amniotic fluid and fetal plasma.

More research is needed to fully understand the benefits and potential Amnio-well

areas like hypersleep stasis

Amnio-well (AL) is a synthetic amniotic fluid developed for potential use in fetal therapy and research. It's designed to mimic the composition of natural amniotic fluid, including electrolytes, pH, albumin, and glucose levels. A study showed that Amnio-well is less toxic to human amnion cells in vitro compared to other solutions like normal saline or lactated Ringer's solution

 A recently described mathematical model of human amniotic fluid dynamics used known and estimated rates of fetal fluid production (lung liquid and urine) and composition (osmolality) to enable calculation of previously unmeasured routes of amniotic fluid resorption, including fetal swallowing and intramembranous (across the amnion) water flow. This "osmolar" model assumed that only free water resorption occurred across the intramembranous route. We hypothesized that intramembranous flow also may include solutes and electrolytes because significant concentration gradients exist between amniotic fluid and fetal plasma. We used mass balance analysis to determine the direction and magnitude of intramembranous sodium flux and to assess the ability of a newly described "sodium" model to predict changes in amniotic fluid volume in response to changes in intramembranous electrolyte flow. Mathematical modeling was used to predict changes in amniotic fluid volume in response to changes in intramembranous electrolyte flow. Study Design: Model predictions were calculated using published values for human amniotic fluid and fetal urine composition and volume. Ovine studies were used to derive lung fluid volumes and composition. Fetal swallowing and intramembranous flow were independently determined using net amniotic fluid osmolar (osmolality model) and sodium (sodium model) balance. Differences between osmolality and sodium model predictions were normalized to calculate the net intramembranous sodium flux, assuming a net balance of intramembranous osmotic solute flow. Results: Both sodium and osmolality models predicted swallowed volume to be greater than intramembranous flow until 28 to 32 weeks' gestation, after which the relationship reversed. However, the sodium model predicted greater intramembranous flow and lower swallowing rates compared with the osmolality model at all gestational ages. Osmolar mass balance required daily intramembranous sodium flux into the amniotic fluid, which increased with gestational age. Furthermore, assuming stable swallowing and intramembranous water flow, the model predicts that 5% increases or decreases in amniotic fluid solute concentrations caused by intramembranous flux result in polyhydramnios or oligohydramnios, respectively. Conclusion: Sodium and osmolality models demonstrate similarities in determinations of amniotic fluid dynamics. However, mass balance equations demonstrate a net intramembranous flow of sodium into the amniotic fluid under normal conditions. Mathematical modeling suggests that small alterations in daily intramembranous sodium flux may evoke large changes in amniotic fluid volume. (Am J Obstet Gynecol 1998;178:484-90.)

Synthetic amniotic fluid

Changes in induction of labor and cesarean delivery post ARRIVE trial: a quasi-experimental analysis Rachel Wood1 , Taylor S. Freret2 , Mark A. Clapp2 , Sarah E. Little1 1 Brigham and Women’s Hospital, Boston, MA, 2 Massachusetts General Hospital, Department of Obstetrics and Gynecology, Boston, MA OBJECTIVE: The ARRIVE trial, published in Aug 2018, showed elective induction of labor (IOL) for low-risk nulliparas at 39- weeks decreased cesarean delivery (CD). We used interrupted time series (ITS) analysis to assess changes in practice patterns in the US after ARRIVE and any impact on CD or birth after 41-weeks gestation. STUDY DESIGN: This study was a population-level ITS analysis using Poisson regression of low-risk nulliparas who delivered at
39- weeks gestation using US birth certificate data. Low-risk was defined as singleton, vertex-presenting, non-anomalous births with no chronic hypertension or gestational or pre-gestational diabetes. AugOct 2018 was used as the dissemination period. Monthly rates and temporal trends of 39-week IOL, CD, and
41-week delivery before and after the dissemination period were compared between Jan 2016-Mar 2020. Seasonality was accounted for with sine and cosine terms with minimal evidence of residual autocorrelation. RESULTS: A total of 2,862,272 births were included (1,829,157 preARRIVE and 1,033,115 post-ARRIVE). In the immediate postdissemination period, 39-week IOL rates were higher than predicted (15.0% vs 13.7%, IRR 1.096, p< 0.001),
41-week delivery rates were lower (14.1% vs. 15.1%, IRR 0.937, p< 0. 001), and CD rates were lower (24.7% vs. 25.1%, IRR 0.984, p< 0. 001). Temporal changes were also noted in the post-dissemination period: an increase of 9/1,000 inductions at 39-weeks per month, decrease of 1.4/ 1,000 CD per month, and decrease of 8.7/1,000 births at
41 weeks per month (p< 0.001 for all) (Figure). CONCLUSION: Publication of the ARRIVE trial was associated with increasing rates of 39-week induction and decreasing rates of CD and
41-week delivery in low-risk nulliparas. This builds on prior reports by incorporating more time post-ARRIVE publication, allowing for analysis of changes in trends over time, and by using a robust quasi-experimental methodology, which can overcome limitations of traditional observational studies. These results suggest that the ARRIVE trial findings are generalizable outside of the clinical trial setting. 16 Creation of a synthetic amniotic fluid for use in fetal therapy Braxton Forde1 , Marc Oria2 , Jose Peiro2 1 Division of Maternal-Fetal Medicine, University of Cincinnati Medical Center, Cincinnati, OH, 2 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH OBJECTIVE: 

