Docosahexaenoic Acid and Lactoferrin Effects on the Brain and Placenta in a Rabbit Model of Intrauterine Growth Restriction

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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The effects of sildenafil citrate on feto–placental development and haemodynamics in a rabbit model of intrauterine growth restriction

Reproduction Fertility and Development ◽

10.1071/rd15330 ◽

2017 ◽

Vol 29 (6) ◽

pp. 1239 ◽

Cited By ~ 6

Author(s):

Jorge López-Tello ◽

María Arias-Álvarez ◽

Maria-Ángeles Jiménez-Martínez ◽

Alicia Barbero-Fernández ◽

Rosa María García-García ◽

...

Keyword(s):

Fetal Growth ◽

Intrauterine Growth Restriction ◽

Rabbit Model ◽

Growth Restriction ◽

Sildenafil Citrate ◽

Placental Development ◽

Negative Effects ◽

Intrauterine Growth ◽

Potential Benefits ◽

The Brain

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto–placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown–rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

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

Experimental Biology and Medicine ◽

10.1177/15353702211003508 ◽

2021 ◽

pp. 153537022110035

Author(s):

Mari Kinoshita ◽

Fàtima Crispi ◽

Carla Loreiro ◽

Eduard Gratacós ◽

Míriam Illa ◽

...

Keyword(s):

Intrauterine Growth Restriction ◽

Intraperitoneal Injection ◽

Rabbit Model ◽

Osmotic Pump ◽

Growth Restriction ◽

Technical Failure ◽

Fetal Therapy ◽

Amniotic Cavity ◽

Intrauterine Growth ◽

Fetal Survival

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.

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Maternal and perinatal outcomes of hyperthyroidsm in pregnancy at Dr. Cipto Mangunkusumo Hospital, Jakarta, period of January 2015 - December 2016

Majalah Obstetri & Ginekologi ◽

10.20473/mog.v29i12021.36-40 ◽

2021 ◽

Vol 29 (1) ◽

pp. 36

Author(s):

Fita Maulina ◽

M Adya F F Dilmy ◽

Ali Sungkar

Keyword(s):

Pregnant Women ◽

Preterm Delivery ◽

Intrauterine Growth Restriction ◽

Fetal Death ◽

Perinatal Outcomes ◽

Growth Restriction ◽

Intrauterine Fetal Death ◽

Adequate Treatment ◽

Intrauterine Growth ◽

In Pregnancy

Objectives: To report maternal and perinatal outcomes of hyperthyroidsm in pregnancy.Case Report: There were 3622 cases of delivering pregnant women during the period of the study. From this number, the prevalence of pregnant women with hyperthyroid was 0.2 %. We reported 9 cases of hyperthyroid in pregnancy. The number of pregnancy complication and outcome on pregnant women with hyperthyroidism were preterm labor (44%) and preeclampsia (22%), both were found in group of mother who did taking antihyperthyroid therapy. In those who did not take antihyperthyroid therapy 11% had spontaneous abortion and 11% had preterm delivery. Fetal complications were intrauterine growth restriction (11%) and intrauterine fetal death (23%), both of these complication were on the group who did not take antihyperthyroid. On the contrary, 44% babies were born with normal birthweight in group who took antihyperthyroid.Conclusion: There were differences noted between the group that took adequate treatment and the group that did not take antihyperthyroid. The incidence of intrauterine growth restriction and intrauterine fetal death were high in group that did not took antihyperthyroid therapy but the incidence of preterm delivery as the maternal complication was high in group that did take the antihyperthyroid therapy.

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The brain development of infants with intrauterine growth restriction: role of glucocorticoids

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2019-0016 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 2

Author(s):

Ying-xue Ding ◽

Hong Cui

Keyword(s):

Endothelial Cells ◽

Brain Injury ◽

Intrauterine Growth Restriction ◽

Growth And Development ◽

Growth Restriction ◽

Microvascular Endothelial Cells ◽

Intrauterine Growth ◽

Growth Restrictions ◽

The Brain

Abstract Brain injury is a serious complication of intrauterine growth restriction (IUGR), but the exact mechanism remains unclear. While glucocorticoids (GCs) play an important role in intrauterine growth and development, GCs also have a damaging effect on microvascular endothelial cells. Moreover, intrauterine adverse environments lead to fetal growth restriction and the hypothalamus-pituitary-adrenal (HPA) axis resetting. In addition, chronic stress can cause a decrease in the number and volume of astrocytes in the hippocampus and glial cells play an important role in neuronal differentiation. Therefore, it is speculated that the effect of GCs on cerebral neurovascular units under chronic intrauterine stimulation is an important mechanism leading to brain injury in infants with growth restrictions.

