Brain Sparing Effect Research Articles

The effect of increased amnion volume severity on fetal Doppler indices and perinatal outcomes in idiopathic polyhydramnios

Aim: To evaluate the relationship between polyhydramnios severity and alterations in Doppler indices and perinatal outcomes in idiopathic polyhydramnios.Methods: This prospective case control study was conducted in a tertiary hospital with 173 singleton pregnancies between 29 and 41 weeks gestational age between May 2015 and December 2016. Polyhydroamnios is classified as mild (amniotic fluid index 25–30 cm), moderate (30.1–35 cm), and severe (>35 cm) and the number of the patients in mild, moderate, and severe groups were 55, 39, and 26, respectively. The results were compared with 53 healthy controls. Fetal echocardiography and Doppler measurements of the groups were made and the perinatal outcomes from each group were noted. The relationship between the results and the severity of polyhydramnios was analyzed statistically.Results: The myocardial performance index was significantly higher in the fetuses of women with severe polyhydramnios compared to the other groups (p = .006). There were statistically significant differences among the groups in terms of first and fifth minutes according to the Apgar scores (p = .011, p = .016 respectively). In the severe polyhydramnios group compared with other groups, the middle cerebral artery pulstatility index was significantly lower (p = .002), while middle cerebral artery peak systolic velocity and umbilical artery pulstatility index values were significantly higher (p = .0001, p = .045).Conclusions: Our study showed an increase in myocardial performance index and middle cerebral artery peak systolic velocity values and a decrease in middle cerebral artery pulstatility index values, especially in the severe idiopathic polyhydramnios group. Idiopathic polyhydramnios were associated with low first and fifth minute Apgar score. Additionally, the increase in umbilical artery pulstatility index value and the decrease in middle cerebral artery pulstatility index value became more apparent with the increase in amniotic fluid volume. It should be taken into consideration that brain sparing effect may develop especially in cases with severe polyhydramnios.

Fetal facial expressions in small-for-gestational-age and growth-restricted fetuses

Objective: To evaluate the frequencies of fetal facial expressions among appropriate-for-gestational-age (AGA), small-for-gestational-age (SGA), and growth-restricted (FGR) fetuses.Methods: Four-dimensional (4D) ultrasound was used to examine the facial expressions of 50 AGA, 25 SGA, and six FGR fetuses between 28 and 35 weeks of gestation. The frequencies of seven facial expressions during 15-minute recordings were assessed. Comparison of facial expressions among the three groups was performed.Results: Mouthing was the commonest facial expression at 28–35 weeks, and the frequency of mouthing was significantly higher than those of the other six facial expressions in AGA fetuses. Mouthing was the most frequent facial expression, but there was no significant difference in the frequency among mouthing, smiling and blinking in SGA fetuses. Moreover, mouthing displayed a significantly higher frequency than the other facial expressions, except for yawning, smiling, and blinking in FGR fetuses. However, there was no significant difference in the frequency of each facial expression among the three groups.Conclusions: Our results suggest that the frequencies of fetal facial expressions are not decreased in either SGA or FGR pregnancies. The absence of a decrease in the frequency of each fetal expression in FGR fetuses may be due to increased brain blood flow because of the brain-sparing effect. Moreover, accelerated maturation and development of the brain function, especially the central dopamine system, might be suspected in SGA and FGR fetuses.

Cerebrovascular hemodynamics in fetuses with congenital heart disease.

