Cause Of Intrauterine Growth Restriction Research Articles

Placenta-anchored tadalafil liposomes rescues intrauterine growth restriction through continuous placental blood perfusion improvement

Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.

INTRAUTERINE GROWTH RESTRICTION (IUGR) AS PART OF FETAL ALCOHOL SYNDROME

Introduction: An investigation was conducted on the effects of alcohol on pregnant women as a possible cause of intrauterine growth restriction. The American Pregnancy Association defines intrauterine growth restriction (IUGR) as a fetal weight below the 10th percentile for gestational age as determined by ultrasound.
 Method: A search of medical literature was performed from January 2010 to January 2022. For this purpose, different scientific databases were used, which were: PUBMED, EBSCO and Google Scholar.
 Results: The fetal period is the time of development from the ninth week to the moment of birth. The most severe form associated with alcohol consumption during pregnancy is Fetal Alcohol Syndrome, which requires a minimum consumption of 12 g per day of absolute alcohol for this syndrome to manifest itself. Infants whose mothers are chronic alcoholics show a characteristic pattern of defects including prenatal and postnatal growth deficiencies, mental deficiency, and other problems.
 Discussion: Environmental factors influence fetal growth, and this has been increasingly emphasized with increasing evidence. With regard to the database collected from different research sources, we can confirm the great relationship that exists on the effects of alcohol consumption by pregnant women on fetal growth. Kazutoshi-cho's study on prenatal exposure to alcohol in Japanese women shows us that the consumption of a weekly dose of alcohol during the second and third trimester has a significant negative relationship with the decrease in body weight, body length and head circumference at birth.
 Conclusion: Excessive alcohol consumption is highly associated with fetal growth restriction (fetal alcohol syndrome). The level of effects may be different depending on the frequency of exposure and dose.

Abstract 028: Sex Differences In Hypertension And Cerebral Oxidative Stress Of Preeclamptic Rat Offspring

Intrauterine growth restriction (IUGR) occurs when the fetus doesn’t receive adequate nutrients. The leading cause of IUGR is placental ischemia, often seen in preeclampsia (PE). Adult IUGR offspring have an increased risk of HTN and oxidative stress (OS), with sex differences. Studies have shown that IUGR males have HTN, cerebrovascular dysfunction (CVD), and cerebral OS at 17 wks; IUGR females are NT with limited CVD and no significant OS. Our study aims to characterize the sex differences in timing and changes of cerebral OS in IUGR offspring. HTN and OS are both present in adult IUGR males, however, the order and timing is unknown. We hypothesize that OS leads to HTN. To test this, we examined the changes in brain OS in 12 wk IUGR and control (CON) males (before HTN), and 17 wk IUGR males (which have HTN) vs CON males. We investigated the same time points in NT females. We divided pups from normal pregnant and PE Sprague-Dawley rats into groups based on pregnancy status and sex. Pups were aged to 12 and 17 wks. We collected brains to measure OS via western blot (Manganese superoxide dismutase) and colorimetric assays: hydrogen peroxide (H 2 O 2 ) and total antioxidant capacity (TAC). 12 wk IUGR and CON offspring were NT with no changes between groups or sex. There were no changes in cerebral H 2 O 2 , TAC, and MnSOD for IUGR offspring compared to their CON. At 17 wks, IUGR males had elevated mean arterial pressure (MAP; 143.0 ± 1.7 vs 133.0 ± 2.7 mmHg; p < 0.01). IUGR females were NT. Cerebral H2O2 levels in IUGR males were elevated (20.5 ± 8.0 vs 3.7 ± 1.0 uM/ mg Protein; p < 0.05) and unchanged in IUGR females. TAC in IUGR males was decreased (157.7 ±21.9 vs 234.9 ± 22.0 mM Trolox/mg Protein; p < 0.05) and unchanged in IUGR females. MnSOD was elevated in females with no differences between groups (150.4 ± 3.8 vs 110.9 ±7.1 IU/Protein/CON%; p < 0.002). All 12 wk rats were NT with no changes in cerebral OS. At 17 wks, IUGR males were HTN with elevated cerebral OS, with no changes in females. The lack of increase in OS at 12 wks, suggest that it’s not a precursor to HTN in males, but rather OS is a downstream effect from HTN. Future studies will look at factors that contribute to HTN and CVD in in IUGR offspring. Studies will also examine why 17 wk female IUGR are protected from HTN and cerebral OS.

