Congenital diaphragmatic hernia: automatic lung and liver MRI segmentation with nnU-Net, reproducibility of pyradiomics features, and a machine learning application for the classification of liver herniation.

Prenatal assessment of lung size and liver position is essential to stratify congenital diaphragmatic hernia (CDH) fetuses in risk categories, guiding counseling, and patient management. Manual segmentation on fetal MRI provides a quantitative estimation of total lung volume and liver herniation. However, it is time-consuming and operator-dependent. In this study, we utilized a publicly available deep learning (DL) segmentation system (nnU-Net) to automatically contour CDH-affected fetal lungs and liver on MRI sections. Concordance between automatic and manual segmentation was assessed by calculating the Jaccard coefficient. Pyradiomics standard features were then extracted from both manually and automatically segmented regions. The reproducibility of features between the two groups was evaluated through the Wilcoxon rank-sum test and intraclass correlation coefficients (ICCs). We finally tested the reliability of the automatic-segmentation approach by building a ML classifier system for the prediction of liver herniation based on support vector machines (SVM) and trained on shape features computed both in the manual and nnU-Net-segmented organs. We compared the area under the classifier receiver operating characteristic curve (AUC) in the two cases. Pyradiomics features calculated in the manual ROIs were partly reproducible by the same features calculated in nnU-Net segmented ROIs and, when used in the ML procedure, to predict liver herniation (both AUC around 0.85).          Conclusion: Our results suggest that automatic MRI segmentation is feasible, with good reproducibility of pyradiomics features, and that a ML system for liver herniation prediction offers good reliability.          Trial registration: https://clinicaltrials.gov/ct2/show/NCT04609163?term=NCT04609163&draw=2&rank=1 ; Clinical Trial Identification no. NCT04609163. What is Known: • Magnetic resonance imaging (MRI) is crucial for prenatal congenital diaphragmatic hernia (CDH) assessment. It enables the quantification of the total lung volume and the extent of liver herniation, which are essential for stratifying the severity of CDH, guiding counseling, and patient management. • The manual segmentation of MRI scans is a time-consuming process that is heavily reliant upon the skill set of the operator. What is New: • MRI lung and liver automatic segmentation using the deep learning nnU-Net system is feasible, with good Jaccard coefficient values and satisfactory reproducibility of pyradiomics features compared to manual results. • A feasible ML system for predicting liver herniation could improve prenatal assessments and CDH patient management.

Fetoscopic endoluminal tracheal occlusion vs expectant management for fetuses with severe left-sided congenital diaphragmatic hernia.

BACKGROUND: The treatment of fetuses with a congenital diaphragmatic hernia is challenging, but there is evidence that fetoscopic endoluminal tracheal occlusion has a benefit over expectant care. In addition, standardization and expertism have a great impact on survival and are probably crucial in centers that rely on expectant management with extracorporeal membrane oxygenation after birth. OBJECTIVE: This study aimed to examine the survival and morbidity rates of fetuses with a severe isolated left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion vs expectant management in high-volume centers. STUDY DESIGN: This was a multicenter, retrospective study that included all consecutive fetuses with severe isolated left-sided congenital diaphragmatic hernia who were expectantly managed in a German center or who underwent fetoscopic endoluminal tracheal occlusion in 3 other European centers (Belgium, France, and Italy). Severe congenital diaphragmatic hernia was defined as having an observed to expected total fetal lung volume ≤35% with intrathoracic position of the liver diagnosed with magnetic resonance imaging. All magnetic resonance images were centralized, and lung volumes were measured by 2 experienced operators who were blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect of the management strategy in the 2 groups on the short- and long-term outcomes. RESULTS: A total of 147 patients who were managed expectantly and 47 patients who underwent fetoscopic endoluminal tracheal occlusion were analyzed. Fetuses who were managed expectantly had lower observed to expected total fetal lung volumes (20.6%±7.5% vs 23.7%±6.8%; P=.013), higher gestational age at delivery (median weeks of gestation, 37.4; interquartile range, 36.6-38.00 vs 35.1; interquartile range, 33.1-37.2; P<.001), and more frequent use of extracorporeal membrane oxygenation (55.8% vs 4.3%; P<.001) than the fetuses who underwent fetoscopic endoluminal tracheal occlusion. The survival rates at discharge and at 2 years of age in the expectant management group were higher than the survival rates of the fetoscopic endoluminal tracheal occlusion group (74.3% vs 44.7%; P=.001 and 72.8% vs 42.5%; P=.001, respectively). After adjustment for maternal age, gestational age at birth, observed to expected total fetal lung volume, and birth weight Z-score, the odds ratios were 4.65 (95% confidence interval, 1.9-11.9; P=.001) and 4.37 (95% confidence interval, 1.8-11.0; P=.001), respectively. CONCLUSION: Fetuses with a severe isolated left-sided congenital diaphragmatic hernia had a higher survival rate when treated in an experienced center in Germany with antenatal expectant management and frequent use of extracorporeal membrane oxygenation during the postnatal period than fetuses who were treated with fetoscopic endoluminal tracheal occlusion in 3 centers in Belgium, France, and Italy.