It is hypothesized that diminished cerebral vascular resistance or the "brain sparing effect" is associated with fetuses with complex congenital heart defects (CHD) and may affect their neurodevelopmental outcome. An alternative explanation is that it is related to the location, cardiac output, pressure, and resistance in left heart obstructive CHDs. We sought to determine the effects of various left and right heart obstructive defects on the cerebral and placental hemodynamics and to evaluate the utility of these variables for the assessment and prognosis of CHDs. A total of 290 fetal echocardiograms were reviewed, including 91 fetuses with CHD and 199 normal ones. The CHD fetuses were divided into four groups, that is, left-sided obstructive lesions (LSOL), hypoplastic left heart syndrome (HLHS), right-sided obstructive lesions (RSOL), and hypoplastic right heart syndrome (HRHS). The pulsatility index of middle cerebral artery (MCA-PI) and umbilical artery (UA-PI) were measured by pulse-wave Doppler, and their Z scores were also derived. Cerebroplacental ratio (CPR) was calculated as: CPR=MCA-PI/UA-PI. There was no significant difference in MCA-PI between the 4 CHD and normal control groups (P>.05). However, MCA-PI and Z score decreased in aortic stenosis but not in interrupted aortic arch or coarctation subgroups, whereas they increased in pulmonary atresia but not pulmonary stenosis or tetralogy of Fallot subgroups compared with normal group (P<.05). There was no significant difference in CPR between any study group or subgroup and normal control group. Our study suggests MCA-PI is lower in aortic stenosis and high in pulmonary atresia but not significantly different in other LSOL, HLHS, RSOL, and HRHS. MCA-PI regulation in CHD is probably more associated with left and right outflow obstruction, location of the obstruction, and hemodynamics rather than "brain sparing effect" or preferential shunting of blood to the fetal brain, heart, and adrenals in the stressed fetus (eg, IUGR). CPR may not be a sensitive measure for the effect of CHDs and their severity on cerebral and placental circulation.

The effect of maternal hyperoxygenation on fetal circulatory system in normal growth and IUGR fetuses. What we can learn from this impact

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.

Learning and memory disabilities in IUGR babies: Functional and molecular analysis in a rat model.

1IntroductionIntrauterine growth restriction (IUGR) is the failure of the fetus to achieve its inherent growth potential, and it has frequently been associated with neurodevelopmental problems in childhood. Neurological disorders are mostly associated with IUGR babies with an abnormally high cephalization index (CI) and a brain sparing effect. However, a similar correlation has never been demonstrated in an animal model. The aim of this study was to determine the correlations between CI, functional deficits in learning and memory and alterations in synaptic proteins in a rat model of IUGR.2MethodsUtero‐placental insufficiency was induced by meso‐ovarian vessel cauterization (CMO) in pregnant rats at embryonic day 17 (E17). Learning performance in an aquatic learning test was evaluated 25 days after birth and during 10 days. Some synaptic proteins were analyzed (PSD95, Synaptophysin) by Western blot and immunohistochemistry.3ResultsPlacental insufficiency in CMO pups was associated with spatial memory deficits, which are correlated with a CI above the normal range. CMO pups presented altered levels of synaptic proteins PSD95 and synaptophysin in the hippocampus.4ConclusionsThe results of this study suggest that learning disabilities may be associated with altered development of excitatory neurotransmission and synaptic plasticity. Although interspecific differences in fetal response to placental insufficiency should be taken into account, the translation of these data to humans suggest that both IUGR babies and babies with a normal birth weight but with intrauterine Doppler alterations and abnormal CI should be closely followed to detect neurodevelopmental alterations during the postnatal period.

Updates in outcomes of stereotactic radiation therapy in acromegaly.

Purpose Treatment of acromegaly has undergone important progress in the last 20years mainly due to the development of new medical options and advances in surgical techniques. Pituitary surgery is usually first-line therapy, and medical treatment is indicated for persistent disease, while radiation (RT) is often used as third-line therapy. The benefits of RT (tumor volume control and decreased hormonal secretion) are hampered by the long latency of the effect and the high risk of adverse effects. Stereotactic RT methods have been developed with the aim to provide more precise targeting of the tumor with better control of the radiation dose received by the adjacent brain structures. The purpose of this review is to present the updates in the efficacy and safety of pituitary RT in acromegalic patients, with an emphasis on the new stereotacticradiation techniques. Methods A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in acromegaly from 2000 to 2016 were included. Results Stereotactic radiosurgery and fractionated stereotactic RT (FSRT) for patients with persistent active acromegaly after surgery and/or during medical therapy provide comparable high rates of tumor control, i.e. stable or decrease in size of the tumor in 93-100% of patients at 5-10 years and endocrinological remission in 40-60% of patients at 5years. Hypofractionated RT is an optimal option for tumors located near the optic structures, due to its lower toxicity for the optic nerves compared to single-dose radiosurgery. The rate of new hypopituitarism varies from 10 to 50% at 5 years and increases with the duration of follow-up. The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and 0-1% for secondary brain tumors) and risk of stroke may be higher in FSRT. Conclusion Although the use of radiotherapy in patients with acromegaly has decreased with advances in medical treatments, it remains an effective treatment option after unsuccessful surgery and/or resistance or unavailability of medical therapy. Long-term studies evaluating secondary morbidity and mortality rate after the new stereotactic techniques are needed, in order to evaluate their potential brain-sparing effect.

