Assessment of Amniotic Fluid Volume in Pregnancy.

Amniotic fluid (AF) is an integral part of the fetal environment and is essential for fetal growth and development. Pathways of AF recirculation include the fetal lungs, swallowing, absorption through the fetal gastrointestinal tract, excretion through fetal urine production, and movement. In addition to being a marker for fetal health, adequate AF is necessary for fetal lung development, growth, and movement. The role of diagnostic imaging is to provide a detailed fetal survey, placental evaluation, and clinical correlation with maternal conditions to help identify causes of AF abnormalities and thereby enable specific therapy. Oligohydramnios prompts evaluation for fetal growth restriction as well as genitourinary issues, including renal agenesis, multicystic dysplastic kidneys, ureteropelvic junction obstruction, and bladder outlet obstruction. Premature preterm rupture of membranes should also be clinically excluded as a cause of oligohydramnios. Clinical trials evaluating amnioinfusion are underway as a potential intervention for renal causes of oligohydramnios. Most cases of polyhydramnios are idiopathic, with maternal diabetes being a common cause. Polyhydramnios prompts evaluation for fetal gastrointestinal obstruction and oropharyngeal or thoracic masses, as well as neurologic or musculoskeletal anomalies. Amnioreduction is performed only for maternal indications such as symptomatic polyhydramnios causing maternal respiratory distress. Polyhydramnios with fetal growth restriction is paradoxical and can occur with maternal diabetes and hypertension. When these maternal conditions are absent, this raises concern for aneuploidy. The authors describe the pathways of AF production and circulation, US and MRI assessment of AF, disease-specific disruption of AF pathways, and an algorithmic approach to AF abnormalities. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy.

BACKGROUND: Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.Glu500del) in the head domain of ß-cardiac myosin. Both patients display an unusual skeletal myopathy phenotype with congenital axial stiffness and muscular hypertonus, but no cardiac involvement. RESULTS: Clinical data, MRI results and histopathological data were collected retrospectively in two unrelated boys (9 and 3.5 years old). Exome sequencing uncovered the same 3-bp in-frame deletion in exon 15 (c.1498_1500delGAG) of the MYH7 gene of both patients, a mutation which deletes a highly conserved glutamate residue (p.Glu500del) in the relay loop of the head domain of the ß-cardiac myosin heavy chain. The mutation occurred de novo in one patient, whereas mosaicism was detected in blood of the father of the second patient. Both boys presented with an unusual phenotype of prenatal polyhydramnios, congenital axial stiffness and muscular hypertonus. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, whereas the other patient exhibited predominantly stiffness and respiratory involvement. We review and compare all patients described in the literature who possess a variant predicted to alter the p.Glu500 residue in the ß-cardiac myosin head domain, and we provide in-silico analyses of potential effects on polypeptide function. CONCLUSION: The data presented here expand the phenotypic spectrum of mutations in the MYH7 gene and have implications for future diagnostics and therapeutic approaches.

Amniotic Aaquaporins (AQP) in Normal and Pathological Pregnancies: Interest in Polyhydramnios.

Polyhydramnios is a common feature diagnosed by ultrasound in the second half of pregnancy. Biochemical analysis of amniotic fluid can be useful when suspecting Bartter syndrome or digestive atresia but in most of cases, no etiology of polyhydramnios is found because of the complex regulation of amniotic fluid. Aquaporins (AQP) are transmembrane channel proteins contributing to water transfers. Some of them are expressed in fetal membranes and placenta. Their expression has been shown to be disrupted in some pathological conditions such as maternal diabetes, often associated with polyhydramnios. AQP-1, 3 and 8 levels in amniotic fluid were retrospectively measured in patients suffering from polyhydramnios (n=21) from 23 weeks of gestation (WG). They were compared to the levels observed in control subjects (n=96) and their relationship with maternal factors and neonatal issues was analyzed. AQP-1, 3, 8 levels were physiologically fluctuating, AQP-1 levels always being the lowest and AQP-3 the highest, with a significant decrease at the end of pregnancy. AQPs/AFP ratios increased about 8 folds during pregnancy, their kinetic profiles reflecting physiological dynamic evolution of amniotic fluid volume. In polyhydramnios, AQP-3 level tended to be decreased whereas AQP-8 level was decreased from mid-gestation whatever the etiology of polyhydramnios. No significant relationship was found between AQPs levels and either the fetal prematurity degree or macrosomia. No specific pattern was observed in idiopathic polyhydramnios, limiting the interest of AQPs dosage in amniotic fluid in the management of those complicated pregnancies.