Impact of Endometrial Preparation on the Maternal and Fetal Cardiovascular Variables of the First Trimester Combined Screening Test.

The modality of endometrial preparation for the transfer of frozen-thawed embryos may influence maternal and fetal adaptation to pregnancy and could thus impact the results of the first trimester combined screening test. We conducted a retrospective cross-sectional study on singleton pregnancies achieved by embryo transfer of a single frozen-thawed blastocyst, comparing two different endometrial preparation protocols: natural cycle (n = 174) and hormone replacement therapy (HRT) (n = 122). The primary outcome was the risk of preeclampsia at the first trimester combined screening test. Secondary endpoints included variable reflecting fetal cardiac function (nuchal translucency and fetal heart rate), maternal adaptation (median arterial blood pressure-MAP and uterine arteries pulsatility index-UtA-PI), and placentation (pregnancy associated plasma protein A and placental growth factor). The risk of early preeclampsia was comparable in the two groups (38% vs. a 28%, p = 0.12). However, women in the natural cycle group showed lower fetal heart rate (159 [155-164] vs. 164 [158-168], p = 0.002) and higher UtA-PI (0.96 [0.74-1.18] vs. 0.72 [0.58-0.90], p < 0.001). The frequency of a screening test at high risk for aneuploidies was similar. The modality of transfer of frozen-thawed embryos is associated with changes in the variables reflecting maternal and fetal cardiovascular function.

To be born twin: effects on long-term neurodevelopment of very preterm infants-a cohort study.

Objective: To examine the effect of twin birth on long-term neurodevelopmental outcomes in a cohort of Italian preterm infants with very low birth weight. Study design: We performed a retrospective cohort study on children born in a tertiary care centre. We included children born between 1 January 2007 and 31 December 2013 with a gestational age (GA) of ≤32 weeks and birth weight of <1,500 g. The infants born from twin pregnancies complicated by twin-to-twin transfusion syndrome and from higher-order multiple pregnancies were excluded. The children were evaluated both at 2 years corrected age and 5 years chronological age with Griffiths mental development scales revised (GMDS-R). The linear mixed effects models were used to study the effect of being a twin vs. being a singleton on GMDS-R scores, adjusting for GA, being born small for gestational age, sex, length of NICU stay, socio-economic status, and comorbidity score (CS) calculated as the sum of the weights associated with each of the major morbidities of the infants. Results: A total of 301 children were included in the study, of which 189 (62.8%) were singletons and 112 (37.2%) were twins; 23 out of 112 twins were monochorionic (MC). No statistically significant differences were observed between twins and singletons in terms of mean general quotient and subscales at both 2 and 5 years. No effect of chorionicity was found when comparing scores of MC and dichorionic twins vs. singletons; however, after adjusting for the CS, the MC twins showed lower scores in the hearing and language and performance subscales at 5 years. Conclusion: Overall, in our cohort of children born very preterm, twin infants were not at higher risk of neurodevelopmental impairment compared with singletons at pre-school age.

Combined Pre- and Postnatal Minimally Invasive Approach to a Complex Symptomatic Congenital Pulmonary Airway Malformation.

