Strategies for intra-amniotic administration of fetal therapy in a rabbit model of intrauterine growth restriction

2021 ◽  
pp. 153537022110035
Author(s):  
Mari Kinoshita ◽  
Fàtima Crispi ◽  
Carla Loreiro ◽  
Eduard Gratacós ◽  
Míriam Illa ◽  
...  

Intrauterine growth restriction affects up to 10% of all pregnancies, leading to fetal programming with detrimental consequences for lifelong health. However, no therapeutic strategies have so far been effective to ameliorate these consequences. Our previous study has demonstrated that a single dose of nutrients administered into the amniotic cavity, bypassing the often dysfunctional placenta via intra-amniotic administration, improved survival at birth but not birthweight in an intrauterine growth restriction rabbit model. The aim of this study was to further develop an effective strategy for intra-amniotic fetal therapy in an animal model. Intrauterine growth restriction was induced by selective ligation of uteroplacental vessels on one uterine horn of pregnant rabbits at gestational day 25, and fetuses were delivered by cesarean section on GD30. During the five days of intrauterine growth restriction development, three different methods of intra-amniotic administration were used: continuous intra-amniotic infusion by osmotic pump, multiple intra-amniotic injections, and single fetal intraperitoneal injection. Technical feasibility, capability to systematically reach the fetus, and survival and birthweight of the derived offspring were evaluated for each technique. Continuous intra-amniotic infusion by osmotic pump was not feasible owing to the high occurrence of catheter displacement and amnion rupture, while methods using two intra-amniotic injections and one fetal intraperitoneal injection were technically feasible but compromised fetal survival. Taking into account all the numerous factors affecting intra-amniotic fetal therapy in the intrauterine growth restriction rabbit model, we conclude that an optimal therapeutic strategy with low technical failure and positive fetal impact on both survival and birthweight still needs to be found.

2015 ◽  
Vol 26 (3) ◽  
pp. 172-182 ◽  
Author(s):  
Sundeep G. Keswani ◽  
Swathi Balaji ◽  
Anna B. Katz ◽  
Alice King ◽  
Khaled Omar ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31497 ◽  
Author(s):  
Elisenda Eixarch ◽  
Dafnis Batalle ◽  
Miriam Illa ◽  
Emma Muñoz-Moreno ◽  
Ariadna Arbat-Plana ◽  
...  

2016 ◽  
Vol 36 (7) ◽  
pp. 628-635 ◽  
Author(s):  
Horacio Figueroa ◽  
Jorge Cifuentes ◽  
Mauricio Lozano ◽  
Cristobal Alvarado ◽  
Claudia Cabezas ◽  
...  

NeuroImage ◽  
2014 ◽  
Vol 100 ◽  
pp. 24-38 ◽  
Author(s):  
Dafnis Batalle ◽  
Emma Muñoz-Moreno ◽  
Ariadna Arbat-Plana ◽  
Miriam Illa ◽  
Francesc Figueras ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0131310 ◽  
Author(s):  
Rui V. Simões ◽  
Emma Muñoz-Moreno ◽  
Rodrigo J. Carbajo ◽  
Anna González-Tendero ◽  
Miriam Illa ◽  
...  

2021 ◽  
Author(s):  
Miriam Illa ◽  
Laura Pla ◽  
Carla Loreiro ◽  
Cristina Miranda ◽  
Montse Mayol ◽  
...  

Abstract Intrauterine growth restriction (IUGR) is associated with suboptimal perinatal outcomes and neurodevelopment in the offspring. We hypothesize that prenatal supplementation with docosahexaenoic acid (DHA) or lactoferrin (Lf) would ameliorate these consequences. At 25 days of gestation, IUGR was surgically induced in pregnant rabbits, which were randomized as follows: no treatment, or DHA or Lf administration. DHA or Lf were administrated orally once per day. Five days later, animals were delivered obtaining controls, untreated IUGR, IUGR treated with DHA and IUGR treated with Lf, and the associated placentas. At postnatal day 1, a functional evaluation was performed and, thereafter, brains were obtained. Neuronal arborization in the prefrontal cortex and the density of pre-oligodendrocytes in the corpus callosum were then evaluated. Untreated IUGR pups presented a higher percentage of stillbirth, lower birth weight, and poorer neurobehavioral performance in comparison with control pups, and these are associated with structural changes in brain and placenta. Regarding treated IUGR animals, although no significant improvements were detected in perinatal data, functional and structural effects were observed in either the brain or the placenta. DHA and Lf supplements in a rabbit model of IUGR were related to neurodevelopmental improvements and an amelioration of the placental changes.


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