Comparative proteome analysis of amniotic fluids and placentas from patients with idiopathic polyhydramnios.

INTRODUCTION: Idiopathic polyhydramnios (IPH) is an abnormal increase in amniotic fluid volume (AFV). This condition has unknown etiologies and is associated with various adverse pregnancy outcomes including maternal and fetal complication. This study aims to establish a comparative proteome profile for the human amniotic fluid (AF) of IPH and normal pregnancies and identify the responsible mediators and pathways that regulate AFV. METHODS: We first employed coupled isobaric tags for relative and absolute quantitation (iTRAQ) proteomics and bioinformatics analysis to examine the differentially expression proteins (DEPs) in the AF of IPH and normal pregnancies. Second, CUL5, HIP1, FSTL3, and LAMP2 proteins were selected for verification in amnion, chorion, and placental tissues by Western blot analysis. RESULTS: We identified 357 DEPs with 282 upregulated and 75 downregulated. Bioinformatics analysis revealed that cell, cellular process, and binding were the most enriched Gene Ontology terms. Amoebiasis, hematopoietic cell lineage, and NF-kappa B signaling pathway were the top significant pathways. In the verification procedure, FSTL3 protein had a highly significant expression in the amnion, chorion, and placentas of IPH and normal AFV groups (p < 0.05). DISCUSSION: Our results provide new insights into idiopathic polyhydramnios and offer fundamental points for future studies on AFV.

Aquaporins in ovine amnion: responses to altered amniotic fluid volumes and intramembranous absorption rates.

Aquaporins (AQPs) are transmembrane channel proteins that facilitate rapid water movement across cell membranes. In amniotic membrane, the AQP-facilitated transfer of water across amnion cells has been proposed as a mechanism for amniotic fluid volume (AFV) regulation. To investigate whether AQPs modulate AFV by altering intramembranous absorption (IMA) rate, we tested the hypothesis that AQP gene expression in the amnion is positively correlated with IMA rate during experimental conditions when IMA rate and AFV are modified over a wide range. The relative abundances of AQP1, AQP3, AQP8, AQP9, and AQP11 mRNA and protein were determined in the amnion of 16 late-gestation ovine fetuses subjected to 2 days of control conditions, urine drainage, urine replacement, or intraamniotic fluid infusion. AQP mRNA levels were determined by RT-qPCR and proteins by western immunoblot. Under control conditions, mRNA levels among the five AQPs differed more than 20-fold. During experimental treatments, mean IMA rate in the experimental groups ranged from 100 ± 120 mL/day to 1370 ± 270 mL/day. The mRNA levels of the five AQPs did not change from control and were not correlated with IMA rates. The protein levels of AQP1 were positively correlated with IMA rates (r(2) = 38%, P = 0.01) while the remaining four AQPs were not. These findings demonstrate that five AQPs are differentially expressed in ovine amnion. Our study supports the hypothesis that AQP1 may play a positive role in regulating the rate of fluid transfer across the amnion, thereby participating in the dynamic regulation of AFV.

Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.

