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

Objective To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). Methods IUGR 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. Results Survival 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. Conclusion Intra-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 insufficienc

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

Objective To evaluate the perinatal effects of a prenatal therapy based on intra-amniotic nutritional supplementation in a rabbit model of intrauterine growth restriction (IUGR). Methods IUGR 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. Results Survival 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. Conclusion Intra-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 insufficienc

Birth weight.

<p>Scatter dot plot of birth weight among controls, intrauterine growth restricted cases (IUGR) or IUGR cases with therapy (IUGR-T). The horizontal line is the mean.* p<0.05 as compared to controls.</p

Ultrasound-Guided Intrauterine Labeling of Rat Fetuses

Aim: To compare intra-amniotic versus fetal subcutaneous injections for selective fetal labeling in multifetal rat pregnancies. Methods: A total of 14 pregnant rats were randomized to receive intra-amniotic injections of dyes (including Fluorescein, Indigo Carmine, or Evans Blue) or fetal subcutaneous injections (of commercial tattoo ink) both guided by ultrasound at 15-17 days of gestation. Survival, injection, and labeling success rates of both techniques were compared. Results: Survival rates (84.4% for intra-amniotic injections vs. 90.9% for fetal subcutaneous injections) and injection success rates (94% for intra-amniotic injections vs. 100% for fetal subcutaneous injections) were similar among both groups. None of the neonates from the intra-amniotic injections group were labeled at birth, while 93% of the neonates from fetal subcutaneous injections group were tagged, showing a visible spot in the skin at birth. Conclusion: Our results suggest that ultrasound-guided fetal subcutaneous injections might be an adequate strategy for selectively labeling fetuses in multifetal pregnant animals

Survival rate in relation to uterine position.

<p>Survival rate among controls, intrauterine growth restricted cases without (IUGR) or with therapy (IUGR-T) in fetuses that are in extreme positions (Control: 32 surviving out of 41; IUGR 20 surviving out of 40; IUGR-T 25 surviving out of 38) and intermediate positions (Control: 50 surviving out of 74; IUGR: 32 surviving out of 78; IUGR-T: 42 surviving out of 68) positions. * p<0.05 as compared to controls; ^# p<0.05 as compared to IUGR.</p

Fetal echocardiographic results in the studied groups.

<p>Fetal echocardiographic results in the studied groups.</p

Survival rate.

<p>Survival rate among controls, intrauterine growth restricted cases (IUGR) or IUGR cases with therapy (IUGR-T) in the overall population (Control: 82 surviving out of 115; IUGR: 52 surviving out of 118; IUGR-T: 67 surviving out of 106) (A) and among newborns weighing 20-30g (IUGR: 14 surviving out of 23; IUGR-T: 22 surviving out of 25) (B). * p<0.05 as compared to controls; ^# p<0.05 as compared to IUGR.</p

Experimental design.

<p>In pregnant rabbit at 25^th day of gestation, IUGR was surgically induced by uteroplacental vessel ligation and intra-amniotic injections were performed. Control fetuses did not undergo vessel ligature and they had sham injection. IUGR fetuses underwent uteroplacental vessel ligature and sham injection. and finally IUGR-T fetuses underwent uteroplacental vessel ligature and therapy administration which is intra-amniotic injection of 300 μl of modified-parenteral nutrient solution. At 30^th day of gestation, cesarean section was performed and uterine horns were exteriorized to perform fetal echocardiography in a subgroup of fetuses from each experimental group. The fetuses were then taken out for survival assessment and biometric measurements and then sacrificed for tissue sampling. Black arrows and yellow circles indicate ligated uteroplacental vessels of fetal sacs in the uterine horn, yellow arrow indicates intra-amniotic injection to the fetal sac and red arrow indicates the ultrasound transducer.</p