Control Fetuses Research Articles

Fetal adrenal demedullation lowers circulating norepinephrine and attenuates growth restriction but not reduction of endocrine cell mass in an ovine model of intrauterine growth restriction.

Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses.

119 A SHORT PERICONCEPTIONAL MATERNAL HYPERGLYCEMIA IS SUFFICIENT TO DISRUPT THE FETO-PLACENTAL PHENOTYPE IN A RABBIT MODEL

Pre-gestational type 1-diabetes (T1D) increases the risk of miscarriage and congenital malformations and programs the offspring to develop metabolic syndrome in adulthood. Management of maternal diabetes is essential during gestation but could be also highly important around the time of conception. Using a rabbit model, the effects of maternal T1D during the periconceptional period on pre-implantation blastocysts have been well documented, but the effects on feto-placental phenotype at 28 dpc (term = 31 days) has not been explored. Diabetes was induced by Alloxan in dams 7 days before mating. Glycemia was maintained at 15 to 20 mmol L–1 with exogenous insulin injections. At 4 dpc, embryos were collected and transferred into nondiabetic recipients. At 28 dpc, control (C) and diabetic (D) fetuses were collected for biometric records, placental analyses including stereology and gene expression, and lipid profiles of feto-placental tissues by gas chromatography. Lipid data were analysed by principal component analysis. D-fetuses were growth retarded, hyperglycemic, and dyslipidemic compared with C fetuses. Moreover, placental efficiency was much higher in D- than in C-fetuses. The volume density of fetal vessels was significantly decreased in D-placentas compared to C-placentas, whereas the volume density of trophoblast tended to increase (P = 0.051). This morphometric disruption was associated with a deregulation of the expression of genes related to nutrient supply and lipid metabolism. In fetal plasma, a specific fatty acid signature was observed in D- and C-groups. Moreover, the composition of placental and fetal liver membranes differed according to maternal status and fetal sex. Tissues from D-fetuses contained significantly more n-6 polyunsaturated fatty acids compared with C. Docosahexaenoic acid decreased whereas linoleic acid increased in the cardiac membranes of D-fetuses, indicating a higher risk of ischemia. This study demonstrates that exposure to high plasma glucose during the short periconceptional period is sufficient to adversely program fetal phenotype by reducing fetal growth, altering placental function and lipid profiles in all fetal tissues.

Hemopoietic Cell Proliferation and Death in the Regenerating Fetal Rat Liver

The proliferation and death of hemopoietic cells in the regenerating liver of 17-day outbred albino rat fetuses were studied during 2 days after resection of 20% of the organ. The mitotic index of hemopoietic cells in the resected liver increased significantly 24 h after the operation in comparison with the control fetuses. No increase in the counts of apoptotic hemopoietic cells was detected in the regenerating liver. Hence, resection of 20% of the liver in rat fetuses stimulated the proliferation of hemopoietic cells and did not stimulate their apoptosis.

Aberrant expression of Xist in aborted porcine fetuses derived from somatic cell nuclear transfer embryos.

Cloned pigs generated by somatic cell nuclear transfer (SCNT) show a greater ratio of early abortion during mid-gestation than normal controls. X-linked genes have been demonstrated to be important for the development of cloned embryos. To determine the relationship between the expression of X-linked genes and abortion of cloned porcine fetuses, the expression of X-linked genes were investigated by quantitative real-time polymerase chain reaction (q-PCR) and the methylation status of Xist DMR was performed by bisulfate-specific PCR (BSP). q-PCR analysis indicated that there was aberrant expression of X-linked genes, especially the upregulated expression of Xist in both female and male aborted fetuses compared to control fetuses. Results of BSP suggested that hypomethylation of Xist occurred in aborted fetuses, whether male or female. These results suggest that the abnormal expression of Xist may be associated with the abortion of fetuses derived from somatic cell nuclear transfer embryos.

A case-control study of maternal periconceptual and pregnancy recreational drug use and fetal malformation using hair analysis.

