ResearchPad - fetuses https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Ultrasound prediction of Zika virus-associated congenital injury using the profile of fetal growth]]> https://www.researchpad.co/article/elastic_article_13878 Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study’s objective was to determine the diagnostic accuracy of femur-sparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femur-sparing profile of growth restriction determined using INTERGROWTH-21st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score ≤ -1.3 had a 52% specificity (95% CI 41–63%), 82% negative predictive value (NPV, 95% CI 73–88%) for the detection of ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81–95%), 81% NPV (95% CI 77–85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81–95%) with superior NPV (87%, 95% CI 84–90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.

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<![CDATA[Placental transfer of Letermovir &amp; Maribavir in the <i>ex vivo</i> human cotyledon perfusion model. New perspectives for <i>in utero</i> treatment of congenital cytomegalovirus infection]]> https://www.researchpad.co/article/elastic_article_11236 Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment. Letermovir (LMV) and Maribavir (MBV) are new CMV antivirals, and potential candidates for fetal treatment.MethodsThe objective was to investigate the placental transfer of LMV and MBV in the ex vivo method of the human perfused cotyledon. Term placentas were perfused, in an open-circuit model, with LMV or MBV at concentrations in the range of clinical peak plasma concentrations. Concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Mean fetal transfer rate (FTR) (fetal (FC) /maternal concentration), clearance index (CLI), accumulation index (AI) (retention of each drug in the cotyledon tissue) were measured. Mean FC were compared with half maximal effective concentrations of the drugs (EC50(LMV) and EC50(MBV)).ResultsFor LMV, the mean FC was (± standard deviation) 1.1 ± 0.2 mg/L, 1,000-fold above the EC50(LMV). Mean FTR, CLI and AI were 9 ± 1%, 35 ± 6% and 4 ± 2% respectively. For MBV, the mean FC was 1.4 ± 0.2 mg/L, 28-fold above the EC50(MBV). Mean FTR, CLI and AI were 10 ± 1%, 50 ± 7% and 2 ± 1% respectively.ConclusionsDrugs’ concentrations in the fetal side should be in the range for in utero treatment of fetuses infected with CMV as the mean FC was superior to the EC50 for both molecules. ]]> <![CDATA[Model based estimation of QT intervals in non-invasive fetal ECG signals]]> https://www.researchpad.co/article/elastic_article_7659 The end timing of T waves in fetal electrocardiogram (fECG) is important for the evaluation of ST and QT intervals which are vital markers to assess cardiac repolarization patterns. Monitoring malignant fetal arrhythmias in utero is fundamental to care in congenital heart anomalies preventing perinatal death. Currently, reliable detection of end of T waves is possible only by using fetal scalp ECG (fsECG) and fetal magnetocardiography (fMCG). fMCG is expensive and less accessible and fsECG is an invasive technique available only during intrapartum period. Another safer and affordable alternative is the non-invasive fECG (nfECG) which can provide similar assessment provided by fsECG and fMECG but with less accuracy (not beat by beat). Detection of T waves using nfECG is challenging because of their low amplitudes and high noise. In this study, a novel model-based method that estimates the end of T waves in nfECG signals is proposed. The repolarization phase has been modeled as the discharging phase of a capacitor. To test the model, fECG signals were collected from 58 pregnant women (age: (34 ± 6) years old) bearing normal and abnormal fetuses with gestational age (GA) 20-41 weeks. QT and QTc intervals have been calculated to test the level of agreement between the model-based and reference values (fsECG and Doppler Ultrasound (DUS) signals) in normal subjects. The results of the test showed high agreement between model-based and reference values (difference < 5%), which implies that the proposed model could be an alternative method to detect the end of T waves in nfECG signals.

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<![CDATA[Lack of mutagenicity, genotoxicity and developmental toxicity in safety assessment tests of Lactobacillus mali APS1]]> https://www.researchpad.co/article/5c1c0aeed5eed0c484426f00

Lactobacillus (L.) mali APS1 isolated from sugary kefir grains has been proven to affect energy and glucose homeostasis. However, without proper safety assessment it cannot be recommended as probiotics for human consumption. For genotoxicity, the Ames test showed no mutagenic effect of L. mali APS1 in the presence or absence of S9 mix metabolic activation. In-vitro mammalian chromosomal aberration test showed that the number of Chinese hamster ovary cells with abnormal chromosomes was <5% after L. mali APS1 treatment. Moreover, L. mali APS1 showed no risk of genotoxicity potential compared to the control. L. mali APS1 administration did not cause significant (p>0.05) changes in body weight, the number of reticulocytes, or in the occurrence percentage of micronucleus in Imprinting Control Region (ICR) mice. Based on the absence of maternal or fetal effects at any dosage level investigated, the teratogenicity could be defined as greater than 1,670 mg/kg b.w./day for maternal general toxicity and fetal development when L. mali APS1 was orally administered by gavage to pregnant SD rats during gestation days 6 to 15.