Congenital pulmonary airway malformation (CPAM) is a rare congenital lung lesion that usually remains asymptomatic during the fetal and neonatal period. However, it can occasionally cause prenatal cardiocirculatory failure and fetal hydrops, requiring a thoraco-amniotic shunt (TAS) placement. In other cases, it can also cause symptoms at birth (such as respiratory distress) and may require urgent surgical intervention. Thoracoscopic lobectomy for neonates is rarely reported. Here, we report a case of right macrocystic CPAM causing fetal hydrops at 27 weeks of gestation. The fetus was treated with a TAS placement that successfully resolved the hydrops. At 39 weeks of gestation, a male neonate was born (weight 2,850 g). The TAS spontaneously displaced during delivery, causing an open pneumothorax (PNX), initially treated with a drainage. His condition gradually worsened, requiring ventilatory support. Computed tomography (CT) scan showed different giant cysts in the context of the right lower lobe, left mediastinal shift, and compression of the rest of the lung. An urgent surgical management was required. A thoracoscopic right lower lobectomy was performed at 10 days of life (weight 2,840 g). The postoperative course was uneventful; the child remained totally asymptomatic and showed a good recovery. To the best of our knowledge, this is the first reported case of open iatrogenic PNX following TAS positioning and the second of neonatal thoracoscopic lobectomy in a newborn weighting less than 3 kg. The purpose of this report is to indicate that minimally invasive surgery is feasible, safe, and effective for the resection of CPAM, even in small newborns.

Pyroptosis: A Promising Mechanism Linking SARS-CoV-2 Infection to Adverse Pregnancy Outcomes.

Pregnancy is characterized by a delicate immune balance; therefore, infectious diseases might increase the risk of adverse pregnancy outcomes (APOs). Here, we hypothesize that pyroptosis, a unique cell death pathway mediated by the NLRP3 inflammasome, could link SARS-CoV-2 infection, inflammation, and APOs. Two blood samples were collected from 231 pregnant women at 11-13 weeks of gestation and in the perinatal period. At each time point, SARS-CoV-2 antibodies and neutralizing antibody titers were measured by ELISA and microneutralization (MN) assays, respectively. Plasmatic NLRP3 was determined by ELISA. Fourteen miRNAs selected for their role in inflammation and/or pregnancy were quantified by qPCR and further investigated by miRNA-gene target analysis. NLRP3 levels were positively associated with nine circulating miRNAs, of which miR-195-5p was increased only in MN+ women (p-value = 0.017). Pre-eclampsia was associated with a decrease in miR-106a-5p (p-value = 0.050). miR-106a-5p (p-value = 0.026) and miR-210-3p (p-value = 0.035) were increased in women with gestational diabetes. Women giving birth to small for gestational age babies had lower miR-106a-5p and miR-21-5p (p-values = 0.001 and 0.036, respectively), and higher miR-155-5p levels (p-value = 0.008). We also observed that neutralizing antibodies and NLRP3 concentrations could affect the association between APOs and miRNAs. Our findings suggest for the first time a possible link between COVID-19, NLRP3-mediated pyroptosis, inflammation, and APOs. Circulating miRNAs might be suitable candidates to gain a comprehensive view of this complex interplay.

Geometric Reliability of Super-Resolution Reconstructed Images from Clinical Fetal MRI in the Second Trimester.

Fetal Magnetic Resonance Imaging (MRI) is an important noninvasive diagnostic tool to characterize the central nervous system (CNS) development, significantly contributing to pregnancy management. In clinical practice, fetal MRI of the brain includes the acquisition of fast anatomical sequences over different planes on which several biometric measurements are manually extracted. Recently, modern toolkits use the acquired two-dimensional (2D) images to reconstruct a Super-Resolution (SR) isotropic volume of the brain, enabling three-dimensional (3D) analysis of the fetal CNS.We analyzed 17 fetal MR exams performed in the second trimester, including orthogonal T2-weighted (T2w) Turbo Spin Echo (TSE) and balanced Fast Field Echo (b-FFE) sequences. For each subject and type of sequence, three distinct high-resolution volumes were reconstructed via NiftyMIC, MIALSRTK, and SVRTK toolkits. Fifteen biometric measurements were assessed both on the acquired 2D images and SR reconstructed volumes, and compared using Passing-Bablok regression, Bland-Altman plot analysis, and statistical tests.Results indicate that NiftyMIC and MIALSRTK provide reliable SR reconstructed volumes, suitable for biometric assessments. NiftyMIC also improves the operator intraclass correlation coefficient on the quantitative biometric measures with respect to the acquired 2D images. In addition, TSE sequences lead to more robust fetal brain reconstructions against intensity artifacts compared to b-FFE sequences, despite the latter exhibiting more defined anatomical details.Our findings strengthen the adoption of automatic toolkits for fetal brain reconstructions to perform biometry evaluations of fetal brain development over common clinical MR at an early pregnancy stage.