ObjectiveMaternal recreational drug use may be associated with the development of fetal malformations such as gastroschisis, brain and limb defects, the aetiology due to vascular disruption during organogenesis. Using forensic hair analysis we reported evidence of recreational drug use in 18% of women with a fetal gastroschisis. Here we investigate this association in a variety of fetal malformations using the same method.MethodsIn a multi-centre study, women with normal pregnancies (controls) and those with fetal abnormalities (cases) gave informed consent for hair analysis for recreational drug metabolites using mass spectrometry. Hair samples cut at the root were tested in sections corresponding to 3 month time periods (pre and periconceptual period).ResultsWomen whose fetus had gastroschisis, compared to women with a normal control fetus, were younger (mean age 23.78±SD4.79 years, 18–37 vs 29.79±SD6 years, 18–42, p = 0.00001), were more likely to have evidence of recreational drug use (15, 25.4% vs 21, 13%, OR2.27, 95thCI 1.08–4.78, p = 0.028), and were less likely to report periconceptual folic acid use (31, 53.4% vs 124, 77.5%, OR0.33, 95thCI 0.18–0.63, p = 0.001). Age-matched normal control women were no less likely to test positive for recreational drugs than women whose fetus had gastroschisis. After accounting for all significant factors, only young maternal age remained significantly associated with gastroschisis. Women with a fetus affected by a non-neural tube central nervous system (CNS) anomaly were more likely to test positive for recreational drugs when compared to women whose fetus was normal (7, 35% vs 21, 13%, OR3.59, 95th CI1.20–10.02, p = 0.01).ConclusionsWe demonstrate a significant association between non neural tube CNS anomalies and recreational drug use in the periconceptual period, first or second trimesters, but we cannot confirm this association with gastroschisis. We confirm the association of gastroschisis with young maternal age.

Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats.

The use of dexamethasone (Dx) stimulates growth, fetal lung maturation and can improve pulmonary hypertension in congenital diaphragmatic hernia (CDH). Our aim was to evaluate the effect of Dx on the lung after fetal pulmonary ventilation in the CDH rat model. Some groups underwent prenatal treatment with dexamethasone (0.4mg/kg) that was given at 18.5 gestational day (GD). Sprague-Dawley rat fetuses were divided into groups: control (C); ventilated control (CV); control exposed to dexamethasone (CDx); ventilated control exposed to dexamethasone (CVDx); congenital diaphragmatic hernia (CDH), ventilated CDH (CDHV), CDH exposed to dexamethasone (CDHDx) and ventilated CDH exposed to dexamethasone (CDHVDx). At 21.5 GD fetuses were delivered by C-section, weighed and ventilated for 30min. We analyzed the lung morphometry by Masson's Trichrome stain, and VEGF, VEGFR1, VEGFR2 and NOS3 expression by immunohistochemistry. All fetuses with CDH, with or without prenatal dexamethasone showed lung and body weight lower than control fetuses (p<0.05). All groups that received dexamethasone showed a decrease in the medial muscular layer of arterioles, the internal diameter of the air spaces (Lma) and length of parenchymal transection/airspace ratio (p<0.05). In the immunohistochemistry, VEGF decreased more in CDHDV group (p<0.05). VEGFR1 showed no difference, whereas VEGFR2 decreased significantly in the CDHDV group (p<0.05). NOS3 increased in the group CDHDV (p<0.05). The use of prenatal dexamethasone added to ventilation alters the VEGF and NO pathways.