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<![CDATA[Fetal Huanjiang mini-pigs exhibit differences in nutrient composition according to body weight and gestational period]]> https://www.researchpad.co/article/5b6003a9463d7e38dd0d05bb

Low birth weight may negatively affect energy storage and nutrient metabolism, and impair fetal growth and development. We analyzed effects of body weight (BW) and gestational period on nutrient composition in fetal Huanjiang mini-pigs. Fetuses with the lowest BW (LBW), middle BW (MBW), and highest BW (HBW) were collected at days 45, 75, and 110 of gestation. Crude protein (CP), crude fat, amino acid (AA), and fatty acid (FA) concentrations were determined. The BW gain, carcass weight, fat percentage, and uterus weight of sows increased as gestation progressed, as did litter weight, average individual fetal weight, fetal body weight, and dry matter (DM). The concentrations of Ala, Arg, crude fat, Gly, Pro, Tyr, C14:0, C16:0, C16:1, C18:1n9c, C18:2n6c, C18:3n3, C18:3n6, C20:0, C20:3n6, saturated FA (SFA), and monounsaturated FA (MUFA) increased significantly as gestation progressed. The percentage of skeleton, and the ratio of the liver, lung, and stomach to BW decreased as gestation progressed. There were also significant reductions in the concentrations of CP, Asp, Glu, His, Ile, Leu, Lys, Phe, Ser, Thr, essential AA (EAA), acidic AA, C17:0, C20:4n6, C22:6n3, unsaturated FA (UFA), polyunsaturated FA (PUFA), n-3PUFA, n-6PUFA as gestation progressed, and reductions in EAA/total AA (TAA), PUFA/SFA, and n-3/n-6 PUFA. The LBW fetuses exhibited the lowest BW and crude fat, C14:0, C16:1, C17:0, C18:2n6c, and MUFA concentrations at days 75 and 110 of gestation. They also exhibited lower Tyr concentration at day 45 of gestation and lower Glu concentration at day 75 of gestation than HBW fetuses. These findings suggest that LBW fetuses exhibit lower amounts of crude fat and several FAs during mid-gestation and late-gestation, which may in turn affect adaptability, growth, and development.

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<![CDATA[Longer Gestation among Children Born Full Term Influences Cognitive and Motor Development]]> https://www.researchpad.co/article/5989db14ab0ee8fa60bccd1e

Children born preterm show persisting impairments in cognitive functioning, school achievement, and brain development. Most research has focused on implications of birth prior to 37 gestational weeks; however, the fetal central nervous system continues to make fundamental changes throughout gestation. Longer gestation is associated with reduced morbidity and mortality even among infants born during the period clinically defined as full term (37–41 gestational weeks). The implications of shortened gestation among term infants for neurodevelopment are poorly understood. The present study prospectively evaluates 232 mothers and their full term infants (50.4% male infants) at three time points across the first postnatal year. We evaluate the association between gestational length and cognitive and motor development. Infants included in the study were full term (born between 37 and 41 weeks gestation). The present study uses the combination of Last Menstrual Period (LMP) and early ultrasound for accurate gestational dating. Hierarchical Linear Regression analyses revealed that longer gestational length is associated with higher scores on the Bayley scales of mental and motor development at 3, 6 and 12 months of age after considering socio-demographic, pregnancy, and infant-level covariates. Findings were identical using revised categories of early, term, and late term proposed by the Working Group for Defining Term Pregnancy. Our findings indicate that longer gestation, even among term infants, benefits both cognitive and motor development.

