Multivariate and regional age-related change in basal ganglia iron in neonates.

In the perinatal period, reward and cognitive systems begin trajectories, influencing later psychiatric risk. The basal ganglia is important for reward and cognitive processing but early development has not been fully characterized. To assess age-related development, we used a measure of basal ganglia physiology, specifically brain tissue iron, obtained from nT2* signal in resting-state functional magnetic resonance imaging (rsfMRI), associated with dopaminergic processing. We used data from the Developing Human Connectome Project (n = 464) to assess how moving from the prenatal to the postnatal environment affects rsfMRI nT2*, modeling gestational and postnatal age separately for basal ganglia subregions in linear models. We did not find associations with tissue iron and gestational age [range: 24.29-42.29] but found positive associations with postnatal age [range:0-17.14] in the pallidum and putamen, but not the caudate. We tested if there was an interaction between preterm birth and postnatal age, finding early preterm infants (GA < 35 wk) had higher iron levels and changed less over time. To assess multivariate change, we used support vector regression to predict age from voxel-wise-nT2* maps. We could predict postnatal but not gestational age when maps were residualized for the other age term. This provides evidence subregions differentially change with postnatal experience and preterm birth may disrupt trajectories.

The effect of preterm birth on thalamic development based on shape and structural covariance analysis.

Acting as a central hub in regulating brain functions, the thalamus plays a pivotal role in controlling high-order brain functions. Considering the impact of preterm birth on infant brain development, traditional studies focused on the overall development of thalamus other than its subregions. In this study, we compared the volumetric growth and shape development of the thalamic hemispheres between the infants born preterm and full-term (Left volume: P = 0.027, Left normalized volume: P < 0.0001; Right volume: P = 0.070, Right normalized volume: P < 0.0001). The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus exhibit higher vulnerability to alterations induced by preterm birth. The structural covariance (SC) between the thickness of thalamus and insula in preterm infants (Left: corrected P = 0.0091, Right: corrected P = 0.0119) showed significant increase as compared to full-term controls. Current findings suggest that preterm birth affects the development of the thalamus and has differential effects on its subregions. The ventral nucleus region, dorsomedial nucleus region, and posterior nucleus region of the thalamus are more susceptible to the impacts of preterm birth.

Brain templates for Chinese babies from newborn to three months of age.

The infant brain develops rapidly and this area of research has great clinical implications. Neurodevelopmental disorders such as autism and developmental delay have their origins, potentially, in abnormal early brain maturation. Searching for potential early neural markers requires a priori knowledge about infant brain development and anatomy. One of the most common methods of characterizing brain features requires normalization of individual images into a standard stereotactic space and conduct of group-based analyses in this space. A population representative brain template is critical for these population-based studies. Little research is available on constructing brain templates for typical developing Chinese infants. In the present work, a total of 120 babies from 5 to 89 days of age were included with high resolution structural magnetic resonance imaging scans. T1-weighted and T2-weighted templates were constructed using an unbiased registration approach for babies from newborn to 3 months of age. Age-specific templates were also estimated for babies aged at 0, 1, 2 and 3 months old. Then we conducted a series of evaluations and statistical analyses over whole tissue segmentations and brain parcellations. Compared to the use of population mismatched templates, using our established templates resulted in lower deformation energy to transform individual images into the template space and produced a smaller registration error, i.e., smaller standard deviation of the registered images. Significant volumetric growth was observed across total brain tissues and most of the brain regions within the first three months of age. The total brain tissues exhibited larger volumes in baby boys compared to baby girls. To the best of our knowledge, this is the first study focusing on the construction of Chinese infant brain templates. These templates can be used for investigating birth related conditions such as preterm birth, detecting neural biomarkers for neurological and neurodevelopmental disorders in Chinese populations, and exploring genetic and cultural effects on the brain.

Intrauterine inflammation and postnatal intravenous dopamine alter the neurovascular unit in preterm newborn lambs.

BACKGROUND: Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses. METHODS: At 119-120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPSDA, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTLDA, n = 7). Post-mortem brain tissue was collected 3-4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit. RESULTS: LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte "end feet" vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS. CONCLUSION: LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.

Histological chorioamnionitis and pathological stages on very preterm infant outcomes.