STEREOTACTIC RADIATION THERAPY IN PITUITARY ADENOMAS, IS IT BETTER THAN CONVENTIONAL RADIATION THERAPY?

A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in pituitary adenomas from 2000 to 2017 were included. Stereotactic radiosurgery (SRS) and fractionated stereotactic RT (FSRT) provide high rates of tumour control i.e. stable or decrease in tumour size, in all types of pituitary adenomas (median 92 - 98%) at 5 years. Endocrinological remission is however significantly lower: 44-52% in acromegaly, 54-64% in Cushing's disease and around 30% in prolactinomas at 5 years. The rate of new hypopituitarism varies from 10% to 50% at 5 years in all tumour types and as expected increases with the duration of follow-up (FU). The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and extremely low for secondary brain tumours), however longer FU is needed to determine rates of secondary tumours. Notably, in acromegaly, there may be a higher risk for stroke with FSRT. Stereotactic radiotherapy can be an effective treatment option for patients with persistent or recurrent pituitary adenomas after unsuccessful surgery (especially if residual tumour is enlarging) and/or resistance or unavailability of medical therapy. Comparison with conventional radiation therapy (CRT) is rather difficult, due to the substantial heterogeneity of the studies. In order to evaluate the potential brain-sparing effect of the new stereotactic techniques, suggested by the current data, long-term studies evaluating secondary morbidity and mortality are needed.

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses

Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7-35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n= 45) of cases remained abnormal and 22% of these (n= 10) had an adverse perinatal outcome. The remaining 48% (n= 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n= 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n= 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n= 42) in the normalizing cerebroplacental ratio group (P value <.001). The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome.

Central Nervous System and Cardiovascular Diseases

ABSTRACT Children with congenital heart diseases (CHD) are at increased risk of neurodevelopmental delay (NDD). In fetuses with CHD, blood streaming in the brain may be partially deoxygenated. Signs of cerebrovascular autoregulation comparable to the “brain-sparing effect” in growth-restricted fetuses may be shown in fetuses with CHD depending on the type of heart disease. This effect appears to be predominantly present in fetuses with left-side obstructive lesions (LSOL). During prenatal counseling, it is recommended to mention the possibility of an increased risk of NDD. The severity of this impairment varies from the type of CHD, being highest up to 40 to 45% in lesions with univentricular heart hemodynamics, such as hypoplastic left heart syndrome (HLHS). The prenatal life plays an important role in determining postnatal neurodevelopmental functions, but the severity of NDD in fetuses with CHD cannot be predicted prenatally. How to cite this article Arduini M. Central Nervous System and Cardiovascular Diseases. Donald School J Ultrasound Obstet Gynecol 2017;11(4):362-366.

Brain Volume and Doppler Velocimetry in Growth-Restricted, Small-for-Gestational-Age, and Appropriate-for-Gestational-Age Fetuses.

Objective This study aims to detect possible differences in fetal brain volumes between growth-restricted fetuses (FGR), small-for-gestational-age (SGA) fetuses with normal Doppler indices, and appropriate-for-gestational-age fetuses (AGA). Study Design Three-dimensional measurements of fetal brain volume and umbilical artery and middle cerebral artery (MCA) pulsatility index (PI) and resistance index (RI) were made in 80 AGA fetuses, 68 SGA fetuses with normal Doppler indices, and 68 FGR with brain-sparing effect between 32 and 36 weeks of gestation. Results MCA-PI and MCA-RI were significantly lower in FGR group compared with the other two groups (p < 0.001). Brain volume was significantly lower in SGA and FGR groups compared with AGA group (p < 0.001). Conclusion Brain volume is significantly lower in SGA and FGR groups compared with AGA group.

