Cord Blood Cytokine Research Articles

Cord blood cytokine profiles in children later diagnosed with autism spectrum disorder: Results from the prospective MARBLES study

In studies investigating the etiology and pathophysiology of autism spectrum disorder (ASD), immune dysregulation is commonly observed, with elevated levels of inflammatory cytokines frequently found in gestational tissues. However, studies investigating the relationship between early immune dysregulation within the umbilical cord blood (CB) compartment and neurodevelopmental outcomes remains limited. In this exploratory study, we utilized data from the prospective Markers for Autism Risk in Babies – Learning Early Signs (MARBLES) study to examine cytokine levels in the plasma fraction of CB in infants later diagnosed with ASD (n = 38) compared to infants typically developing (TD) at age 3 years (n = 103), using multiplex cytokine assays. Our findings reveal altered levels of several inflammatory cytokines in children later diagnosed with ASD, including increased granulocyte colony-stimulating factor (G-CSF) and decreased interleukin-1α (IL-1α), IL-1β, and IL-4 in CB. Furthermore, we identified several associations between behaviors and levels of cytokines, chemokines and growth factors. IL-1α, IL-17A, interferon γ-induced protein 10 (IP-10), and epidermal growth factor (EGF) were associated with worse scores on Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) assessments. In summary, our study demonstrates dysregulated levels of inflammatory cytokine mediators in the CB of children later diagnosed with ASD and that inflammatory mediators were associated with ASD severity, comorbid behaviors, and neurodevelopmental measures. These findings have important implications for the possible predictive value of early cytokine measures in neurodevelopmental outcomes and subsequent behavioral manifestations.

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion

BackgroundEvidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. ObjectiveWe evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. MethodsWe measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269–314) and cytokine secretion (n = 217–302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. ResultsEach ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (−45.1, −4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. ConclusionsPrenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.

Vertical Transmission of SARS-CoV-2-Specific Antibodies and Cytokine Profiles in Pregnancy.

Despite intensive characterization of immune responses after COVID-19 infection and vaccination, research examining protective correlates of vertical transmission in pregnancy are limited. Herein, we profiled humoral and cellular characteristics in pregnant women infected or vaccinated at different trimesters and in their corresponding newborns. We noted a significant correlation between spike S1-specific IgG antibody and its RBD-ACE2 blocking activity (receptor-binding domain-human angiotensin-converting enzyme 2) in maternal and cord plasma (P < .001, R > 0.90). Blocking activity of spike S1-specific IgG was significantly higher in pregnant women infected during the third trimester than the first and second trimesters. Elevated levels of 28 cytokines/chemokines, mainly proinflammatory, were noted in maternal plasma with infection at delivery, while cord plasma with maternal infection 2 weeks before delivery exhibited the emergence of anti-inflammatory cytokines. Our data support vertical transmission of protective SARS-CoV-2-specific antibodies. This vertical antibody transmission and the presence of anti-inflammatory cytokines in cord blood may offset adverse outcomes of inflammation in exposed newborns.

Cord blood granulocyte Colony-Stimulating factor level as an optimal predictor of umbilical cord arteritis associated with brain injury at term equivalent age in preterm neonates