Amnioinfusion fluid during fetal interventions (saline or Ringer’s) is more acidic and nutrient poor than amniotic fluid. We created a synthetic amniotic fluid for use in fetal therapy and evaluated it’s impact upon amniotic epithelium in vitro. STUDY DESIGN: Placentas from unlabored cesareans were collected and amniotic epithelium was isolated/cultured per protocol. A synthetic fluid was created with equivalent pH, electrolyte, albumin, and glucose concentrations, to human amniotic fluid, termed “Amniowell” (AL)

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Cultured amniotic epithelium was exposed to normal saline (NS), Lactated Ringer’s (LR) or AL. Culture media was a control. To simulate the normal turnover of amniotic fluid, at 6, 12, 18, and 24 hours, 25%, 50%, 75%, and 100% (respectively) of the fluid was replaced with culture media. Cells were evaluated for rates of early and late apoptosis, and necrosis. To examine if cells could be "rescued" after amnioinfusion or if damage was progressive, experimentation was repeated and cells were grown in culture for an additional 48 hours. Experimentation was repeated on full thickness amnion explants. RESULTS: Flow cytometry revealed high fidelity of culture, with > 95% of cells expressing PanCK and EPCAM, < 1% expression of hematopoetic/immune markers, and < 5% expression of mesenchyme markers. After exposure to NS or LR, only 44% and 52% of cells were alive at 24 hours, compared with 85% for control and 89% in AL (Figure 1, p < 0.001). After exposure and 48 hour “rescue,” flow cytometry revealed that only only 21% and 44% of cells exposed to NS and LR were living, compared to 88% and 94% for control and AL (Figure 1, p < 0.001). Tissue staining after amnioinfusion on full thickness amnion tissue revealed that 32%

Placentas from unlabored cesareans were collected and amniotic epithelium was isolated/cultured per protocol. A synthetic fluid was created with equivalent pH, electrolyte, albumin, and glucose concentrations, to human amniotic fluid, termed “Amnio-well” (AL). Cultured amniotic epithelium was exposed to normal saline (NS), Lactated Ringer’s (LR) or AL. Culture media was a control. To simulate the normal turnover of amniotic fluid, at 6, 12, 18, and 24 hours, 25%, 50%, 75%, and 100% (respectively) of the fluid was replaced with culture media. Cells were evaluated for rates of early and late apoptosis, and necrosis. To examine if cells could be "rescued" after amnioinfusion or if damage was progressive, experimentation was repeated and cells were grown in culture for an additional 48 hours. Experimentation was repeated on full thickness amnion explants.

Results

Flow cytometry revealed high fidelity of culture, with > 95% of cells expressing PanCK and EPCAM, < 1% expression of hematopoetic/immune markers, and < 5% expression of mesenchyme markers. After exposure to NS or LR, only 44% and 52% of cells were alive at 24 hours, compared with 85% for control and 89% in AL (Figure 1, p < 0.001). After exposure and 48 hour “rescue,” flow cytometry revealed that only only 21% and 44% of cells exposed to NS and LR were living, compared to 88% and 94% for control and AL (Figure 1, p < 0.001). Tissue staining after amnioinfusion on full thickness amnion tissue revealed that 32% and 20% of cells exposed to NS and LR were apoptotic within 24 hours of exposure, vs only 7% in AL and 4% in control (p< 0.001).

Conclusion

The current fluids used for amnioinfusion in fetal cases are toxic to human amnion in vitro. It is possible this impacts the rate of membrane rupture post-surgery and consideration should be given to use of a fluid similar to amniotic fluid.

Another opinion

• Toxicity Study:

  A study compared the effects of normal saline, lactated Ringer's solution, and Amnio-well on cultured human amnion cells. The results showed that Amnio-well had significantly lower toxicity, according to the American Journal of Obstetrics & Gynecology.