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MgSO 4 has been used for the past two decades as neuroprotective treatment in a variety of preterm conditions. Despite the putative advantages of MgSO 4 as a neuroprotective agent in the preterm brain, the short- and long-term molecular function of MgSO 4 as a neuroprotective agent has not been fully elucidated. Neuregulin (NRG1)-ErbB4 signaling plays a critical role in embryonic brain development, in the biology of dopaminergic, GABAergic, and glutamatergic systems. We hypothesize that this pathway may be associated with the neuroprotective role of MgSO 4 . The current study aims to investigate the ability of MgSO 4 to modulate the normal developing expression pattern of selected genes related to the NRG1-ErbB, dopaminergic, GABAergic, and glutamatergic systems. We demonstrate that overall short-term treatment of dam rats with MgSO 4 affects the expression of fetal brain NRG1, NRG3, ErbB4, GAD67, tyrosine hydroxylase (TH), dopamine D 2 and D 1 receptors, GluN1, and GluN2B. More specifically, the administration of MgSO 4 alters the expression of NRG-ErbB, GAD67, TH, and D2R at early gestation day 16 (GD16) regardless of the activation of the maternal immune system by lipopolysaccharide (LPS). Our data suggest that MgSO 4 treatment may affect the expression of major neuronal systems and pathways mostly at an early gestation day. These changes might be an initial clue (foundation stone) in the molecular mechanism that underlies the beneficial effect of MgSO 4 as a neuroprotective agent for the developmental brain.

Background: Maternal inflammation is a risk factor for neonatal brain injury and future neurological deficits. Pomegranates have been shown to exhibit anti-inflammatory, anti-apoptotic and anti-oxidant activities., Objective: We hypothesized that pomegranate juice (POM) may attenuate fetal brain injury in a rat model of maternal inflammation., Study Design: Pregnant rats (24 total) were randomized for intraperitoneal lipopolysaccharide (100 μg/kg) or saline at time 0 at 18 days of gestation. From day 11 of gestation, 12 dams were provided ad libitum access to drinking water, and 12 dams were provided ad libitum access to drinking water with pomegranate juice (5 mL per day), resulting in 4 groups of 6 dams (saline/saline, pomegranate juice/saline, saline/lipopolysaccharide, pomegranate juice/lipopolysaccharide). All dams were sacrificed 4 hours following the injection and maternal blood and fetal brains were collected from the 4 treatment groups. Maternal interleukin-6 serum levels and fetal brain caspase 3 active form, nuclear factor-κB p65, neuronal nitric oxide synthase (phosphoneuronal nitric oxide synthase), and proinflammatory cytokine levels were determined by enzyme-linked immunosorbent assay and Western blot., Results: Maternal lipopolysaccharide significantly increased maternal serum interleukin-6 levels (6039 ± 1039 vs 66 ± 46 pg/mL; P < .05) and fetal brain caspase 3 active form, nuclear factor-κB p65, phosphoneuronal nitric oxide synthase, and the proinflammatory cytokines compared to the control group (caspase 3 active form 0.26 ± 0.01 vs 0.20 ± 0.01 U; nuclear factor-κB p65 0.24 ± 0.01 vs 0.1 ± 0.01 U; phosphoneuronal nitric oxide synthase 0.23 ± 0.01 vs 0.11 ± 0.01 U; interleukin-6 0.25 ± 0.01 vs 0.09 ± 0.01 U; tumor necrosis factor-α 0.26 ± 0.01 vs 0.12 ± 0.01 U; chemokine (C-C motif) ligand 2 0.23 ± 0.01 vs 0.1 ± 0.01 U). Maternal supplementation of pomegranate juice to lipopolysaccharide-exposed dams (pomegranate juice/lipopolysaccharide) significantly reduced maternal serum interleukin-6 levels (3059 ± 1121 pg/mL, fetal brain: caspase 3 active form (0.2 ± 0.01 U), nuclear factor-κB p65 (0.22 ± 0.01 U), phosphoneuronal nitric oxide synthase (0.19 ± 0.01 U) as well as the brain proinflammatory cytokines (interleukin-6, tumor necrosis factor-α and chemokine [C-C motif] ligand 2) compared to lipopolysaccharide group., Conclusion: Maternal pomegranate juice supplementation may attenuate maternal inflammation-induced fetal brain injury. Pomegranate juice neuroprotective effects might be secondary to the suppression of both the maternal inflammatory response and inhibition of fetal brain apoptosis, neuronal nitric oxide synthase, and nuclear factor-κB activation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The objectives of study were to assess and compare the effects of maternal hyperoxygenation on fetal circulation, in fetuses with intrauterine growth retardation and normal fetal growth., Methods: Twelve singleton pregnant women with normal fetal growth and 12 singleton pregnant women with intrauterine growth restriction were recruited. Mean gestational age of 35.2 ± 3.5 and 34.7 ± 3.9 weeks, respectively. Doppler blood flow velocity waveforms were obtained from the middle cerebral artery, umbilical, main and proximal right pulmonary arteries. Pulsatility indices were calculated for all the vessels. Peak systolic velocity was determined for the middle cerebral artery. Following baseline measurements; each woman received 70% humidified oxygen for 10 min. Doppler measurements were then repeated., Results: The pulsatility index in the middle cerebral artery increased significantly from 1.5 ± 0.27 to 1.88 ± 0.48, respectively (p = .006) in the high-risk group. However, it did not change significantly in the low-risk group. Hyperoxygenation caused a significant decrease in pulsatility indices in the pulmonary arteries for both groups., Conclusions: Hyperoxygenation interrupts the relative brain-sparing effect in the intrauterine growth retardation group, but it did not significantly change the pulsatility index of the middle cerebral artery in fetuses with adequate weight. The pulsatility index in the pulmonary arteries decreased significantly following hyperoxygenation.