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<![CDATA[Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdce78

The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model. Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection. The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains, providing a better analogy to the human condition than approaches involving immunodeficient, genetically modified animals, or direct ZIKV injection into the brain. When injected via the jugular vein into the blood of pregnant females harboring conceptuses from early gastrulation to organogenesis stages, akin to the human second and fifth week of pregnancy, ZIKV infects maternal tissues, placentas and embryos/fetuses. Early exposure to ZIKV at developmental day 5 (second week in humans) produced complex manifestations of anterior and posterior dysraphia and hydrocephalus, as well as severe malformations and delayed development in 10.5 days post-coitum (dpc) embryos. Exposure to the virus at 7.5–9.5 dpc induces intra-amniotic hemorrhage, widespread edema, and vascular rarefaction, often prominent in the cephalic region. At these stages, most affected embryos/fetuses displayed gross malformations and/or intrauterine growth restriction (IUGR), rather than isolated microcephaly. Disrupted conceptuses failed to achieve normal developmental landmarks and died in utero. Importantly, this is the only model so far to display dysraphia and hydrocephalus, the harbinger of microcephaly in humans, as well as arthrogryposis, a set of abnormal joint postures observed in the human setting. Late exposure to ZIKV at 12.5 dpc failed to produce noticeable malformations. We have thus characterized a developmental window of opportunity for ZIKV-induced teratogenesis encompassing early gastrulation, neurulation and early organogenesis stages. This should not, however, be interpreted as evidence for any safe developmental windows for ZIKV exposure. Late developmental abnormalities correlated with damage to the placenta, particularly to the labyrinthine layer, suggesting that circulatory changes are integral to the altered phenotypes.

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<![CDATA[Reference Charts for Fetal Cerebellar Vermis Height: A Prospective Cross-Sectional Study of 10605 Fetuses]]> https://www.researchpad.co/article/5989da8eab0ee8fa60b9f1a7

Objective

To establish reference charts for fetal cerebellar vermis height in an unselected population.

Methods

A prospective cross-sectional study between September 2009 and December 2014 was carried out at ALTAMEDICA Fetal–Maternal Medical Centre, Rome, Italy. Of 25203 fetal biometric measurements, 12167 (48%) measurements of the cerebellar vermis were available. After excluding 1562 (12.8%) measurements, a total of 10605 (87.2%) fetuses were considered and analyzed once only. Parametric and nonparametric quantile regression models were used for the statistical analysis. In order to evaluate the robustness of the proposed reference charts regarding various distributional assumptions on the ultrasound measurements at hand, we compared the gestational age-specific reference curves we produced through the statistical methods used. Normal mean height based on parametric and nonparametric methods were defined for each week of gestation and the regression equation expressing the height of the cerebellar vermis as a function of gestational age was calculated. Finally the correlation between dimension/gestation was measured.

Results

The mean height of the cerebellar vermis was 12.7mm (SD, 1.6mm; 95% confidence interval, 12.7–12.8mm). The regression equation expressing the height of the CV as a function of the gestational age was: height (mm) = -4.85+0.78 x gestational age. The correlation between dimension/gestation was expressed by the coefficient r = 0.87.

Conclusion

This is the first prospective cross-sectional study on fetal cerebellar vermis biometry with such a large sample size reported in literature. It is a detailed statistical survey and contains new centile-based reference charts for fetal height of cerebellar vermis measurements.

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<![CDATA[A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdbcbc

Background

Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis.

Methods

Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements.

Results

There were 284 abstracts identified, 16 papers were included in the review and the meta-analysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) [95% CI 0.01, 0.16]) and femur length (0.06 [0.01, 0.10]) and reduced third trimester head size (0.18 SD [0.13, 0.23]), femur length (0.27 SD [0.21, 0.32]) and estimated fetal weight (0.18 SD [0.11, 0.24]). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD [0, 0.19]) and third (0.15 SD [0.03, 0.26]) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked.

Conclusions

Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy.

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<![CDATA[Enhanced Pulmonary Vascular and Alveolar Development via Prenatal Administration of a Slow-Release Synthetic Prostacyclin Agonist in Rat Fetal Lung Hypoplasia]]> https://www.researchpad.co/article/5989d9d6ab0ee8fa60b65f8b