Amniotic fluid volume during mid-to-late gestation depends mainly on the urine excretion from the foetal kidneys and partly on the fluid secretion from the foetal lungs during foetal breathing-like movements. Urine is necessary for foetal breathing-like movements, which is critical for foetal lung development. Bilateral renal agenesis and/or obstruction of the urinary tract lead to oligohydramnios, which causes infant death within a short period after birth due to pulmonary hypoplasia. Lrp4, which functions as an agrin receptor, is essential for the formation of neuromuscular junctions. Herein, we report novel phenotypes of Lrp4 knockout (Lrp4(-/-)) mice. Most Lrp4(-/-) foetuses showed unilateral or bilateral kidney agenesis, and Lrp4 knockout resulted in polyhydramnios. The loss of Lrp4 compromised foetal swallowing and breathing-like movements and downregulated the expression of aquaporin-9 in the foetal membrane and aquaporin-1 in the placenta, which possibly affected the amniotic fluid clearance. These results suggest that amniotic fluid removal was compromised in Lrp4(-/-) foetuses, resulting in polyhydramnios despite the impairment of urine production. Our findings indicate that amniotic fluid removal plays an essential role in regulating the amniotic fluid volume.

Amniotic fluid biochemistry in isolated polyhydramnios: a series of 464 cases.

OBJECTIVE: To report amniotic fluid biochemistry in a large series of 464 cases of isolated polyhydramnios in order to analyze both the outcome and the benefit of amniotic fluid biochemistry. METHODS: This retrospective cohort (2008-2012) included polyhydramnios cases for which amniotic fluid samples were sent to our laboratory for biochemical analysis (total protein, alpha-fetoprotein and gamma-glutamyl transpeptidase) so as to investigate the etiology. A Bartter index and an esophageal atresia index were defined. Final diagnoses were compared between groups to determine the association between these indices and the frequency and type of adverse outcomes. RESULTS: Among 464 cases of polyhydramnios considered isolated at ultrasound examination, severe fetal diseases were diagnosed in 136 (29.3%): 46 (9.9%) chromosomal anomalies, 28 (6%) Bartter syndrome, 23 (4.95%) other genetic syndromes, 22 (4.75%) swallowing disorders and 17 (3.7%) uro-nephrological disorders. Amniotic fluid biochemistry identified esophageal atresia with 66.6% (10/15) sensitivity and 100% specificity and Bartter syndrome with 85.7% (24/28) sensitivity and 84.2% specificity. CONCLUSION: Isolated polyhydramnios is associated with a high risk of severe fetal diseases. Molecular cytogenetics and amniotic fluid biochemistry are helpful tools.

Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates.

OBJECTIVE: Uterine overdistention is thought to induce preterm labor in women with twin and multiple pregnancies, but the pathophysiology remains unclear. We investigated for the first time the pathogenesis of preterm birth associated with rapid uterine distention in a pregnant nonhuman primate model. STUDY DESIGN: A nonhuman primate model of uterine overdistention was created using preterm chronically catheterized pregnant pigtail macaques (Macaca nemestrina) by inflation of intraamniotic balloons (N = 6), which were compared to saline controls (N = 5). Cesarean delivery was performed due to preterm labor or at experimental end. Microarray, quantitative reverse transcriptase polymerase chain reaction, Luminex (Austin, TX), and enzyme-linked immunosorbent assay were used to measure messenger RNA (mRNA) and/or protein levels from monkey (amniotic fluid, myometrium, maternal plasma) and human (amniocytes, amnion, myometrium) tissues. Statistical analysis employed analysis of covariance and Wilcoxon rank sum. Biomechanical forces were calculated using the law of Laplace. RESULTS: Preterm labor occurred in 3 of 6 animals after balloon inflation and correlated with greater balloon volume and uterine wall stress. Significant elevations of inflammatory cytokines and prostaglandins occurred following uterine overdistention in an "inflammatory pulse" that correlated with preterm labor (interleukin [IL]-1ß, tumor necrosis factor [TNF]-α, IL-6, IL-8, CCL2, prostaglandin E2, prostaglandin F2α, all P < .05). A similar inflammatory response was observed in amniocytes in vitro following mechanical stretch (IL1ß, IL6, and IL8 mRNA multiple time points, P < .05), in amnion of women with polyhydramnios (IL6 and TNF mRNA, P < .05) and in amnion (TNF-α) and myometrium of women with twins in early labor (IL6, IL8, CCL2, all P < .05). Genes differentially expressed in the nonhuman primate after balloon inflation and in women with polyhydramnios and twins are involved in tissue remodeling and muscle growth. CONCLUSION: Uterine overdistention by inflation of an intraamniotic balloon is associated with an inflammatory pulse that precedes and correlates with preterm labor. Our results indicate that inflammation is an early event after a mechanical stress on the uterus and leads to preterm labor when the stress is sufficiently great. Further, we find evidence of uterine tissue remodeling and muscle growth as a common, perhaps compensatory, response to uterine distension.

