Intrauterine Fetal Growth Retardation Research Articles

Pathogenetic associations of indicators of prenatal screening of the firsr trimester of pregnancy with fetal growth retardation

Objective. To determine the relationship between the indicators of prenatal screening of the 1st trimester and the intrauterine growth retardation (IUGR).
 Materials and methods. A prospective cohort study was carried out. Group 1 included 75 patients with fetal intrauterine growth retardation, group 2 414 women who gave birth to a live, full-term healthy baby with normal weight and height parameters. In all patients, the anamnestic parameters, indicators of PAPP-A, b-hCG, PlGF, thickness of the collar space and the pulsation index of the uterine arteries (PI UA) were compared.
 Results. A number of significant differences in the anamnestic parameters were found between the groups. In group 1, multiparous women were met more often (16 % compared with 2.9% in group 2, p0.001), women after сesarean section (13.3% and 5.6%, respectively, p=0.013), women with a history of spontaneous and artificial abortions (46.7% and 34.1 %, p=0.036). In addition, in group 1, patients were more likely to have uterine myoma in 9.3 % versus 3.4% in group 2 (p=0.019). In group 1, during the first trimester screening, PAPP-A values ​​were lower 1.238 (0.682.05) IU/ml versus 2.25 (1.283.9) IU/ml in group 2 (p0.001), and PlGF 13.73 (10.2219.09) IU/ml versus 17.19 (12.125.38) in group 2 (p=0.002). There were no significant differences in the level of b-hCG. The average pulsation index of the uterine arteries, on the contrary, in group 1 in the first trimester was higher than in group 2 1.73 (1.422.11) and 1.55 (1.321.85), respectively (p=0.024).
 Conclusions. Thus, a number of anamnestic data and screening indicators for the first trimester have a statistically significant relationship with the presence of IUGR of the fetus; therefore, these indicators can be used to assess the risk of this pregnancy complication.

Dietary N-carbamylglutamate or L-arginine improves fetal intestinal amino acid profiles during intrauterine growth restriction in undernourished ewes.

Our previous studies demonstrated that prenatal in utero growth restriction impairs postnatal intestinal function. Thus, improving postpartal intestinal absorption capacity and growth by manipulating the maternal diet prepartum is of importance. This work was conducted to determine whether supplementation of N-carbamylglutamate (NCG) or rumen-protected L-arginine (RP-Arg) increased fetal intestinal amino acid (AA) profiles in intrauterine growth retardation (IUGR) fetuses. On d 35 of gestation, Hu ewes (n = 32) carrying twin fetuses were randomized into 4 groups (8 ewes and 16 fetuses in each group), where diets were as follows: 100% of nutrient requirements recommended by National Research Council (NRC, 2007) (CON); 50% of nutrient requirements recommended by NRC (2007) (RES); RES + RP-Arg (20 g/d), (RES + ARG); and RES + NCG (5 g/d), (RES + NCG). On d 110 of gestation, both fetal and maternal tissues were collected and weighed. Compared with RES, solute carrier family 1, member 5 (SLC1A5) was upregulated (P < 0.05) within fetal jejunum, duodenum and ileum when supplementing NCG and RP-Arg. Relative to RES, RP-Arg or NCG supplementation to RES resulted in upregulation (P < 0.05) of peptide transporter 1 protein abundance within the fetal ileum. NCG or RP-Arg supplementation to RES also upregulated phosphorylated mechanistic target of rapamycin (pmTOR)-to-mTOR ratio in the fetal ileum induced by IUGR (P < 0.05). As a result, during IUGR, supplementation of Arg or NCG affected intestinal AA profiles in the fetus in part through controlling mTOR signal transduction as well as AA and peptide transport. Future studies should be conducted to understand the role (if any) of the placenta on the improvement of growth and AA profiles independent of the fetal intestine. This would help demonstrate the relative contribution of intestinal uptake in fetal life.