Structural Study of Gubernaculum Testis in Fetuses with Prune Belly Syndrome

We compared and contrasted the structure of the gubernaculum testis in fetuses with prune belly syndrome and normal controls. We studied a total of 6 gubernacula from 3 male fetuses with prune belly syndrome and a total of 14 from 7 male fetuses without an anomaly. Gubernacular specimens were cut into 5 μm sections and stained with Masson trichrome to quantify connective tissue and smooth muscle cells, with Weigert stain to observe elastic fibers and with picrosirius red with polarization to observe collagen. Immunohistochemical analysis was done with tubulin to observe the nerves. Images were captured with a BX51 microscope and DP70 camera (Olympus®). Stereological analysis was done with Image-Pro and ImageJ (MediaCybernetics®) using a grid to determine volumetric density. Means were statistically compared with the Mann-Whitney test. All tests were 2-sided with p <0.05 considered statistically significant. Prune belly syndrome fetuses were at 17 to 31 weeks of gestation and control fetuses were at 12 to 35 weeks of gestation. Quantitative analysis showed no difference in the volumetric density of smooth muscle cells in prune belly syndrome vs control gubernacula (mean 15.70% vs 19%, p = 0.2321). Collagen fiber analysis revealed a predominance of green areas in prune belly syndrome gubernacula, suggesting collagen type III, and a predominance of red areas in control gubernacula, suggesting collagen type I. Elastic fibers were significantly smaller in prune belly syndrome gubernacula than in control gubernacula (mean 14.06% vs 24.6%, p = 0.0190). Quantitative analysis demonstrated no difference in the volumetric density of nerves in prune belly syndrome or control gubernacula (mean 5.200% vs 3.158%, p = 0.2302). The gubernaculum in fetuses with prune belly syndrome had altered concentrations of collagen and elastic fibers. These structural alterations could be one of the factors involved in cryptorchidism in prune belly syndrome.

Timing of delivery and neonatal outcomes for small-for-gestational-age fetuses.

To investigate whether antenatal recognition of small-for-gestational-age (SGA) fetuses with normal maternal and fetal Doppler values delivered after 34 weeks' gestation is associated with changes in the risk of adverse maternal and neonatal outcomes. In this retrospective study, we included 313 singleton SGA fetuses and 313 appropriate-for-gestational-age control fetuses born between 34 and 42 weeks' gestation from 2009 to 2012. Small-for-gestational-age fetuses identified before delivery (n = 124), for whom antenatal surveillance was performed until delivery (estimated fetal weight twice weekly and Doppler evaluation of the fetal compartment once weekly), were compared to those not identified at delivery (n = 189). The latter group did not undergo antenatal surveillance for several reasons (women for whom a sonographic evaluation or gynecologic consultation was not performed in the third trimester and incorrect sonographic biometric evaluation in the third trimester). Main outcome measures were mode of delivery, perinatal complications, and neonatal intensive care unit admission. The risk of serious fetal complications was assessed by cross-tabulation analysis adjusted for gestational age and degree of SGA. Prenatally recognized SGA fetuses were smaller and delivered earlier than unrecognized SGA fetuses (P< .05). Fetal acidemia (pH <7.10) was significantly more common in unrecognized SGA fetuses (3.7% versus 0%). Small-for-gestational-age fetuses at or below the 3rd percentile were more commonly recognized prenatally and hospitalized in the neonatal intensive care unit. Unrecognized SGA fetuses also had worse fetal outcomes compared to controls (P< .05). Recognized and unrecognized SGA fetuses were born significantly more frequently by cesarean delivery (P < .05). No significant differences in perinatal outcomes were found between recognized SGA deliveries with or without medical induction. Antenatal recognition of SGA fetuses delivered after 34 weeks' gestation might improve perinatal outcomes. Medical induction of labor did not modify neonatal outcomes among prenatally recognized SGA fetuses.

