Maternal Inflammatory Markers Research Articles

Evaluating Maternal Risk Factors Impacting Fetal Intima–Media Thickness of the Abdominal Aorta Measured at 28 Weeks of Gestation

Background and Objectives: Cardiovascular disease risk can exist in utero, influenced by maternal health factors. This study evaluates maternal characteristics and biochemical markers that correlate with the fetal intima–media thickness (IMT), aiming to identify interventions that could minimize prenatal influences on later cardiovascular disease. Methods: In this observational study approved by the Institutional Review Board at The Obstetrics and Gynecology Clinic of the Timisoara Municipal Emergency Hospital, we recruited pregnant women aged 15–40 years, divided into groups based on their lipid profiles and gestational diabetes risk. The data collection had, as its main focus, ultrasound measurements, along with demographic, clinical, and biochemical parameters. The IMT of the fetal abdominal aorta was measured at 28 weeks of gestation. Results: Notable differences were observed in the TNF-alpha levels (8.66 ± 3.87 pg/mL vs. 4.96 ± 3.37 pg/mL), hsCRP levels (0.94 ± 0.46 mg/L vs. 0.60 ± 0.52 mg/L), and the area under the curve (AUC) for hsCRP at 0.738 with a sensitivity of 84.41% and specificity of 79.01%. Compound score 2, integrating inflammatory markers and lipid profiles, exhibited a good diagnostic accuracy (AUC = 0.789) with a sensitivity of 86.35% and specificity of 81.42%. A regression analysis indicated strong associations of TNF-alpha and hsCRP with an increased fetal IMT, suggesting potential early markers of cardiovascular risk, presenting hazard ratios (HRs) of 2.21 (95% CI: 1.15–5.28) and 2.87 (95% CI: 1.11–4.23), respectively, both with p-values of less than 0.0001. Compound score 2 further indicated an increased risk (HR = 4.27; 95% CI: 1.19–8.32). Conclusions: Statistically significant correlations were found between an increased fetal IMT and elevated maternal inflammatory markers (TNF-alpha and hsCRP), suggesting that these could serve as early indicators of cardiovascular risk. This study supports the potential for targeted prenatal interventions to reduce cardiovascular risk factors from the fetal stage, emphasizing the importance of monitoring inflammatory markers in pregnant women at risk.

Comparison of the Fetomaternal Outcome in Women With Preterm Premature Rupture of Membranes on Expectant Management Versus Delivery at 34 Weeks.

This study aimed to study feto-maternal outcomes in women with preterm prelabor rupture of membranes (PTPROM) on expectant management versus delivery at 34 weeks of gestation and correlate the period of latency and inflammatory markers with delivery outcomes. We have chosen this research topic as there is a paucity of specific guidelines regarding the optimal period of gestation for delivering women with PTPROM. The study correlated the feto-maternal outcomes in women with PTPROM on expectant management till 37 weeks versus delivery at 34 weeks with a period of latency and maternal inflammatory markers. This was a prospective observational study conducted on 262 women with PTPROM from 28-33+6 weeks of gestation. Women were monitored till 37 weeks with biweekly total leukocyte count and weekly C-reactive protein, urine routine microscopy, urine culture, high vaginal culturesensitivity, and ultrasound. Women were monitored expectantly till 37 weeks. However, intervention was done at any time during the feto-maternal compromise. There were 52 women who delivered <34 weeks and 210 women who delivered ≥34 weeks. Feto-maternal outcomes were documented. Group A was assigned to women who delivered before 34 weeks and Group B was assigned to women who delivered after 34 weeks. Statistical analysis was done using SPSS software.A p-value <0.05 was considered significant. Amongthe study group, 238 (90.8%) women were managed expectantly while 24(9.1%) required intervention. A latency of 3-4 weeks was observed in 131(50%) women.Chorioamnionitis developed in 7 women (4.4%) in group A and 13 women (4.9%) in group B. Neonates developed sepsis in 5.7% in group A and 5.8 % in group B and were comparable in both the groups (p=1.000). Early neonatal death (END) occurred in 10 (3.8%) amongwhich seven died because of low birth weight (LBW), two due to sepsis, and one due to respiratory distress. LBW was significantly associated with END (p<0.001) Conclusion: Expectant management beyond 34 weeks with close monitoring can improve neonatal outcomes without increasing maternal morbidity in women with PTPROM.

Effect of a High Linoleic Acid Diet on Pregnant Women and Their Offspring.