Early versus Late Enteral Feeding in Preterm Intrauterine Growth Restricted Neonates with Antenatal Doppler Abnormalities

Background: Placental insufficiency and decreased placental nutrition transfer from the mother to the fetus are the underlying causes of intra-uterine growth restriction (IUGR), a serious and very frequent issue in the perinatal period. Due to a lack of recent research in the area, the current study aims to compare the outcomes of two different feeding strategies for preterm infants with abnormal Doppler readings: early vs. delayed initiation of enteral feeds. Then we implement the better of the two feedings regimens into our standard clinical practice. Objective: The objective of the study was to compare early and late enteral feeding in preterm intrauterine growth restricted neonate to evaluate time to reach full feed, risk of feed Intolerance, weight gain at 10th day of life and length of hospital stays. Study Design: The Randomized Control Trial. Settings: This study was conducted in the neonatology department Tertiary Care Hospital (Nursery MCH Centre, Pakistan Institute of Medical Sciences, Islamabad Pakistan. Duration: 1st June 2022 to 1st December 2022. Methods: The sample was collected from the by non-probability consecutive sampling technique. Babies of any sex who meet the requirements during the first 72 hours of life. A total of 80 newborns were recruited out of them n=40 infants were found as early feeding and n=40 was assigned to late feeding. Demographic and baseline information (admission date, age, gender, gestational age, birth weight) of enrolled neonates recorded in the prescribed proforma. Effects of early or late feeding were monitored daily for 10 days. The outcomes in terms of time to reach full feed, weight gain at 10th day of life and feed intolerance were recorded and compared in both groups. All the information entered on the predesigned proforma by the researcher himself to comply with the study protocol attached. Results: A total of 80 newborns were recruited out of them n=40 infants were found as early feeding and n=40 was assigned to late feeding. The base line characteristics including birth weight, gestational age, respiratory support etc. were not statistically significant. Also, there is no difference of NEC (0.267) and FI (0.312) in early and late feeding groups. The Cox regression HR: 1.21 (95% CI: 0.829-3.72); p = 0.326). In both groups, the early feeding arm had a shorter median duration by 7 days. Further, the data was compared between early and late feeding group to determined which group is quicker for discontinuation of PN. Conclusion: Our study finds that using the feeding initiation and advancement method and AREDF on Doppler with exclusive breast milk results in faster PN cessation and does not increase the incidence of NEC or FI in preterm IUGR infants between 27 and 33 weeks of age.

Novel genes associated with a placental phenotype in knockout mice also respond to cellular stressors in primary human trophoblasts