ObjectiveThe study aimed 1) to evaluate the association between the presence or absence of umbilical cord arteritis (UCA) and the cord blood cytokine levels, and 2) morbidity and mortality of preterm neonates; and 3) to identify predictive markers for UCA of preterm neonates. Study designIn this single-center retrospective observational cohort study, preterm neonates born at gestational age (GA) < 36 weeks were categorized pathologically according to the severity of intrauterine inflammation; those without UCA as Group 1, those with UCA as Group 2, and those without any intrauterine inflammation as Group 3 (control), and subgroup analyses classified by their GA were performed. We compared morbidity and mortality, and eight representative cytokine levels in cord blood samples between the groups. Subsequently, receiver operating characteristics (ROC) curves for UCA diagnosis for each cytokine were created, and values of areas under the curve (AUC) were calculated to determine the optimal predictive markers. ResultsIn total, 105 patients (36, 58, and 11 in Groups 1, 2, and 3, respectively) were included. Multivariate logistic analysis revealed that patients with UCA had higher incidence of brain injury (Odds Ratio [OR] = 8.53, P = 0.0049, 95% Confidence Interval [CI]: 1.91 – 38.0), at term equivalent age in the subgroup analysis with GA < 32 weeks. Although the median value of cord blood granulocyte colony-stimulating factor (G-CSF) was significantly higher in Group 2 than in Group 1 or 3, only the G-CSF level was found to be high in the subgroup analysis with GA < 32 weeks. For UCA diagnosis, the AUC values of G-CSF were the highest among eight cytokines including interleukin 6 (IL-6). These findings were similar in the subgroup analysis with GA < 32 weeks. ConclusionsPreterm neonates, especially born at GA < 32 week, had higher morbidity from brain injury in the group with UCA. The cord blood G-CSF level was highly accurate for predicting UCA and could thus be used as an optimal biomarker.

Association of prenatal obesity and cord blood cytokine levels with allergic diseases in children: A 10-year follow-up cohort study

Background and aimAlthough studies have associated elevated prenatal obesity with increased risk of various diseases in offspring, little is known regarding the immune system. The aim of this study was to evaluate the relationship between prenatal obesity and levels of cytokines in umbilical cord blood and development of allergic disease during the first 10 years of life in an offspring. MethodsA cohort of term infants born at the ShaoXing Women and Children Hospitals in China in 2011 was enrolled in this study. Flow cytometry was performed to measure levels of various cord blood cytokines, namely IL1β, IL2, IL10, IL6, IL8, IL17, IL12, TNF-α and IFN-γ. Next, logistic regression was used to explore the association of prenatal BMI with the development of allergic disease. The relationship between levels of each cord blood cytokine with prenatal BMI, and allergic disease development was tested using linear and logistic regression analyses, respectively. ResultsAfter 10 years of follow-up, higher prenatal BMI was significantly associated with development of allergic disease in children (HR = 2.45, 95% CI:1.08–5.57, P = 0.033). We also adjusted for maternal age, education and infant gender, and found that prenatal BMI was significantly associated with higher levels of IL12 (P = 0.023) and IL1β (P = 0.049) in cord blood. Moreover, we adjusted for maternal age, education, allergic dermatitis, gestation age and infant gender, and found that increase in each unit (1.26 pg/ml) in IL17 was associated with a 55.5% higher risk of allergic disease in 10-year-old children (HR = 1.55, 95%Cl: 0.99–2.45, P = 0.056). Meanwhile, after adjusting for maternal age, education level, gestation age, prenatal BMI, gestational weight gain, infant gender and birthweight, we found that for every unit increase in IL10, IL6 and IL1β, the risk of overweight/obesity in children after 10-year follow-up increased by 18.7% (HR = 1.19, 95%Cl: 1.01–1.40, P = 0.042), 13.9% (HR = 1.14, 95%Cl: 1.02–1.27, P = 0.021) and 41.3% (HR = 1.41, 95%Cl: 1.02–1.95, P = 0.036), respectively. ConclusionsPrenatal obesity was positively correlated with allergic diseases in offspring. Cord blood cytokine may play mediating roles in the associations of prenatal obesity with offspring allergic diseases.

Maternal imprinting and determinants of neonates' immune function in the SEPAGES mother-child cohort.