Imaging of fetal thymus in pregnant women with rheumatic diseases

OBJECTIVE To determine whether certain rheumatic diseases will affect the fetal thymus diameter when compared to uncomplicated singleton pregnancies. Additionally, we created a reference chart for fetal thymus size in healthy singleton pregnancies from 19 to 37 weeks of gestation. METHODS Sonographic fetal thymus size was retrospectively evaluated in 190 healthy pregnant women, and 84 pregnancies of mothers suffering from systemic lupus erythematosus, antiphospholipid syndrome (APS), or Sjogren's syndrome between 19 and 37 weeks of gestation. These fetuses were matched one-to-one for gestational age with control fetuses. The thymic-thoracic ratio (TT-ratio) was defined as the quotient of the anteroposterior thymic and the intrathoracic mediastinal diameter. RESULTS Rheumatic diseases often affect pregnancy outcome, especially in case of primary APS. The TT ratio of fetuses of mothers suffering from rheumatic disease was equal to controls (P=0.807). CONCLUSIONS Ours is the first study to assess the correlation of fetal thymus size in high-risk pregnancies with rheumatic diseases in comparison to controls. Women with rheumatic diseases deal with pregnancy complications more frequently than controls. Our data suggest that maternal rheumatic diseases do not affect the fetal thymus size.

OP25.05: Corpus callosum differences assessed by MRI in term small for gestational age fetuses and its association with neurobehaviour

To evaluate corpus callosum (CC) morphometry by MRI in term small for gestational age (SGA) fetuses compared to controls and its association with neurobehavioral outcome. 117 SGA and 73 control fetuses with normal umbilical Doppler were imaged using a 3T MRI scanner at 37 weeks of gestation, obtaining T2 HASTE anatomical acquisition in the three orthogonal planes. CC length, thickness, total area and the areas after a subdivision in 7 portions were blindly assessed by semi-automatic delineation. All measurements were corrected by the cephalic index. Neonatal neurobehaviour was evaluated with the Neonatal Behavioral Assessment Scale (NBAS) at 42 ± 1 week. Statistical analyses were performed by multivariate analysis of covariance adjusting for gender, smoking and body mass index. The association between CC measurements and NBAS scores in SGA was assessed by ordinal regression taking into account the same covariates plus age at NBAS test, considering the dependent variable the amount of NBAS test's clusters under the 5th centile. SGA fetuses showed significantly smaller total CC area (SGA: 1.3996 ± 0.26 vs. control: 1.664 ± 0.31; p < 0.01) and smaller genu, rostral body, anterior midbody, posterior midbody, isthmus and splenium areas. Overall, we found a significant association between smaller CC measures and worse neurobehavioral outcome in SGA newborns, particularly a smaller total area (p = 0.03), rostrum (p = 0.02), genu (p = 0.03), rostral body (p = 0.02), anterior midbody (p = 0.03) and splenium (p = 0.03) had a significant negative effect on the number of abnormal NBAS clusters. CC development was significantly altered in term SGA fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk.

Speckle tracking echocardiography in fetuses diagnosed with congenital diaphragmatic hernia.

The aim of this study is to evaluate cardiac function in fetuses with congenital diaphragmatic hernia (CDH) using speckle tracking. Case-control study assessed cardiac contractility in consecutive fetuses with CDH. Controls were anatomically normal fetuses, adjusted for gestational age. Speckle tracking software calculated ventricular peak longitudinal velocity, displacement and strain. Pulmonary hypoplasia was assessed using observed/expected lung-to-head ratio (O/E LHR). Thirty-eight fetuses with CDH (29 left and nine right) were evaluated at a mean gestational age of 26.9 ± 2.5 weeks. In six fetuses, the acquired images were of insufficient quality (feasibility 83%). Velocity and displacement showed regional differences, as well as significant differences between the ventricular walls, similar to control fetuses. Strain measurements also demonstrated regional differences yet less uniformly arranged. In left CDH, we observed increased strain values in the left ventricle compared with controls (-18.7 ± 7.2 vs -15.1 ± 4.9). There was no correlation between strain values in the left ventricle and O/E LHR. In fetuses with right CDH, deformation analysis was not different from controls. In fetuses with CDH, no cardiac dysfunction could be detected despite the often concurrent hypoplasia of ipsilateral cardiac structures. In fetuses with left CDH, the decrease in ventricular size coincides with increased strain values in the free left ventricular wall.

Impaired fetal myocardial deformation in intrahepatic cholestasis of pregnancy.