IntroductionPlacental insufficiency is a leading cause of intrauterine growth restriction, contributing to perinatal morbidity and mortality. The molecular regulation of placental development and what causes placental insufficiency is poorly understood. Recently, a panel of genes were found to cause significant placental dysmorphologies in mice with severely growth restricted off-spring. We aimed to assess whether these genes were also implicated in human intrauterine growth restriction. MethodsWe explored the expression of nine genes in primary cytotrophoblast cells in hypoxic (n = 6) and glucose starvation (n = 5) conditions in vitro. We also explored whether the genes were dysregulated in intrauterine growth restricted human placental samples (n = 11), with (n = 20) or without preeclampsia compared to gestationally matched controls (<34 weeks gestation) (n = 17). ResultsHypoxic stress significantly upregulated the expressions of BRD2 (p = 0.0313), SMG9 (p = 0.0313) genes. In contrast, glucose starvation significantly suppressed Kif1bp (p = 0.0089) in primary cytotrophoblasts. The FRYL, NEK9, CHTOP, PSPH, ATP11A, HM13 genes did not change under hypoxia or glucose starvation conditions. The expression of these genes was not altered in placenta from patients with intrauterine growth restriction, compared to gestationally matched controls. DiscussionWe demonstrate that some of the genes that cause a placental phenotype in mice, respond to hypoxic and glucose mediated stress in human cytotrophoblast isolations. Despite this, they are unchanged in placenta from patients with intrauterine growth restriction. Therefore, dysregulation of these genes is less likely to contribute to preterm intrauterine growth restriction in humans.

The Proteome Landscape of Human Placentas for Monochorionic Twins with Selective Intrauterine Growth Restriction

In perinatal medicine, intrauterine growth restriction (IUGR) is one of the greatest challenges. The etiology of IUGR is multifactorial, but most cases are thought to arise from placental insufficiency. However, identifying the placental cause of IUGR can be difficult due to numerous confounding factors. Selective IUGR (sIUGR) would be a good model to investigate how impaired placentation affects fetal development, as the growth discordance between monochorionic twins cannot be explained by confounding genetic or maternal factors. Herein, we constructed and analyzed the placental proteomic profiles of IUGR twins and normal cotwins. Specifically, we identified a total of 5481 proteins, of which 233 were differentially expressed (57 up-regulated and 176 down-regulated) in IUGR twins. Bioinformatics analysis indicates that these differentially expressed proteins (DEPs) are mainly associated with cardiovascular system development and function, organismal survival, and organismal development. Notably, 34 DEPs are significantly enriched in angiogenesis, and diminished placental angiogenesis in IUGR twins has been further elaborately confirmed. Moreover, we found decreased expression of metadherin (MTDH) in the placentas of IUGR twins and demonstrated that MTDH contributes to placental angiogenesis and fetal growth in vitro. Collectively, our findings reveal the comprehensive proteomic signatures of placentas for sIUGR twins, and the DEPs identified may provide in-depth insights into the pathogenesis of placental dysfunction and subsequent impaired fetal growth.

Therapeutic advances in overcoming intrauterine growth restriction induced metabolic syndrome.

Intrauterine growth restriction (IUGR) remains a great public health challenge as it affects neonatal survival and influences their normal biological development and metabolism. Several clinical researches have revealed the occurrence of metabolic syndrome, such as insulin resistance, obesity, type 2 diabetes mellitus, oxidative stress, dyslipidemia, as direct results of IUGR. Therefore, it is essential to understand its underlying mechanism, impact and develop effective therapies. The purpose of this work is to review the current knowledge on IUGR induced metabolic syndrome and relevant therapies. Here in, we elaborate on the characteristics and causes of IUGR by pointing out recent research findings. Furthermore, we discuss the impact of IUGR on different organs of the body, followed by preclinical studies on IUGR using suitable animal models. Additionally, various metabolic disorders with their genetic implications, such as insulin resistance, type 2 diabetes mellitus, dyslipidemia, obesity are detailed. Finally, the current therapeutic options used in the treatment of IUGR are summarized with some prospective therapies highlighted.