Objective: The brain sparing phenomenon in the fetus is a protective mechanism aimed at maintaining sufficient blood flow towards the brain during chronic or acute fetal stress, such as that caused by hypoxemia or utero-placental insufficiency. In this study we investigated whether the brain sparing effect can also be elicited by a physiological stress associated with maternal posture. Study design Twenty-three low-risk pregnant women participated in the study. Between 36 and 40 weeks' gestation, Doppler flow velocity waveforms were obtained from the fetal middle cerebral and the umbilical artery in the supine and the left lateral decubitus positions. Pulsatility index, systolic/diastolic index, and peak systolic velocities were measured and comparison was made between the left lateral and supine positions., Results: The pulsatility index in the middle cerebral artery decreased from 1.78±0.27 in the left lateral decubitus position to 1.29±0.16 in supine position (p<0.0001). Peak systolic velocity decreased from 46.05±7.85cm/s to 39.43±7.95cm/s, respectively (p=0.001). The pulsatility index in the umbilical artery decreased from 0.89±0.13 in the left lateral position to 0.74±0.11 in the supine position (p<0.0001)., Conclusions: This study demonstrates that the supine position in late pregnancy, causing aortic and venacaval compression, leads to brain auto-regulation that activates the brain sparing effect in the fetus. This protective mechanism, shown here for the first time to be linked to a physiological stress, may provide the basis for a novel approach in the assessment of fetal wellbeing., (Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the ability to diagnose structural fetal anomalies during or soon after an extended nuchal translucency (NT) examination., Methods: The study population included all women who had a routine NT examination in the ultrasound division of one of three centers. Also included in the study were women referred to these centers following an abnormal NT examination. The sonographers were instructed to pay attention to fetal anomalies while performing the NT examination. Each examination was initially attempted transabdominally. Failure to obtain adequate views transabdominally was an indication for a transvaginal examination. When a structural fetal anomaly was detected or suspected, a full fetal anomaly scan was performed. When a diagnosis could not be established, fetal anatomy scan was repeated after 14 weeks of gestation. Fetal cardiac scanning was performed transvaginally, immediately or within 3 days after an increased NT was observed. When fetal anomalies were diagnosed the patients were informed about the possibilities of terminating the pregnancy or continuing the work-up and follow-up. Overall, ascertainment of fetal outcome was available in 85% of the study population., Results: We performed 4467 NT examinations during the study period and additional 123 fetal cardiac scanning following an abnormal NT examination. Overall, we performed 365 fetal cardiac scanning between 11 and 14 weeks of gestation. The fetal anomalies detected included the following: three skeletal anomalies, seven brain anomalies, four urinary system anomalies, four abdominal anomalies, two facial anomalies, and 13 cardiac anomalies. Six of the 13 cardiac anomalies were found in the atrioventricular canal. One third of the patients (11/33) elected to discontinue the pregnancy a short time after the detection of the congenital anomaly (until 14 weeks of gestation) and half of the patients (16\33) asked for termination of pregnancy later. More than 60% of the patients (20/33) with congenital anomalies detected following the NT examination refused to have chorionic villous sampling (CVS) or amniocentesis., Conclusion: The opportunity to scan the fetal anatomy in the early stages of pregnancy, when the NT examination is performed, justifies the approach of extended NT examination., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this study was to detect normal changes in fetal two-dimensional speckle-tracking echocardiography-derived values for global and regional longitudinal left and right ventricular strain, strain rate, and time to peak (T2P) global strain during pregnancy., Methods: Forty-four healthy fetuses were examined prospectively during the second-trimester and third-trimester ultrasound examinations (20-24 and 30-34 weeks, respectively). Clips with high frame rates (mean, 120 frames/sec) of two-dimensional (B-mode) grayscale images of apical or basal four-chamber views of both ventricles were used for offline analyses of global and regional walls and segments (basal, mid, and apical) of myocardial strain and strain rate as well as T2P global strain in the longitudinal direction., Results: There were statistically significant decreases in global and regional strain of the right ventricle between the second and third trimesters. No statistically significant changes were observed in global and regional strain of the left ventricle. Global and regional strain rates of both ventricles decreased in a similar way during pregnancy. The mean T2P longitudinal left ventricular global strain (adjusted for heart rate) increased mildly during fetal life. Whereas T2P longitudinal strain of the left ventricle at 20 to 24 weeks was statistically significantly shorter than that of the right ventricle, no difference in T2P longitudinal strain was found at 30 to 34 weeks of gestation between both ventricles., Conclusions: The establishment of these changes between the second-trimester and third-trimester two-dimensional speckle-tracking echocardiography-derived reference values is a mandatory prerequisite for its use in evaluating (pathologic) changes in both ventricular functions during pregnancy., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Objective: Because the fetal innate immune system is responsive, while still maturing during the preterm period, we hypothesized that the early activation of fetal inflammatory pathways may have an impact on the ultimate expression of immune competency., Study Design: Pregnant Sprague Dawley rats (n = 7; Harlan Sprague Dawley Inc, Jerusalem, Israel) at 18 days gestation received intraperitoneal injections of saline solution or lipopolysaccharides (500 microg/kg). Pups were delivered spontaneously. At postnatal day 24, pups received intraperitoneal lipopolysaccharide (100 microg/kg), and plasma cytokine levels were measured before and 4 hours after lipopolysaccharide administration., Results: In response to lipopolysaccharides, pups of the lipopolysaccharide-injected dams had significantly (P < .05) reduced interleukin-6 (median [25th,75th percentile], 229 [84,6086] vs 4745 [2765,6643] pg/mL), interleukin-1beta (median [25th,75th percentile], 820 [125,1196] vs 1682 [1515,2127] pg/mL), tumor necrosis factor-alpha (median [25th,75th percentile], 4.8 [1.2,91] vs 163 [46,205] pg/mL), and interleukin-10 responses, when compared with saline solution-injected dams., Conclusion: Maternal lipopolysaccharide exposure suppresses offspring innate immune response to inflammatory stimuli. These results suggest that maternal inflammatory exposures during pregnancy may impair newborn infant innate responses and increase susceptibility to infection., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Objective: To assess internal jugular vein blood flow patterns during the second half of pregnancy in normal and growth-restricted fetuses., Methods: We did Doppler ultrasound studies of internal jugular veins and the inferior vena cavas longitudinally on 21 normal singleton fetuses from 20 weeks to term, and on eight growth-restricted fetuses with absent end-diastolic flow at the umbilical artery (UA). The three components of the venous flow velocity waveforms were used to calculate peak velocity ratio: Peak systolic velocity (S wave) minus reverse peak velocity (R wave) divided by peak velocity during early diastole (D wave) and velocity time integral ratio: systolic velocity time integral minus reverse velocity time integral divided by velocity time integral during early diastole. Statistical analysis of longitudinal measurements used K-related samples Friedman test; groups were compared with Mann-Whitney U test and chi(2) test., Results: In normal fetuses we found significant increases in peak velocity ratio and velocity time integral ratio of internal jugular veins and the inferior vena cavas throughout gestation. The mean +/- standard deviation (SD) of the internal jugular veins peak velocity ratio (1.12 +/- 0.4 versus 1.46 +/- 0.15, P <.05) and velocity time integral ratio (1.1 +/- 0.2 versus 1.55 +/- 0.17, P <.05) were significantly lower in growth-restricted fetuses compared with normal fetuses at 28-32 weeks' gestation but inferior vena cava indices were not. None of the eight growth-restricted fetuses had umbilical venous pulsations or changes in inferior vena cava or ductus venosus blood flow patterns. All had arterial pH above 7.15 at birth., Conclusion: Growth-restricted fetuses with absent end-diastolic velocity in the UA have changes in internal jugular vein blood flow patterns that probably indicate increased cerebral blood flow, more evidence of redistribution of blood flow in growth-restricted fetuses that can be used to maintain them.