Decreased umbilical orexin-A level is associated with idiopathic polyhydramnios.

OBJECTIVE: To evaluate the association between orexin-A level and idiopathic polyhydramnios. DESIGN: Case-control study. SETTING: Tertiary-level university hospital. POPULATION: Ten term pregnant women with idiopathic polyhydramnios and, as the control group, 20 pregnant women with normal amniotic fluid levels. METHODS: Amniotic fluid level was measured at admission for delivery using enzyme-linked immunosorbent assay. Maternal blood was obtained from a cannulated vein immediately before delivery, and umbilical blood was collected at the time of delivery, before the separation of the placenta. MAIN OUTCOME MEASURES: Maternal and umbilical levels of orexin-A. RESULTS: Mean umbilical serum orexin-A level was significantly lower than maternal serum orexin-A level. Umbilical serum orexin-A level was positively correlated with maternal serum orexin-A level, but negatively correlated with amniotic fluid index and birthweight. Umbilical serum orexin-A level was lower in the idiopathic polyhydramnios group than in the control group. However, no difference in maternal serum orexin-A level was observed between the two groups. CONCLUSIONS: Idiopathic polyhydramnios was associated with decreased umbilical serum orexin-A levels. Our results provide evidence that orexin-A expression may be involved in amniotic fluid regulation, causing polyhydramnios by downregulation.

The expression and regulation of aquaporins in placenta and fetal membranes.

Previous studies by our group as well as other researchers have found expression of Aquaporins (AQPs) 1, 3, 8, and 9 in human chorioamniotic membranes and placenta. Our previous study found that the alteration of the expression of AQPs 1, 3, 8, and 9 in placenta and fetal membranes was an adaptive response to maintain amniotic fluid homeostasis in case of abnormal amniotic fluid volume, which is likely to affect the intramembranous absorption and transport of water and solute from mother to fetus. However, the actual regulation mechanisms of intramembranous absorption and placental water flow are not yet clear, making it difficult to treat abnormal amniotic fluid volume effectively. Several studies found that many factors, including hormone levels, osmotic pressure, temperature, and oxygen concentration, regulate expression of AQPs in placenta, fetal membranes, and other mammalian organs through several signal transduction pathways, such as the cAMP, the MAPK, the PI3K/AKT, and the PKC pathways. These factors could provide potential therapeutic targets for the treatment of abnormal amniotic fluid volume.

Clinical significance of amniotic fluid glucose concentration in polyhydramnios.

OBJECTIVE: To evaluate whether amniotic fluid glucose concentration can predict poor neonatal outcome in cases with polyhydramnios as an overall assessment. METHODS: In this retrospective study, we have reviewed 42 consecutive pregnant women with singleton gestations complicated with polyhydramnios who gave birth at one tertiary care center between January 2003 and September 2010. Perinatal clinical findings were reviewed, and the neonatal outcome, such as livebirth or stillbirth and early neonatal death, was compared. A p value less than 0.05 was considered to be significant. RESULTS: Thirteen of 42 neonates had a poor outcome, including stillbirth or early neonatal death. Multiple logistic regression analysis showed that amniotic fluid glucose (p = 0.042) was significant factor influencing poor neonatal prognosis [odds ratio 0.66; 95% confidence interval 0.44-0.98]. Receiver operating characteristics curve and sensitivity and specificity curve showed that the optimal cut-off value of amniotic fluid glucose concentration for predicting poor neonatal outcome was 17 mg/dl. CONCLUSIONS: Amniotic glucose concentration less than 17 mg/dl and the presence of congenital heart anomaly were better predictors for a poor postnatal outcome in cases with polyhydramnios.