AIMS: Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. METHODS: Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. RESULTS: The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). CONCLUSIONS: Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.

Brain MRI findings and their association with visual impairment in young adolescents born very preterm.

PURPOSE: Very preterm birth increases risk for neonatal white matter injury, but there is limited data on to what extent this persists into adolescence and how this relates to ophthalmological outcomes. The aim of this study was to assess brain MRI findings in 12-year-old children born very preterm compared to controls and their association with concurrent ophthalmological outcomes. METHODS: We included 47 children born very preterm and 22 full-term controls (gestational age <32 and >37 weeks, respectively). Brain MRI findings were studied in association with concurrent ophthalmological outcomes at 12-year follow-up. RESULTS: Evans index (0.27 vs 0.25, p<0.001) and a proposed "posterior ventricle index" (0.47 vs 0.45, p=0.018) were increased in children born very preterm. Higher gestational age associated with larger corpus callosum area (ß=10.7, 95%CI 0.59-20.8). Focal white matter lesions were observed in 15 (32%) of very preterm children and in 1 (5%) of full-term controls. Increased posterior ventricle index increased risk for visual acuity ≤1.0 (OR=1.07×1011, 95%CI=7.78-1.48×1021) and contrast sensitivity <0.5 (OR=2.6×1027, 95%CI=1.9×108-3.5×1046). Decreased peritrigonal white matter thickness associated with impaired visual acuity (ß=0.04, 95%CI 0.002-0.07). CONCLUSION: More white matter lesions and evidence of lower white matter volume were found in children born very preterm compared with full-term controls at 12-year follow-up. The association between larger posterior ventricle index and reduced visual acuity and contrast sensitivity suggests disturbances of the posterior visual pathway due to diffuse white matter lesions.

Clinical and Histological Associations of Chronic Inflammatory Lesions in Preterm Placentas: Uncovering the Hidden Dangers.

BACKGROUND: Chronic placental inflammatory lesions (CPIL) include chronic deciduitis (CD), villitis of unknown etiology (VUE), and chronic chorioamnionitis (CCA). The frequency of these lesions and their relationship with various clinicopathological parameters in preterm birth (PTB) is presented. MATERIAL AND METHODS: Preterm placentas from April 2018 to December 2020 were reviewed for presence of CPIL. PTB was classified as spontaneous, indicated, or mixed phenotype. The association of CPIL with clinical parameters like gestational age, birth weight, obstetric complications, and placental parameters like placental dimensions, weight, vascular malperfusion, acute inflammatory lesions, and basal plate myometrial fibers were analyzed. RESULTS: The study included 538 preterm placentas with 54.3% from indicated PTB. CD was more common (28.4%) than VUE (17.8%) and CCA (12.6%). CD showed significant association with VUE and CCA (both P = .0001) and VUE with CCA (P = .0001). CD was more common in indicated PTB (33.8%, P = .002) and associated with lower birth weight (1591 g vs 1705 g, P = .003), lower placental weight (270.7 g vs 296.9 g, P = .004), length (14.2 cm vs 14.8 cm, P = .006), breadth (11.7 cm vs 12.2 cm, P = .007), maternal vascular malperfusion (P = .004), and basal plate myometrial fibers (P = .02). High-grade and multifocal low-grade VUE was associated with reduced placental length (13.9 cm vs 14.6 cm, P = .02)and breadth (11.5 cm vs 12.1 cm, P = .01). CCA did not show any other association. CONCLUSION: CPIL are common in PTB and their coexistence suggested a common pathogenic mechanism. Placental examination is the only definite way to identify as they lack clinical signs and symptoms. The smaller placental size associated with these lesions may suggest alter mechanisms for adverse pregnancy outcomes.

Ultrastructural Features of Left Ventricle Cardiomyocytes in Preterm Newborn Rats.

The structure of left ventricular cardiomyocytes of 1 day preterm newborn rats was studied using transmission electron microscopy. It was shown that the relative area of the nucleus in cardiomyocytes of preterm rats is lower, and the relative area of the cytoplasm is higher than in full-term rats, while the relative areas of myofibrils and mitochondria do not differ. In cardiomyocytes of preterm rats damaged mitochondria, subsegmental myofibrillar contracture, and cytoplasmic swelling were found on the first postnatal day. Preterm birth in rats, in contrast to birth at term, is accompanied by the development of a number of ultrastructural damages in cardiomyocytes.