Prevalence and Factors Associated With Intertwin Birth Weight Discordance Among Same-Sex Twins in Lombardy, Northern Italy.

This population-based cohort study investigated the prevalence, potential risk factors, and consequences of birth weight discordance (BWD) among same-sex twins. We retrieved data from the automated system of healthcare utilization databases of Lombardy Region, Northern Italy (2007-2021). BWD was defined as 30% or more disparity in birth weights between the larger and the smaller twin. Multivariate logistic regression was used to analyze the risk factors of BWD in deliveries with same-sex twins. In addition, the distribution of several neonatal outcomes was assessed overall and according to BWD level (i.e., ≤20%, 21-29, and ≥30%). Finally, a stratified analysis by BWD was performed to assess the relationship between assisted reproductive technologies (ART) and neonatal outcomes. We identified 11,096 same-sex twin deliveries; 556 (5.0%) pairs of twins were affected by BWD. Multivariate logistic regression analysis showed that maternal age ≥35 years (OR 1.26, 95% CI [1.05,5.51]), low level of education (OR 1.34, 95% CI [1.05, 1.70]), and ART (OR 1.16, 95% CI [0.94, 1.44], almost significant due to the low power) were independent risk factors for BWD in same-sex twins. Conversely, parity (OR 0.73, 95% CI [0.60, 0.89]) was inversely related. All the adverse outcomes observed were more common among BWD pairs than non-BWD ones. Instead, a protective effect of ART was observed for most neonatal outcomes considered among BWD twins. Our results suggest that conception after ART increases the risk of developing a high disparity between the weights of the two twins. However, the presence of BWD may complicate twin pregnancies, compromising neonatal outcomes, regardless of the modality of conception.

SARS-CoV-2 Seroconversion and Pregnancy Outcomes in a Population of Pregnant Women Recruited in Milan, Italy, between April 2020 and October 2020.

The possible link between SARS-CoV-2 infection and adverse pregnancy outcomes has so far demonstrated heterogeneous results in terms of maternal, fetal, and neonatal complications. We aim to investigate the correlation between SARS-CoV-2 seroconversion and/or neutralization titer and pregnancy outcomes. We analyzed a population of 528 pregnant women followed up from the first trimester of gestation until delivery. For each woman, we collected a first blood sample between 11 and 13 weeks of gestation and a second sample in the perinatal period (between peripartum and puerperium) to assess the presence of SARS-CoV-2 antibodies and/or microneutralization titer (MN titer). Data on pregnancy outcomes (gestational age at delivery, preterm birth before 34 weeks, hypertensive disorders, gestational diabetes, and abnormal fetal growth) were collected. We observed that serologic status per se is not associated with major pregnancy complications. On the contrary, the MN titer was associated with increased odds of gestational diabetes. Although we mainly reported asymptomatic SARS-CoV-2 infections and the absence of severe maternal and neonatal adverse outcomes, SARS-CoV-2 infection might challenge the maternal immune system and explain the moderate increase in adverse outcome odds.

Upper Respiratory Microbiome in Pregnant Women: Characterization and Influence of Parity.

During pregnancy, the woman's immune system changes to support fetal development. These immunological modifications can increase the risk of respiratory diseases. Because the respiratory microbiome is involved in airway homeostasis, it is important to investigate how it changes during pregnancy. Additionally, since parity is associated with immune system alterations and cohabitants shared a similar microbiome, we investigated whether having a child may influence the respiratory microbiome of pregnant women. We compared the microbiome of 55 pregnant with 26 non-pregnant women using 16S rRNA gene sequencing and analyzed taxonomy, diversity, and metabolic pathways to evaluate the differences among nulliparous, primiparous, and multiparous women. The microbiome was similar in pregnant and non-pregnant women, but pregnant women had higher alpha diversity (Chao1 p-value = 0.001; Fisher p-value = 0.005) and a lower abundance of several metabolic pathways. Multiparous pregnant women had a higher relative abundance of Moraxella (p-value = 0.003) and a lower abundance of Corynebacterium (p-value = 0.002) compared with primiparous women. Both multiparous (pregnant) and primiparous/multiparous (non-pregnant) women reported a higher abundance of Moraxella compared with primiparous (pregnant) or nulliparous ones (p-value = 0.001). In conclusion, we characterized for the first time the upper airway microbiome of pregnant women and observed the influence of parity on its composition.