[Implications of retinoid pathway in human fetal membranes: study of target genes]. / Étude de la voie des rétinoïdes au sein des membranes fœtales humaines: mise en évidence de gènes cibles.

Retinoids (active derivatives of vitamin A) were already demonstrated to be important morphogenes and their implication at the placental and fetal level was already established. A new field of research is now developed in order to show their role on fetal membranes constituted by amnion and chorion. To describe the role of retinoids on these membranes, our studies were focused on target gene research. Firstly, all metabolism enzymes needed to vitamin A pathways were demonstrated to be present and active in signal transduction. Secondly, a bioinformatic analysis was performed to assess a list of potential target genes that could be classified in different biological pathways (inflammation, retinoids, hormones, vascularization, extracellular matrix and water homeostasis). Then, it was demonstrated that the gene coding for PLAT, implied in the degradation of extracellular matrix during programmed or premature rupture of membranes, is regulated by retinoids in a two steps mechanism. Finally, preliminary data showed that some aquaporins, which control water transport across membranes, are expressed and regulated by retinoids in the fetal membranes. A disregulation in pathologies like oligo or poly-hydramnios can be anticipated. Improvement of our knowledge about the retinoid implications is a key point in order to obtain a precise and complete documented cartography of the vitamin A (regulating) in amniotic membranes (regulated) that will permit the development of new diagnostic and therapeutic strategies.

Biochemical amniotic fluid pattern for prenatal diagnosis of esophageal atresia.

Prenatal diagnosis of esophageal atresia (EA) may improve the outcome of affected neonates by allowing optimization of both prenatal and postnatal care. Prenatal sonographic detection is based on polyhydramnios and/or nonvisualization of the fetal stomach bubble, two signs with a large number of etiologies. We evaluated a biochemical approach to improving diagnostic efficiency. We compared amniotic fluid biochemical markers in 44 EA cases with 88 polyhydramnios and 88 nonpolyhydramnios controls. Both matched for GA with cases. Total proteins, alpha-fetoprotein (AFP), and digestive enzyme activities were assayed, including gamma-glutamyl transpeptidase (GGTP). We defined an EA index (AFP multiplied by GGTP). A significant difference (p < 0.0001) was observed for total protein, AFP, GGTP, and EA index between the EA group and each of the two control groups. No statistical difference was observed for any marker between the two most frequent EA subgroups (type I and type III) or between the two control groups. Using a cutoff of 3 for the EA index, 98% sensitivity and 100% specificity were observed for amniotic fluid prenatal diagnosis of EA, whatever the anatomical type. A large prospective series is required to confirm these results.

The expression of aquaporin 8 and aquaporin 9 in fetal membranes and placenta in term pregnancies complicated by idiopathic polyhydramnios.

BACKGROUND: Aquaporins are a family of membrane-bound water channel proteins that regulate the flow of water across a variety of biological membranes. The expression of aquaporin 8 and aquaporin 9 has been demonstrated in human chorioamniotic membrane and placenta. But their roles in the pathophysiology of polyhydramnios are unclear. AIMS: To study the expression of aquaporin 8 and aquaporin 9 in fetal membranes and placenta in term pregnancies complicated by idiopathic polyhydramnios and to explore the association between aquaporin expressions and polyhydramnios. SUBJECTS: The placentas were collected from 51 patients who underwent elective Cesarean sections at term, of which 21 cases had idiopathic polyhydramnios and the other 30 had normal amniotic fluid volume. OUTCOME MEASURES: Real-time polymerase chain reaction and immunohistochemistry techniques were used to determine the expression and localization of aquaporin 8 and aquaporin 9 in the amnion, chorion and placenta. RESULTS: Expression of aquaporin 8 and aquaporin 9 was detected in the amnion, chorion and placenta and located in amnion epithelia, chorion cytotrophoblasts and placental trophoblast. Compared to normal amniotic fluid volume group, the expression of aquaporin 8 in amnion, and aquaporin 9 in amnion and chorion, were significantly increased in idiopathic polyhydramnios group; however, their expression in the placenta was significantly decreased. CONCLUSIONS: When polyhydramnios occurs, expression of aquaporin 8 and aquaporin 9 in fetal membranes and placenta is an adaptive change, which may be involved in the regulation of amniotic fluid volume. However, the modulation factors of the aquaporin 8 and aquaporin 9 expressions need further study.