S-43-3: INTRAUTERINE GROWTH RESTRICTION CAUSES AN ALTERATION IN KIDNEY GENE EXPRESSION

High blood pressure (BP) and kidney disease are the leading cause of death in the world population. Experimental and epidemiological studies indicate that the fetal environment is critical in determining adult cardiovascular (CV)-renal outcome. It is known that intrauterine growth restriction (IUGR) or low birth weight (LBW) induces an increased risk of hypertension and kidney disease in later life. Placental insufficiency is the common cause of IUGR. Low birth weight is a significant public health problem globally and is associated with short- and long-term consequences. About 15–20% of all births worldwide are LBW, representing more than 20 million births a year. Clinical studies indicate that birth weight is positively associated with glomerular filtration rate (GFR) and negatively associated with BP. Also, animal models of IUGR exhibit a higher susceptibility to ANGII induced high BP and kidney damage in response to acute ischemic reperfusion injury. Thus, these data suggest that IUGR programs greater risk of hypertension and renal dysfunction. However, the exact mechanisms linking an adverse fetal environment with a later increased risk of these diseases are unclear. Objective: This study aims to evaluate the global genetic change in the kidney of the animal model of IUGR. Design: female C57Bl/6J were mated with male C57bl/6J. Upon confirming the pregnancy by sperm plug (day 0 of gestation), the pregnant animal will be undergone reduced uterine perfusion surgery (RUP) or shame surgery at day 13 of gestation. The offspring of RUP mom will be labeled as IUGR, and from the sham will be labeled as control. The offspring will be used for blood pressure measurement using radio-telemetry and kidney microarray analysis when they reach 24 weeks. Results: Th IUGR offspring significantly has an increase in blood pressure compared to the control. The kidneys of male IUGR have 6529 gene upregulation compared to male control. The make IUGR also has 5713 genes dow-regulation as compared to same-sex control. The female IUGR has 1635 genes upregulated and 1513 genes downregulated compared to the kidney from the female control group. Conclusion: the complication during pregnancy, such as reduced uterine perfusion, which is commonly found in preeclampsia programs, alters gene expression in the kidneys of their offspring. This finding suggests that IUGR causes the gene alteration in the kidneys, which is the primary organ in controlling the blood pressure of the offspring, and may lead to the development of hypertension and kidney disease.

WNT5A, β‑catenin and SUFU expression patterns, and the significance of microRNA deregulation in placentas with intrauterine growth restriction.

Placental insufficiency is a common cause of intrauterine growth restriction (IUGR). It affects ~10% of pregnancies and increases fetal and neonatal morbidity and mortality. Although Wnt and Hh pathways are crucial for embryonic development and placentation, their role in the pathology of IUGR is still not sufficiently explored. The present study analyzed the expression of positive regulators of the Wnt pathway, WNT5A and β‑catenin, and the expression of the Hh pathway negative regulator suppressor of fused (SUFU). Immunohistochemical and reverse transcription‑quantitative PCR (RT‑qPCR) assays were performed on 34 IUGR and 18 placental tissue samples from physiologic singleton‑term pregnancies. Epigenetic mechanisms of SUFU gene regulation were also investigated by methylation‑specific PCR analysis of its promoter and RT‑qPCR analysis of miR‑214‑3p and miR‑378a‑5p expression. WNT5A protein expression was higher in endothelial cells of placental villi from IUGR compared with control tissues. That was also the case for β‑catenin protein expression in trophoblasts and endothelial cells and SUFU protein expression in trophoblasts from IUGR placentas. The SUFU gene promoter remained unmethylated in all tissue samples, while miR‑214‑3p and miR‑378a‑5p were downregulated in IUGR. The present results suggested altered Wnt and Hh signaling in IUGR. DNA methylation did not appear to be a mechanism of SUFU regulation in the pathogenesis of IUGR, but its expression could be regulated by miRNA targeting.

Placental microRNAs relate to early childhood growth trajectories.

