quickly diagnose a decrease in amniotic fluid volume and take necessary actions for patients. Various modalities are suggested for patients with oligo-hydramnios, including maternal hydration, antioxidant supplements, and essential amino acids. The use of non-invasive methods that do not require hospitalization and have fewer complications is now receiving more attention.
Ways to Improve Oligohydramnios
One of the simplest ways to improve oligo-hydramnios is maternal hydration. According to physiological principles, the transfer of water between the mother and fetus is regulated by osmotic forces. Due to the higher concentration of electrolytes in the fetus, more fluid is transferred to the fetus. Studies also show that therapeutic fluid can increase amniotic fluid volume in these patients.
L-Arginine
L-arginine is a semi-essential amino acid that is used by all cells in the body. L-arginine consists of an alpha-amino group, an alpha-carboxylic acid group, and a side chain of a three-carbon aliphatic chain in the guanidine group. L-arginine is a precursor to nitric oxide, which is known as a vasodilator. Nitric oxide regulates gonadotropin hormones, egg maturation, ovulation, uterine tube movements, uterine contractions during labor, sperm capacitation, erection, and ejaculation, all of which are functions of this molecule in the reproductive system. L-arginine also regulates placental perfusion. Nitric oxide penetrates smooth muscle cells of blood vessels and causes vasodilation through platelet stabilization in a GMP-dependent process.
Side Effects of L-Arginine
In the present study, no significant side effects were observed in patients receiving L-arginine. Research has also shown that this therapeutic method is safe for pregnant women. Therefore, it seems that maternal hydration combined with this method of treatment is both safe and effective.
Amniotic Fluid Function
Decreased amniotic fluid during labor leads to umbilical cord compression and fetal hypoxia. The results of the present study showed that the average Apgar score in the L-arginine receiving group was higher than that in the fluid therapy group, which could be due to the larger volume of amniotic fluid in these patients. Limitations of this study include not measuring the serum L-arginine level to ensure medication compliance, lack of long-term follow-up for complications and mortality, and the inability to generalize the results because only patients with idiopathic oligohydramnios in the third trimester were included.
It is recommended that studies be conducted with a larger sample size and different doses of L-arginine. The findings of this study suggest that in pregnant women with reduced amniotic fluid volume, L-arginine intake combined with therapeutic fluid infusion, which increases amniotic fluid volume, could lead to better outcomes.
What Happens Due to Decreased Amniotic Fluid?
Decreased amniotic fluid during labor leads to umbilical cord compression and fetal hypoxia. The results of the present study showed that the average Apgar score in the L-arginine receiving group was higher than that in the fluid therapy group, which could be due to the larger volume of amniotic fluid in these patients. Limitations of this study include not measuring the serum L-arginine level to ensure medication compliance, lack of long-term follow-up for complications and mortality, and the inability to generalize the results because only patients with idiopathic oligohydramnios in the third trimester were included.
It is recommended that studies be conducted with a larger sample size and different doses of L-arginine. The findings of this study suggest that in pregnant women with reduced amniotic fluid volume, L-arginine intake combined with therapeutic fluid infusion, which increases amniotic fluid volume, could lead to better outcomes.