[Expression of aquaporin 8 in human fetal membrane and placenta of idiopathic polyhydramnios].

OBJECTIVE: To determine the expression of Aquaporin 8(AQP8) in the fetal membrane and placenta of idiopathic polyhydramnios. METHODS: The amnion, chorion and placenta were collected from 12 term pregnancies with idiopathic polyhydramnios( polyhydramnios group) and 12 term pregnancies who were normal (control group). The expression of AQP8 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of AQP8 protein was detected by immunohistochemistry. RESULTS: The expression of AQP8 mRNA in amnion, chorion and placenta of polyhydramnios group was (0.78 +/- 0.13), (0.58 +/- 0.10), and (0.86 +/- 0.15) respectively, and that of control group was (0. 39 0.07), (0.45 +/- 0.09), and (0.34 +/- 0.09) respectively. The expression of AQP8 protein in amnion, chorion and placenta of polyhydramnios group was (0.195 +/- 0.024), (0.170 +/- 0.028), and (0.193 +/- 0.024) respectively, and that of control group was (0.151 +/- 0.018), (0.156 +/- 0.024), and (0.152 +/- 0.023) respectively. In all 3 types of tissues the expression of AQP8 mRNA of polyhydramnios group was higher than that of control group (P < 0.05). In amnion and placenta the expression of AQP8 protein of polyhydramnios group was also increased compared to that of control group (P < 0.05), but in chorion the difference in AQP8 protein expression between the two groups was not significant (P > 0.05). CONCLUSION: The expression of AQP8 mRNA and protein is significantly increased in the amnion and placenta of polyhydramnios, suggesting that AQP8 may play an important role in the regulation of amniotic fluid volume.

[Expression of aquaporin 3 and aquaporin 9 in placenta and fetal membrane with idiopathic polyhydramnios.].

OBJECTIVE: To investigate the pathogenesis role of aquaporin 3 and aquaporin 9 in idiopathic polyhydramnios by detecting their expression and distribution in fetal membranes and placenta. METHODS: Twenty-one of term pregnancy women with idiopathic polyhydramnios were enrolled as patient group matched with 30 women with normal term pregnancy as control group. The expression and localization of aquaporin 3 and aquaporin 9 in fetal membranes and placenta were detected by real-time polymerase chain reaction and streptavidin peroxidase immunohistochemiscal staining. RESULTS: (1) The mRNA expressions of aquaporin 3 and aquaporin 9 were detected in amnion, chorion and placental tissue in both patient group and control group. Both aquaporin 3 and aquaporin 9 were demonstrated positive staining in the amnion epithelia, chorion cytotrophoblasts and placental trophoblast. (2) The ratio of aquaporin 3 and aquaporin 9 mRNA expressions in amnion in patient group comparing to those in control group were 5.00 and 3.25, while in chorion they were 2.03 and 2.08. When compared with those in amnion and chorion of control group, there was a significant difference (P < 0.01). However, the relative change fold of aquaporin 3 and aquaporin 9 in placental trophoblast in patient group were decreased in comparison of those in control group, which also showed statistical difference (P < 0.01). (3) The expression of aquaporin 3 and aquaporin 9 protein in amnion were 7.5 +/- 2.0 and 11.1 +/- 1.8 in patient group, while they were 5.3 +/- 1.6 and 5.6 +/- 2.3 in control group. In chorion, the expression of aquaporin 3 and aquaporin 9 protein was 7.5 +/- 2.0 and 10.0 +/- 1.6 in patient group, respectively, while in control group, they were 5.4 +/- 2.2 and 5.6 +/- 2.1. When compared with those proteins in control group, it exhibited statistical difference (P < 0.05). However, in placental trophoblast of patient group, the expression of aquaporin 3 and aquaporin 9 protein were 3.5 +/- 1.4 and 4.0 +/- 2.5, respectively, which were significantly decreased than 5.6 +/- 1.3 and 7.1 +/- 2.9 in control group (P < 0.05). CONCLUSIONS: The alterations of aquaporin 3 and aquaporin 9 expressions in fetal membrane and placenta might be an adaptive response to idiopathic polyhydramnios. Further investigation should be needed to clarify the regulatory mechanism of aquaporin 3 and aquaporin 9 expressions.

