Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal growth restriction.

Hatice Gulcin Gumus,Miriam Illa,Eduard Gratacos,Monica Zamora,Laura Pla,Fatima Crispi

doi:10.1371/journal.pone.0193240

Abstract

ObjectiveTo evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR).MethodsIUGR was surgically induced in pregnant rabbits at gestational day 25 by ligating 40–50% of uteroplacental vessels of each gestational sac. At the same time, modified-parenteral nutrition solution (containing glucose, amino acids and electrolytes) was injected into the amniotic sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham injections were performed in the rest of fetuses (IUGR group n = 118). A control group without IUGR induction but sham injection was also included (n = 115). Five days after the ligation procedure, a cesarean section was performed to evaluate fetal cardiac function, survival and birth weight.ResultsSurvival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals (survival rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02), whereas, birth weight (controls mean 43g ± SD 9 vs. IUGR 36g ± SD 9 vs. IUGR-T 35g ± SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR groups.ConclusionIntra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR. These results provide an opportunity to develop new intra-amniotic nutritional strategies to reach the fetus by bypassing the placental insufficiency.

Highlights

Intrauterine growth restriction (IUGR) is generally defined as a significant reduction in fetal growth rate resulting in a birth weight in the lowest 10th percentile
Survival was significantly improved in the IUGR fetuses that were treated with intra-amniotic nutritional supplementation as compared to non-treated IUGR animals, whereas, birth weight and fetal cardiac function were similar among the IUGR groups
Intra-amniotic injection of a modified-parenteral nutrient solution appears to be a promising therapy for reducing mortality among IUGR

Summary

Introduction

Intrauterine growth restriction (IUGR) is generally defined as a significant reduction in fetal growth rate resulting in a birth weight in the lowest 10th percentile It affects 7–10% of all pregnancies [1] and is considered a major contributor to perinatal morbidity and mortality, responsible for about 20–50% of perinatal deaths. We hypothesized that the administration of a complete nutrient composition (combining essential nutrients such as glucose, amino acids and electrolytes) in a single intra-amniotic injection could improve the outcomes of IUGR. We planned to administrate this complete nutrient composition therapy by intra-amniotic injections based on the fetus capacity of swallowing amniotic fluid, by which essential nutrients delivered intra-amniotically would reach the gastrointestinal tract and be absorbed [31,32], potentially compensating the nutrient deficiency caused by placental insufficiency

Methods

Results

Discussion

Conclusion