MRI-visible Perivascular Spaces in the Neonatal Brain.

Background Mounting evidence suggests that perivascular spaces (PVSs) visible at MRI reflect the function of the glymphatic system. Understanding PVS burden in neonates may guide research on early glymphatic-related pathologic abnormalities. Purpose To perform a visual and volumetric evaluation of PVSs that are visible at MRI in neonates and to evaluate potential associations with maturation, sex, and preterm birth. Materials and Methods In this retrospective study, T2-weighted brain MRI scans in neonates from the Developing Human Connectome Project were used for visual grading (grades 0-4) of PVSs in the basal ganglia (BG) and white matter (WM) and for volumetric analysis of BG PVSs. The BG PVS fraction was obtained by dividing the BG PVS volume by the deep gray matter volume. The association between postmenstrual age at MRI and BG PVS burden was evaluated using linear regression. PVS burden was compared according to sex and preterm birth using the Mann-Whitney test. Results A total of 244 neonates were evaluated (median gestational age at birth, 39 weeks; IQR, 6 weeks; 145 male neonates; 59%), including 88 preterm neonates (median gestational age at birth, 33 weeks; IQR, 6 weeks; 53 male neonates; 60%) and 156 term neonates (median gestational age at birth, 40 weeks; IQR, 2 weeks; 92 male neonates; 59%). For BG PVSs, all neonates showed either grade 0 (90 of 244; 37%) or grade 1 (154 of 244; 63%), and for WM PVSs, most neonates showed grade 0 (227 of 244; 93%). The BG PVS fraction demonstrated a negative relationship with postmenstrual age at MRI (r = -0.008; P < .001). No evidence of differences was found between the sexes for BG PVS volume (P = .07) or BG PVS fraction (P = .28). The BG PVS volume was smaller in preterm neonates than in term neonates (median, 45.3 mm3 [IQR, 15.2 mm3] vs 49.9 mm3 [IQR, 21.3 mm3], respectively; P = .04). Conclusion The fraction of perivascular spaces (PVSs) in the basal ganglia (BG) was lower with higher postmenstrual age at MRI. Preterm birth affected the volume of PVSs in the BG, but sex did not. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Huisman in this issue.

Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries.

Approximately 15 million babies are born prematurely every year and many will face lifetime motor and/or cognitive deficits. Children born prematurely are at higher risk of developing perinatal brain lesions, especially white matter injuries (WMI). Evidence in humans and rodents demonstrates that systemic inflammation-induced neuroinflammation, including microglial and astrocyte reactivity, is the prominent processes of WMI associated with preterm birth. Thus, a new challenge in the field of perinatal brain injuries is to develop new neuroprotective strategies to target neuroinflammation to prevent WMI. Serotonin (5-HT) and its receptors play an important role in inflammation, and emerging evidence indicates that 5-HT may regulate brain inflammation by the modulation of microglial reactivity and astrocyte functions. The present study is based on a mouse model of WMI induced by intraperitoneal (i.p.) injections of IL-1ß during the first 5 days of life. In this model, certain key lesions of preterm brain injuries can be summarized by (i) systemic inflammation, (ii) pro-inflammatory microglial and astrocyte activation, and (iii) inhibition of oligodendrocyte maturation, leading to hypomyelination. We demonstrate that Htr7 mRNA (coding for the HTR7/5-HT7 receptor) is significantly overexpressed in the anterior cortex of IL-1ß-exposed animals, suggesting it as a potential therapeutic target. LP-211 is a specific high-affinity HTR7 agonist that crosses the blood-brain barrier (BBB). When co-injected with IL-1ß, LP-211 treatment prevented glial reactivity, the down-regulation of myelin-associated proteins, and the apparition of anxiety-like phenotypes. Thus, HTR7 may represent an innovative therapeutic target to protect the developing brain from preterm brain injuries.

Abnormal Microscopic Findings in the Placenta Correlate With the Severity of Fetal Heart Failure.