Immune function in pregnancy is influenced by host-specific and environmental factors. This may impact fetal immune development, but the link between maternal and neonatal immune function is still poorly characterized. Here, we investigate the relationship between maternal and neonatal immune function, and identify factors affecting the association between maternal and child cytokine secretion. In the French prospective cohort SEPAGES, blood samples were obtained from pregnant women (n=322) at gestational week 20 ± 4 and from their child at birth (n=156). Maternal and cord blood cytokine and chemokine (CK) levels were measured at baseline in all subjects and after T cell or dendritic cell activation with phytohemagglutinin or R848 (in total 29 and 27 measures in maternal and cord blood samples, respectively). Associations between environmental, individual factors and CK level were estimated by linear regression modeling. The maternal-cord blood CK relations were assessed by Pearson correlation and regression models. We observed that pregnant women and neonates displayed specific CK secretion profiles in the innate and adaptive compartments at baseline and upon activation. Activation of T cells in cord blood induced high levels of IL-2, but low levels of IFNγ, IL-13 or IL-10, in comparison to maternal blood samples. Elsewhere, neonatal innate immune responses were characterized by low production of IFNα, while productions of IL-1β, IL-6, IL-8, IL-10 and TNFα were higher than maternal responses. Strong correlations were observed between most CK after activation in maternal and cord blood samples. Strikingly, a statistical association between global mother and child cytokine profiles was evidenced. Correlations were observed between some individual CK of pregnant women and their children, both at baseline (MCP1, RANTES) and after activation with R848 (IL-6, IL-8 and IL-10). We looked for factors which could influence cytokine secretion in maternal or cord blood, and found that leucocyte counts, maternal age, pre-conception BMI, smoking and season were associated with the levels of several CK in mothers or children. Our study reveals in utero immune imprinting influencing immune responses in infants, opening the way to investigate the mechanisms responsible for this imprinting. Whether such influences have long lasting effects on children health warrants further investigation.

Imbalanced Inflammatory Responses in Preterm and Term Cord Blood Monocytes and Expansion of the CD14+CD16+ Subset upon Toll-like Receptor Stimulation

Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes-except for lower IL-1β levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14+CD16+). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state.

Maternal plasma transforming growth factor-β1 (TGF-β1) and newborn size: the Araraquara Cohort Study

ObjectiveTo investigate associations of maternal and cord blood cytokine patterns with newborn size and body composition. MethodsThis cross-sectional study involved 70 pregnant women and their healthy newborns selected from the “Araraquara Cohort Study”. Newborn anthropometric measurements were recorded at birth. Body composition was evaluated by air displacement plethysmography. Maternal blood samples were collected from pregnant women between 30 and 36 weeks of gestation, and umbilical cord blood samples were collected immediately after placenta discharge. The concentrations of the cytokines were determined in plasma by ELISA. Multiple linear regression models were used to assess associations between maternal and cord blood cytokine concentrations and newborn anthropometry and body composition measurements. ResultsMaternal plasma TGF-β1 concentration was inversely associated with newborn weight (β = -43.0; p = 0.012), length (β = -0.16, p = 0.028), head circumference (β = -0.13, p = 0.004), ponderal index (β = -0.32, p = 0.011) and fat-free mass (β = -0.05, p = 0.005). However, the association persisted just for head circumference (β = -0.26; p = 0.030) and ponderal index (β = - 0.28; p = 0.028), after adjusting for pre-gestational BMI, gestational weight gain, gestational age, hours after delivery, newborn sex, smoking and alcohol consumption. ConclusionsMaternal plasma TGF-β1 concentration may be involved in the regulation of newborn size, mainly head circumference and ponderal index. Further cohort studies are necessary to investigate the role of TGF-β1 in different trimesters of pregnancy and its effect during the early stages of fetal development.

LB1534. Cord blood and maternal cytokine levels following SARS-CoV-2 infection during pregnancy