P-gp expression inhibition mediates placental glucocorticoid barrier opening and fetal weight loss

BackgroundPrenatal adverse environments can cause fetal intrauterine growth retardation (IUGR) and higher susceptibility to multiple diseases after birth, related to multi-organ development programming changes mediated by intrauterine overexposure to maternal glucocorticoids. As a glucocorticoid barrier, P-glycoprotein (P-gp) is highly expressed in placental syncytiotrophoblasts; however, the effect of P-gp on the occurrence of IUGR remains unclear.MethodsHuman placenta and fetal cord blood samples of IUGR fetuses were collected, and the related indexes were detected. Pregnant Wistar rats were administered with 30 mg/kg·d (low dose) and 120 mg/kg·d (high dose) caffeine from gestational day (GD) 9 to 20 to construct the rat IUGR model. Pregnant mice were administered with caffeine (120 mg/kg·d) separately or combined with sodium ferulate (50 mg/kg·d) from gestational day GD 9 to 18 to confirm the intervention target on fetal weight loss caused by prenatal caffeine exposure (PCE). The fetal serum/placental corticosterone level, placental P-gp expression, and related indicator changes were analyzed. In vitro, primary human trophoblasts and BeWo cells were used to confirm the effect of caffeine on P-gp and its mechanism.ResultsThe placental P-gp expression was significantly reduced, but the umbilical cord blood cortisol level was increased in clinical samples of the IUGR neonates, which were positively and negatively correlated with the neonatal birth weight, respectively. Meanwhile, in the PCE-induced IUGR rat model, the placental P-gp expression of IUGR rats was decreased while the corticosterone levels of the placentas/fetal blood were increased, which were positively and negatively correlated with the decreased placental/fetal weights, respectively. Combined with the PCE-induced IUGR rat model, in vitro caffeine-treated placental trophoblasts, we confirmed that caffeine decreased the histone acetylation and expression of P-gp via RYR/JNK/YB-1/P300 pathway, which inhibited placental and fetal development. We further demonstrated that P-gp inducer sodium ferulate could reverse the inhibitory effect of caffeine on the fetal body/placental weight. Finally, clinical specimens and other animal models of IUGR also confirmed that the JNK/YB-1 pathway is a co-regulatory mechanism of P-gp expression inhibition, among which the expression of YB-1 is the most stable. Therefore, we proposed that YB-1 could be used as the potential early warning target for the opening of the placental glucocorticoid barrier, the occurrence of IUGR, and the susceptibility of a variety of diseases.ConclusionsThis study, for the first time, clarified the critical role and epigenetic regulation mechanism of P-gp in mediating the opening mechanism of the placental glucocorticoid barrier, providing a novel idea for exploring the early warning, prevention, and treatment strategies of IUGR.

PECULIARITIES OF PREGNANCY COURSE, CHILDBIRTH, AND MORPHOFUNCTIONAL STATE OF PLACENTA IN WOMEN WITH INTRAUTERINE FETAL GROWTH RETARDATION

Fetal growth retardation is a severe obstetric pathology that is accompanied by significant reproductive losses and the cost of treating newborns. The aim of the study is to investigate the clinical difference between the course of pregnancy, childbirth, and morphofunctional state of the placenta in women who gave birth to children with low birth weight before gestational age and normal anthropometric parameters. Materials and methods. The study included 37 women; the individuals of the main group gave birth to a child with low birth weight before gestational age (n = 25), the comparison group consisted of women who had uneventful pregnancy and children born with normal anthropometric parameters (n = 12) . Results and discussion. Pregnancy and childbirth in the main group were registered mostly within the age range of 30 and 39, burdened with bad habits, accompanied by somatic and obstetric pathology. The predominant mode of preterm delivery in most of the main group was cesarean section caused by fetal distress in contrast to women in the comparison group. Analysis of the morphofunctional state of the placenta from the women in the main groups revealed both general structural-adaptive and structural-morphological changes that indicated compensatory hyperplasia of placental tissue in women with foetal intrauterine growth retardation that is characteristic of the compensated stage of chronic placental insufficiency. Conclusion. The multicomponent impact of various factors may contribute to an increased risk of fetal growth retardation and its progression, so timely correction of risk factors will help to improve the management of pregnancy and perinatal outcomes.

Dietary rumen-protected L-arginine or N-carbamylglutamate attenuated fetal hepatic inflammation in undernourished ewes suffering from intrauterine growth restriction.

