Creation of a novel synthetic amniotic fluid for use in fetal therapy with in vitro testing on human amniotic membranes

Forde, Braxton; Marc, Oria; Lampe, Kristin; Martin, Séverine; Peiró, José L.

doi:10.1016/j.ajogmf.2023.101055

Cited by 2 publications

(1 citation statement)

References 22 publications

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“…It thus again stands to reason that the increased amniotic fluid lactate may be a reflection of both the fetal and uterine stress from the fetoscopic surgery. Lactate is also know to decrease pH, and given the concerns for alterations in amniotic fluid pH leading to amniotic membrane damage (Forde et al, 2023), one must wonder if a longer or more stressful surgery for a fetus would correlate to an increased risk of adverse outcomes postoperatively. Further study into the amniotic fluid lactate and long-term outcomes is warranted.…”

Section: Discussionmentioning

confidence: 99%

Acute Fetal Metabolomic Changes in Twins Undergoing Fetoscopic Surgery for Twin-Twin Transfusion Syndrome

Forde,

Martin,

Watanabe-Chailland

et al. 2024

Twin Res Hum Genet

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Fetuses undergo major surgical stress as well as fluid shifts secondary to both twin-twin transfusion (TTTS) as well as the fetoscopic surgery for treatment of TTTS. While the pathophysiology of TTTS is understood, the acute metabolic changes that fetuses experience from fetoscopic surgery are not. We sought to evaluate the changes in recipient metabolomic profile secondary to TTTS surgery. Amniotic fluid was collected at the beginning and end of four TTTS surgical cases performed from 12/2022−2/2023. Samples were immediately processed and evaluated via NMR-based Metabolomics Facility protocol. In univariate analysis, 12 metabolites (glucose, lactate, and 10 key amino acids) showed statistically significant changes between the beginning and end of the surgery. Among these, 11 metabolites decreased at the end, while only lactate increased. Supervised oPLS-DA modeling revealed pyruvate and lactate as the two metabolites most impact on the variance between cases, and that 40% of metabolomic changes could be attributed directly to the timing that the sample was taken (i.e., if pre- or postoperatively). These results indicate significant metabolic changes in the recipient twin during fetoscopic surgery for TTTS. These findings of decreased glucose, increased lactate, and decreased amnio acids would indicate increased catabolism during surgery. This study raises questions regarding optimal maternal and fetal nutrition during surgery and if nutritional status could be optimized to further improve twin survival during fetoscopic surgery.

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Section: Discussionmentioning

confidence: 99%

Acute Fetal Metabolomic Changes in Twins Undergoing Fetoscopic Surgery for Twin-Twin Transfusion Syndrome

Forde,

Martin,

Watanabe-Chailland

et al. 2024

Twin Res Hum Genet

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Comparison of Amnio‐Exchange With a Novel Synthetic Amniotic Fluid Versus Commercially Used Fluids for Fetal Therapy: An In Vivo Rodent Model

Martin,

Peiro,

Oria

et al. 2024

Prenatal Diagnosis

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ObjectiveNormal Saline (NS) and Lactated Ringer's (LR) damage human amniotic epithelium in vitro when compared with a synthetic amniotic fluid (Amnio‐well, AW). We sought to evaluate the effect of amnio‐exchange with NS, LR, and AW in vivo.MethodsOn day E17.5, pregnant rats underwent amnio‐exchange with NS, LR, or AW. Fetuses in each pregnant rat that did not undergo amnio‐exchange acted as controls. Amnions were harvested at E20.5 and ultrastructure evaluated via electron microscopy. Protein levels of cleaved matrix metalloproteinase 9 (MMP9) and collagen 1 (Col1a) were evaluated via Western Blot. Connexin‐43 expression was evaluated via immunofluorescence (IF).ResultsThere was an increase in amnion microfractures and epithelial cellular shrinkage with NS and LR compared with control and AW. The cleaved MMP9/Col1 ratio was increased 3.9‐fold in NS (p < 0.001) and 4.5‐fold LR (p = 0.0201) relative to control, whereas AW expression was similar to control (p = 0.636). Connexin‐43 was also increased on IF in NS and LR relative to AW (mean gray intensity 26.5 ± 4.5, 26.5 ± 6.7, 19.2 ± 3.4, p < 0.001).ConclusionAmnio‐exchange with NS and LR led to increased amniotic microfractures and collagen degradation compared with synthetic amniotic fluid. Larger models are warranted to validate or refute these findings.

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Creation of a novel synthetic amniotic fluid for use in fetal therapy with in vitro testing on human amniotic membranes

Cited by 2 publications

References 22 publications

Acute Fetal Metabolomic Changes in Twins Undergoing Fetoscopic Surgery for Twin-Twin Transfusion Syndrome

Acute Fetal Metabolomic Changes in Twins Undergoing Fetoscopic Surgery for Twin-Twin Transfusion Syndrome

Comparison of Amnio‐Exchange With a Novel Synthetic Amniotic Fluid Versus Commercially Used Fluids for Fetal Therapy: An In Vivo Rodent Model

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