To investigate changes in fetal myocardial deformation in intrahepatic cholestasis of pregnancy. Patients with intrahepatic cholestasis of pregnancy were divided into 2 groups according to the total maternal serum bile acid concentration: mild cholestasis (10-40 μmol/L) and severe cholestasis (>40 μmol/L). Fetal echocardiography and velocity vector imaging were performed on women with cholestasis and control patients. The left ventricular global longitudinal strain and strain rate were measured. Clinical characteristics, maternal serum bile acid levels, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in umbilical vein blood were compared between groups. The relationships among fetal myocardial deformation, maternal total bile acids, and cord NT-proBNP were analyzed. Twenty women with mild cholestasis, 20 with severe cholestasis, and 40 control patients were enrolled. There were no significant differences in maternal and gestational ages between the case and control groups. Maternal bile acids and NT-proBNP were significantly higher in fetuses of mothers with cholestasis than control fetuses. The left ventricular longitudinal strain (-10.56% ± 1.83% versus -18.36% ± 1.11%; P < .01), systolic strain rate (-1.63 ± 0.18 versus -2.04 ± 0.18 secondsz(-1); P < .01), and diastolic strain rate (1.37 ± 0.18 versus 1.83 ± 0.14 seconds(-1); P < .01) were significantly decreased in fetuses with severe cholestasis compared with control fetuses. There were positive correlations between fetal myocardial deformation and maternal total bile acids (r = 0.705, 0.643, and 0.690, respectively; P < .01) and between myocardial deformation and NT-proBNP (r = 0.672, 0.643, and 0.647; P < .01). Fetal myocardial deformation is impaired in severe intrahepatic cholestasis of pregnancy. Further investigation is needed to determine whether fetal echocardiography and velocity vector imaging can help predict which fetuses of mothers with cholestasis are likely to have poor outcomes.

DUCTUS VENOSUS FLOW, DIASTOLIC DYSFUNCTION AND MYOCARDIAL HYPERTROPHY IN FETUSES OF DIABETIC MOTHERS

Infants of diabetic mothers have an established risk of developing myocardial hypertrophy even with adequate maternal metabolic control. The pulsatility index of ductus venosus flow may be a useful parameter for assessing the role of myocardial hypertrophy due to maternal diabetes in fetal diastolic ventricular function. Aim of the work: To test the hypothesis that the pulsatility index of ductus venosus (PIDV) is higher and the mitral & tricuspid early diastolic/atrial systole velocity ratios (E/A ratios) are lower in the fetuses of diabetic mothers (FDM) with myocardial hypertrophy (MH) than in the FDM with no MH and in the control fetuses of non-diabetic mothers (FNDM). Subjects and methods: Cross-sectional study included fetuses with gestational ages ranging from 20 to 36 weeks, divided into the following 3 groups: 10 FDM with MH (group I), 20 FDM with no MH (group II), and 30 FNDM (group III, control). The Doppler echocardiogram assessed the PIDV through the ratio (systolic velocity – pre-systolic velocity)/mean velocity. The mitral and tricuspid E/A ratios were also assessed. Results: The mean PIDV in groups I, II, and III were 1.28 ± 0.5, 0.73 ± 0.09, and 0.59±0.09, respectively. Using ANOVA test, the mean pulsatility index was significantly higher in group I than in group II and III (P 0.001). Comparing the pulsatility index of ductus venosus in group II with that in group III, a statistically significant difference (P=0.02) was observed. The mean mitral E/A ratios in groups I, II and III were 0.68 ± 0.04, 0.73 ± 0.06 and 0.68 ± 0.1, respectively. When applying the ANOVA, the mitral E/A ratios were non significant between the three groups (P = 0.17). The mean tricuspid E/A ratios in groups I, II and III were 0.69 ± 0.05, 0.71 ± 0.03 and 0.68 ± 0.07, respectively. When applying the ANOVA, the tricuspid E/A ratios were non significant between the three groups (P = 0.19). Conclusion: DV PI is significantly greater in FDM with MH than in FDM with no MH and in FNDM. It is a useful parameter than E/A ratios of the mitral and the tricuspid valves for assessing fetal diastolic function. Key words: Ductus venosus, maternal diabetes; fetal myocardial hypertrophy, diastolic dysfunction.