This study aimed to explore whether dietary rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation to feed-restricted pregnant ewes counteracts fetal hepatic inflammation and innate immune dysfunction associated with intrauterine growth retardation (IUGR) in ovine fetuses. On d 35 of pregnancy, twin-bearing Hu ewes (n = 32) were randomly assigned to 4 treatment groups (8 ewes and 16 fetuses per group) and fed diets containing 100% of the NRC requirements (CON), 50% of the NRC requirements (RES), RES + RP-Arg (20 g/d) (RESA), or RES + NCG (5 g/d) (RESN). At 08:00 on d 110 of gestation, fetal blood and liver tissue samples were collected. The levels of triglyceride, free fatty acid, cholesterol and β-hydroxybutyrate in the fetal blood of RESA and RESN groups were lower (P < 0.05) than those of the RES group, but were higher (P < 0.05) than those of the CON group. The interleukin (IL)-6 and IL-1 levels in fetal blood and liver tissue as well as the myeloid differentiation primary response 88 (MyD88), transforming growth factor β (TGFβ), and nuclear factor kappa B (NF-κB) mRNA levels in the fetal liver were decreased (P < 0.05) by the NCG or RP-Arg supplementation compared to the RES treatment. Similarly, the toll-like receptor (TLR)-4, MyD88, TGFβ, and p-c-Jun N-terminal kinase (JNK) protein levels in the fetal liver were reduced (P < 0.05) in the NCG and RP-Arg -supplemented groups compared to the RES group. These results showed that dietary supplementation of RP-Arg or NCG to underfed pregnant ewes could protect against IUGR fetal hepatic inflammation via improving lipid metabolism, down-regulating the TLR-4 and the inflammatory JNK and NF-κB signaling pathways, and decreasing cytokine production in ovine fetal blood and liver tissue.

Comparison of Head Circumference and Abdominal Circumference Ratio in Normotensive and patients with Pregnancy Induced Hypertensive Disorders after 28 weeks of gestation

Background: Hypertensive disorders are an important medical problem of gestation. Hypertensive disorders of pregnancy (HDP) are a significant cause for maternal and fetal morbidity as well as mortality. Intrauterine growth retardation (IUGR) commonly describes the condition of fetus whose size or growth is subnormal. IUGR fetus is frequently described as symmetrical and asymmetrical IUGR in term of their body proportions. Asymmetric growth retardation is typically linked to uteroplacental inadequacy. Hypertension is one of the maternal causes of placental insufficiency. Aim: To compare head circumference and abdominal circumference ratio in normotensive and patients with pregnancy induced hypertensive disorders after 28 weeks of gestation. Methodology: A cross sectional analytical study was carried on 113 pregnant females in which 57 women were normotensive and 56 women were hypertensive. All individuals were scanned by two- dimensional ultrasound following 28 weeks of pregnancy to evaluate sonographic parameters HC and AC. The HC/AC ratio was estimated by dividing head circumference with abdominal circumference. Results: Out of 57 normotensive patients 27 (36.48%) fetuses were diagnosed with IUGR having HC/AC ratio more than 1, while 30 had normal HC/AC ratio. In 56 hypertensive patients 47(63.51%) fetuses were diagnosed with IUGR having HC/AC ratio greater than 1, however 9(23.07%) fetuses had HC/AC ratio within normal range. So out of total 113 patients, 74 fetuses were found with IUGR while 39 fetuses had HC/AC ratio within normal ranges. Our study found that a cut off value of ≥ 1.0974 for HC/AC ratio could be used as diagnostic parameter in predicting IUGR. Conclusion: HC/AC ratio is a useful parameter for the detection of IUGR. Keywords: Head Circumference, Abdominal Circumference, Intra Uterine Growth Retardation

Gene polymorphism of the xenobiotic biotransformation system and the intrauterine fetal growth retardation in female workers of industrial enterprises

Intrauterine growth retardation is recognized as one of the leading causes of incidence and mortality in infancy and early childhood in all the countries of the world. The causes and mechanisms of development of this process are decisive when choosing the tactics of nursing such children. Of particular importance is the understanding of the functioning of the mother-placenta-fetus system, in particular the mechanisms of suppression of the detoxification function of the placenta in connection with the polymorphisms of the genes of the I and II phases of the xenobiotic biotransformation system. The aim of the study was to determine the relationship between the polymorphism of the genes of the I and II phases of the xenobiotic biotransformation system with the intrauterine fetal growth retardation in women living in the South of the Kemerovo region and working under harmful labor conditions. A survey of 39 women of reproductive age living in the territory of Novokuznetsk was carried out, 20 of them worked at various enterprises of the city. The study group included 14 women who gave birth to children with intrauterine growth retardation of varying severity. The comparison group (control) consisted of 25 women. They did not have spontaneous miscarriages and they carried a child without the intrauterine growth retardation. The work investigated the frequency of occurrence of polymorphisms of genes of the xenobiotic biotransformation system - CYP1A2*1F, GSTM1 (they determine the activity of detoxification enzymes), as well as their combinations - in a group of working women and housewives who gave birth to children with intrauterine growth retardation. The forms of genes associated with the intrauterine fetal growth retardation, as well as genes associated with the resistance to this pathology, were identified. Combinations of gene forms of different phases of the xenobiotic biotransformation and their relationship with intrauterine fetal growth retardation were shown. There were no statistically reliable differences between various cohorts of women. A positive association of a high risk of the intrauterine fetal growth retardation in women with A/A CYP1A2*1F genotype and deletion polymorphism of the GSTM1 "-" gene has been shown. The heterozygous form of the C/A CYP1A2*1F gene polymorphism is statistically reliably associated with the resistance to this pathology, as well as the normally functioning GSTM1 "+" gene. Genotype A/A CYP1A2*1F in the combination with the deletion polymorphism of GSTM1 "-" gene is statistically reliably associated with intrauterine fetal growth retardation, and C/A CYP1A2*1F genotype in the combination with normally functioning GSTM1 "+" gene is associated with a low risk of the intrauterine fetal growth retardation. Comparative analysis of the relationship of the studied forms of genes of the xenobiotic biotransformation system with the intrauterine fetal growth retardation in the groups of female workers and housewives did not show statistically reliable differences.