Nutritional intake during pregnancy can affect gestational length, fetal development, and impact postnatal growth and health in offspring. Perturbations in maternal nutrition with either an excess or deficiency in nutrients during pregnancy may have harmful effects on the offspring's development and increase the risk of developing chronic diseases later in life. In pregnancy, nutrients transfer from the mother to the fetus via the placenta. Essential fatty acids, linoleic acid (LA) and alpha linoleic acid (ALA), can only be obtained in the diet. In Western countries, the ratio of LA and ALA in the diet has increased dramatically in recent decades. Some animal and human studies have found a correlation between maternal intake of LA and birth weight; however, the association varies. In contrast, some human studies have demonstrated inconclusive findings regarding the correlation between cord blood levels of LA and birth outcomes. In addition, high dietary LA intake in animal studies in pregnancy increased the production of inflammatory markers such as prostaglandins, leukotrienes, cytokines, and tumour necrosis factor-alpha. This review aims to highlight the effect of high dietary LA intake during pregnancy on birth outcomes, obesity, maternal inflammatory markers, and the transfer of fatty acids across the placenta.

Effectiveness and pregnancy outcomes of ultrasound-indicated and physical examination-indicated cervical cerclage: a retrospective study from a single centre

ObjectivePreterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide, and cervical incompetence (CIC) is a significant contribution. Cervical cerclage (CC) is an effective obstetric intervention. However, many clinical factors affect the success rate of surgery. The objective was to investigate and compare the pregnancy and neonatal outcomes of patients who underwent ultrasound- and physical examination-indicated cervical cerclage and to explore the influencing factors of preterm delivery before 34 weeks.MethodsThe sociodemographic characteristics and clinical data of patients with a diagnosis of cervical incompetence who underwent ultrasound- and physical examination-indicated transvaginal cervical cerclage at Nanjing Maternal and Child Health Hospital from January 2020 to December 2022 were retrospectively analyzed. The pregnancy and neonatal outcomes of the patients were evaluated. Continuous variables were compared using Student’s t test (for normally distributed data) or the Mann-Whitney U test (for nonnormally distributed data). Categorical variables were analysed using the chi-square test or Fisher’s exact test. Additionally, logistic regression analyses and receiver operating characteristic curves were used to evaluate the associations of inflammatory markers with maternal and neonatal outcomes.ResultsThis study included 141 participants who underwent cervical cerclage, including 71 with ultrasound-indicated cerclage and 70 with physical examination-indicated cerclage. Compared to those in the ultrasound-indicated cerclage group, the duration from cerclage to delivery, birth weight, and APGAR score in the physical examination-indicated cerclage group were significantly lower, and the rates of delivery at < 28 weeks, < 32 weeks, < 34 weeks, and < 37 weeks of gestation and neonatal mortality were significantly higher (all P < 0.05). Compared to those in the physical ultrasound-indicated cerclage group, in the physical examination-indicated cerclage group, maternal blood inflammatory markers, such as C-reactive protein (CRP), the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI) were significantly higher (P < 0.05). Additionally, maternal blood inflammatory markers, such as the CRP, white blood cell count, platelet to lymphocyte ratio (PLR), SII, and SIRI were significantly higher in the group with delivery before 34 weeks of gestation. Furthermore, the results demonstrated that twin pregnancy had the highest OR for preterm delivery before 34 weeks of gestation (OR = 3.829; 95% CI 1.413–10.373; P = 0.008), as well as the following: the SII level (OR = 1.001; 95% CI 1.000-1.002; P = 0.003) and CRP level (OR = 1.083; 95% CI 1.038–1.131; P = 0.022). The risk factors for preterm delivery before 34 weeks of gestation were twin gestation, an increased SII level and an increased CRP level, which had good combined predictive value.ConclusionIn patients with cervical insufficiency, ultrasound-indicated cervical cerclage appears to lead to better pregnancy outcomes than physical examination-indicated cerclage. Twin pregnancy and maternal blood inflammatory markers, such as the CRP level and the SII, are associated with preterm delivery before 34 weeks of gestation.

Predicting the Outcomes of In Vitro Fertilization Using Baseline Maternal Serum Inflammatory Markers: A Retrospective Cohort Study.