Acute recurrent polyhydramnios: a combination of amniocenteses and NSAID may be curative rather than palliative.

Acute recurrent polyhydramnios is a rare occurrence characterized by a poor fetal outcome. This is a case report describing a 34-year-old woman presenting with acute recurrent polyhydramnios. Treatment with non-steroidal anti-inflammatory drugs (NSAID) and therapeutic amniocenteses was initiated immediately and resulted in a decreased amniotic fluid production from 30 weeks' gestation. Even after the discontinuation of NSAID treatment, the amniotic fluid production normalized, and the woman delivered a healthy boy at 39 weeks 2 days' gestation. Amniotic prolactin was measured at three occasions using an enzyme-linked immunosorbent assay. As in normal pregnancies, amniotic prolactin levels decreased by 80% from highest to lowest value in this case of resolving acute recurrent polyhydramnios.

Stretching, mechanotransduction, and proinflammatory cytokines in the fetal membranes.

In the third trimester of normal pregnancy, the human fetal membranes become increasingly distended and use mechanotransduction and its downstream signaling to remodel and function. Their overdistension either by multifetal pregnancy or by polyhydramnios often leads to preterm birth, but the mechanism is unclear. Stretching of the fetal membranes in vitro upregulates several cytokines and enzymes that can drive collagen degradation, leading to membrane rupture. The sensitivity of this response appears to be specific for different cell types and is likely to result from differential activation of some key transcription factors and cofactors. Few cytokines in the fetal membranes respond to stretch: the most robust of these is pre-B-cell colony-enhancing factor (PBEF). This is constitutively expressed and protects the amnion cells from apoptosis caused by chronic static distension. However, it can also be stimulated by inflammation, infection, and hypoxia and upregulates a number of proinflammatory cytokines, chemokines, and enzymes important in the initiation of parturition. Therefore, it is proposed here that PBEF functions in normal pregnancy to protect the amnion cells as they become increasingly stretched, but if stimulated, it can initiate key events leading to parturition.

Steady-state levels of aquaporin 1 mRNA expression are increased in idiopathic polyhydramnios.

OBJECTIVE: Polyhydramnios is a condition associated with significant perinatal morbidity. While the exact pathophysiology of this condition is unknown in the absence of obvious anatomic or organic etiologies, impaired intramembranous water transport has been shown. Previous studies from our laboratory have shown that the water channel aquaporin 1 (AQP1) is expressed in human fetal membranes from term pregnancies with normal amniotic fluid (AF) volume. Therefore, we hypothesized that in pregnancies with idiopathic polyhydramnios, AQP1 expression might be reduced in fetal membranes from pregnancies with this AF volume disorder. STUDY DESIGN: Placentas were collected from women at term (37-40 weeks) who presented with either polyhydramnios (amniotic fluid index [AFI] >24.0 cm) or normal AF volume (AFI 5.0-23.9 cm). Immediately after delivery, the membranes (amnion and chorion) directly overlying the placenta and the free-floating reflected membranes were sampled (total of 4 samples from each placenta). RNA was isolated from each sample and expression was quantified using real-time reverse transcriptase polymerase chain reaction (PCR) and relative quantification of gene expression. RESULTS: Relative to pregnancies with normal AF volume, there was an increase in expression of the water channel AQP1 in all regions of the fetal membranes. The greatest increase (33-fold) was seen in the reflected amnion. CONCLUSION: AQP1 expression is increased in polyhydramnios. This finding suggests that alterations in AQP1 expression may be a compensatory response to and not a cause of idiopathic polyhydramnios. We speculate that therapies focused on regulating AQP1 expression may be useful for treating this condition.