ULTRASOUND MEASUREMENT OF TRANSCEREBELLAR DIAMETER (TCD)/ABDOMINAL CIRCUMFERENCE (AC) RATIO IN NORMAL AND GROWTH RESTRICTED FETUSES ABOVE TWENTY WEEKS OF GESTATION

Background: Intrauterine growth retardation (IUGR) is an obstetrical syndrome that is generally associated with increased mortality and morbidity. In IUGR, maternal placental blood flow is extremely compromised and that worsen the inter-villous circulation leading to an end-stage fetal distress. Objective: To compare TCD/AC ratio in both normal and growth restricted fetuses in second and third trimesters and to find if there is any correlation between TCD/AC ratio and EFW. Patients and methods: The study was conducted on 100 singleton pregnant women at EL-Sayed Galal University Hospital and Damanhour Teaching Hospital in the period between March 2019 till May 2020 and the patients were divided into two main equal groups. Group I included pregnant females with normally growing fetuses and Group II included pregnant females with growth restricted fetuses above 20 weeks of gestation. Results: This study demonstrated the usefulness of the single cut-off value (13.75%) of the TCD/AC ratio which may contribute to the early identification of SGA infants. The problem lied in identifying the process at the onset or before the IUGR has become severe. Usually the first parameter to decrease is the fetal AC due to depletion of hepatic glycogen and subcutaneous fat stores. The TCD/AC ratio, which utilized a single cut-off value (13.75%) independent of GA, improved diagnostic sensitivity and specificity in these cases. The possible contribution of the TCD/AC ratio in identifying the fetal growth failure itself, which was more important than predicting weight at birth to be further evaluated. There was no correlation between TCD/AC ratio and EFW and no statistical significant correlation between TCD/AC ratio and UA Doppler. Conclusion: In IUGR fetuses, the fetal TCD was less affected than fetal head circumference (HC) suggesting preferential preservation of cerebellar growth relative to other cranial structures. The TCD/AC ratio was helpful in recognizing abnormal fetal growth even when the GA was uncertain since this ratio was gestational age-independent.

Specialties of course of early and late preeclampsia in women in Vinnitsya region

Annotation. Preeclampsia is one of the leading causes of maternal and perinatal death, and it complicates from 5 to 8% of all pregnancies. The aim of the research was to show the differences in anamnesis, diagnostics and prognosis, in groups of pregnant with hypertensive disorders. Retrospective investigation included 138 delivery histories and perinatal record cards from Vinnitsya Municipal Clinical Maternity hospital №1, in a period from 2016 till 2018. Women were divided into two investigated groups: I – 36 women with early preeclampsia, and II group – 52 women with late preeclampsia, and a control group of 50 women. The structure of somatic and gynecological diseases of pregnant women was studied, the severity of preeclampsia and the condition of the newborn were assessed according to the Apgar scale. Statistical processing of the obtained results was performed by odds ratio, its standard error and 95% confidence interval were calculated according to D. G. Altman (1991). It is established that in women with obesity or excessive body weight (every second women in groups), and those who had cardiovascular disorders (twice more often with late preeclampsia) developed preeclampsia more often, comparing to control group. All cases of antenatal and early neonatal death of newborn were registered in a group with early preeclampsia, which points out on heavier flow of the disease and different pathogenesis. Cases of early pregnancy toxemia and edema of pregnant occurred twice more often, in group with early preeclampsia, and ran more heavy (up to the development of ascites), comparing to the second group. Debut of symptoms was earlier, that requires earlier prophylaxis (since week 12). Fetal intrauterine growth retardation, reversible and high resistant blood stream during ultrasound were marked only in group with EP. In future, this research together with pathohistological investigation of placentas and immunohistochemical research of those tissues, can underlie predictive and preventive personalized system for early and late preeclampsia.