Lung hypoplasia and pulmonary hypertension are the major causes of mortality in neonates with congenital diaphragmatic hernia (CDH). Although the prostaglandin pathway plays a pivotal role in lung development, the reported efficacy of postnatal prostaglandin agonist treatment is suboptimal. We hypothesized that prenatal treatment with ONO-1301SR, a slow-release form of a novel synthetic prostacyclin agonist with thromboxane inhibitory activity, might enhance the development of lungs exhibiting hypoplasia in the fetal period. On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to establish a CDH-related lung hypoplasia model, whereas normal rats received the vehicle only. The same day, either ONO-1301SR or a placebo was also randomly administered. On E21.5, the fetuses of the normal group and those exhibiting CDH were analyzed. Prenatal ONO-1301SR administration had no influence on the incidence of nitrofen-induced CDH. The lung-to-body weight ratio in the CDH+ONO group was greater than that in the CDH group. Histologically, the medial wall in the CDH+ONO group was two-thirds thinner than that in the CDH group. In addition, the number of Ttf-1-positive cells and the capillary density were ≥1.5 times greater in the CDH+ONO group than in the CDH group, and this increase was associated with higher expression of vascular endothelial growth factor and stromal cell-derived factor in the CDH+ONO group, suggesting enhanced development of the alveolar and capillary networks. Thus, prenatal ONO-1301SR was protective against the progression of lung hypoplasia associated with CDH in a nitrofen-induced rat model, indicating the potential of this treatment for pathologies exhibiting lung hypoplasia.

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<![CDATA[Prenatal Diagnosis and Evaluation of Sonographic Predictors for Intervention and Adverse Outcome in Congenital Pulmonary Airway Malformation]]> https://www.researchpad.co/article/5989da3dab0ee8fa60b88cef

Objective

To describe antenatal findings and evaluate prenatal risk parameters for adverse outcome or need for intervention in fetuses with congenital pulmonary airway malformation (CPAM).

Methods

In our retrospective study all fetuses with a prenatal diagnosis of CPAM detected in our tertiary referral center between 2002 and 2013 were analyzed. Sonographic findings were noted and measurements of mass-to-thorax-ratio (MTR), congenital pulmonary airway malformation volume-ratio (CVR) and observed to expected lung-to head-ratio (o/e LHR) were conducted and correlated to fetal or neonatal morbidity and mortality and/or need for prenatal intervention.

Results

67 fetuses with CPAM were included in the study. Hydropic fetuses were observed in 16.4% (11/67) of cases, prenatal intervention was undertaken in 9 cases; 7 pregnancies were terminated. The survival rate of non-hydropic fetuses with conservatively managed CPAM was 98.0% (50/51), the survival rate for hydropic fetuses with intention to treat was 42.9% (3/7). 10 (18.2%) children needed respiratory assistance. Fetuses with a CVR of <0.91 were significantly less likely to experience adverse outcome or need for prenatal intervention with sensitivity, specificity and positive/negative predictive value of 0.89, 0.71, 0.62 and 0.93, respectively. A MTR (mass-to-thorax-ratio) of < 0.51 had a positive predictive value of 0.54 and a negative predictive value of 0.96 of adverse events with a sensitivity of 0.95 and a specificity of 0.63. The negative predictive value for o/e LHR of 45% was 0.84 with sensitivity, specificity and positive predictive value of 0.73, 0.68 and 0.52, respectively.

Conclusions

The majority of cases with CPAM have a favorable outcome. MTR and CVR are able to identify fetuses at risk, the o/e LHR is less sensitive.

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<![CDATA[Safety evaluation of a vaccine: Effect in maternal reproductive outcome and fetal anomaly frequency in rats using a leishmanial vaccine as a model]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdbc02

While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed. Rats were mated and allocated in three groups: Control—rats received saline; Adjuvant—rats received the adjuvant MPLA, and Vaccine—rats received the combination of MPLA and peroxidoxin. The administration was subcutaneously at the dorsal region, three times (days 0, 7, 14 of pregnancy). On day 21 of pregnancy, all rats were bled for biochemical and immunological measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The immunization with peroxidoxin induced a significant production of circulating IgG levels compared to other groups but caused a significant in post-implantation loss (14.7%) when compared to Control (5.0%) and Adjuvant (4.4%) groups. Furthermore, a significantly high rate of fetal visceral anomalies, such as hydronephrosis and convoluted ureter, was also observed in animals that received vaccine when compared to Control or Adjuvant groups. These data indicate the importance of safety evaluation of vaccines during pregnancy and the limited use of peroxidoxin administration during pregnancy. More importantly, the safety monitoring of immunization with MPLA derived from Bordetella pertussis demonstrated no reproductive outcomes associated with adjuvant administration, suggesting its safe use during pregnancy.