Abstract Background Pregnant people and fetuses are uniquely vulnerable to SARS-CoV-2, a driver of inflammation and immune dysregulation. Prior investigations have shown that pregnant people with SARS-CoV-2 are at higher risk of severe illness, mortality, and obstetric complications. We investigated the impact of SARS-CoV-2 infection severity and latency on maternal and infant cytokine levels. Methods We collected maternal blood and cord blood at delivery from mother-infant dyads (Chicago, IL; 3/2020-1/2022). A multiplex cytokine panel (IsoPlexis) was run on plasma from 93 SARS-CoV-2 infected dyads and 32 matched controls. Clinical data was abstracted by chart review, including latency (acute being ≤14 days and distant &amp;gt;14 days from SARS-CoV-2 infection to delivery) and severity (NIH criteria: asymptomatic, mild, moderate, severe/critical). Kruskal-Wallis tests with post-hoc pairwise Dunn Tests were used (α=0.05). Results SARS-CoV-2 exposed infants had lower levels of MIP-1b (p=0.037) and PDGF (p=0.008) than controls [Fig 1]. There were no differences in maternal blood cytokines at time of delivery following SARS-CoV-2 infection during pregnancy (pooled analysis of all SARS-CoV-2). Stratifying by latency, acutely exposed infants showed higher levels of MCP-1 than controls or those with distant maternal SARS-CoV-2 (p=0.016). There were no significant differences in maternal cytokines between control, acute, and distant SARS-CoV-2. In mothers with acute SARS-CoV-2, differences in levels of IL-1B (p=0.011) and IL-10 (p=0.046) were observed across severity groups, with a significant linear trend for each among severity groups (p for trend &amp;lt; 0.001, respectively). Severe/critical acute infection resulted in higher maternal granzyme and IL-8 than mild infection (p=0.037 and 0.047) [Fig 2]. There were no differences across severity groups in 1) mothers with distant infection, 2) infants with acute maternal infection, or 3) infants with distant maternal infection. Maternal and infant cytokine levels in acute SARS-CoV-2 infection across severity Conclusion Cytokine levels in SARS-CoV-2 positive dyads were altered only in the setting of acute or more severe infection and demonstrated anti-inflammatory, anti-viral, and anti-angiogenic responses. In acute infection, greater severity drives higher levels of both a pro- and anti-inflammatory cytokine in pregnant people. Disclosures All Authors: No reported disclosures.

The Association among Malaria in Pregnancy, Neonatal inflammation, and Neurocognitive Development in a Cohort of Malawian Infants.

Malaria in pregnancy (MIP) causes poor birth outcomes, but its impact on neurocognitive development has not been well characterized. Between 2012 and 2014, we enrolled 307 mother-infant pairs and monitored 286 infants for neurocognitive development using the Malawi Developmental Assessment Tool at 6, 12, and 24 months of age. MIP was diagnosed from peripheral blood and placental specimens. Cord blood cytokine levels were assessed for a subset of neonates. Predictors of neurodevelopment were examined using mixed-effect logistic regression for developmental delay. Among the participants, 78 mothers (25.4%) had MIP, and 45 infants (15.7%) experienced severe neurocognitive delay. MIP was not associated with differences in cord blood cytokine levels or neurocognitive development. Preterm birth, low birthweight, increasing maternal education level, and increasing interleukin 6 levels were associated significantly with delay. The results highlight the prevalence of severe delay and a need for broad access to early childhood support in this setting.

Cord blood immune profile: Associations with higher prenatal plastic chemical levels

Prenatal exposure to plastic chemicals has been associated with alterations to early-life immune function in children. However, previous studies have generally been small and focused on limited repertoires of immune indices. In a large population-based pre-birth cohort (n = 1074), third-trimester measurements of eight phthalate metabolites and three analogues of bisphenols were used to estimate prenatal exposure to phthalate and bisphenol compounds. In cord blood, immune cell populations were measured by flow cytometry and an extensive panel of cytokines and chemokines were measured by multiplex immunoassay. We used these cord blood analytes to estimate “early life” immune profiles. The full study sample comprises data from 774 infants with prenatal plastic metabolite measurements and any cord blood immune data. Multiple linear regression analysis was used to evaluate whether prenatal phthalate and bisphenol exposure was prospectively associated with cord blood immune cell populations and cytokine and chemokine levels. Generally, inverse associations were observed between prenatal phthalate exposure and cord blood immune indices. Higher exposure to di-n-butyl phthalate was associated with lower cord blood levels of platelet-derived growth factor (PDGF) and interferon gamma-induced protein 10 (IP-10); higher exposure to the sum of dibutyl phthalates was associated with lower cord blood levels of IP-10; and higher exposure to benzyl butyl phthalate was associated with lower cord blood levels of interleukin 1 beta (IL-1β). There was less evidence of associations between bisphenols and cord blood immune indices. These results extend previous work examining prenatal plastic chemical exposure and early-life immune development and highlight the importance of further examination of potential associations with health-related outcomes.