Association of sflt-1 as a maternal serum biomarker in preeclampsia: A case–control tertiary care hospital based study

Objectives: Preeclampsia (PE) is a multisystemic disorder portrayed by the new beginning of circulatory pressure more noteworthy than 140/90 mmHg and proteinuria with 0.3 g in a 24 h on dip stick emerging after 20 weeks of incubation. The hidden pathophysiology of PE includes endothelial brokenness and vasospasm beginning principally in the placenta. The unusual growth of blood vessels in placenta leads to poor perfusion. This relative hypoxic condition in placenta causes arrival of antiangiogenic factors into the maternal blood dissemination which prompts the modifications in maternal fundamental endothelial functions and causes hypertension. Soluble fms-like tyrosine kinase (sFlt) can form a heterodimer, binding with vascular endothelial growth Factor A and placental growth factor. In preeclamptic subjects, there will be an imbalance in anti-angiogenesis factors and there will be incomplete arterial transformation and cytotrophoblast cell division. Due to imbalance in sFlt levels in preeclamptic women it effects in the blood vessels by constriction and leads to endothelial dysfunction. This study aim is to compare the maternal serum concentration of sFlt levels in normotensive pregnant women to preeclamptic women in early and late gestational weeks. Material and Methods: Out of 300 participants in the case–control study, 150 were preeclamptic women as cases and 150 as normotensive pregnant women as controls participated in the present study. A 5 ml of maternal venous blood was collected; the serum was separated and stored at –800°C till the analysis. Using commercially available enzyme-linked immunosorbent assay (ELISA) kits from Chongqing Biospes Co., Ltd., (suppliers: Infobio Company, New Delhi) was measured with ELISA microplate reader at 450 nm (Merilyzer Eiaquant Company). Results: Out of 300 participants in the study, 46 pregnant women were early gestational weeks and 254 were late gestational weeks. The complications due to severe PE such as intrauterine death are 15%, intrauterine fetal growth retardation 33%, and premature 15%. The statistical analyses were performed by Statistical Packages for the Social Sciences Software 22. The area under the receiver operating characteristic curve is 0.82, with 91% sensitivity, and 79% specificity. The significance in the maternal serum sFlt levels was calculated by the Mann–Whitney U-test. By comparing the cases and controls, it was found that maternal serum sFlt1 were significantly higher in preeclamptic women with Z = 2.96 and U = 9021 with P = 0.005 significance. Conclusion: This is the first South Indian study. If we compare the sFlt1 levels in early and late gestational weeks, in late gestational weeks in controls and PE the levels were highly significant than early gestational weeks of PE and controls. Maternal serum sFlt can be used as a preeclamptic diagnostic marker in South Eastern Kolar population.

P118: Maternal inflammation due to benzene exposure leads to fetal resorption and intrauterine growth retardation

P118: Maternal inflammation due to benzene exposure leads to fetal resorption and intrauterine growth retardation

Prenatal diagnosis of umbilical artery thrombosis in the second trimester: a case report

Objective Thrombosis of umbilical artery is a rare condition. The diagnosis is established commonly in the third trimester after detection of fetal distress or intrauterine growth retardation, or could be established after delivery. Also, the management of the condition is conflicting after the diagnosis. Case(s) Here we reported an umbilical artery thrombosis case that was diagnosed in the second trimester after referral for an umbilical cord cyst. After the diagnosis at 24th week of pregnancy, she had been followed up weekly. She had been delivered electively at the 34th week of pregnancy uneventfully. The diagnosis was confirmed postnatally. Conclusion The prenatal diagnosis of umbilical arterial thrombosis is so important to prevent perinatal morbidity. When umbilical cord cysts are detected, further evaluation is required in terms of umbilical artery thrombosis.