Fetal Sex Modulates Developmental Response to Maternal Malnutrition

The incidence of obesity and metabolic diseases is dramatically high in rapidly developing countries. Causes have been related to intrinsic ethnic features with development of a thrifty genotype for adapting to food scarcity, prenatal programming by undernutrition, and postnatal exposure to obesogenic lifestyle. Observational studies in humans and experimental studies in animal models evidence that the adaptive responses of the offspring may be modulated by their sex. In the contemporary context of world globalization, the new question arising is the existence and extent of sex-related differences in developmental and metabolic traits in case of mixed-race. Hence, in the current study, using a swine model, we compared male and female fetuses that were crossbred from mothers with thrifty genotype and fathers without thrifty genotype. Female conceptuses evidence stronger protective strategies for their adequate growth and postnatal survival. In brief, both male and female fetuses developed a brain-sparing effect but female fetuses were still able to maintain the development of other viscerae than the brain (mainly liver, intestine and kidneys) at the expense of carcass development. Furthermore, these morphometric differences were reinforced by differences in nutrient availability (glucose and cholesterol) favoring female fetuses with severe developmental predicament. These findings set the basis for further studies aiming to increase the knowledge on the interaction between genetic and environmental factors in the determination of adult phenotype

Brain sparing effect in growth-restricted fetuses is associated with decreased cardiac acceleration and deceleration capacities: a case-control study.

Phase rectified signal averaging (PRSA) is a new method of fetal heart rate variability (fHRV) analysis that quantifies the average acceleration (AC) and deceleration capacity (DC) of the heart. The aim of this study was to evaluate AC and DC of fHR [recorded by trans-abdominal fetal electrocardiogram (ta-fECG)] in relation to Doppler velocimetry characteristics of intrauterine growth restriction (IUGR). Prospective case-control study. Single third referral centre. IUGR (n=66) between 25 and 40 gestational weeks and uncomplicated pregnancies (n=79). In IUGR the nearest ta-fECG monitoring to delivery was used for PRSA analysis and Doppler velocimetry parameters obtained within 48hours. AC and DC were computed at s=T=9. The relation was evaluated between either AC or DC and Doppler velocimetry parameters adjusting for gestational age at monitoring, as well as the association between either AC or DC and IUGR with or without brain sparing. In IUGRs there was a significant association between either AC and DC and middle cerebral artery pulsatility index (PI; P=0.01; P=0.005), but the same was not true for uterine or umbilical artery PI (P>0.05). Both IUGR fetuses with and without brain sparing had lower AC and DC than controls, but this association was stronger for IUGRs with brain sparing. Our study observed for the first time that AC and DC at PRSA analysis are associated with middle cerebral artery PI, but not with uterine or umbilical artery PI, and that there is a significant decrease of AC and DC in association with brain sparing in IUGR fetuses from 25weeks of gestation to term. Brain sparing in IUGR fetuses is associated with decreased acceleration and deceleration capacities of the heart.

Twin-reversed arterial perfusion sequence associated with decreased fetal cerebral vascular impedance.

Twin-reversed arterial perfusion (TRAP) sequence affects 1% of monochorionic twin pregnancies and is caused by abnormal vascular connections between a pump twin and an acardiac mass. The effects of abnormal vascular connections on cerebral vasculature in the pump twin are unknown. We hypothesize that abnormal cerebral vascular impedance, as assessed by the pulsatility index (PI), is present in pump twins and that fetal intervention alters cerebral impedance. Fetal echocardiograms performed between 2010 and 2013 in pregnancies diagnosed with TRAP (n = 19), recorded at presentation, and uncomplicated monochorionic twin pregnancies (controls, n = 18; 36 fetuses) were analyzed. In all subjects, the middle cerebral artery (MCA)-PI, combined cardiac output (CCO) and cardiothoracic ratio were calculated, and the values for cases and controls were compared. The mean gestational age at the time of echocardiography was 20 weeks in both groups. MCA-PI was lower in TRAP cases than in controls (1.55 (95% CI, 1.47-1.64) vs 1.74 (95% CI, 1.65-1.82), respectively; P = 0.004). CCO in TRAP cases was mildly elevated for gestational age (199.7 (95% CI, 138.4-261.1) mL/min) compared with that of controls (131.4 (95% CI, 102.2-160.7) mL/min). In six TRAP cases with a second echocardiogram available, the mean MCA-PI increased after intervention, from 1.5 (95% CI, 1.3-1.7) to 1.8 (95% CI, 1.4-2.2). TRAP pump twins have lower cerebral vascular impedance than do controls, suggestive of a brain-sparing effect. MCA-PI appeared to increase in a small group of pump twins after intervention. These findings suggest a fetal cerebral autoregulatory response to a high cardiac output state that begins to change after fetal intervention. The long-term implications for neurodevelopmental outcome warrant further study.

