Intrauterine growth restriction predisposes to airway inflammation without disruption of epithelial integrity in postnatal male mice

Author(s):  
Kevin Looi ◽  
Anthony Kicic ◽  
Peter B. Noble ◽  
Kimberley C. W. Wang

Abstract Evidence from animal models demonstrate that intrauterine growth restriction (IUGR) alters airway structure and function which may affect susceptibility to disease. Airway inflammation and dysregulated epithelial barrier properties are features of asthma which have not been examined in the context of IUGR. This study used a maternal hypoxia-induced IUGR mouse model to assess lung-specific and systemic inflammation and airway epithelial tight junctions (TJs) protein expression. Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11 to 17.5 (IUGR group; term, GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A Control group was housed under normoxic conditions throughout pregnancy. Offspring weights were recorded at 2 and 8 weeks of age and euthanized for bronchoalveolar lavage (BAL) and peritoneal cavity fluid collection for inflammatory cells counts. From a separate group of mice, right lungs were collected for Western blotting of TJs proteins. IUGR offspring had greater inflammatory cells in the BAL fluid but not in peritoneal fluid compared with Controls. At 8 weeks of age, interleukin (IL)-2, IL-13, and eotaxin concentrations were higher in male IUGR compared with male Control offspring but not in females. IUGR had no effect on TJs protein expression. Maternal hypoxia-induced IUGR increases inflammatory cells in the BAL fluid of IUGR offspring with no difference in TJs protein expression. Increased cytokine release, specific to the lungs of IUGR male offspring, indicates that both IUGR and sex can influence susceptibility to airway disease.

2017 ◽  
Vol 20 (5) ◽  
pp. 389-394 ◽  
Author(s):  
Chenyu Gou ◽  
Xiangzhen Liu ◽  
Xiaomei Shi ◽  
Hanjing Chai ◽  
Zhi-ming He ◽  
...  

CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta.


2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  

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.


2021 ◽  
Vol 225 (02) ◽  
pp. 125-128
Author(s):  
Hasan Eroğlu ◽  
Nazan Vanlı Tonyalı ◽  
Gokcen Orgul ◽  
Derya Biriken ◽  
Aykan Yucel ◽  
...  

Abstract Purpose To evaluate the usability of first-trimester maternal serum ProBNP levels in the prediction of intrauterine growth restriction (IUGR). Methods In this prospective study, blood samples taken from 500 women who applied to our polyclinic for routine serum aneuploidy screening between the 11–14th gestational weeks were centrifuged. The obtained plasma samples were placed in Eppendorf tubes and stored at −80+°C. For the final analysis, first-trimester maternal serum ProBNP levels of 32 women diagnosed with postpartum IUGR and 32 healthy women randomly selected as the control group were compared. FGR was defined as estimated fetal weight below the 10th percentile for the gestational age. Results The mean ProBNP levels were statistically and significantly higher in the women with intrauterine growth restriction (113.73±94.69 vs. 58.33±47.70 pg/mL, p<0.01). At a cut-off level of 50.93, ProBNP accurately predicted occurrence of IUGR (AUC+= 0.794 (95% confidence interval 0.679–0.910), p+= 0.001) with sensitivity and specificity rates of 78.1 and 69.0%, respectively. Conclusion First-trimester serum ProBNP level was significantly higher in women who developed IUGR compared to healthy controls. First-trimester ProBNP level can be used as a potential marker to predict the development of IUGR in pregnant women.


2003 ◽  
Vol 105 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Dietmar SCHLEMBACH ◽  
Ernst BEINDER ◽  
Juergen ZINGSEM ◽  
Ute WUNSIEDLER ◽  
Matthias W. BECKMANN ◽  
...  