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<![CDATA[Inflammation-induced fetal growth restriction in rats is associated with increased placental HIF-1α accumulation]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc8b4

Introduction

Hypoxia-inducible factor 1-alpha (HIF-1α) is the oxygen-sensitive subunit of the transcription factor HIF-1, and its expression is increased in placentas from pregnancies complicated by pre-eclampsia (PE). Fetal growth restriction (FGR) and PE often share a common pathophysiology; however, it is unknown whether increased placental HIF-1α occurs in FGR. We previously demonstrated that aberrant maternal inflammation in rats resulted in altered utero-placental perfusion and FGR, both of which were prevented by administration of the nitric oxide mimetic glyceryl trinitrate (GTN). Our aim here was to determine whether abnormal maternal inflammation causing FGR is linked to placental HIF-1α accumulation and whether GTN administration could prevent increases in placental HIF-1α.

Methods

Levels of inflammatory factors in maternal plasma were measured using a multiplex assay after an injection of low-dose lipopolysaccharide (LPS) to rats on gestational day (GD) 13.5. Following three additional daily LPS injections from GD14.5–16.5, GD17.5 placentas were harvested for HIF-1α immunolocalisation; serial sections were also stained for the hypoxia marker pimonidazole. A subset of rats received LPS injections along with GTN delivered continuously (25 μg/h via a transdermal patch) on GD12.5-GD17.5.

Results

Within two hours of LPS administration, levels of maternal pro-inflammatory cytokines were increased compared with saline-treated controls. GD17.5 placentas of growth-restricted fetuses exhibited increased HIF-1α accumulation; however, this did not correlate with pimonidazole staining for which no differences were observed between groups. Furthermore, the LPS-mediated increases in maternal inflammatory cytokine levels and placental HIF-1α accumulation did not occur in rats treated with GTN.

Discussion

Our results demonstrate that inflammation-induced FGR is associated with increased placental HIF-1α accumulation; however, expression of this transcription factor may not correlate with regions of hypoxia in late-gestation placentas. The GTN-mediated attenuation of placental HIF-1α accumulation in LPS-treated rats provides insight into the mechanism by which GTN improves inflammation-induced complications of pregnancy.

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<![CDATA[The electrical heart axis and ST events in fetal monitoring: A post-hoc analysis following a multicentre randomised controlled trial]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcc3b

Objective

Reducing perinatal morbidity and mortality is one of the major challenges in modern health care. Analysing the ST segment of the fetal electrocardiogram was thought to be the breakthrough in fetal monitoring during labour. However, its implementation in clinical practice yields many false alarms and ST monitoring is highly dependent on cardiotocogram assessment, limiting its value for the prediction of fetal distress during labour. This study aims to evaluate the relation between physiological variations in the orientation of the fetal electrical heart axis and the occurrence of ST events.

Methods

A post-hoc analysis was performed following a multicentre randomised controlled trial, including 1097 patients from two participating centres. All women were monitored with ST analysis during labour. Cases of fetal metabolic acidosis, poor signal quality, missing blood gas analysis, and congenital heart disease were excluded. The orientation of the fetal electrical heart axis affects the height of the initial T/QRS baseline, and therefore the incidence of ST events. We grouped tracings with the same initial baseline T/QRS value. We depicted the number of ST events as a function of the initial baseline T/QRS value with a linear regression model.

Results

A significant increment of ST events was observed with increasing height of the initial T/QRS baseline, irrespective of the fetal condition; correlation coefficient 0.63, p<0.001. The most frequent T/QRS baseline is 0.12.

Conclusion

The orientation of the fetal electrical heart axis and accordingly the height of the initial T/QRS baseline should be taken into account in fetal monitoring with ST analysis.

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<![CDATA[Competition for Materno-Fetal Resource Partitioning in a Rabbit Model of Undernourished Pregnancy]]> https://www.researchpad.co/article/5989db2cab0ee8fa60bd189c