2076927 Is the Brain-Sparing Effect Described in Fetuses With Congenital Heart Disease Evident in the First Trimester?

2076927 Is the Brain-Sparing Effect Described in Fetuses With Congenital Heart Disease Evident in the First Trimester?

Cerebral and somatic NIRS-determined oxygenation in IUGR preterm infants during transition

Background: Fetal growth restriction (intra-uterine growth restriction [IUGR]) has a considerable impact on perinatal morbidity. Preterm IUGR infants are prone to impaired intestine function. Near-infrared spectroscopy (NIRS) has been used to monitor oxygenation status of the brain and of the intestine.Patients and methods: We conducted a prospective case–control study at our NICU in 20 preterm infants of whom 10 infants complicated by compared with 10 non-IUGR preterm infants. Splanchnic and cerebral regional oximetry values were measured with NIRS. Three hours of consecutive recordings were performed in the first 24 h of life, T0, and during the transitional period, T1. The cerebral/splanchnic oxygenation ratio, CSOR, (cerebral regional saturations [rScO2]/splanchnic regional saturations [rSsO2]) was also calculated.Results: Both in the IUGR and the non-IUGR infants, at T0 and T1 monitoring time-points, the rSO2 values were higher in the cerebral district when compared to those of the splanchnic area. Comparison of the NIRS parameters between the IUGR and non-IUGR infants at T0 showed no difference in rScO2, while rSsO2 was significantly lower in the IUGR group. At T1, rScO2 was significantly lower and rSsO2 higher in the IUGR group.Conclusions: Cerebral/splanchnic vascular adaptation of IUGR infants to the extra-uterine environment is characterized by a postnatal persistence of the brain sparing effect with reperfusion in the transitional period.

Cerebroplacental ratio in prediction of adverse perinatal outcome and fetal heart rate disturbances in uncomplicated pregnancy at 40 weeks and beyond.

IntroductionThe aim of the study was to determine the usefulness of Doppler velocimetry, based on cerebroplacental ratio (C/U) evaluation, in predicting intrapartum fetal heart rate abnormalities and adverse neonatal outcome in uncomplicated pregnancies at 40 weeks and beyond.Material and methodsOne hundred and forty-eight women in uncomplicated pregnancies, between 40 and 42 completed weeks, were divided into control and study groups: with the absence (n = 79) and with the presence of a fetal brain-sparing effect (n = 69), respectively. Pulsatility and resistance indices in the middle cerebral, the umbilical artery and the C/U ratio were evaluated daily by Doppler ultrasonography. C/U < 1.1 was reported as suggestive of a brain-sparing effect. Abnormal flow indices were analyzed and compared to adverse pregnancy and neonatal outcome determinants.ResultsIn the abnormal C/U group the abnormal CTG records were significantly more frequently observed (62.3%) than in normal C/U group (19.0%) (p = 0.0001). The comparison of selected Doppler indices revealed that C/U showed the highest sensitivity in prediction of both the intrapartum abnormal FHR (74.1%) and the adverse neonatal outcome (87.8%).ConclusionsThe C/U index shows the highest sensitivity in prediction of FHR abnormalities and adverse neonatal outcome in uncomplicated pregnancies at 40 weeks and beyond. The C/U index is useful in clinical practice in antenatal monitoring of these women in order to select those at high risk of intra- and postpartum complications.

Maternal and fetal blood levels of S100 and ischaemia modified albumin in term intrauterine growth restricted fetuses with abnormal umbilical artery Doppler values

The purpose of this study was to investigate whether levels of fetal hypoxia markers, S100 and ischaemia modified albumin (IMA) change in cases of intrauterine growth restriction (IUGR). This case–control study included 15 intrauterine growth restricted fetuses and 20 age-matched controls. During delivery of the fetuses, cord blood and maternal blood S100 and IMA levels were studied. The fetal weight and umbilical cord pH values of IUGR fetuses were significantly lower than the control group. The mean maternal and umbilical cord blood values of S100 and IMA were similar in the two groups. IMA levels in cord blood of the IUGR group were significantly higher than maternal levels, whereas umbilical and maternal levels of IMA did not differ among control cases. In cases without brain sparing effect in Doppler ultrasonography, umbilical cord S100 and IMA levels do not change significantly in IUGR when compared with appropriate-for-gestational-age (AGA) fetuses.