Achieving pregnancy through in vitro fertilization (IVF) remains a challenge, with less than one-third of women succeeding. There is a pressing need for reliable predictive tools to assess the likelihood of post-IVF pregnancy. While some serum inflammatory biomarkers have been investigated for their predictive potential, substantial knowledge gaps persist. This study examined the utility of different inflammatory markers in predicting IVF outcomes. Inflammatory markers including the white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet count, mean platelet volume, platelet distribution width, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate, and vitamin D3 were assessed. Study outcomes were chemical pregnancy (positive serum beta-human chorionic gonadotropin 2 weeks post-embryo transfer), clinical pregnancy (detection of pregnancy sac via transvaginal ultrasonography), and viable pregnancy (detection of fetal heart rate). Univariate and multivariate logistic regression analyses were conducted, with multivariate analysis incorporating age, body mass index, infertility duration, type, and etiology, as well as all studied serum inflammatory markers, embryo count, stage, quality, and endometrial thickness. Lower NLR (p<0.001, odds ratio [OR]=0.372 [0.247-0.559]) and CRP (p=0.035, odds ratio=0.956 [0.916-0.997]) predicted chemical pregnancy in univariate analysis, with NLR maintaining significance in multivariate analysis (p=0.022, OR=0.319 [0.120-0.848]). Lower NLR (p<0.001, OR=0.309 [0.198-0.482]) and PLR (p=0.013, OR =0.994 [0.990-0.999]) predicted clinical pregnancy, with NLR surviving multivariate analysis (p=0.005, OR = 0.217 [0.075-0.626]). Lower NLR (p<0.001, OR = 0.320 [0.198-0.516]) also predicted viable pregnancy, maintaining statistical significance in multivariate analysis (p = 0.002, OR = 0.177 [0.058-0.541]). Other studied inflammatory markers did not predict IVF outcomes. NLR emerged as a robust independent predictor of pregnancy attainment after IVF.

Predictive Role of Maternal Laboratory Parameters and Inflammatory Scores in Determining Systemic Inflammatory Response Syndrome in Newborns at Birth.

The incidence of Neonatal Systemic Inflammatory Response Syndrome (SIRS) is a critical concern in neonatal care. This study aimed to identify maternal laboratory parameters predictive of SIRS in newborns, focusing on the establishment of diagnostic cutoffs and evaluating the predictive power of these biomarkers. This prospective cohort study was conducted from January 2023 to January 2024 across several regional hospitals specializing in neonatal care. It included 207 mother-newborn pairs, divided into groups based on the neonatal development of SIRS (66 cases) or its absence (141 controls). Key maternal parameters measured included inflammatory markers and liver enzymes, analyzed using standard biochemical methods. The study applied receiver operating characteristic (ROC) analysis to establish optimal cutoff values and conducted multivariate logistic regression to determine hazard ratios (HRs) for SIRS prediction, with adjustments for potential confounders. The study identified significant ROC/AUC values for several biomarkers. The neutrophil-to-lymphocyte ratio (NLR) demonstrated an AUC of 0.926, with a cutoff value of 3.64, achieving 81.8% sensitivity and 90.9% specificity (p < 0.001). The systemic immune-inflammation index (SII) showed an AUC of 0.819 and a cutoff of 769.12, with 75.8% sensitivity and 81.8% specificity (p < 0.001). Multivariate regression analysis highlighted that neonates with maternal SII values above this cutoff were three times more likely to develop SIRS (HR 3.09, 95% CI 2.21-4.17, p < 0.0001). Other notable biomarkers included dNLR and ALRI, with respective HRs of 1.88 (p = 0.018) and 1.75 (p = 0.032). These findings confirm the significant predictive value of specific maternal inflammatory markers for neonatal SIRS. These findings support the utility of these biomarkers in prenatal screening to identify neonates at increased risk of SIRS, potentially guiding preemptive clinical interventions.

Correlating maternal and cord-blood inflammatory markers and BDNF with human fetal brain activity recorded by magnetoencephalography: An exploratory study