Poor placental function is a common cause of intrauterine growth restriction, which in turn is associated with increased risks of adverse health outcomes. Our prior work suggests that birthweight and childhood obesity-associated genetic variants functionally impact placental function and that placental microRNA are associated with birthweight. To address the influence of the placenta beyond birth, we assessed the relationship between placental microRNAs and early childhood growth. Using the SITAR package, we generated two parameters that describe individual weight trajectories of children (0-5 years) in the New Hampshire Birth Cohort Study (NHBCS, n = 238). Using negative binomial generalized linear models, we identified placental microRNAs that relate to growth parameters (FDR < 0.1), while accounting for sex, gestational age at birth, and maternal parity. Genes targeted by the six growth trajectory-associated microRNAs are enriched (FDR < 0.05) in growth factor signaling (TGF/beta: miR-876; EGF/R: miR-155, Let-7c; FGF/R: miR-155; IGF/R: Let-7c, miR-155), calmodulin signaling (miR-216a), and NOTCH signaling (miR-629). Growth-trajectory microRNAs target pathways affecting placental proliferation, differentiation and function. Our results suggest a role for microRNAs in regulating placental cellular dynamics and supports the Developmental Origins of Health and Disease hypothesis that fetal environment can have impacts beyond birth. We found that growth trajectory associated placenta microRNAs target genes involved in signaling pathways central to the formation, maintenance and function of placenta; suggesting that placental cellular dynamics remain critical to infant growth to term and are under the control of microRNAs. Our results contribute to the existing body of research suggesting that the placenta plays a key role in programming health in the offspring. This is the first study torelate molecular patterns in placenta, specifically microRNAs, to early childhood growth trajectory.

PSI-9 Disrupting Cxcl12-Cxcr4 Chemokine Axis at the Fetal-Maternal Interface During Implantation Results in Altered Expression of Angiogenic and Insulin-Like Growth Factors in Ovine Placenta Midgestation

Abstract Placental dysfunction is a fundamental cause of intrauterine growth restriction, and fetal morbidity and mortality in livestock. Though causes of placental dysfunction are not well characterized, origin of disease transpires during placental development (placentation). The C-X-C motif chemokine ligand 12 (CXCL12) working through its receptor CXCR4 is implicated in placentation but precise roles of this axis are unclear. Using an in vivo sheep model, we demonstrated that suppressing CXCL12-CXCR4 signaling at the fetal-maternal interface reduces placental vascularization. We hypothesized these negative impacts early in gestation would result in compromised placental development and vascularization at midgestation. To test, onday 12 post-breeding, osmotic pumps were surgically installed in 22 ewes and delivered either CXCR4 inhibitor (AMD3100) at 1.5X dose, (n=8) or 3X dose (n=8) or saline (n=6) into the uterine lumen ipsilateral to the corpus luteum for 14 days. On day 90 placental tissues were collected and maternal and fetal placenta components separated and analyzed. The objectives were to determine if suppressing CXCL12-CXCR4 actions at the fetal-maternal interface during implantation results in reduced placental and vascular development at midgestation. Gene expression for angiogenic factors and members of the insulin-like growth factor family were analyzed using Real-time qPCR. Of the targets tested, mRNA expression was significantly altered by AMD3100 treatment for the vascular endothelial growth factor receptors (FLT-1 and KDR) primarily in maternal placenta. Expression of insulin-like growth factors 1 and 2, IGF-binding protein 3, and placental lactogen were significantly altered in fetal placenta with AMD3100 treatment compared to control. Our preliminary data underscore the importance of CXCL12-CXCR4 signaling during placentation and provide strong evidence that altering CXCL12-mediated signaling during early placentation induces enduring placental effects manifesting later in gestation. A greater understanding of CXCL12/CXCR4 functions may reveal methods to improve reproductive success and fetal health.

INTRAUTERINE GROWTH RESTRICTION - AN IMPORTANT EPIGENETIC PREMISE FOR ADULT CARDIOVASCULAR DISEASES

Given multiple causalities, the fetus develops an intrauterine growth restriction that compensatory stimulates the adaptative phenomena; both, the determining cause of intrauterine growth restriction and the adaptative reactions, will initiate epigenetic changes which will affect the long-term structure and functionality of the heart and will modify the cardiovascular reactivity. The study is based on a systematic review of 20 existing studies that certifies a link between epigenetic changes and adult cardiovascular disease.Against the background of epigenetic changes, postnatal nutritional and behavioral factors are added which lead to pathologies in adult life, so the proper functioning and development of the body starts from the first moments of intrauterine life and contuse postnatal, creating the premises for a healthy life. However, it is difficult to assess the environmental factors that interact with the human body and how this combination of factors determines a predisposition to cardiovascular disease.