This study was conducted to investigate the association of maternal and/or fetal factor V Leiden (FVL) and G20210A prothrombin mutation with HELLP syndrome. FVL and G20210A prothrombin mutation were determined using PCR. Sixty-three pregnant women, 36 of them diagnosed with HELLP syndrome, were included in the study. Overall, 68 children were born as a result of these pregnancies and blood sampling was possible in 28 out of 39 children from HELLP patients and 25 out of 29 children from the control women. The prevalence of a maternal FVL was elevated 2-fold in HELLP patients compared with the control women [six out of 36 (16.7%) compared with two out of 27 (7.4%); P=0.282]. None of the HELLP patients and only one woman in the control group was found to be positive for the G20210A prothrombin mutation (P=0.251). The fetal carrier frequency was four out of 28 compared with three out of 25 for FVL (P=0.811), and two out of 28 compared with one out of 25 for G20210A prothrombin mutation (P=0.629). Intrauterine growth restriction (IUGR) was significantly higher in fetuses found to be positive for a thrombophilic mutation (P=0.022). IUGR occurred in seven out of ten fetuses with a thrombophilic mutation compared with 11 out of 43 in fetuses without a mutation. The prevalence of FVL, but not of the G20210A prothrombin mutation, seems to be elevated in women with HELLP syndrome. A fetal thrombophilic mutation does not contribute significantly to the clinical features of the HELLP syndrome. Our results demonstrate a fetal contribution to IUGR. Fetal thrombophilic mutations may lead to placental microthrombosis, which consecutively could lead to a disturbed fetoplacental blood flow and thus cause growth restriction.


Author(s):  
Gul Nihal Buyuk ◽  
Z.Asli Oskovi-Kaplan ◽  
Aysegul Oksuzoglu ◽  
H.Levent Keskin

Abstract Objectives The aim of our study was to analyze the mean platelet volume levels as a potential marker of altered placentation in intrauterine growth restriction (IUGR) cases. Methods A total of 126 term singleton pregnant women with IUGR fetuses and 345 healthy pregnant controls were recruited and compared. Results The mean platelet volume was significantly higher in the IUGR group (10.8±0.9 fl) than the control group (9.9±1.1 fl) (p=0.03). The mean hemoglobin was lower in IUGR group (11.3 (8.3–14.5) g/dl) than the control group (11.9 (8.2–13.0) g/dl) (p=0.04). The optimal cut-off MPV for prediction of IUGR was ≥10.55 fl, with a sensitivity of 59% and a specificity of 75%. Conclusion Increased MPV levels in term pregnant women may be particularly helpful for discrimination and prediction of high-risk fetuses when IUGR is suspected.


2015 ◽  
Vol 143 (11-12) ◽  
pp. 701-706 ◽  
Author(s):  
Monica Hăşmăşanu ◽  
Sorana Bolboacă ◽  
Tudor Drugan ◽  
Melinda Matyas ◽  
Gabriela Zaharie

Introduction. Linear growth failure is caused by multiple factors including parental factors. Objective. The aim of this study was to evaluate parental risk factors for intrauterine growth restriction (IUGR) on a population of Romanian newborn infants in a tertiary level maternity facility for a period of 2.5 years. Methods. A retrospective matched case-control study was conducted in the Emergency County Hospital of Cluj-Napoca, a university hospital in North-Western Romania. The sample was selected from 4,790 infants admitted to the Neonatal Ward at 1st Gynecology Clinic between January 2012 and June 2014. Results. The age of mothers was significantly lower in the IUGR group compared to controls (p=0.041). A significantly higher percentage of mothers had hypertension in the IUGR group compared to those in the control group (p<0.05). No other significant differences were identified with regard to the investigated characteristics of mothers between IUGR infants compared to controls (p>0.13). The age of fathers of infants with IUGR proved significantly lower compared to controls (p=0.0278). The analysis of infants? comorbidities revealed no significant difference between groups for respiratory distress, hyperbilirubinemia, hypocalcaemia, and heart failure (p>0.27). Intracranial hemorrhage, necrotizing enterocolitis and hypoglycemia were significantly higher in the IUGR group compared to controls. The logistic regression identified hypertension as a significant risk factor for IUGR (OR=2.4, 95% CI [1.3-4.5]). Conclusion. Although the age of the mothers and fathers proved significantly lower in the IUGR group compared to controls, only hypertension in the mothers proved significant risk factors for IUGR.


2019 ◽  
Vol 21 (1) ◽  
pp. 62
Author(s):  
Gabriela Corina Zaharie ◽  
Monica Hasmasanu ◽  
Ligia Blaga ◽  
Melinda Matyas ◽  
Daniel Muresan ◽  
...  