The Relationship Between Cord Blood Cytokine Levels and Perinatal Characteristics and Bronchopulmonary Dysplasia: A Case-Control Study.

ObjectiveTo establish the association between serial levels of inflammatory cytokines in cord blood and perinatal characteristics and bronchopulmonary dysplasia (BPD) in preterm infants.Methods147 premature infants with gestational age ≤32 weeks who were born and hospitalized in the First Affiliated Hospital of Zhengzhou University between July 2019 and August 2021 were enrolled in this retrospective case–control study. Multiple microsphere flow immunofluorescence was used to detect seven cytokines in cord blood collected within 24 h of birth. Demographics, delivery characteristics, maternal factors, neonatal characteristics, and clinical outcomes were collected for the two groups. An unconditional logistic regression model was used in this study to assess the clinical variables.ResultsIL-6 cord blood levels at birth were significantly higher in the BPD group than in the non-BPD group, but the odds ratio (OR) was very small (OR = 1). No differences in other cytokine concentrations were observed between the two groups. Multivariable logistic regression analysis demonstrated that increased maternal white blood cell (WBC) count on admission and lower birth weight increased the risk of BPD progression.ConclusionsIncreased IL-6 cord blood levels at birth in preterm infants may have trivial significance for predicting BPD. Furthermore, higher maternal WBC count on admission and lower birth weight increased the risk of BPD.

Associations Between Eczema and Attention Deficit Hyperactivity Disorder Symptoms in Children.

BackgroundEpidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined.ObjectiveWe aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pro-inflammatory cytokines and gut microbiome.MethodsThe modified International Study of Asthma and Allergies in Childhood questionnaire and Computerized Diagnostic Interview Schedule for Children Version IV were administered to assess reported eczema within the first 18 months and presence of ADHD symptoms at 54 months, respectively. Skin prick testing at 18 months, cytokines in maternal blood during pregnancy and cord blood and the mediating role of the gut microbiome at 24 months were assessed.ResultsAfter adjusting for confounders, eczema with or without a positive skin prick test was associated with doubling the risk of ADHD symptoms. No differences in maternal and cord blood cytokines were observed in children with and without eczema, or children with and without ADHD. Gut microbiome dysbiosis was observed in children with eczema and children with ADHD. Children with eczema also had lower gut bacterial Shannon diversity. However, the relationship between eczema and ADHD was not mediated by gut microbiome.ConclusionEarly life eczema diagnosis is associated with a higher risk of subsequent ADHD symptoms in children. We found no evidence for underlying inflammatory mechanism or mediation by gut microbiome dysbiosis. Further research should evaluate other mechanisms underlying the link between eczema and ADHD.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/NCT01174875], identifier [NCT01174875].

Association between Prenatal Obesity, Cord Blood Cytokine Levels and Children's Allergic Diseases in the 10-Year Follow-Up Cohort

Association between Prenatal Obesity, Cord Blood Cytokine Levels and Children's Allergic Diseases in the 10-Year Follow-Up Cohort

Inflammatory cytokines, placental pathology, and neurological outcomes in infants born to preterm preeclamptic mothers.

Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and neurological outcomes after preeclampsia are understudied. We prospectively examined a cohort of maternal-infant dyads with preeclampsia for maternal inflammatory cytokines at time of preeclampsia diagnosis and delivery, and fetal cord blood cytokines (IL-1β, IL-6, IL-8, and TNF-α). Placentas were analyzed for inflammatory and vascular pathologies. Neurodevelopmental assessment of infants utilizing the Pediatric Stroke Outcome Measure (PSOM) was conducted at 6-month corrected gestational age. Eighty-one maternal-newborn dyads were examined. Worse neurological outcomes were not associated with elevated maternal / fetal cytokines. Early preterm birth (gestational age ≤ 32 weeks) was associated with worse neurological outcomes at 6-months regardless of maternal/ fetal cytokine levels, placental pathology, or cranial ultrasound findings (OR 1.70, [1.16-2.48], p = 0.006). When correcting for gestational age, elevated IL-6 approached significance as a predictor for worse developmental outcome (OR 1.025 [0.985-1.066], p = 0.221). Pathological evidence of maternal malperfusion and worse outcomes were noted in early preterm, although our sample size was small. Our study did not demonstrate an obvious association of inflammation and placental pathology in preeclampsia and adverse neurodevelopmental outcome at 6-month corrected age but does suggest maternal malperfusion at earlier gestational age may be a risk factor for worse outcome.