Intrauterine Growth Restriction Causes Abnormal Embryonic Dentate Gyrus Neurogenesis in Mouse Offspring That Leads to Adult Learning and Memory Deficits.

Human infants who suffer from intrauterine growth restriction (IUGR), which is a failure to attain their genetically predetermined weight, are at increased risk for postnatal learning and memory deficits. Hippocampal dentate gyrus (DG) granule neurons play an important role in memory formation; however, it is unknown whether IUGR affects embryonic DG neurogenesis, which could provide a potential mechanism underlying abnormal postnatal learning and memory function. Using a mouse model of the most common cause of IUGR, induced by hypertensive disease of pregnancy, we first assessed adult learning and memory function. We quantified the percentages of embryonic hippocampal DG neural stem cells (NSCs) and progenitor cells and developing glutamatergic granule neurons, as well as hippocampal volumes and neuron cell count and morphology 18 and 40 d after delivery. We characterized the differential embryonic hippocampal transcriptomic pathways between appropriately grown and IUGR mouse offspring. We found that IUGR offspring of both sexes had short-term adult learning and memory deficits. Prenatally, we found that IUGR caused accelerated embryonic DG neurogenesis and Sox2+ neural stem cell depletion. IUGR mice were marked by decreased hippocampal volumes and decreased doublecortin+ neuronal progenitors with increased mean dendritic lengths at postnatal day 18. Consistent with its known molecular role in embryonic DG neurogenesis, we also found evidence for decreased Wnt pathway activity during IUGR. In conclusion, we have discovered that postnatal memory deficits are associated with accelerated NSC differentiation and maturation into glutamatergic granule neurons following IUGR, a phenotype that could be explained by decreased embryonic Wnt signaling.

An Ovarian Dermoid Cyst in Pregnancy: A Rare Cause of Intrauterine Growth Restriction

The most common ovarian tumour presenting during pregnancy are dermoid cysts, usually present in the second trimester. Mostly dermoid cysts are diagnosed during ultrasound in antenatal period. We report a case of large unilateral dermoid cyst which was missed in all USG done in antenatal period but diagnosed intra-operatively while performing caesarean section for Intra uterine growth restriction (IUGR) with fetal distress. Ovarian cystectomy was done and remaining ovarian tissues were preserved. The large dermoid cyst hampered the proper growth of the fetus in utero leading to IUGR and fetal distress. Ovarian dermoid cyst in antenatal period, a rare cause of IUGR and its successful management prompted us to report this case.

The Role of Measuring Placental Volume for the Prediction of Preeclampsia and Intrauterine Growth Restriction (IUGR)*