BACKGROUND: This study investigated the association between placental pathology and fetal heart failure.Methods and Results: Singletons with a congenital heart defect (CHD) and/or arrhythmia (n=168) and gestational age-matched controls (n=52) were included in the study. The associations between macro- and microscopic abnormal findings of the placenta and the severity of fetal heart failure were evaluated using the cardiovascular profile (CVP) score. Nine features were microscopically identified and assessed in sections of the placenta: premature villi, edematous villi, fibrotic villi, chorioamnionitis, chorangiosis, fibrin deposition, subchorionic hematoma, infarcted villi, and nucleated red blood cells in villous vessels. Among singletons with CHD and/or arrhythmia, the final CVP score was ≥8 in 140 cases, 6 or 7 in 15 cases, and ≤5 in 13 cases. Microscopic analysis showed that the frequency and severity of premature and edematous villi and increased nucleated red blood cells in villous vessels were greater in cases of fetal heart failure. These microscopic findings were more common and severe in cases with a final CVP score ≤5 than in gestational age-matched controls. The prevalence of abnormal macroscopic findings of the placenta and umbilical cord was similar regardless of the severity of fetal heart failure. CONCLUSIONS: Premature and edematous villi and increased nucleated red blood cells in villous vessels were correlated with the severity of fetal heart failure in cases of CHD and/or arrhythmia.

Placental inflammation and pregnancy outcomes: A prospective, observational study in South Asia: The PURPOSe study.

OBJECTIVE: To examine inflammatory lesions in placentas of stillbirths, preterm neonatal deaths and term controls in India and Pakistan. DESIGN: Prospective, observational study. SETTING: Three hospitals in India and a large maternity hospital in Pakistan. POPULATION: The enrolled participants with placentas available for histology evaluation included stillbirths (n = 814), preterm live births who died within 28 days of birth (n = 618) and term live birth controls (n = 201). From this same population, polymerase chain reaction (PCR) analysis for pathogens was performed on 809 stillbirth placentas, 614 neonatal death placentas and the placentas of 201 term controls. Placentas from preterm infants who lived beyond day 28 (n = 1432) were only available from India. METHODS: A prospective observational study of placental inflammatory lesions defined by the Amsterdam criteria and on the same placentas, multiplex PCR evaluation for 75 pathogens using TaqMan Array Cards. MAIN OUTCOME MEASURES: Any placental inflammatory lesions, including chorioamnionitis, funisitis, villitis and intervillitis and their association with various pathogens. RESULTS: In the Indian liveborn preterm infants, placental inflammation of any kind was present in 26.2% of those who died versus 16.6% of those who lived (p = 0.0002). Chorioamnionitis was present in 25.8% of those who died versus 16.3% of those who lived (p = 0.0002) and funisitis was present in 4.1% of those who died versus 1.5% of those who lived, (p = 0.005). Across all three sites, in the placentas of the 201 term controls, 18.9% had any inflammation, 16.9% had chorioamnionitis, 5.5% had funisitis, 0.5% had intervillitis and none had villitis. Overall, for stillbirths, any inflammation was observed in 30.2%, chorioamnionitis in 26.9%, funisitis in 5.7%, intervillitis in 6.0% and villitis in 2.2%. For the neonatal deaths, any inflammation was present in 24.9%, chorioamnionitis in 23.3%, funisitis in 8.1%, intervillitis in 1.9% and villitis in 0.5%. Compared with the placentas of term controls, in neonatal deaths, only chorioamnionitis was significantly increased (23.3% versus 16.9%, p = 0.05). Among stillbirths, the rates of any inflammation, chorioamnionitis, intervillitis and villitis were similar across the birthweight groups. However, funisitis was more common in the placentas of stillborn fetuses weighing 2500 g or more (13.8%) compared with 1.0% for those weighing less than 1000 g and 4.8% for stillborn fetuses weighing 1000-2499 g. In the PCR studies, Ureaplasma spp. were by far the most common pathogens found and generally were more commonly found in association with inflammatory lesions. CONCLUSIONS: Chorioamnionitis was the most common type of placental inflammatory lesion regardless of whether the placentas evaluated were from term controls, stillbirths or neonatal deaths. For stillbirths, inflammation in each inflammation category was more common than in the term controls and significantly more so for any inflammation, chorioamnionitis, intervillitis and villitis. For neonatal deaths, compared with the placentas of term controls, all inflammation categories were more common, but only significantly so for chorioamnionitis. Ureaplasma spp. were the most common organisms found in the placentas and were significantly associated with inflammation.