Prenatal exposure to bisphenols, immune responses in cord blood and infantile eczema: A nested prospective cohort study in China

Increasing evidence shows that human exposure to bisphenols can increase the risk of allergic disease, such as child asthma. However, the mechanism by which exposure to bisphenols causes allergic disease is unclear. In addition, the effects of exposure to bisphenols during pregnancy on infantile eczema have been poorly studied. The aim of our study was to investigate the effect of bisphenols (BPA, BPF and BPS) exposure during pregnancy on immune cells in cord blood, and on the occurrence of infantile eczema. 111 mother-child pairs with urine samples from pregnant women and cord blood were recruited from a birth cohort established in February 2019 in Shenyang, China. The levels of urinary bisphenols and Th1-, Th2-, Treg- and Th17-related genes, and cytokines in cord blood, as well as the incidence of infantile eczema at 6 and 12 months follow up were determined. Our results show that BPA, BPF and BPS were detected in 100%, 63.1% and 46.8% of the urine samples, respectively. The median concentration of urine specific gravity adjusted BPA (SG-BPA) was 7.46 ng/mL. High SG-BPA levels during pregnancy was independently associated with increased risk of infantile eczema (adjusted OR = 2.731, 95%CI: 1.064–7.012, P = 0.037). Higher levels of FOXP3 gene in cord blood had a significantly lower risk of developing eczema in infants (adjusted OR=0.430, 95%CI: 0.190–0.972, P = 0.042). However, BPS and BPF levels were not associated with infantile eczema. FOXP3 gene levels in cord blood mediated the relationship between SG-BPA levels during pregnancy and infantile eczema (indirect effect: β = 0.350 [CI:0.011,1.077]). Our findings indicate that high levels of BPA exposure during pregnancy increase the risk of infantile eczema, which may be associated with down-regulation of FOXP3 gene expression in cord blood.

About the absence of the need to prescribe antibacterial therapy to newborns from mothers with clinical chorioamnionitis

Background. The diagnosis of a woman in labor chorioamnionitis (CA) implies a high risk of infectious complications for the mother and fetus, which determines the need for additional examination of infants and the decision on the appointment of antibacterial therapy. The purpouse of this study was determine the need to administration antibiotic therapy to full-term newborns from mothers diagnosed with chorioamnionitis. Materials and methods. 113 full-term newborns were examined, of which the main group consisted of children whose mothers were diagnosed with chorioamnionitis (n = 77), the comparison group children born to healthy mothers (n = 36). All children performed clinical and laboratory monitoring, including a clinical analysis of capillary blood in the first 24 hours of life; determination of the level of C-reactive protein (CRP) in venous blood on the 3rd day of life. Bacteriological examination of newborns included sampling of material from the ear fold, buccal mucosa, umbilical cord blood, as well as the contents of the tracheobronchial tree (TBD) during respiratory therapy with mechanical ventilation. Special research methods included studies of the proinflammatory cytokines (IL-1, IL-6) in umbilical cord blood. Histological CA was diagnosed in the presence of morphological and functional signs of inflammation in the placenta. Results. Newborns of the main group more often developed respiratory disorders requiring respiratory and oxygen therapy (p = 0,045). The production of IL-1, IL-6 in umbilical cord blood in the examined newborns of the main group was higher than in the comparison group [Odds Ratio (OR) 8.4; 95% Confidence Interval (CI): 1.067.9; OR 7.4; 95% CI: 2.521.7 respectively]. The study of blood samples revealed leukocytosis (34109) 6.5% vs 0%, p 0.05) and a shift in the leukocyte count to young forms of neutrophils (45.4% vs 16.7%, p 0.05) in the peripheral blood of infants of the main group. Infants exposed to maternal clinical chorioamnionitis had increased level of CRP 10.3 times more frequent (95% CI: 2.837.1) than in newborns in the comparison group. With dynamic clinical and laboratory monitoring, 72 children of the main group (93.5%) had no data for the course of the infection, as a result of which they did not receive antibiotic therapy. Conclusion: Administration antibiotic therapy to clinically healthy full-term newborns from mothers diagnosed with chorioamnionitis is unjustified. Infants of this group require clinical laboratory, dynamic observation with laboratory control, including a clinical blood test and determination of the CRP level, which is a preferred alternative to the appointment of antibiotic therapy.