Preeclampsia is today one of the most important causes of perinatal and maternal death around the world. Vascular growth and development during placental process and the implantation are essential for successful pregnancy and outcome. Intrauterine growth restriction (IUGR), affecting 3–7% of all newborns, is the failure of the fetus to reach its growth potential in utero accordance with gestational week. IUGR, which has a negative effect on perinatal mortality and morbidity, is also the weight of the fetus being lower than expected. The most common cause of intrauterine growth restriction (IUGR) in the developed world is placental insufficiency. In this context, the aim of this study is to predict preeclampsia and IUGR in the first trimester with placental volume measurement by using 3D ultrasonography imaging methods in women who were pregnant between 11 and 14 weeks with CRL measurement between 45-84 mm. Quantitative analysis method was used to test the hypothesis of the research and to investigate the relationship between variables. Statistical analysis was done using SPSS 21. 450 pregnant women, who enrolled in the patient information management system, were the sample of our study. These women applied for the first three months screening test in the Perinatology Department of Manisa Celal Bayar University Hafsa Sultan Hospital and the sample was studied with permission from the ethics committee The relation between placental volume and smoking, weight, gravida, maternal age, gestational age, fetal weight, IUGR, and preeclampsia were found insignificant. In addition, the relationship between the weight of the baby, the relationship between maternal weight, age, gravida and the weeks of pregnancy were also found significant. Preeclampsia appeared in 16 out of 448 cases. Of these 16 cases, 11 (78.6%) had a placental volume of 0-32mm3 and the placenta volume of 5 cases (1.2%) was more than 32mm3. Thus, the relation between placental volume and preeclampsia was statistically found significant (p= 0.000). IUGR was also occurred in 16 out of 448 cases. In 14 cases of these, placental volume was between 0-32 mm3 and placenta volume was more than 32 mm3 in 2 cases. The relation between placental volume and IUGR was also statistically found significant (p = 0.000). The relation between placental volume and preeclampsia and IUGR was statistically found significant (p = 0.000).

Placentae for Low Birth Weight Piglets Are Vulnerable to Oxidative Stress, Mitochondrial Dysfunction, and Impaired Angiogenesis.

Intrauterine growth restriction (IUGR) is associated with fetal mortality and morbidity. One of the most common causes of IUGR is placental insufficiency, including placental vascular defects, and mitochondrial dysfunction. In addition, a high level of oxidative stress induces placental vascular lesions. Here, we evaluated the oxidative stress status, mitochondrial function, angiogenesis, and nutrient transporters in placentae of piglets with different birth weights: <500 g (L), 500–600 g (LM), 600–700 g (M), and >700 g (H). Results showed that placentae from the L group had higher oxidative damage, lower adenosine triphosphate and citrate synthase levels, and lower vascular density, compared to those from the other groups. Protein expression of angiogenic markers, including vascular endothelial cadherin, vascular endothelial growth factor A, and platelet endothelial cell adhesion molecule-1, was the lowest in the L group placentae compared to the other groups. In addition, the protein levels of glucose transporters GLUT1 and GLUT3 were downregulated in the L group, compared to the other groups. Furthermore, oxidative stress induced by H2O2 inhibited tube formation and migration in porcine vascular endothelial cells. Collectively, placentae for lower birth weight neonates are vulnerable to oxidative damage, mitochondrial dysfunction, and impaired angiogenesis.

Intra-uterine growth restriction induced by maternal low-protein diet causes long-term alterations of thymic structure and function in adult male rat offspring.

Early malnutrition, the first environmental cause of intra-uterine growth restriction, impairs development of the thymus. Alterations of the thymic structure and function are reported at young ages in murine and ovine models. However, descriptions of thymic consequences of fetal malnutrition at adulthood are scarce. The present study investigates thymic structure, protein expression and cell selection process observed at postnatal day 180 (PND180) in male offspring of rats exposed to maternal low-protein diet (mLPD) compared with control diet during gestation. The thymic index was lower in adult offspring exposed to mLPD (P<0·05). The thymic cortico-medullar ratio was lower in adult offspring exposed to mLPD (P<0·05). At PND180, the protein expression of the lymphotoxin β receptor (P<0·05), the autoimmune regulator (P<0·05) and Forkhead Box P3 (FoxP3; P<0·05) was all significantly lower in the mLPD group. The CD4+:CD8+ single-positive thymocyte subpopulation ratio and CD4+:CD8+ lymphocyte subpopulation ratio were increased in the mLPD group (P<0·05). Among CD3+ lymphocytes, the proportions of CD4+CD8+ double-positive lymphocytes, CD31+ recent thymic emigrants and CD4+FoxP3+ lymphocytes were not significantly different between mLPD and control groups. These findings suggest mLPD during gestation induced long-lasting alterations in the development of thymic structure and thymic cell maturation and selection process in adult male rat offspring.