Morphological study of the placenta in deliveries with pre-eclampsia: Results from a prospective, observational study in India and Pakistan (PURPOSe).

OBJECTIVE: To compare placental findings in women with and without pre-eclampsia. DESIGN: The PURPOSe study included women with stillbirths, women with preterm births and women at term as controls. The placenta of each case was evaluated using the Amsterdam criteria. SETTING: Two sites and five tertiary care hospitals of south Asia (Three in India and two in Pakistan). POPULATION: Pregnancies in India and Pakistan with placental histology including women with documented hypertension and documented proteinuria and women with neither hypertension nor proteinuria. METHODS: We compared the placental findings of the two groups using the Amsterdam criteria and further evaluated the placental findings in women with and without pre-eclampsia who had a stillbirth, preterm live birth, or term live birth (control). MAIN OUTCOME MEASURES: The main outcome measures were the frequency of maternal and fetal vascular malperfusion and the frequency of placental inflammation and its components, chorioamnionitis, funisitis, villitis and intervillitis in women with and without pre-eclampsia. RESULTS: A total of 733 women had pre-eclampsia and 2334 women had neither hypertension nor proteinuria. In the placentas of women with pre-eclampsia, 57.3% had maternal vascular malperfusion compared with 37.1% in women without pre-eclampsia (p < 0.0001). There was not a significant difference in the prevalence of fetal vascular hypertension between mothers with (17.1%) and without (14.8%, p = 0.6118) pre-eclampsia. When placentas were classified as 'histologically normal' or not, 61.3% of those from pre-eclamptic pregnancies were classified as abnormal, whereas if there was no pre-eclampsia, only 45.0% were classified as histologically abnormal (p < 0.0001). We also considered rates of placental maternal vascular malperfusion in women with and without pre-eclampsia with stillbirth, preterm neonatal death, and term live birth. In women at term with no pre-eclampsia, 16.7% of the placentas had features of maternal vascular malperfusion. This occurred in 79.9% of women with stillbirths with pre-eclampsia compared with 51.8% of those without pre-eclampsia. Maternal vascular malperfusion was present in 49.7% of preterm live births with pre-eclampsia compared with 33.8% without pre-eclampsia. We also evaluated the inflammatory lesions by whether the mother had or did not have pre-eclampsia. When all inflammatory lesions were considered, women with pre-eclampsia had significantly fewer inflammatory lesions than those women without pre-eclampsia (17.1% versus 23.6% p = 0.001). Each of the specific inflammatory lesions was less common in placentas of women with pre-eclampsia than those with chorioamnionitis (16.1% versus 21.9%, p = 0.004) and funisitis (1.5% versus. 5.1%, p = 0.0004). CONCLUSIONS: Of placental lesions in women with pre-eclampsia, maternal vascular malperfusion was the most common. Inflammatory lesions were less common in women with pre-eclampsia.

Endometrial and placental stem cells in successful and pathological pregnancies.

The endometrium is a dynamic tissue that undergoes extensive remodeling during the menstrual cycle and further gets modified during pregnancy. Different kinds of stem cells are reported in the endometrium. These include epithelial stem cells, endometrial mesenchymal stem cells, side population stem cells, and very small embryonic-like stem cells. Stem cells are also reported in the placenta which includes trophoblast stem cells, side population trophoblast stem cells, and placental mesenchymal stem cells. The endometrial and placental stem cells play a pivotal role in endometrial remodeling and placental vasculogenesis during pregnancy. The dysregulation of stem cell function is reported in various pregnancy complications like preeclampsia, fetal growth restriction, and preterm birth. However, the mechanisms by which it does so are yet elusive. Herein, we review the current knowledge of the different type of stem cells involved in pregnancy initiation and also highlight how their improper functionality leads to pathological pregnancy.

Can amniotic fluid protect developing fetal lungs against the harmful effects of oxidative stress?