Maternal Obesity Is Associated With Higher Cord Blood Adipokines in Offspring Most Notably in Females.

Deleterious long-term effects in the offspring from women with pregravid obesity have been described; however, the evidence supporting early metabolic and inflammatory markers in the offspring at birth and gender differences are conflicting. The present study aimed to compare cord blood adipokines and cytokines concentrations and anthropometric characteristics of the offspring of women with maternal obesity (MO) and normal-weight mothers (NWM). Also, maternal and neonatal variables on the association of maternal body mass index (BMI) with cord blood adipokines were evaluated. A cross-sectional analysis of a subsample of mother-child dyads participating in a cohort study (n = 221) was assessed. Anthropometrics, cord blood adipokines (leptin and adiponectin) and cytokines (interleukin [IL]-1β, IL-4, IL-10, IL-12 p40, IL-12p70, IL-13, and tumor necrosis factor α) concentrations in the offspring of normal-weight women (BMI >18.5 and <24.9 kg/m2) and women with pregravid obesity (BMI > 30 kg/m2) without comorbidities was performed. Offspring from mothers with obesity had higher birth weight, a higher proportion of large for gestational age, higher ponderal index, and heavier placentae than offspring from normal-weight mothers (P < 0.05). Within the offspring from women with obesity, males had significantly higher weight, length, the proportion of large-for-gestational-age newborns, higher weight for length ratio. Males had more efficient placentas than females (P < 0.05). Higher adiponectin and leptin in both sexes and higher leptin in female offspring of mothers with obesity after adjusting for birth size (P < 0.05) were found. Higher IL-12p40 in the offspring of women with MO with no other differences in other cytokines among groups were evidenced. Maternal obesity associates with a higher concentration of adiponectin and leptin in their offspring at birth. There is a relevant effect on anthropometrics in male offspring and on leptin in female newborn. Further studies need to evaluate the extension of these effects in postnatal life. NCT02903134.

Air Pollution, Neonatal Immune Responses, and Potential Joint Effects of Maternal Depression.

Prenatal maternal exposure to air pollution may cause adverse health effects in offspring, potentially through altered immune responses. Maternal psychosocial distress can also alter immune function and may increase gestational vulnerability to air pollution exposure. We investigated whether prenatal exposure to air pollution is associated with altered immune responses in cord blood mononuclear cells (CBMCs) and potential modification by maternal depression in 463 women recruited in early pregnancy (1999–2001) into the Project Viva longitudinal cohort. We estimated black carbon (BC), fine particulate matter (PM2.5), residential proximity to major roadways, and near-residence traffic density, averaged over pregnancy. Women reported depressive symptoms in mid-pregnancy (Edinburgh Postnatal Depression Scale) and depression history by questionnaire. Immune responses were assayed by concentrations of three cytokines (IL-6, IL-10, and TNF-α), in unstimulated or stimulated (phytohemagglutinin (PHA), cockroach extract (Bla g 2), house dust mite extract (Der f 1)) CBMCs. Using multivariable linear or Tobit regression analyses, we found that CBMCs production of IL-6, TNF-a, and IL-10 were all lower in mothers exposed to higher levels of PM2.5 during pregnancy. A suggestive but not statistically significant pattern of lower cord blood cytokine concentrations from ever (versus never) depressed women exposed to PM2.5, BC, or traffic was also observed and warrants further study.