Extracellular vesicles and their miRNA contents counterbalance the pro-inflammatory effect of air pollution during physiological pregnancy: A focus on Syncytin-1 positive vesicles.

The impact of exposure to respirable particulate matter (PM) during pregnancy is a growing concern, as several studies have associated increased risks of adverse pregnancy and birth outcomes, and impaired intrauterine growth with air pollution. The molecular mechanisms responsible for such effects are still under debate. Extracellular vesicles (EVs), which travel in body fluids and transfer microRNAs (miRNAs) between tissues (e.g., pulmonary environment and placenta), might play an important role in PM-induced risk. We sought to determine whether the levels of PM with aerodynamic diameters of ≤10 µm (PM10) and ≤2.5 µm (PM2.5) are associated with changes in plasmatic EV release and EV-miRNA content by investigating 518 women enrolled in the INSIDE study during the first trimester of pregnancy. In all models, we included both the 90-day averages of PM (long-term effects) and the differences between the daily estimate of PM and the 90-day average (short-term effects). Short-term PM10 and PM2.5 were associated with increased concentrations of all seven EV types that we assayed (positive for human antigen leukocyte G (HLA-G), Syncytin-1 (Sync-1), CD14, CD105, CD62e, CD61, or CD25 determinants), while long-term PM10 showed a trend towards decreased EV concentrations. Increased Sync-1 + EV levels were associated with the plasmatic decrease of sVCAM-1, but not of sICAM-1, which are circulating biomarkers of endothelial dysfunction. Thirteen EV-miRNAs were downregulated in response to long-term PM10 and PM2.5 variations, while seven were upregulated (p-value < 0.05, false discovery rate p-value (qFDR) < 0.1). Only one EV-miRNA (hsa-miR-221-3p) was downregulated after short-term variations. The identified PM-modulated EV-miRNAs exhibited putative roles in inflammation, gestational hypertension, and pre-eclampsia, as highlighted by miRNA target analysis. Our findings strongly support the hypothesis that EVs have an important role in modulating PM exposure effects during pregnancy, possibly through their miRNA cargo.

Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilization.

BACKGROUND: In pregnancies obtained by in-vitro fertilization (IVF) the exact day of conception is known. For that reason, IVF pregnancies are currently dated according to the day of oocytes retrieval and consequent embryo transfer. The aim of the present study is to determine whether the knowledge of the exact day of conception in IVF pregnancies is a sufficient argument against dating these pregnancies by first trimester ultrasound measurement of the crown-rump length (CRL), as it is recommended in natural conceptions. METHODS: A retrospective study was performed, including all women with singleton pregnancies conceived by IVF who underwent the first-trimester ultrasound scan for the screening of aneuploidies between January 2014 and June 2019. For each pregnancy GA was determined using two alternative methods: one based on the date of embryo transfer (GAIVF), and one based on ultrasound measurement of CRL (GAUS). GA were compared to search for any discrepancy. The impact of pregnancy dating on obstetric outcome was evaluated. RESULTS: Overall, 249 women were included. Comparing GAUS and GAIVF, a median difference of 1 [0 - 2] days emerged (p<0.001), with GAUS being in advance compared to GAIVF. This discrepancy persisted when subgroups were analyzed comparing different IVF procedures (conventional IVF versus ICSI, cleavage versus blastocyst transfer, frozen versus fresh transfer). No impact of the dating method on obstetric outcomes was observed, being no differences in the rate of preterm birth or abnormal fetal growth. CONCLUSIONS: In IVF pregnancies GAUS and GAIVF are not overlapping, since GAUS is mildly greater than GAIVF. This could be due to an anticipated ovulation and fertilization in IVF pregnancy, rather than an accelerated embryo development. For that reason, it would be appropriate to date IVF pregnancies according to GAUS, despite a known date of conception, to re-align IVF pregnancies to natural ones.

Prenatal ultrasound findings associated with PIGW variants: One more piece in the FRYNS syndrome puzzle? PIGW-related prenatal findings.