Aim: To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction (IUGR) pregnancies.Material and method: A cohort of IUGR infants were evaluated by serial echocardiographies at delivery and at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the control group according to gestational age (AGA).Results: Left heart measurements were significantly lower in IUGR newborns compared to AGA babies. Left ventricular size increased at follow-up inthe IUGR group (p<0.05). Systolic dysfunction (the myocardial performance index (MPI)> 0.47) was identified in 40% of the neonates in the IUGR group (16/40), respectively 4.76% in the control group. IUGR neonates had a significantly increased proportion of systolic malfunction (p=0.004).Conclusion: IUGR patients had reduced left ventricle dimensions compared to AGA babies. The MPI stands out as a marker of leftheart function in newborns. Systolic dysfunction was a hallmark of the cardiac adaptation in IUGR neonates. 


2021 ◽  
Vol 18 (4) ◽  
pp. 268-274
Author(s):  
Gokmen Sukgen ◽  
◽  
Omer Kaya ◽  

Introduction. Although there are various reasons for intrauterine growth restriction (IUGR), the main cause is inadequate utero- placental and feto-placental circulation. Aim. To determine the predictive values of fetal middle cerebral artery/descending aorta (MCA/DA) Doppler parameter in the evaluation of perinatal outcomes in pregnancies with IUGR. Material and methods. 15 with IUGR and 35 normal newborn, who were born at the 34th gestational week or over included into the study. Doppler ultrasonography (US) measurements were performed. The ratio of pulsatility index/resistive index (PI/ RI) from MCA, umbilical artery (Umb), DA was determined. Neonatal characteristics such as Apgar scores, neonatal intensive care unit (NICU) requirement, weight and sex were also recorded. Results. In the IUGR group, mean MCA/DA RI-PI, MCA/UmB RI-PI were 0.88±0.19, 0.86±0.28, 1.22±0.18 and 1.55±0.39, respectively. In the control group, mean MCA/DA RI-PI, MCA/UmB RI-PI were 1.15±0.13, 1.09±0.41, 1.37±0.35 and 1.82±0.44, respectively. There were statistically significant relationship between MCA/DA PI with cord blood pH value and NICU requirement, age with gravida, parity, MCA/UmB RI, MCA/UmB PI; gravida with age and parity; parity with age, gravida, weight, MCA/DA RI, PI ratios. Conclusion. Intrauterine MCA and DA Doppler US parameters of IUGR can be used safely in predicting perinatal outcomes in pregnancies with IUGR over 34 weeks.


2021 ◽  
pp. 875647932110547
Author(s):  
Elham Keshavarz ◽  
Marjan Rustazade Sheikhyusefi ◽  
Ensi Khalili Pouya ◽  
Masoumeh Mirzamoradi ◽  
Mehdi Khazaei ◽  
...  

Objective: The objective of this study was to evaluate the association between reduced fetal thymus size and intrauterine growth restriction (IUGR). This study was devised to determine the association between thymus size and any abnormal Doppler indices within the fetal umbilical artery (UA), as well as the middle cerebral artery (MCA). Materials and Methods: Forty-six pregnancies between 20 and 38 weeks of gestation with IUGR and 46 normal pregnancies within similar gestational age (GA) range were included. The transverse diameter of fetal thymus was measured. In the IUGR group, the fetal umbilical artery (UA) and middle cerebral artery (MCA) Doppler flow velocities were recorded. Results: The mean GA of fetuses with IUGR (33.5 weeks) was higher than control group (30.3 weeks). To adjust for the effect of GA, analysis of covariance (ANCOVA) was performed. The adjusted mean thymus diameters were 19.02 mm in IUGR and 21.25 within the control group (mean difference = 2.23 mm; P = .02). The mean (±SD) thymus size in 16 fetuses, with abnormal Doppler findings, was significantly lower than in the group with normal Doppler findings, 17.45 (±2.50) vs 22.02 (±5.39) mm; P < .001. Conclusion: IUGR may be associated with reduced fetal thymus size, especially when coupled with abnormal Doppler findings. The thymus size in a group of IUGR fetuses, with abnormal Doppler findings, was smaller than IUGR fetuses, with normal Doppler findings.


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