Transcerebellar Diameter to Abdominal Circumference Ratio in Assessment of Normal Fetal Growth

Background: Intrauterine growth restriction (IUGR) and its early detection were correlated with a high risk of perinatal mortality and morbidity and management are helpful in decreasing the neonatal risks. Transcerebellar diameter to abdominal circumference ratio becomes a gestational age independent parameter, which may be helpful for early detection of IUGR. Objectives: Study the accuracy of transcerebellar diameter/abdominal circumference ratio (TCD/AC ratio) for the evaluation of normal fetal development. Patients and methods: Our Prospective observatory research included 500 women with uncomplicated pregnancy attending the outpatient clinic of Al Azhar university hospitals for routine antenatal care. Routine ultrasound parameters were measured as well as transcerebellar diameter. In all patients, the TCD/AC ratio was also determined. Results: Our study concluded that difference in TCD/AC ratio between patients with IUGR vs. patients with no IUGR is statistically significant with p value 13 this cutoff value with 99.03 % sensitivity and 83.45 % specificity, 58.0 with a positive predictive value and 99.7 with a negative predictive value. Conclusions: TCD/AC ratio seems to become an age-independent constant parameter and a comparatively good IUGR indicator in gestational age groups of 18-34 weeks which may be helpful for early identification of fetal intrauterine growth retardation (IUGR).

Fetal Metabolomic Alterations Following Porcine Reproductive and Respiratory Syndrome Virus Infection.

PRRSV infection in third-trimester pregnant sows can lead to fetal death and abortions, although the mechanisms triggering these effects are not well understood. Since resistant and susceptible fetuses can coexist in the same litter, we propose that there may be differential mechanisms used by some fetuses to evade infection and/or disease progression. Our objectives were to investigate possible differences in the metabolome of PRRSV-infected and non-infected fetuses, as well as the interaction of altered intrauterine growth development and PRRSV infection to elucidate possible causes of fetal death following PRRSV infection. Near-term serum samples collected from fetuses on gestation day 106, 21 days post PRRSV-2 infection, were processed by direct flow injection mass spectrometry (DI-MS) and nuclear magnetic resonance (NMR) techniques. Experiment one investigated disease progression with 24 fetuses selected from each of four phenotypic groups: fetuses from non-inoculated gilts (CTRL); fetuses from inoculated gilts that escaped infection (UNINF); infected high viral load viable fetuses (INF); and infected high viral load meconium-stained fetuses (MEC). Experiment two investigated the interaction of intrauterine growth retardation (IUGR) and PRRSV infection by analyzing differences among: non-infected normal development (CON-N); CON-IUGR; PRRS infected normal development (PRRS-N); and PRRS-IUGR. Univariate and multivariate (PCA, PLS-DA) statistics determined group differences among various contrasts, and the most important metabolites associated with disease progression and fetal development. Significant differences in the metabolome were observed, especially between PRRSV-negative fetuses (CTRL and UNINF) and MEC fetuses, while INF fetuses appear to span both groups. The two metabolites with highest variable importance in projection (VIP) scores related to disease progression were alpha-aminoadipic acid (alpha-AAA) and kynurenine (KYN), having the highest concentration in MEC and INF fetuses, respectively, compared to CTRL and UNINF. In experiment two, non-IUGR fetuses were found to have increased levels of lysoPCs, PCs and amino acids compared to IUGR fetuses, while the near complete absence of lysoPCs and PCs in IUGR fetuses, even during infection, indicate a distinctive response to infection compared to non-growth retarded fetuses. Possible markers of PRRSV fetal susceptibility, such as alpha-AAA, kynurenine and lysoPCs, are presented and discussed.

Relation of the Renal Artery Color Doppler With the Umbilical Artery and Amniotic Fluid Index in Fetuses Affected by Intrauterine Growth Retardation

Objectives: This study was performed to investigate the relationship between the renal artery color Doppler with the umbilical artery and amniotic fluid index (AFI) in fetuses affected by intrauterine growth retardation (IUGR). Materials and Methods: This was a descriptive cross-sectional diagnostic study and the target population included pregnant mothers who were diagnosed to have fetuses with IUGR referring to the Al-Zahra treatment center in Tabriz. At least 40 samples were referred between October 2019 and May 2020. The patients were evaluated using the transabdominal ultrasound of the umbilical artery and fetal renal artery, and then using the color Doppler values of the umbilical artery and fetal renal artery. Results: The present research was performed on 40 pregnant females with an IUGR fetus with umbilical artery percentile upper that 95% whose minimum to maximum age range was 22-38 years. There is no relationship between umbilical artery and renal artery color Doppler. In addition, umbilical artery color Doppler is not related to amniotic fluid, also renal artery color Doppler demonstrated no significant correlation with amniotic fluid index. Conclusions: Based on our results, the PI of the umbilical artery had no significant correlation with that of the renal artery. In addition, there was no significant correlation with the PI of the renal artery and AFI.