OBJECTIVE: We describe the prenatal ultrasound findings and autopsy of three fetuses with multiple congenital anomalies (MCA) whose diagnostic workup suggested the same genetic etiology. We conducted a literature review to corroborate the molecular results and find evidence that the identified variants are responsible for the phenotype seen. METHODS: Trio-based Exome Sequencing (ES) analysis was performed on chorionic villus samples. We reviewed available reports dealing with prenatal manifestations of genes involved in the Glycosylphosphatidylinositols (GPI) biosynthesis defects (GPIBDs). RESULTS: Prenatal findings shared by all the three pregnancies included facial dysmorphisms, brain malformations of the posterior fossa, skeletal and genitourinary anomalies. ES analysis identified homozygous variants of uncertain significance in PIGW in the three fetuses. Prenatal findings of the three pregnancies overlapped with those previously described for PIGW variants and with those associated with PIGN, PIGV and PIGA variants. CONCLUSION: Based on the phenotypic overlap between the prenatal findings in our three cases and other cases with pathogenic variants in other genes involved in GPIBDs, we speculate that the variants identified in the three fetuses are likely causal of their phenotype and that the PIGWclinical spectrum might extend to MCA, mainly involving brain, skeletal and genitourinary systems. Moreover, we suggest that also PIGW could be involved in Fryns/Fryns-like phenotypes.

The role of magnetic resonance imaging in the diagnosis and prognostic evaluation of fetuses with congenital diaphragmatic hernia.

In recent years, magnetic resonance imaging (MRI) has largely increased our knowledge and predictive accuracy of congenital diaphragmatic hernia (CDH) in the fetus. Thanks to its technical advantages, better anatomical definition, and superiority in fetal lung volume estimation, fetal MRI has been demonstrated to be superior to 2D and 3D ultrasound alone in CDH diagnosis and outcome prediction. This is of crucial importance for prenatal counseling, risk stratification, and decision-making approach. Furthermore, several quantitative and qualitative parameters can be evaluated simultaneously, which have been associated with survival, postnatal course severity, and long-term morbidity. CONCLUSION: Fetal MRI will further strengthen its role in the near future, but it is necessary to reach a consensus on indications, methodology, and data interpretation. In addition, it is required data integration from different imaging modalities and clinical courses, especially for predicting postnatal pulmonary hypertension. This would lead to a comprehensive prognostic assessment. WHAT IS KNOWN: • MRI plays a key role in evaluating the fetal lung in patients with CDH. • Prognostic assessment of CDH is challenging, and advanced imaging is crucial for a complete prenatal assessment and counseling. WHAT IS NEW: • Fetal MRI has strengthened its role over ultrasound due to its technical advantages, better anatomical definition, superior fetal lung volume estimation, and outcome prediction. • Imaging and clinical data integration is the most desirable strategy and may provide new MRI applications and future research opportunities.

Family history is key to the interpretation of exome sequencing in the prenatal context: unexpected diagnosis of Basal Cell Nevus Syndrome.

OBJECTIVES: To reach a molecular diagnosis for a family with two consecutive fetuses presenting with multiple congenital anomalies. METHODS: The two fetuses underwent prenatal ultrasound, autopsy, radiologic, and genetic investigation. Genetic analysis included karyotype and array-CGH for both fetuses and trio-based whole exome sequencing (WES) only for the second fetus. RESULTS: WES results, initially focusing on recessive or dominant de novo variants, were negative.However, as a result of new relevant information regarding family history, the variant c.648_651dup in the PTCH1 gene was identified as causative of the fetal phenotype. CONCLUSIONS: This case further highlights how WES data analysis and interpretation strongly rely on family history and robust genotype-phenotype correlation. This is even more relevant in the prenatal setting, where access to fetal phenotype is limited and prenatal recognition of many morbid genes is not fully explored. We also provide a detailed description of the prenatal manifestations of Basal Cell Nevus Syndrome.

Maternal air pollution exposure during the first trimester of pregnancy and markers of inflammation and endothelial dysfunction.