Objective: To examine possible changes in cardiac function in fetuses of pregestational diabetic mothers., Methods: We conducted a prospective longitudinal study of 31 women whose pregnancies were between 22 weeks' gestation and term, and who had pregestational diabetes. All diabetic women included in the study had glycosylated hemoglobin lower than 6.5%. All patients included in the study had an early ultrasound confirming gestational age. Doppler studies of the blood flow through the mitral and tricuspid valves were done every 4 weeks using a pulsed-wave Doppler ultrasound device with a 3.5- or 5-MHz transducer. The following indices were calculated from the flow velocity waveforms: the peak velocity during the rapid ventricular filling (E wave) and during the atrial systole (A wave), and the ratio between these velocities (E/A ratio); and the velocity time integral of the atrioventricular blood flow (this integral correlates with volume flow). A comparison between the Doppler indices obtained in fetuses of diabetic women and of normal women was made by using the Mann-Whitney test., Results: Each patient had four to five fetal echocardiographic examinations at 22, 26, 30, 34, and 38 weeks' gestation. The E/A ratio of the mitral and tricuspid valves did not increase in fetuses of diabetic women during the third trimester and was significantly higher in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The velocity time integral of the mitral and tricuspid valves multiplied by heart rate was higher, but not significantly, in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The E-wave of the mitral and tricuspid valves increased in both groups throughout gestation. The A-wave of the mitral and tricuspid valves increased only in fetuses of diabetic women throughout the third trimester and was significantly higher at 34 and 38 weeks' gestation compared with fetuses of nondiabetic women., Conclusion: Differences in atrioventricular blood flow patterns between fetuses of diabetic women and normal fetuses do not necessarily result from differences in cardiac compliance.

