Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Review of the Evaluation of Pulmonary Hypoplasia as an Important Determinant of Clinical Outcomes in Infants with Congenital Diaphragmatic Hernia.

Pulmonary hypoplasia is one of main causes of neonatal mortality and morbidity in patients with congenital diaphragmatic hernia. With most cases diagnosed prenatally, the emphasis is put on prediction of the severity of this defect. Several attempts are made to reduce the mortality and provide optimal prenatal and postnatal care. Appropriate estimation of risk of pulmonary hypoplasia also provides an important inclusion criterion for prenatal intervention. The main tool used for the detection and prediction of pulmonary hypoplasia is ultrasound, with an increasing number of available formulas to estimate the risk of occurrence of this phenomenon and complication associated with it. For most of the formulas used in this measurement method, the main limitations are either gestational-age dependency or limited research. Other imaging methods used to assess the risk of pulmonary hypoplasia involve magnetic resonance imaging and vascular assessment of affected lungs. The limitation in these remains the limited accessibility. Currently, the most widely used indexes are observed-to-expected lungs-to-head ratio and presence of liver herniation. These are the 2 most commonly used measurement methods, as they are the basis for patient qualification for fetoscopic endoluminal tracheal occlusion. This article aims to review the evaluation of pulmonary hypoplasia or hypoplastic lung disease as an important determinant of clinical outcomes in infants with congenital diaphragmatic hernia. In this review, we emphasize the importance of early prenatal diagnosis of congenital diaphragmatic hernia and present a summary of different methods of prenatal risk assessment of lung hypoplasia in congenital diaphragmatic hernia.

Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance.

Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). The aim of this preliminary study was to determine the maternal miRNA expression profile of women carrying fetuses with SB. Therefore, six women carrying fetuses with SB and twenty women with euploid healthy fetuses were enrolled in this study. Using NanoString technology, we evaluated the expression level of 798 miRNAs in both plasma and amniotic fluid samples. A downregulation of miR-1253, miR-1290, miR-194-5p, miR-302d-3p, miR-3144-3p, miR-4536-5p, miR-548aa + miR-548t-3p, miR-548ar-5p, miR-548n, miR-590-5p, miR-612, miR-627-5p, miR-644a, and miR-122-5p, and an upregulation of miR-320e, let-7b-5p, miR-23a-3p, miR-873-3p, and miR-30d-5p were identified in maternal amniotic fluid samples in SB when compared to the control group. The target genes of these miRNAs play a predominant role in regulating the synthesis of several biological compounds related to signaling pathways such as those regulating the pluripotency of stem cells. Moreover, the maternal plasma expression of miR-320e was increased in pregnancies with SB, and this marker could serve as a valuable non-invasive screening tool. Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. Our findings emphasize the role of miRNA as a predictive factor that could potentially be useful in prenatal genetic screening for SB.

The randomized Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trials on fetal surgery for congenital diaphragmatic hernia: reanalysis using pooled data.

BACKGROUND: Two randomized controlled trials compared the neonatal and infant outcomes after fetoscopic endoluminal tracheal occlusion with expectant prenatal management in fetuses with severe and moderate isolated congenital diaphragmatic hernia, respectively. Fetoscopic endoluminal tracheal occlusion was carried out at 27+0 to 29+6 weeks' gestation (referred to as "early") for severe and at 30+0 to 31+6 weeks ("late") for moderate hypoplasia. The reported absolute increase in the survival to discharge was 13% (95% confidence interval, -1 to 28; P=.059) and 25% (95% confidence interval, 6-46; P=.0091) for moderate and severe hypoplasia. OBJECTIVE: Data from the 2 trials were pooled to study the heterogeneity of the treatment effect by observed over expected lung-to-head ratio and explore the effect of gestational age at balloon insertion. STUDY DESIGN: Individual participant data from the 2 trials were reanalyzed. Women were assessed between 2008 and 2020 at 14 experienced fetoscopic endoluminal tracheal occlusion centers and were randomized in a 1:1 ratio to either expectant management or fetoscopic endoluminal tracheal occlusion. All received standardized postnatal management. The combined data involved 287 patients (196 with moderate hypoplasia and 91 with severe hypoplasia). The primary endpoint was survival to discharge from the neonatal intensive care unit. The secondary endpoints were survival to 6 months of age, survival to 6 months without oxygen supplementation, and gestational age at live birth. Penalized regression was used with the following covariates: intervention (fetoscopic endoluminal tracheal occlusion vs expectant), early balloon insertion (yes vs no), observed over expected lung-to-head ratio, liver herniation (yes vs no), and trial (severe vs moderate). The interaction between intervention and the observed over expected lung-to-head ratio was evaluated to study treatment effect heterogeneity. RESULTS: For survival to discharge, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion was 1.78 (95% confidence interval, 1.05-3.01; P=.031). The additional effect of early balloon insertion was highly uncertain (adjusted odds ratio, 1.53; 95% confidence interval, 0.60-3.91; P=.370). When combining these 2 effects, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion with early balloon insertion was 2.73 (95% confidence interval, 1.15-6.49). The results for survival to 6 months and survival to 6 months without oxygen dependence were comparable. The gestational age at delivery was on average 1.7 weeks earlier (95% confidence interval, 1.1-2.3) following fetoscopic endoluminal tracheal occlusion with late insertion and 3.2 weeks earlier (95% confidence interval, 2.3-4.1) following fetoscopic endoluminal tracheal occlusion with early insertion compared with expectant management. There was no evidence that the effect of fetoscopic endoluminal tracheal occlusion depended on the observed over expected lung-to-head ratio for any of the endpoints. CONCLUSION: This analysis suggests that fetoscopic endoluminal tracheal occlusion increases survival for both moderate and severe lung hypoplasia. The difference between the results for the Tracheal Occlusion To Accelerate Lung growth trials, when considered apart, may be because of the difference in the time point of balloon insertion. However, the effect of the time point of balloon insertion could not be robustly assessed because of a small sample size and the confounding effect of disease severity. Fetoscopic endoluminal tracheal occlusion with early balloon insertion in particular strongly increases the risk for preterm delivery.