Amphetamine–Dextroamphetamine and Pregnancy: Neonatal Outcomes After Prenatal Prescription Mixed Amphetamine Exposure

Objective: A retrospective cohort study was performed to evaluate whether birthweight was less among infants of women taking amphetamine–dextroamphetamine during pregnancy at our academic institution. Method: We identified mother–infant pairs with documented exposure to amphetamine–dextroamphetamine in pregnancy from 2005 through 2015. Patients were matched 2:1 with unexposed controls. Charts were reviewed for known causes of intrauterine growth restriction. Analysis of birthweight used generalized estimating equation blocking on matching. Medical histories were analyzed with χ2 test or Fisher’s exact test. Results: We identified 53 exposed mother–infant pairs. The difference in mean birthweight of infants exposed to amphetamine–dextroamphetamine versus those not exposed was 26.9 g, which is not significant (95% confidence interval [CI] = [−141, 195 g]; p = .75). A significant difference was noted for exposed versus unexposed mothers for comorbid psychiatric illness and history of substance abuse (p < .001). Conclusion: With a limited sample size, our study suggests no significant difference in birthweight.

204 Discriminating intrauterine growth-restricted piglets through near-infrared spectroscopy of amniotic fluids

The occurrence of intrauterine growth restriction (IUGR) is a great concern in animal production systems, leading to substantial economic losses. The multifactorial causes of IUGR make their prediction before or during pregnancy a challenging task. The amniotic fluid, containing chemical secretions of both the developing fetus and the amnion-allantois membrane, may offer a unique opportunity to investigate the causes of IUGR in piglets. Here we applied near-infrared spectroscopy (NIRS) as a rapid tool to discriminate the chemical composition of the amniotic fluid from IUGR fetuses at different gestational ages. The uteri of gravid sows were dissected at 60% (n=6 sows) and 90% (n=6 sows) of gestational age. Amniotic fluids were collected with a sterile 10-mL syringe connected to an 18-G needle under visual guidance, and samples without blood contamination were kept at 4°C while the fetus was measured. Samples were selected according to fetal weight and were classified as small (mean − 2 SD), medium (mean), and large (mean + 2 SD) sizes in each litter. Selected samples were kept at −80°C until NIRS transmittance spectra collection (350-2500nm). At 60% of gestational age, male fetuses weighed 96±1.2, 133±1.7, and 159±1.9g and female fetuses weighed 117±1.1, 137±1.8, and 152±1.8g for small, medium, and large groups, respectively. The fetal weights at 90% of gestational age averaged 517±0.6, 757±0.6, and 912±0.7g for males and 532±0.6, 718±0.9, and 911±0.6g for females for small, medium, and large sizes, respectively. Chemometric analysis of the amniotic fluid spectra was applied to the wavelength range 1300-1600nm using a balanced data set (n=425) with an 80/20 calibration/validation distribution for linear discriminant analysis (LDA-PCA). Overall, we were able to discriminate samples according to fetal size and gestational age; LDA-PCA showed the highest size classification occurring with spectra derived from the small fetuses with an accuracy of 94.5-100% and 100% and 70.6% for the calibration and validation processes from 60% and 90% of gestational age, respectively. By contrast, when the analysis considered each sex at 60% of gestational age, the medium and small fetuses presented the highest size classification for females and males correspondingly. At 90% of gestational age, the large fetuses presented the best discrimination for both sexes. In conclusion, we were able to detect and discriminate chemical changes of the amniotic fluid from different fetuses using NIRS, indicating that this fluid contains molecules that may characterise IUGR in piglets. These observations will permit future investigations to identify specific molecules associated with IUGR that would lead to possible real-time corrective actions before birth. This work was supported by USDA-ARS grant no. 58-6402-3-018.

Патоморфологічні особливості послідів у вагітних із затримкою росту плода

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.