The relative contribution of rapid ventricular filling to total ventricular filling increases as gestational age advances. A possible explanation for this observation is that the fetal cardiac compliance improves throughout gestation.

Doppler velocimetry is very useful as an antepartum surveillance tool that is able to detect pathologies of the fetus and predict the development of acidosis and hypoxia. Appropriate use can help us to decrease the mortality and morbidity in identifying earlier compromised fetuses.

Objectives: Our purpose was to study hemodynamic changes in peripheral and central blood vessels and to correlate these changes with the computerized fetal heart rate pattern in fetuses with absent end-diastolic velocity in the umbilical artery., Study Design: Doppler studies of the umbilical artery, the middle cerebral artery, and aortic and pulmonic outflow, together with computerized fetal heart rate monitoring, were performed every 2 to 4 days until delivery in 13 fetuses with absent end-diastolic velocity in the umbilical artery. The pulsatility index was calculated from the flow velocity waveforms obtained from the umbilical and middle cerebral arteries. The velocity time integral (an index of cardiac output) and the heart rate were calculated from the flow velocity waveforms obtained from the aortic and pulmonic outflow., Results: Two fetuses were delivered immediately after the first examination because of repetitive fetal heart rate decelerations. One fetus was excluded from the study because of major malformations. Ten had three to eight tests each. Six had a biphasic change of the middle cerebral artery, which consisted of a decrease (p < 0.001) followed by an increase in the pulsatility index (p < 0.05). When the middle cerebral artery lost its vasodilation, there was an increase in the middle cerebral artery/umbilical artery pulsatility index ratio (p < 0.05). Left cardiac output decreased (p < 0.05), resulting in an increase in the pulmonary/aortic velocity time integral x heart rate ratio (p < 0.05). Reduced fetal heart rate variation (< 30 msec) developed in all six fetuses, and they were delivered because of repetitive fetal heart rate decelerations. Four fetuses with only a decrease in the middle cerebral artery pulsatility index did not have reduced fetal heart rate variation or decelerations, the aortic velocity time integral x heart rate didn't decrease, and the pulmonic/aortic velocity time integral x heart rate ratio didn't increase. These fetuses were delivered for reasons other than fetal distress. The middle cerebral artery pulsatility index correlated with the aortic velocity time integral x heart rate (r = -0.53, p < 0.0001), and the middle cerebral artery/umbilical artery pulsatility index correlated with the pulmonic/aortic velocity time integral x heart rate (r = 0.56, p < 0.0001)., Conclusion: Abnormal fetal heart rate patterns occur in fetuses with absent end-diastolic velocity in the umbilical artery when the middle cerebral artery begins to lose its compensatory maximal dilation. The increase in the middle cerebral artery pulsatility index is associated with a significant reduction in left ventricular output without significant changes in right ventricular function. Thus it appears that a loss of autonomic reactivity occurs in the brain first and is followed within a few days by a similar response in the heart, as shown by the decreased fetal heart rate variation.

The article presents a study that identifies the sonographic dimensions of the facial profile of the fetus in normal pregnancy. The study was undertaken through a cross-sectional study of 397 normal healthy fetus at 14-33 weeks of gestation. Results of the study showed that there was a significant linear correlation between the gestational age (GA) of the fetus and the distance from the tip of its nose to its mouth which can be used as a tool for the diagnosis of abnormal fetal facial pressure.