First trimester examination of fetal anatomy: clinical practice guideline by the World Association of Perinatal Medicine (WAPM) and the Perinatal Medicine Foundation (PMF).

This recommendation document follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation. We aim to bring together groups and individuals throughout the world for precise standardization to implement the ultrasound evaluation of the fetus in the first trimester of pregnancy and improve the early detection of anomalies and the clinical management of the pregnancy. The aim is to present a document that includes statements and recommendations on the standard evaluation of the fetal anatomy in the first trimester, based on quality evidence in the peer-reviewed literature as well as the experience of perinatal experts around the world.

Longitudinal changes in maternal left atrial volume index and uterine artery pulsatility indices in uncomplicated pregnancy.

BACKGROUND: Data on the relationship between longitudinal changes in maternal volume-dependent echocardiographic parameters and placentation in uncomplicated pregnancy are limited. OBJECTIVE: This study aimed to evaluate changes in volume-dependent echocardiographic parameters in uncomplicated pregnancy to test the hypothesis of the existence of an association between volume-dependent echocardiographic parameters and Doppler ultrasound parameters of fetal circulation and the uterine artery in uncomplicated pregnancy and to establish which of the volume-dependent echocardiographic parameters best depicts volume changes and correlates best with Doppler ultrasound of fetal circulation and the uterine artery in healthy pregnancy. STUDY DESIGN: Data from 60 healthy pregnant women were analyzed. A complete echocardiographic study was performed at 11 to 13, 20 to 22, and 30 to 32 weeks' gestation: left ventricular end-diastolic volume, early diastolic peak flow velocity, late diastolic peak flow velocity, left atrial area, and left atrial volume index were assessed. Obstetrical assessment was performed including fetal growth and uterine artery pulsatility index. Fetal well-being was assessed by umbilical and middle cerebral artery blood flow. Serum pregnancy-associated plasma protein A and free ß-human chorionic gonadotropin were assessed during the routine first-trimester scan (11-13 weeks' gestation). RESULTS: Left ventricular end-diastolic volume and left atrial area increased significantly between 11 to 13 and 20 to 22 weeks' gestation but not between 20 to 22 and 30 to 32 weeks' gestation. Left atrial volume index measured at 30 to 32 weeks' gestation correlated with uterine artery pulsatility indices in 3 trimesters. Changes in the left atrial volume index between the third and first trimesters correlated significantly with the uterine artery pulsatility index measured at 20 to 22 weeks' gestation (r=-0.345; P=.020) and at 30 to 32 weeks' gestation (r=-0.452; P=.002). Changes in the left atrial volume index between the second and first trimesters significantly correlated with the uterine artery pulsatility index measured in the first trimester (r=-0.316; P=.025). CONCLUSION: Our study showed that in an uncomplicated pregnancy, among volume-dependent echocardiographic parameters, left atrial volume index increased between both the first and second trimesters and the second and third trimesters and correlated with parameters of Doppler ultrasound of the fetal circulation and the uterine artery. Our results expand on the previous observation on the relationship between maternal cardiovascular adaptation and placentation in women with heart diseases to the population of healthy women with uncomplicated pregnancy.

Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium.

BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.

Role of sphingolipids in the pathogenesis of intrahepatic cholestasis.

BACKGROUND & AIMS: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder that affects from 0.2% to 15.6% pregnant women. The disease is connected with increased risk of fetal morbidity and mortality, but is unfortunately detected quite late. The diagnosis of ICP is based on only one manifestation: pruritus which mainly affects soles and palms. METHODS: Twenty intrahepatic cholestasis of pregnancy (ICP) women and twenty healthy pregnant women (control group) took part in the study. In the study group, blood sampling for baseline measurements was performed on the first day of hospital stay - before the commencement of treatment with ursodeoxycholic acid (UDCA) - and repeated after 7 days of 900 mg UDCA per day. An additional blood sample was collected on the second day after childbirth. In the control group, blood samples were collected directly after hospital admission. We compared plasma sphingolipids in samples of the subjects from ICP and ICP + UDCA-treated groups as well as the ICP group after delivery with the healthy controls. RESULTS: Of all sphingolipids, the median values of C16-Cer and C18-Cer were significantly higher in the plasma of cholestasis patients not treated with UDCA as compared to the control. Following 7 days of UDCA treatment, a considerable decrease in C16-Cer, C18-Cer and the total concentration of bile acids was noted as compared to the baseline. CONCLUSION: It is known that sphingolipids serve as modulators of liver regeneration. We assume these substances could be potential markers for detecting early onsets of intrahepatic cholestasis of pregnancy.

Vascular anastomoses in intrauterine growth in monochorionic twins.

Objectives To evaluate the impact of placental anastomoses on the intrauterine growth of monochorionic (MC) twins. Methods A prospective study was conducted in a group of 53 MC twins. Intrapartally umbilical cords were clamped to identify placental sides corresponding to each twin. The postnatal dye injection technique was administered to evaluate vascular anastomoses, their number and type and visualize placental territory sharing patterns. Data from digital analysis were correlated with obstetrical follow-up. Results Vascular anastomoses were revealed in 88.7% of cases. Arteriovenous (AV) anastomoses occurred in 75.4% and arterioarterial (AA) in 71.1% while venovenous (VV) in 26.4%. In the subgroup of MC twins without placental anastomoses, significantly higher birthweight difference and discordance were revealed when compared to MC twins without anastomoses (382.0 vs. 22 g; P = 0.03 and 49.14% vs. 16.02%; P = 0.03). On the other hand, in subgroups of MC twins with at least one AA anastomosis, twins' birthweights were similar (p = ns) despite significantly higher placental territory sharing discordance (30.44% vs. 15.81%; P = 0.31). Conclusions Vascular anastomoses have a major impact on the intrauterine growth of MC twins. In certain cases, they may cause specific complications; however, in general, they regulate intertwin blood exchange and may compensate unequal placental territory.

The use of atosiban prolongs pregnancy in patients treated with fetoscopic endotracheal occlusion (FETO).

Objective To evaluate the impact of atosiban as a tocolytic agent in patients treated with the fetoscopic endotracheal occlusion (FETO) procedure due to congenital diaphragmatic hernia (CDH). As premature birth after fetoscopy remains a serious concern, an effort to reduce prematurity is required. Methods A total of 43 patients with severe CDH treated with FETO were enrolled in this study. The study group consisted of 22 patients who received atosiban during the FETO procedure and a control group of 21 patients who did not receive atosiban during the FETO procedure. Demographic data, gestational age (GA) at delivery, cervical length and GA at premature rupture of membranes (PROM) were evaluated. Results The GA at delivery was significantly different between the two groups studied. The median GA at delivery was 32.6 and 34.5 weeks in the no-atosiban vs. atosiban groups, respectively (P = 0.013). The median cervical length was 29.9 and 31.2 mm for the no-atosiban and atosiban groups, respectively, and was not statistically significant (P = 0.28). There were no significant correlations between groups for the occurrence of PROM, GA at the time of PROM, duration of the procedures, parity, maternal body mass index (BMI) or age. In the univariate linear regression model, the only factor independently associated with GA at delivery was the use of atosiban during FETO procedures (ß = 0.375; P < 0.013). Conclusion In cases of severe CDH treated with FETO, the use of atosiban as a tocolytic agent during the procedure prolonged pregnancy by 2 weeks. Cervical length, duration of FETO or maternal characteristics were not associated with GA at delivery.