The Melatonin and Enriched Environment Ameliorated Low Protein-Induced Intrauterine Growth Retardation by IGF-1 And mtor Signaling Pathway and Autophagy Inhibition in Rats.

Sprague-Dawley rats were randomly allocated to 3 groups: control (C), model (M) and EE+MEL group. Animals were housed in an enriched environment (EE+MEL group) or remained in a standard environment (C group, M group). IUGR rat model was built by feeding a low protein diet during pregnancy. MEL was administered by gavaging. At day 1 post-birth, the baseline characteristics and serum biochemical parameters, morphology of liver and small intestine, enzyme activities, and mRNA expression levels of fetal rats were determined. The autophagy marker LC3 and Beclin1 were determined by western blot analysis. EE+MEL markedly improved the baseline characteristics, hepatic and intestinal morphology of IUGR fetuses. In addition, the lactase activities in the fetal intestine were markedly increased by the EE+MEL. The levels of serum somatostatin (SST), Growth hormone (GH), GH releasing hormone (GHRH), Insulin-like Growth Factor 1 (IGF-1), triiodothyronine (T3), and tetraiodothyronine (T4) were found to be recovered by EE+MEL. In addition, the EE+MEL significantly ameliorated the mRNA expression of SST, GHRH, and GHRH receptor (GHRHR), GH, GHR, IGF-1, and IGF-1 receptor (IGF1R), IGF binding protein-1 (IGFBP1), mammalian target of rapamycin (mTOR), S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) in fetuses. In IUGR fetal livers, LC3 and Beclin1 were found to be increased at birth, while LC3 and Beclin1 were observed to be significantly decreased in the EE+MEL group. EE+MEL could improve fetal rats' baseline characteristics, serum biochemical parameters, birth weight, intestinal and hepatic morphology and enzyme activities. These effects could be explained by the activation of the IGF-1/IGFBP1 and IGF-1/mTOR/S6K1/4EBP1 signaling pathway and autophagy inhibition.

First Korean case of factor V Leiden mutation in pregnant woman with a history of recurrent pregnancy loss

Thrombophilia refers to inherited or acquired hemostatic disorders that result in a predisposition to blood clot formation. When combined with the hypercoagulable state that is characteristic of pregnancy, there is an increased risk of severe and recurrent pregnancy complications. Activated protein C resistance caused by factor V Leiden (FVL) mutation is known to be the most common cause of inherited thrombophilia in Caucasian population. FVL mutation has been related to pregnancy complications associated with hypercoagulation, e.g. miscarriage, intrauterine fetal demise, placental abruption, and intrauterine growth retardation. Although the FVL mutation is easily detected using molecular DNA techniques, patients who are heterozygous for this disorder often remain asymptomatic until they develop a concurrent prothrombotic condition. Because there are potentially serious effects of FVL mutation for pregnancy, and because effective treatment strategies exist, early detection and treatment of this condition might be considered.

Reference intervals for thyroid stimulating hormone and free thyroxine during pregnancy in our healthcare area

Although porcine reproductive and respiratory syndrome virus (PRRSV) readily crosses the maternal fetal interface (MFI) in third trimester, fetal resilience varies within litters. The aim of this study was to characterize PRRSV-2 concentration in MFI and fetuses at five time points after experimental inoculation of late gestation gilts and use this information to classify potentially resistant, resilient and susceptible fetuses. The secondary objective was to verify the relationship between PRRS viral load and intrauterine growth retardation (IUGR). Three PRRSV-inoculated pregnant gilts and 1 sham-inoculated control were euthanized at five time points in days post infection (DPI; 2, 5, 8, 12, 14). The preservation status of each fetus was determined and MFI samples adjacent to the umbilical stump of each fetus, as well as serum, thymus, umbilical cord and amniotic fluid were collected. Viral load was quantified using probe-based reverse-transcriptase quantitative PCR (RT-qPCR) targeting PRRSV NVSL 97-7895 ORF7. Our result show the MFI was largely PRRSV infected by 2 DPI and virus was first detected in fetal sera and umbilical cord by 5 DPI, and in fetal thymus and amniotic fluid by 8 DPI. This indicates that PRRSV-2 quickly crossed the placenta and traveled toward the fetus via umbilical circulation within one week of the dam’s inoculation. Fetal compromise was first observed on 8 DPI and increased progressively through to 14 DPI. However, several factors were associated with fetal resilience. The random forest model identified that ‘viral load in fetal thymus’ and duration of infection (‘DPI’) as the most important factors predicting fetal resilience and resistance. Moreover, IUGR fetuses had lower viral load and were less frequently compromised or dead compared to non-IUGR and average cohorts. Understanding the mechanisms of fetal resilience to PRRSV will improve selection strategies for replacement gilts.