BACKGROUND: Maternal exposure to air pollutants has been associated with pregnancy complications and adverse birth outcomes. Endothelial dysfunction, an imbalance in vascular function, during pregnancy is considered a key element in the development of pre-eclampsia. Environmental exposure to particulate matter (PM) during the first trimester of pregnancy might increase maternal inflammatory status thus affecting fetal growth, possibly leading to preterm delivery. OBJECTIVES: The purpose of the study was to evaluate possible effects of PM10 and PM2.5 exposure on fetal growth in healthy pregnant women at the end of the first trimester of pregnancy by investigating the relationship between circulating biomarkers of inflammation (IL-6), early systemic prothrombotic effects (CRP, plasma fibrinogen, PAI-1) and endothelial dysfunction (sICAM-1 and sVCAM-1). METHODS: 295 pregnant women were recruited. Individual PM exposure was assigned to each subject by calculating the mean of PM10 and PM2.5 daily values observed during the 30, 60, and 90 days preceding enrolment (long-term) and single lag days back to fourteen days (short-term), and circulating plasma biomarkers were determined. RESULTS: For long-term exposure, we observed an increase in sVCAM-1 and a decrease of PAI-1 levels for each 10 µg/m3 increase in PM10 concentration. Decreases in IL-6 and CRP levels were associated with each 10 µg/m3 PM2.5 increase. For short-term exposure, the levels of sVCAM-1 and PAI-1 were found to be associated with PM10 exposure, whereas fibrinogen levels were associated with PM2.5 exposure. Maternal plasmatic fibrinogen levels were negatively associated with the crown-rump length (p-value = 0.008). DISCUSSION: The present study showed that both long- and short-term exposures to PM are associated with changes in circulating levels of biomarkers in pregnant women reflecting systemic inflammation and endothelial dysfunction/activation. Our findings support the hypothesis that inflammation and endothelial dysfunction might have a central role in modulating the detrimental effects of air pollution exposure during pregnancy.

Intrauterine Ultrasound-Guided Laser Coagulation as a First Step for Treatment of Prenatally Complicated Bronchopulmonary Sequestration: Our Experience and Literature Review.

INTRODUCTION: Prenatal ultrasound-guided laser coagulation (USLC) for complicated bronchopulmonary sequestrations has been described but a consensus on the procedure and on the following management is still lacking. We present our experience and provide a literature review. METHODS: Retrospective review of patients treated in our center. Literature review and combined analysis of perinatal data were performed. RESULTS: Five cases were treated at our center, all presenting with severe hydrothorax. Four met the criteria for fetal hydrops. Four cases underwent postnatal computed tomography (CT) scan: in one case, there was no evidence of persistent bronchopulmonary sequestration. The other three underwent thoracoscopic resection, in two, a viable sequestration was found. Including our series, 57 cases have been reported, with no mortality and a success rate of 94.7%. Mean gestational age (GA) at the procedure was 28 ± 3.4 weeks and mean GA at birth and birth weight (BW) were 38.6 ± 2.3 weeks and 3,276 ± 519.8 g, respectively. In 80.6% of the cases investigated postnatally, a residual mass was found, 50% of cases who showed prenatal arterial flow cessation had a persistent sequestration postnatally, and 26.3% of cases underwent postnatal sequestrectomy. Both patients in our series had pathology examination confirming a viable bronchopulmonary sequestration. CONCLUSION: Prenatal USLC seems to be a valid option for bronchopulmonary sequestration complicated by severe hydrothorax and/or fetal hydrops. Authors believe that this procedure should aim to reverse fetal distress and allow pregnancy continuation, and it should not be considered a definitive treatment. The currently available data do not support changes of the common postnatal management.

Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group.

Fetal lower urinary tract obstruction (LUTO) is associated with high mortality and postnatal morbidity caused by lung hypoplasia and impaired kidney function. Specific diagnostic features that can guide clinical approach and decisions are lacking; thus, the European Reference Network for Rare Kidney Diseases established a work group to develop recommendations regarding the clinical definition, diagnosis and management of prenatally detected LUTO. The work group recommends the use of antero-posterior diameter of renal pelvis as the most reliable parameter for suspecting obstructive uropathies and for suspecting prenatal LUTO in the presence of fetal megacystis. Regarding prenatal and postnatal prognosis of fetuses with LUTO, the risk of fetal and neonatal death depends on the presence of oligohydramnios or anhydramnios before 20 weeks' gestation, whereas the risk of kidney replacement therapy cannot be reliably foreseen before birth. Parents of fetuses with LUTO must be referred to a tertiary obstetric centre with multidisciplinary expertise in prenatal and postnatal management of obstructive uropathies, and vesico-amniotic shunt placement should be offered in selected instances, as it increases perinatal survival of fetuses with LUTO.