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Relationship between abnormal fetal testing and adverse perinatal outcomes in intrauterine growth restriction

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2007.01.010 ◽

2007 ◽

Vol 196 (5) ◽

pp. e48-e51 ◽

Cited By ~ 19

Author(s):

Juan M. Gonzalez ◽

David M. Stamilio ◽

Serdar Ural ◽

George A. Macones ◽

Anthony O. Odibo

Keyword(s):

Intrauterine Growth Restriction ◽

Perinatal Outcomes ◽

Growth Restriction ◽

Intrauterine Growth ◽

Adverse Perinatal Outcomes

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Impact of diet on the persistence of early vascular remodeling and stiffening induced by intrauterine growth restriction and a maternal high-fat diet

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00127.2019 ◽

2019 ◽

Vol 317 (2) ◽

pp. H424-H433 ◽

Cited By ~ 1

Author(s):

Thomas A. Miller ◽

R. Blair Dodson ◽

Anastasiya Mankouski ◽

Kyle N. Powers ◽

Yueqin Yang ◽

...

Keyword(s):

Arterial Stiffness ◽

High Fat Diet ◽

Intrauterine Growth Restriction ◽

Vascular Remodeling ◽

Structural Changes ◽

Growth Restriction ◽

Female Rats ◽

High Fat ◽

Regular Diet ◽

Intrauterine Growth

Intrauterine growth restriction (IUGR) and maternal high-fat diet (HFD) independently predispose offspring to hypertension. In a rat model, IUGR more so than maternal HFD increases arterial stiffness with vascular remodeling as early as postnatal day (PND) 21. The trajectory of such early vascular changes remains unknown. We hypothesized that IUGR would increase blood pressure (BP), arterial stiffness, and markers of ongoing detrimental vascular remodeling in adult rats exposed to a maternal HFD regardless of weaning diet. Adult female rats were fed either a regular diet (RD) or an HFD before mating through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either a RD or HFD through PND 60. For both control and IUGR rats, this design resulted in the following three diet groups: offspring from RD dams weaned to a RD and offspring from HFD dams weaned to a RD or to an HFD (IHH). In both males and females, only IHH increased systolic BP, but IUGR and HFD both alone and in combination increased arterial stiffness. Aortas contained fewer but thicker elastin bands in IHH rats and IUGR offspring from dams fed an HFD and weaned to a regular diet. IHH increased aortic lysl oxidase protein. In summary, the PND 21 rat mediators of vascular remodeling from IUGR and maternal HFD normalize by PND 60 while changes in elastin and arterial stiffness persist. We speculate that the longer-term risk of hypertension from dietary mediators is augmented by underlying IUGR-induced structural changes to the extracellular matrix. NEW & NOTEWORTHY We report that a combined insult of intrauterine growth restriction and maternal high-fat diet increases the risk of early cardiovascular pathology both independently and in conjunction with a continued high-fat diet in offspring.

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Placental elasticity assessment by point shear wave elastography in pregnancies with intrauterine growth restriction

Journal of Perinatal Medicine ◽

10.1515/jpm-2019-0238 ◽

2019 ◽

Vol 47 (8) ◽

pp. 841-846 ◽

Cited By ~ 6

Author(s):

Murat Akbas ◽

Faik M. Koyuncu ◽

Burcu Artunç-Ulkumen

Keyword(s):

Pregnant Women ◽

Shear Wave ◽

Intrauterine Growth Restriction ◽

Perinatal Outcomes ◽

Shear Wave Elastography ◽

Growth Restriction ◽

Intrauterine Growth ◽

The Mean ◽

Adverse Perinatal Outcomes ◽

Doppler Indices

Abstract Background Placental elasticity varies in different diseases. Our objective was to evaluate placental elasticity using point shear wave elastography (pSWE) in pregnancies with intrauterine growth restriction (IUGR). Methods A total of 66 pregnant women with IUGR and 81 healthy pregnant women were enrolled. Placental elasticity was measured using the transabdominal pSWE method. Ten measurements were made, and the mean was accepted as the mean placental elasticity value in each case. The results for IUGR pregnancies and controls were compared. Results The mean pSWE values were significantly higher in pregnancies with IUGR, which means that women with IUGR have stiffer placentas (P < 0.001). Furthermore, the pSWE values were significantly and positively correlated with Doppler indices and adverse perinatal outcomes. Conclusion The pregnancies with IUGR had stiffer placentas than the healthy controls. The utilization of pSWE for placental elasticity may be useful in the diagnosis and management of IUGR as a supplement to the existing ultrasonography methods.

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