Cervical Measurement and Pessary Application in Relation to Gestational Age at Delivery in Patients Treated with Fetoscopic Endotracheal Occlusion.

OBJECTIVE: To evaluate the impact of cervical length and cervical pessary application in congenital diaphragmatic hernia (CDH) treated by the fetoscopic endotracheal occlusion (FETO) procedure. METHODS: The study group consisted of 80 patients with severe CDH treated by FETO. Cervical length measurement was performed by transvaginal ultrasound in all patients within the 24 h prior to the FETO procedure. The study group (n = 44) had cervical pessaries applied routinely within the 24 h following the FETO procedure, whereas the control group (n = 36) were not offered pessaries and only had cervical length measurement performed. RESULTS: The median cervical length was 31 (range 22-45) mm. The median gestational age at delivery was 34.7 (range 27.8-39.2) weeks. Gestational age at delivery correlated significantly with gestational age at balloon removal (r = 0.768; p < 0.0001) and premature rupture of membranes (r = 0.501; p = 0.003). There was no significant correlation between gestational age at delivery and cervical length before the procedure (r = 0.141; p = 0.26) or pessary application (r = 0.081; p = 0.51). In the multivariate linear regression model, the only factor independently associated with gestational age at delivery was gestational age at fetoscopic balloon removal (ß = 0.713; p < 0.0001). CONCLUSION: In cases of severe CDH treated by the FETO procedure, neither cervical length before the procedure nor cervical pessary application was associated with gestational age at delivery.

Is there a future for cell-free fetal dna tests in screening for preeclampsia?

CffDNA screening is a powerful diagnostic tool in the prenatal diagnosis algorithm for chromosomal abnormalities. With detailed ultrasound examination as the mainstay of first-trimester risk assessment, cffDNA has been shown to be superior to first-trimester combined screening (FTCS) in false-positive rates for trisomy 21 detection. In light of the growing interest in cffDNA testing and the possibility of it replacing first-trimester biochemistry, we decided to investigate the usefulness of cffDNA tests in early-pregnancy risk assessment for preeclampsia (PE). The aim of this review paper was to evaluate clinical application of first-trimester cfDNA in predicting PE, as well as to investigate its possible use in first-trimester PE screening enhancement, also in cases where biochemistry is not performed.

The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications.

OBJECTIVES: The aim of this study was to determine if the levels of biochemical aneuploidy markers in in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to verify if biochemical markers could predict pregnancy outcome in IVF/ICSI gestations. METHODS: This was a prospective observational study performed in a group of 551 patients who underwent a combined first trimester prenatal screening (ultrasound scan and serum markers). All patients were divided into two groups according to the mode of conception: IVF/ICSI pregnancies (study group) and spontaneous conceptions (control group). The concentrations of first trimester biochemical markers were presented as multiples of median (MoM) and were compared between the study and control groups. Analysed pregnancy complications included: preterm delivery (PTD), small for gestational age (SGA), gestational hypertension (GH), preeclampsia (PE) and gestational diabetes (GDM). RESULTS: The analysis was performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with complete data regarding obstetric outcome. There were no significant differences in the concentrations of biochemical markers between the analysed groups. Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive than in normotensive patients, although the difference was not significant. Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed in 18 (9.8%) and 25 delivered preterm (13.6%). CONCLUSIONS: The trend for lower PAPP-A MoM was visible in all affected patients, although the results did not reach statistical significance. The first trimester biochemical markers in assisted reproduction technique (ART) pregnancies do not seem to have additional effect on predicting the risk of pregnancy complications.

Early 2D/3D ultrasound diagnosis of pleural effusion in fetuses with Turner syndrome.

Most guidelines on ultrasound examinations during pregnancy do not recommend routine early pregnancy scan in uncomplicated and asymptomatic pregnancies (ie, before 10 weeks based on last menstrual period). There is, however, a growing patient's expectation to have an early scan to confirm dating and verify the pregnancy is intrauterine and viable. We present three well-documented cases of patients who had an early (7-8 weeks) dating transvaginal scan revealing pleural effusion in the embryo. In all cases cytogenetic analysis confirmed monosomy for the X chromosome, consistent with a clinical diagnosis of Turner syndrome.

The practical use of acetylsalicylic acid in the era of the ASPRE trial. Update and literature review.