Genomic imprinting analysis of Igf2/H19 in porcine cloned fetuses using parthenogenetic somatic cells as nuclear donors

To gain insight into parthenogenesis in pigs, we report for the first time that using parthenogenetic somatic cells as nuclear donors (PSCNT), the porcine parthenogenetic fetus can develop to gestational day 39. Weight and morphological analysis revealed that PSCNT fetuses were smaller and developmentally retarded when compared to normally fertilized controls. Quantitative gene expression analysis indicated that in PSCNT fetuses, H19 was over-expressed, whereas Igf2 was significantly reduced (p < 0.05) compared with their controls. In addition, bisulfite-sequencing PCR results demonstrated that H19 differentially DNA methylated regions (DMRs) were hypomethylated in PSCNT fetuses, while Igf2 DMRs were hypermethylated in both PSCNT and control fetuses. Our results suggest that extended development of the porcine parthenogenetic fetus can be accomplished using PSCNT and that abnormal DNA methylation of H19 DMRs might contribute to the critical barrier of parthenogenesis in pigs.

A physiological increase in insulin suppresses muscle-specific ubiquitin ligase gene activation in fetal sheep with sustained hypoglycemia.

Decreased glucose transfer to the fetus is characteristic of pregnancies complicated by maternal under nutrition and placental insufficiency. Chronic experimental restriction of glucose transfer to the sheep fetus for the final 40% of gestation with a maternal insulin infusion (HG fetuses) results in fetal hypoglycemia, hypoinsulinemia, and decreased rates of fetal growth and protein accretion compared to controls (CON). Lower rates of fetal protein accretion are due to increased fetal protein breakdown and not decreased protein synthesis. However, the specific skeletal muscle pathways responsible for increased protein breakdown have not been determined. Nor has it been determined if low fetal glucose or insulin concentrations are more important for regulating these skeletal muscle protein breakdown pathways. We tested whether chronic restriction of glucose transfer to the fetus increased the ubiquitin–proteosome pathway or autophagy‐lysosome pathway in fetal sheep skeletal muscle and found no evidence for an increase in the autophagy‐lysosome pathway. However, HG fetuses had increase mRNA expression of MaFBx1 (twofold, P <0.01) and a trend for increased mRNA expression of MuRF1 (P =0.08) compared to CON. A subset of chronically hypoglycemic fetuses received an isoglycemic insulin infusion for the final 7 days of the maternal insulin infusion (HG + INS fetuses) and had MaFBx1 and MuRF1 mRNA concentrations similar to CON fetuses. These results demonstrate that fetuses exposed to sustained hypoglycemia have decreased protein accretion due to activation of the skeletal muscle ubiquitin–proteosome pathway and that a fetal hyperinsulinemic clamp can suppress this pathway even in the context of continued hypoglycemia.

Effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver

This study investigated the effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver. Eighteen ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.175MJMEkgBW−0.75d−1, n=6), Restricted Group 2 (RG2, 0.33MJMEkgBW−0.75d−1, n=6) and a Control Group (CG, ad libitum, 0.67MJMEkgBW−0.75d−1, n=6). Fetuses were recovered at slaughter on d 140. Fetuses in the RG1 group exhibited decreased (P<0.05) liver weight, total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD), cholinesterase (CHE), total protein (TP), globulin (GLB), and alanine transaminase (ALT). In addition, intermediate changes were found in the RG2 fetuses, including decreased liver weight, T-AOC and CHE (P<0.05). In contrast, increases in fetal hepatic collagen fibers and reticular fibers, glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOs), monoamine oxidase (MAO), albumin (ALB)/GLB, aspartate transaminase (AST), and AST/ALT were found in the RG1 fetuses (P<0.05). The RG2 fetuses had increased fetal hepatic collagen fibers, NOs and MAO (P<0.05) relative to the control fetuses. These results indicate that impaired fetal hepatic growth, fibrosis, antioxidant imbalance and dysfunction were associated with maternal undernutrition.