Low Maternal Dietary Folate Alters Retrotranspose by Methylation Regulation in Intrauterine Growth Retardation (IUGR) Fetuses in a Mouse Model.

BackgroundMaternal folate deficiency-mediated metabolic disruption is considered to be associated with the risk of intrauterine growth retardation (IUGR), but the exact mechanism remains unclear. The retrotransposon long interspersed nucleotide element-1 (LINE-1), which can induce birth defects via RNA intermediates, plays crucial roles during embryonic development. We investigated potential relationships between maternal folate and DNA methylation, and possible roles of LINE-1 in IUGR.Material/MethodsThe IUGR model was established by feeding female mice 1 of 3 diets – control diet (CD), folate-deficient diet for 2 weeks (FD2w), and folate-deficient diet for 4 weeks (FD4w) – prior to mating. Maternal serum folate, 5-methyltetrahydrofolate (5-MeTHF), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) concentrations and global DNA methylation were assessed by LC/MS/MS method. LINE-1 methylation levels in fetuses were examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. LINE-1 expression levels were validated by real-time PCR.ResultsMaternal folate deficiency caused plasma folate and 5-MeTHF levels to decrease and SAH level to increase in the FD4w group. Compared with the CD group, methylation levels of genomic DNA and LINE-1 decreased significantly in placenta and fetal tissues from the FD4w group. Expression of LINE-1 open reading frame 1 (ORF1) protein was elevated in fetal liver tissues. Furthermore, a strong correlation was found between methylation and disrupted one-carbon metabolism, implying that dietary folate plays important roles during embryogenesis.ConclusionsMaternal dietary folate deficiency impaired one-carbon metabolism, leading to global DNA and LINE-1 hypomethylation, and then increased retrotransposition in fetuses, which can lead to IUGR.

Melatonin decreases and cytokines increase in women with placental insufficiency

Purpose: To investigate the levels of melatonin, proinflammatory and anti-inflammatory cytokines in pregnant women with placental insufficiency (PI).Materials and Methods: The PI was manifested as the intrauterine growth restriction syndrome of fetus (IUGR) in the third pregnancy trimester. The control group consisted of 20 women with uncomplicated pregnancy in the same term. The blood concentrations of melatonin, proinflammatory cytokines, such as tumor necrotizing factor-α (TNF-α), interleukin-1-β (IL-1-β), interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-4 (IL-4), and interleukin-10 (IL-10), were studied.Results: The concentration of melatonin was found to decrease significantly if pregnancy was complicated by intrauterine fetal growth retardation (study group −126.87 ± 14.87 pg/ml, control group −231.25 ± 21.56 pg/ml, p < .001). The levels of proinflammatory cytokines in the study group were significantly higher as compared with the control group (TNF-α: study group −10.05 ± 1.35 pg/ml, control group −5.60 ± 1.50 pg/ml, p < .05; IL-1-β: study group −14.67 ± 2.13 pg/ml, control group −3.96 ± 0.92 pg/ml, p < .001; IL-6: study group −6.91 ± 0.99 pg/ml, control group −2.69 ± 0.99 pg/ml, p < .05). The same is true about anti-inflammatory cytokines (IL-4: study group −5.97 ± 0.50 pg/ml, control group −3.74 ± 0.62 pg/ml, p < .05; IL-10: study group −11.40 ± 1.50 pg/ml, control group −4.70 ± 3.20 pg/ml, p < .001). A moderate negative correlation between melatonin and IL-1-β in the group with PI (r = −0.3776, p = .0097), a closed negative correlation between the same indexes in the control group (r = −0.6785, p = .001), and a moderate negative correlation between melatonin and TNF-α (r = −0.4908, p = .02) were found.Conclusions: The blood level of melatonin significantly decreases in case of placental insufficiency, manifested as intrauterine fetal growth restriction. Strengthening of the proinflammatory immunity shown as the increasing of the levels of TNF-α, IL-1-β, and IL-6 levels is also present in case of IUGR. Increase of the serum concentration of the anti-inflammatory cytokines, such as IL-4 and IL-10, in our opinion, can be explained by activation of compensatory mechanisms, which decrease the risk of premature labor.