BACKGROUND: Preterm births cause fetuses to be born without completing the development of their organs. Due to this undesirable situation, it is the pulmonary tissue which has to be most exposed to harmful effects of extrauterine environment. Early disappearance of the prophylactic and constructive effects of amniotic fluid (AF) on developing tissues, such as pulmonary tissue, facilitates the formation of pulmonary morbidities resulting from oxygen. Setting out from this knowledge, we wanted, in addition to assessing the beneficent effects of AF on pulmonary tissue, to study the importance of AF in morbidities of this tissue thought to originate from oxygen. METHODS: In this experimental study, while the study group was made up of the fetuses of pregnant rats exposed to hyperbaric oxygen, (hyperoxic pregnant rat fetuses-HPRF), the control group was formed of the fetuses of the rats pregnant in the usual room setting (normoxic pregnant rat fetuses-NPRF). The pulmonary and hepatic tissues taken from the fetuses of these pregnant rats on the 21st day of their pregnancy were compared biochemically and histologically. For biochemical assessment, total glutathione (tGSH), catalase (CAT), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) values and for histopathological assessment, apoptosis, alveolar wall count (AWC), vena centralis count (VCC) were included. RESULTS: Statistical significance was found in the pulmonary tissue values of tGSH on behalf of NPRF, and MDA on behalf of HPRF (p < 0.05). In liver tissue, statistical significance was detected in tGSH and CAT values in favor of NPRF and in MDA, and TNF-α values in favor of HPRF (p < 0.05). DISCUSSION: : Our study has demonstrated that AF protects the pulmonary tissue from the harmful effects of oxygen in the intrauterine period. In addition, our data have suggested that the pulmonary tissue's being deprived of the useful effects of AF owing to premature birth may be an important trigger in the occurrence of the pulmonary morbidities thought to result from oxygen.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Chronic Deciduitis With Plasma Cells: A Quantitative and Clinicopathological Analysis Concerning Different Trimesters.

Background: Chronic deciduitis is a chronic inflammatory placental disease. It is associated with severe perinatal complications, especially recurrent miscarriage, preterm birth, preterm labor, and preterm prelabor rupture of membranes.Methods: This study presents a detailed quantification of plasma cells and lymphocytes, and regards clinicopathological associations concerning different trimesters in 99 cases displaying chronic deciduitis with plasma cells (CD), 23 cases from the second trimester and 76 cases from the third trimester, respectively. The control group without CD consisted of matched placentas concerning the gestational weeks.Results: In every instance lymphocytes were more numerous than plasma cells. The mean value/highest score in ten high power fields were 50/321 for plasma cells, and 460/995 for lymphocytes, respectively. In the second trimester the scores for plasma cells were significantly higher than in the third trimester. In the third trimester preterm labor occurred significantly more often in cases with chronic deciduitis related to the control group (P < .05).Conclusion: In chronic deciduitis the plasma cell count is usually higher in the second compared to the third trimester. A brisk infiltration of the decidua with plasma cells could probably point to a more severe clinical manifestation and a higher risk for preterm labor and preterm birth.

Fetoplacental pathology of equine abortion, premature birth, and neonatal loss due to Chlamydia psittaci.

This report describes the fetoplacental pathology of Chlamydia psittaci-associated abortion, premature birth, and neonatal loss in 46 of 442 equine abortion investigations between 2015 and 2019. Seven abortions, 26 premature births, and 13 neonatal deaths with positive C. psittaci polymerase chain reaction (PCR) were evaluated. In 83% of cases (38/46), C. psittaci infection was considered as the primary cause of loss based on quantitative PCR (qPCR) confirmation, pathological findings, and exclusion of other causes, and was supported by Chlamydia spp immunolabeling in fetoplacental lesions. Lymphohistiocytic placentitis with vasculitis (36/38) affected the amnion, umbilical cord, and chorioallantois at the umbilical vessel insertion and/or cervical pole. Lymphohistiocytic chorionitis in the subvillous stroma extended to the allantois mostly without villous destruction. Lymphohistiocytic amnionitis and funisitis occurred at the amniotic cord attachment. Lymphohistiocytic hepatitis was observed in 19/38 cases and pneumonia was identified in 26 cases. Chlamydia spp immunolabeled in placenta, lung, liver, or splenic tissue in the cases that were tested (14/38). C. psittaci infection was not the cause of loss in 2 cases with other diseases and of uncertain significance in 6 cases with no conclusive cause of loss. immunohistochemistry (IHC) was negative for 6 of these cases (6/8). The highest Chlamydia load was detected in pooled placental tissues by qPCR. qPCR and IHC had 83% congruence at a qPCR cut-off of 1 gene copy. IHC limits of detection corresponded to infections with 2 × 102 gene copies identified by qPCR. This study confirms the etiological role of C. psittaci as a cause of naturally occurring equine reproductive loss.

Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2.

Spontaneous preterm birth (SPTB) is the leading cause of neonatal death and morbidity worldwide. Both maternal and fetal genetic factors likely contribute to SPTB. We performed a genome-wide association study (GWAS) on a population of Finnish origin that included 247 infants with SPTB (gestational age [GA] < 36 weeks) and 419 term controls (GA 38-41 weeks). The strongest signal came within the gene encoding slit guidance ligand 2 (SLIT2; rs116461311, minor allele frequency 0.05, p = 1.6×10-6). Pathway analysis revealed the top-ranking pathway was axon guidance, which includes SLIT2. In 172 very preterm-born infants (GA <32 weeks), rs116461311 was clearly overrepresented (odds ratio 4.06, p = 1.55×10-7). SLIT2 variants were associated with SPTB in another European population that comprised 260 very preterm infants and 9,630 controls. To gain functional insight, we used immunohistochemistry to visualize SLIT2 and its receptor ROBO1 in placentas from spontaneous preterm and term births. Both SLIT2 and ROBO1 were located in villous and decidual trophoblasts of embryonic origin. Based on qRT-PCR, the mRNA levels of SLIT2 and ROBO1 were higher in the basal plate of SPTB placentas compared to those from term or elective preterm deliveries. In addition, in spontaneous term and preterm births, placental SLIT2 expression was correlated with variations in fetal growth. Knockdown of ROBO1 in trophoblast-derived HTR8/SVneo cells by siRNA indicated that it regulate expression of several pregnancy-specific beta-1-glycoprotein (PSG) genes and genes involved in inflammation. Our results show that the fetal SLIT2 variant and both SLIT2 and ROBO1 expression in placenta and trophoblast cells may be correlated with susceptibility to SPTB. SLIT2-ROBO1 signaling was linked with regulation of genes involved in inflammation, PSG genes, decidualization and fetal growth. We propose that this receptor-ligand couple is a component of the signaling network that promotes SPTB.

Maternal Marijuana Exposure, Feto-Placental Weight Ratio, and Placental Histology.

OBJECTIVE: Marijuana use is associated with placenta-mediated adverse pregnancy outcomes including fetal growth restriction, but the mechanism remains uncertain. The objective was to evaluate the association between maternal marijuana use and the feto-placental weight ratio (FPR). Secondarily, we aimed to compare placental histology of women who used marijuana to those who did not. STUDY DESIGN: This was a secondary analysis of singleton pregnancies enrolled in a multicenter and case-control stillbirth study. Prior marijuana use was detected by electronic medical record abstraction or cord homogenate positive for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Prior tobacco use was detected by self-report or presence of maternal serum cotinine. Stillbirths and live births were considered separately. The primary outcome was FPR. Association of marijuana use with FPR was estimated with multivariable linear modeling adjusted for fetal sex, preterm birth, and tobacco use. Comparisons between groups for placental histology were made using Chi-square and stratified by live birth and stillbirth, term and preterm deliveries, and fetal sex. RESULTS: Of 1,027 participants, 224 were stillbirths and 803 were live births. Overall, 41 (4%) women used marijuana during the pregnancy. The FPR ratio was lower among exposed offspring but reached statistical significance only for term stillbirths (mean 6.84 with marijuana use vs. mean 7.8 without use, p < 0.001). In multivariable modeling, marijuana use was not significantly associated with FPR (p = 0.09). There were no differences in histologic placental features among those with and without marijuana use overall or in stratified analyses. CONCLUSION: Exposure to marijuana may not be associated with FPR. Similarly, there were no placental histologic features associated with marijuana exposure. Further study of the influence of maternal marijuana use on placental development and function is warranted to better understand the association between prenatal marijuana use and poor fetal growth. KEY POINTS: · Maternal marijuana exposure was not associated with the feto-placental weight ratio.. · Marijuana exposure was not associated with differences in placental histology.. · Concerning trend toward lower feto-placental weight ratios among marijuana-exposed stillbirths..