Corpus callosum differences assessed by fetal MRI in late-onset intrauterine growth restriction and its association with neurobehavior

The aim of this study is to evaluate corpus callosum (CC) development by Magnetic Resonance Imaging (MRI) in late-onset intrauterine growth restricted (IUGR) fetuses compared to appropriate for gestational age and its association with neurobehavioral outcome. One hundred and seventeen late-onset IUGR and 73 control fetuses were imaged using a 3T MRI scanner at term, obtaining T2 half-Fourier acquisition single-shot turbo spin-echo anatomical slices. CC length, thickness, total area and the areas after a subdivision in 7 portions were assessed. Neonatal Behavioral Assessment Scale test was performed on IUGR newborns at 42 ± 1 weeks. IUGR fetuses showed significantly smaller CC (Total CC Area IUGR: 1.3996 ± 0.26 vs. AGA: 1.664 ± 0.31; p < 0.01) and smaller subdivision areas as compared with controls. The differences were slightly more pronounced in fetuses with very low birth weight and/or abnormal brain and/or abnormal uterine Doppler. CC measurements were significantly associated with neurobehavioral outcome in IUGR cases. CC development was significantly altered in late-onset IUGR fetuses and correlated with worse neurobehavioral performance. CC could be further explored as a potential imaging biomarker to predict abnormal neurodevelopment in pregnancies at risk.

Relationship of Isolated Single Umbilical Artery to Fetal Growth, Aneuploidy, and Perinatal Mortality

The umbilical cord normally contains 2 arteries and a single vein. When an umbilical artery is absent, the condition is called single umbilical artery (SUA). The reported prevalence of SUA varies from 0.5% at the second-trimester prenatal ultrasound and in umbilical cord specimens from live-born infants to 2.1% in fetal deaths, autopsies, or aborted fetuses. Approximately 33% of fetuses with SUA have additional structural anomalies, and 10% are affected with aneuploidy. In ~65% of cases, SUA seems to be an isolated finding. In pregnancies with an apparently isolated SUA (iSUA), aneuploidy or fetal size (small for gestational age [SGA]) may become apparent later in pregnancy or at birth. This systematic review was undertaken to assess outcome of iSUA diagnosed at the midtrimester ultrasound scan and to determine whether data are sufficient to determine appropriate management of pregnancies with diagnosed iSUA. MEDLINE, EMBASE, and the Cochrane Library databases were searched for articles reporting on SUA. Randomized controlled trials, cohort studies, and case-control studies were eligible if they described 30 or more cases of apparent iSUA identified by ultrasound before a mean gestational age of 24 weeks. All studies that allowed construction of a 2 × 2 table were included, with the incidence of the outcome of interest in SUA fetuses and 3-vessel cord fetuses. Quantitative data on the outcome variables included incidence of SGA and perinatal mortality, median or mean birth weight, and frequency of aneuploidy. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined for the occurrence of SGA, perinatal mortality, and frequency of aneuploidy in iSUA fetuses compared with those in 3-vessel cord fetuses. Of 449 articles, the final analysis included 3 cohort and 4 case-control studies, reporting on 68 and 297 cases of apparent iSUA, with a total of 982 patients with an iSUA. The mean gestational age at diagnosis of SUA was 19.0 to 24.3 weeks. A non–statistically significant association was found between iSUA and SGA at birth (OR for SGA in fetuses with iSUA, 1.6; 95% CI, 0.97–2.6; P = 0.06), with ORs in the cohort studies ranging from 1.1 to 3.3. In 3 of the case-control studies, iSUA fetuses did not have significantly lower mean birth weights compared with control fetuses (mean weight, 3154 vs 3176 g; mean difference, 51 g; 95% CI, −154.7 to 52.6 g; P = 0.33). The OR for preterm birth in fetuses with an iSUA compared with control fetuses was 2.1 (95% CI, 1.4–3.2) for delivery before 37 weeks and 3.3 (95% CI, 1.4–7.7) for delivery before 34 weeks. Although there was a positive association between iSUA and increased perinatal mortality, it did not meet statistical significance (OR, 2.0; 95% CI, 0.9–4.2; P = 0.07). Among 695 iSUA cases reported in 16 studies, 4 cases of aneuploidy (0.58%) occurred; the mean maternal age was 30.1 years. These results indicate that iSUA is associated with a nonsignificant trend for increased risk for SGA and perinatal mortality. The relatively low birth weight in iSUA neonates may occur as a result of a relatively high prevalence of preterm birth. On the basis of this review, no firm conclusions can be drawn about the association between iSUA and aneuploidy. More large-scale, prospective cohort studies are necessary to clarify these associations and identify appropriate management protocols for iSUA fetuses.