It is now well established that acetylsalicylic acid - one of the most widely prescribed drugs today - has brought a new era in maternal-fetal medicine. The History of medicine mentions several antecedents. Extracts made from willow contained in clay tablets are reported in both ancient Sumer and Egypt. In 400 BC, Hippocrates referred to the use of salicylic tea to reduce fevers. In the 1950s, acetylsalicylic acid entered the Guinness Book of Records as the highest selling painkiller. There is little doubt that acetylsalicylic acid - one of the first drugs to enter common usage - remains one of the most researched drugs in the world.

Contemporary management of prenatally diagnosed spina bifida aperta - an update.

Spina bifida aperta is a relatively common congenital defect that occurs in the general population. Once the disorder has been diagnosed, a discussion, that can be emotionally-charged, ensues about whether to treat it prenatally or to only offer surgery postnatally. Given that there are good arguments for and against both options, it is of paramount importance to gain a good understanding of the major advantages and disadvantages of the various surgical approaches. The aim of our paper is to summarize current knowledge about spina bifida and the potential benefits of prenatal surgery.

The severity of anaemia depletes cerebrovascular dilatory reserve in children with sickle cell disease: a quantitative magnetic resonance imaging study.

Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease (SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow (CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lead to cerebral ischaemia. The purpose of this study was to investigate CBF and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) in children with SCD and to correlate these with haematological markers of anaemia. Baseline CBF was measured using arterial spin labelling. Blood-oxygen level-dependent MRI in response to a CO2 stimulus was used to acquire CVR. In total, 28 children with SCD (23 not on any disease-modifying treatment, 5 on chronic transfusion) and 22 healthy controls were imaged using MRI. Transfusion patients were imaged at two time points to assess the effect of changes in haematocrit after a transfusion cycle. In children with SCD, CBF was significantly elevated compared to healthy controls, while CVR was significantly reduced. Both measures were significantly correlated with haematocrit. For transfusion patients, CBF decreased and CVR increased following a transfusion cycle. Lastly, a significant correlation was observed between CBF and CVR in both children with SCD and healthy controls.

Congenital diaphragmatic hernia: pathogenesis, prenatal diagnosis and management - literature review.

Congenital diaphragmatic hernia (CDH) is a developmental discontinuity of the diaphragm. It allows abdominal viscera to herniate into the chest and leads to lung hypoplasia. Congenital diaphragmatic hernia is one of the most severe birth defects, with extremely high neonatal mortality. This paper presents a review of the available literature on prenatal diagnosis, management and treatment options for CDH. In selected cases, a prenatal procedure to improve neonatal survival is possible. The authors of this manuscript believe their work might contribute to a better understanding of congenital diaphragmatic hernia and patient selection for the FETO (fetal endoscopic tracheal occlusion) surgery or expectant management.

Developmental trajectories of cerebrovascular reactivity in healthy children and young adults assessed with magnetic resonance imaging.

KEY POINTS: Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels. Normal development in children is associated with significant changes in blood pressure, cerebral blood flow (CBF) and cerebral oxygen metabolism. Therefore, it stands to reason that CVR will also undergo changes during this period. The study acquired magnetic resonance imaging measures of CVR and CBF in healthy children and young adults to trace their changes with age. We found that CVR changes in two phases, increasing with age until the mid-teens, followed by a decrease. Baseline CBF declined steadily with age. We conclude that CVR varies with age during childhood, which prompts future CVR studies involving children to take into account the effect of development. ABSTRACT: Cerebrovascular reactivity (CVR) reflects the vasculature's ability to accommodate changes in blood flow demand thereby serving as a critical imaging tool for mapping vascular reserve. Normal development is associated with extensive physiological changes in blood pressure, cerebral blood flow and cerebral metabolic rate of oxygen, all of which can affect CVR. Moreover, the evolution of these physiological parameters is most prominent during childhood. Therefore, the aim of this study was to use non-invasive magnetic resonance imaging (MRI) to characterize the developmental trajectories of CVR in healthy children and young adults, and relate them to changes in cerebral blood flow (CBF). Thirty-four healthy subjects (17 males, 17 females; age 9-30 years) underwent CVR assessment using blood oxygen level-dependent MRI in combination with a computer controlled CO2 stimulus. In addition, baseline CBF was measured with a pulsed arterial spin labelling sequence. CVR exhibited a gradual increase with age in both grey and white matter up to 14.7 years. After this break point, a negative correlation with age was detected. Baseline CBF maintained a consistent negative linear correlation across the entire age range. The significant age-dependent changes in CVR and CBF demonstrate the evolution of cerebral haemodynamics in children and should be taken into consideration. The shift in developmental trajectory of CVR from increasing to decreasing suggests that physiological factors beyond baseline CBF also influence CVR.