The major goal of animal production is to obtain abundant and healthy meat for consumers. Maternal food restriction (MFR) is often applied in farms to reduce production costs. However, the suitability of MFR in livestock animals is questionable, as this management may compromise maternal fitness due to a severe negative energetic balance and can induce Intrauterine Growth Restriction (IUGR) and prenatal programming in the offspring. Here, we sought to determine, using pregnant rabbits, the consequences of MFR on maternal endocrine and metabolic status and conceptus development. Pregnant dams were distributed into three groups: CONTROL (ad libitum feeding throughout the entire pregnancy; mean pregnancy length being around 31 days), UNDERFED (50% MFR during the entire pregnancy) and EARLY-UNDERFED (50% MFR only during the preimplantation period, Days 0–7). Maternal leptin concentrations and glycemic and lipid profiles were determined throughout pregnancy, whilst conceptus development was assessed ex-vivo at Day 28. Placental parameters were determined by macroscopic and histological evaluations and apoptotic assessments (TUNEL and Caspase-3). The main results of the study showed that, despite MFR altered maternal plasma lipid concentration (P<0.05), there were no effects on maternal bodyweight, plasma leptin concentration or glycemic profile. Fetal crown-rump lengths were reduced in both undernourished groups (P<0.001), but a significant reduction in fetal weight was only observed in the UNDERFED group (P<0.001). Growth in both undernourished groups was asymmetrical, with reduced liver weight (P<0.001) and significantly increased brain: fetal weight-ratio (P<0.001) and brain: liver weight-ratio (P<0.001) when compared to the CONTROL group. A significant reduction in placental weight was only observed in the UNDERFED group (P<0.001), despite both undernourished groups showing higher apoptotic rates at decidua and labyrinth zone (P<0.05) than the CONTROL group. Thus, these groups evidenced signs of placental degeneration, necrosis and stromal collapse. In summary, MFR may encourage the mother to make strategic decisions to safeguard her metabolic status and fitness at the expense of growth reduction in the litter, resulting in enhanced apoptotic and pathological processes at placental level and IUGR.

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<![CDATA[Levels of Adipokines in Amniotic Fluid and Cord Blood Collected from Dichorionic-Diamniotic Twins Discordant for Fetal Growth]]> https://www.researchpad.co/article/5989da6eab0ee8fa60b93e5f

Objective

To compare the concentrations of adipokines in amniotic fluid (AF) and cord blood collected from discordant dichorionic-diamniotic (DCDA) twin fetuses.

Study Design

The study population included DCDA twins discordant for fetal growth (birth weight difference >10%) who either underwent mid-trimester amniocentesis for routine clinical indication (Cohort 1) or whose amniotic fluid was collected at the time of delivery (Cohort 2). In both cohorts, cord blood was collected at delivery.

Results

A total of 92 twin pairs were enrolled (n = 49 in Cohort 1; n = 43 in Cohort 2). In Cohort 1, the concentrations of adiponectin (median, 68.5 ng/mL vs 61.4 ng/mL; p<0.05) and leptin (median, 13.9 ng/mL vs 11.2 ng/mL; p<0.1) in mid-trimester AF were significantly higher in smaller compared with larger twins. In Cohort 2, the concentration of serpin E1 (median, 246.0 ng/mL vs 182.8 ng/mL; p<0.01) in AF at delivery was significantly higher in smaller twins, but no difference was noted in adiponectin and leptin concentrations. Levels of adiponectin (median, 10425.5 ng/mL vs 11552.0 ng/mL; p<0.005) and leptin (median, 2.1 ng/mL vs 2.6 ng/mL; p<0.005) were significantly lower in the cord blood of smaller twins whereas cord blood concentrations of serpin E1 (median, 15.5 ng/mL vs 13.3 ng/mL; p<0.05) was higher in the smaller twins.

Conclusion

In discordant DCDA twin pairs, concentrations of adiponectin, leptin, and serpin E1 in mid-trimester AF, AF at delivery, and cord blood at birth vary significantly but predictably between the smaller and larger twins.

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<![CDATA[Stillbirths at Term: Case Control Study of Risk Factors, Growth Status and Placental Histology]]> https://www.researchpad.co/article/5989da88ab0ee8fa60b9cd2b

Objective

To investigate the proportion of stillbirths at term associated with abnormal growth using customized birth weight percentiles and to compare histological placental findings both in underweight stillborn fetuses and in live births.

Methods

A retrospective case-control study of 150 singleton term stillbirths. The livebirth control groups included 586 cases of low-risk pregnancies and 153 late fetal growth restriction fetuses. Stillbirths and livebirths from low-risk pregnancies were classified using customized standards for fetal weight at birth, as adequate for gestational age (AGA; 10-90th percentile), small (SGA; <10th percentile) or large for gestational age (LGA; >90th percentile). Placental characteristics in stillbirth were compared with those from livebirths using four categories: inflammation, disruptive, obstructive and adaptive lesions.