Morpho-functional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure

Thyroid hormones (TH) and glucocorticoids strongly contribute to the maturation of fetal tissues in the preparation for extrauterine life. Influence of maternal dexamethasone (Dx) administration on thyroid glands morpho-functional characteristics of near term rat fetuses was investigated applying unbiased stereology. On the 16th day of pregnancy dams received 1.0mg/Dx/kg/b.w., followed by 0.5mg/Dx/kg/b.w. on the 17th and 18th days of gestation. The control females received the same volume of saline. The volume of fetal thyroid was estimated using Cavalieri’s principle; the physical/fractionator design was applied for the determination of absolute number of follicular cells in mitosis and immunohistochemically labeled C cells; C cell volume was measured using the planar rotator. The functional activity of thyroid tissue was provided from thyroglobulin (Tg) and thyroperoxidase (TPO) immunohistochemical staining. Applying these design-based modern stereological methods it was shown that Dx treatment of gravid females led to a significant decrease of fetal thyroid gland volume in 19- and 21-day-old fetuses, due to decreased proliferation of follicular cells. The Tg and TPO immunohistochemistry demonstrated that intensive TH production starts and continues during the examined period in control and Dx-exposed fetuses. Under the influence of Dx the absolute number of C cells was lower in both groups of near term fetuses, although unchanged relation between the two populations of endocrine cells, follicular and C cells suggesting that structural relationships within the gland are preserved. In conclusion maternal glucocorticoid administration at the thyroid gland level exerts growth-inhibitory and maturational promoting effects in near term rat fetuses.

Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract obstruction

Fetuses with pulmonary outflow tract obstruction (POTO) have altered blood flow to the pulmonary vasculature. We sought to determine whether pulmonary vascular impedance, as assessed by the pulsatility index (PI), is different in fetuses with POTO compared with normal controls. Branch pulmonary artery PI was evaluated in age-matched normal control fetuses (n=22) and 20 POTO fetuses (pulmonary stenosis n=15, pulmonary atresia n=5). Pulsed-wave Doppler was performed in the proximal (PA1), mid (PA2) and distal (PA3) branch pulmonary artery. The direction of flow in the ductus arteriosus was noted. The study and control groups were compared with Student's t-test and ANOVA. A linear mixed model evaluated the relationship between PI and ductus arteriosus flow patterns. There was no difference in PI between control, pulmonary stenosis and pulmonary atresia subjects at PA1 and PA2; however, there was a significant difference at PA3. Subjects with pulmonary atresia had a lower PI at PA3 than did controls (P=0.003) and pulmonary stenosis subjects (P=0.003). Subjects with retrograde flow in the ductus arteriosus had lower PIs in PA2 and PA3 than did those with antegrade flow (P=0.01 and 0.005, respectively). The PI in PA3 was lower in fetuses that required prostaglandin postnatally than in those that did not (P=0.008). Fetuses with pulmonary atresia or severe pulmonary stenosis with retrograde flow in the ductus arteriosus have decreased PI in the distal pulmonary vasculature. Our findings indicate the capacity of the fetal pulmonary vasculature to vasodilate in response to anatomical obstruction of flow.