PO-0393 Recovery Of Occipital-frontal Circumference Z-score Of Healthy Very Preterm Infants At Term-equivalent Age Does Not Reflect A Brain Sparing Effect

<h3>Background and aims</h3> To evaluate the growth of occipito-frontal circumference (OFC), length and weight, between birth and term equivalent age (TEA) of very preterm infants and to compare to somatometry of term-born control infants. <h3>Methods</h3> We assessed prospectively a cohort of infants born at ≤32 weeks gestation and term control newborns. Infants with cerebral abnormalities were excluded. Measurements of OFC, length and weight were performed at birth and TEA for preterm and at birth for term infants. Brain volume was estimated by a previously described ultrasonographic model (Graca A, <i>Early Hum Dev</i> 2013). Z-scores for somatometric variables were determined based on Fenton 2013 growth charts and z-scores for estimated brain volume were defined in controls. We used paired samples t-test to compare z-scores between birth and TEA for preterms and independent samples t-test to compare z-scores between preterm infants at TEA and controls. <h3>Results</h3> We assessed 128 infants (72 preterms and 56 controls). Weight and length z-scores decreased significantly between birth and TEA and were significantly inferior to controls, whereas OFC z-scores increased and were identical at TEA to controls (Figure). Estimated brain volume was nevertheless significantly inferior for preterm infants at TEA. <h3>Conclusion</h3> Recovery of OFC z-score of healthy very preterm infants at TEA does not reflect a brain sparing effect, since despite OFC growing in a opposite direction than weight and length, estimated brain volume is significantly lower than controls.

The management of extremely preterm infants

Extreme prematurity is associated with an increased risk of mortality, morbidities and long-term neurodevelopmental impairment. Optimizing prenatal, perinatal and postnatal care is essential to improve long-term outcome of extremely preterm babies. Intrauterine growth restriction (IUGR) has been associated with a poorer neurological outcome and prenatal care should aim to an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. In the clinical phase of IUGR, hemodynamic adaptation occurs with blood flow redistribution preferentially to the brain, the so-called “brain sparing effect”. However, controversy remains as to whether “brain-sparing” indicates a higher risk of brain injury or is a protective mechanism [1]. The mechanisms underlying fetal growth restriction, also determine a limitation of lung growth and maturation, thus making the lung more vulnerable to postnatal damage and increasing the risk of bronchopulmonary dysplasia (BPD), the most significant respiratory complication of prematurity [2]. Current evidence suggests that the risk of BPD may be partially related to other antenatal factors as choriamniositis (CA), which is a leading cause of very preterm delivery. Whereas CA promotes lung maturation, mediated by prenatal inflammation mechanisms, and thereby decreases the severity of respiratory distress syndrome, it also seems to increase the risk of BPD, making the lung more susceptible to subsequent postnatal insults [3]. Neonatal resuscitation and postnatal management during the first minutes of life also play an important role in determining early and long-term outcome of VLBW. A multifaced intervention in respiratory care in the delivery room immediately after birth, including a sustained lung inflation procedure and a non invasive starting ventilation, seems to be effective in improving respiratory outcome [4]. Delayed umbilical cord clamping has received increasing attention in the management at birth of preterm infants as it seems to be beneficial and safe, being associated with less delivery room resuscitation interventions, improved haemodynamic stability and decreased rates of intraventricular hemorrhage [5]. Different pathophysiological mechanisms are involved in injuring the premature brain, in particular infection-inflammation, pre- and/or postnatal malnutrition, and abnormalities in systemic and cerebral haemodynamics and oxygen supply. Preventative measures are key to reduce neurological morbidities in an extremely preterm population and research projects are focusing on the possibility to stabilize cerebral oxygenation in the first days of life through the application of cerebral near-infrared spectroscopy oximetry and implementation of clinical treatment guidelines in order to reduce the risk of brain damage [6].

A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up.