Results

There was a higher rate of SGA (26% vs 6%, p<0.001) and LGA fetuses (10.6% vs 5.6%, p<0.05) in the stillbirth group. Among stillbirth fetuses, almost half of the SGA were very low birthweight (≤3°percentile) (12% vs 0.3%, p<0.001). The disruptive (7.3% vs 0.17%;p<0.001), obstructive (54.6% vs 7.5%;p<0.001) and adaptive (46.6% vs 35.8%;p<0.001) findings were significantly more common in than in livebirth-low risk. Placental characteristics of AGA and SGA stillbirth were compared with those of AGA and FGR livebirth. In stillbirths-SGA we found a higher number of disruptive (12.8% vs 0%; p<0.001), obstructive (58.9% vs 23.5%;p<0.001) and adaptive lesions (56.4% vs 49%; p 0.47) than in livebirth-FGR.

Conclusion

The assessment of fetal weight with customized curves can identify fetuses which have not reached their genetically determined growth potential and are therefore at risk for adverse outcomes. Placental evaluation in stillbirths can reveal chronic histological signs that might be useful to clinical assessment, especially in underweight fetuses.

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<![CDATA[Clusters of amniotic fluid cells and their associated early neuroepithelial markers in experimental myelomeningocele: Correlation with astrogliosis]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc798

Myelomeningocele (MMC) is the most common and severe disabling type of spina bifida resulting in the exposure of vulnerable spinal cord to the hostile intrauterine environment. In this study, we sought to examine the cellular content of fetal amniotic fluid (AF) in MMC and explore a correlation between these cells and pathological development of MMC. MMC was induced in fetal rats by exposing pregnant mothers to all-trans retinoic acid and AF samples were collected before term. Cells were isolated from AF samples and morphologically and phenotypically characterized in short-term cultures. In addition, the spinal cord injury in MMC fetuses was assessed by immunohistochemical examination of astrogliosis. We identified a population of cells from the AF of MMC fetuses (MMC-AF) that formed adherent clusters of tightly packed cells, which were absent from the AF of normal control fetuses (norm-AF). MMC-AF clusters contained cells co-expressing adherens junction associated proteins (ZO-1), N-cadherin and F-actin at sites of cell-cell contacts. In addition, they expressed markers of early neuroepithelial cells such as SOX-1 and Pax-6 along with other stem/progenitor cell markers such as SOX-2 and nestin. Subpopulations of cells in MMC-AF clusters also expressed more advanced differentiation markers such as doublecortin and GFAP. We found that the appearance of cluster forming cells in cultures from MMC-AF correlated with activation of astrogliosis associated with the spinal cord injury in MMC fetuses. In summary, we identified a neuroepithelial cell population in the AF of MMC fetuses that formed adherent clusters in culture and we characterized cellular markers of these cells. Our data suggests that the phase of the disease is a crucial factor in the emergence of these cells into the AF and that these cells may provide a new and important platform for studying the progression of MMC and development of improved strategies for the repair and diagnosis of MMC prenatally.

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<![CDATA[A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbeb4

Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS) diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.

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<![CDATA[PLoS Biology Issue Image | Vol. 16(7) July 2018]]> https://www.researchpad.co/article/5b6d8c4b463d7e2ccdcccfea

Deconstructing the principles of ductal network formation in the pancreas

In the pancreas of mammals, digestive enzymes are transported from their production site in acini (clusters of cells that secrete the enzymes) to the intestine via a network of ducts. During organ development in fetuses, the ducts initially form by the coordinated polarization of cells to form small holes, which will connect and fuse, to constitute a meshwork. This hyperconnected network further develops into a treelike structure by the time of birth. This study by Dahl-Jensen et al. uses methods originally developed to analyze road, rail, web, or river networks to quantify the network properties at different developmental stages. The authors find that the pancreatic network properties are similar between individuals at specific time points but eventually change to achieve the most economical and optimized structure to deliver pancreatic juice into the duodenum. The image shows a confocal immunofluorescent microscopy image of the pancreas from a mouse embryo at 18.5 days' gestation. Pancreatic ducts (as well as the surrounding duodenum) are shown in green (stained for β-catenin) and the islets of Langerhans appear in red (stained for insulin).

Image Credit: Dror Sever

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