BackgroundDuring gestation, the brain development of the fetus is affected by many biological markers, where inflammatory processes and neurotrophic factors have been of particular interest in the past decade. AimThis exploratory study is the first attempt to explore the relationships between biomarker levels in maternal and cord-blood samples and human fetal brain activity measured with non-invasive fetal magnetoencephalography (fMEG). MethodTwenty-three women were enrolled in this study for collection of maternal serum and fMEG tracings immediately prior to their scheduled cesarean delivery. Twelve of these women had a preexisting diabetic condition. At the time of delivery, umbilical cord blood was also collected. Biomarker levels from both maternal and cord blood were measured and subsequently analyzed for correlations with fetal brain activity in four frequency bands extracted from fMEG power spectral densities. ResultsRelative power in the delta, alpha, and beta frequency bands exhibited moderate-sized correlations with maternal BDNF and cord-blood CRP levels before and after adjusting for confounding diabetic status. These correlations were negative for the delta band, and positive for the alpha and beta bands. Maternal CRP and cord-blood BDNF and IL-6 exhibited negligible correlations with relative power in all four bands. Diabetes did not appear to be a strong confounding factor affecting the studied biomarkers. ConclusionsMaternal BDNF levels and cord-blood CRP levels appear to have a direct correlation to fetal brain activity. Our findings indicate the potential use of these biomarkers in conjunction with fetal brain electrophysiology to track fetal neurodevelopment.

Relationship Between Vaginal and Gut Microbiome on Stress and Depression in Pregnancy [ID 2683607

INTRODUCTION: Pregnancy is a period of significant stress and weight gain; however, the effect of the vaginal and gut microbiome on pregnancy, depression, stress, and the neonate is not completely understood. METHODS: An IRB-approved prospective cohort study was performed for pregnant individuals and their neonates. The Perceived Stress Scale (PSS) and Center for Epidemiologic Studies Depression Scale (CES-D) surveys were administered in the antepartum and postpartum patient, vaginal and fecal microbiome samples were collected, and neonate umbilical cord blood and fecal specimens were also collected. Using full-length 16S rRNA sequencing, fecal and vaginal community composition was characterized. Additionally, possible covariates such as body mass index, cohabitation status, educational attainment, dietary intake, public/private insurance status, chronic health conditions, and pregnancy complications were captured. RESULTS: The study sample consisted of 35 pregnant individuals, average age 30 years, and half primiparous. Increased early pregnancy stress (PSS greater than or equal to 14) was associated with increased abundance of fecal taxa, and increased stress from late pregnancy through postpartum was associated with increased abundance of fecal microbial pathogens. Depressed participants (CES-D greater than or equal to 16) experienced steeper decreases in prenatal vaginal microbiome diversity. In late pregnancy, maternal stress and depression scores were associated with elevated maternal inflammatory markers (CCL2). At delivery, neonatal umbilical CCL2 concentration was negatively correlated with relative abundance of maternal fecal lactobacilli. CONCLUSION: These findings highlight the relationship between stress and depression in pregnancy, the microbiome of the pregnant patient, and inflammatory markers in the pregnant patient and the neonate.

In premature rupture of membranes, maternal serum delta neutrophil index may be a predictive factor for histological chorioamnionitis and affect fetal inflammatory markers: A retrospective cross-sectional study.

We aimed to investigate the predictive value of delta neutrophil index (DNI) for histological choriomanionitis (HCAM) and the effect of maternal inflammatory markers on neonatal outcomes and fetal inflammatory parameters. In this retrospective cross-sectional study, 68 pregnant women without HCAM (group 1) and 46 pregnant women diagnosed with HCAM (group 2) were divided into two groups. Demographic stories of the groups; maternal hematological parameters; maternal DNI and systemic inflammatory index (SII) values; outcomes of newborns; fetal inflammatory markers were recorded and compared between groups. Maternal DNI, and SII levels were significantly higher in group 2 (p value<.05 for all). Admission to the neonatal unit (NICU) was higher in group 2 than in group 1 (p=.0001). We found that fetal inflammatory markers were significantly higher in group 2 (p values .001 for CRP, .0001 for DNI, and .002 for leukocyte). Maternal DNI was determined to be significantly diagnostic at a value of ≥1.3 in HCAM (p=.001). We observed that SII had a significant predictive value of 953036.6 (p=.019) for NICU admission. There is also a positive correlation between fetal inflammatory markers and maternal inflammatory markers. We found that maternal inflammatory markers are high in HCAM, maternal DNI can predict patients who will develop HCAM, maternal SII value can predict NICU admission, fetal inflammatory markers are high in HCAM, and these markers are affected by maternal inflammatory markers.

EP19.14: Fetal fibronectin, cervical length and maternal blood inflammatory markers for predicting impending delivery in twin pregnancies with preterm labour

EP19.14: Fetal fibronectin, cervical length and maternal blood inflammatory markers for predicting impending delivery in twin pregnancies with preterm labour

Maternal inflammatory, lipid and metabolic markers and associations with birth and breastfeeding outcomes.

Conditions in utero influence intrauterine and postnatal infant growth and a few studies indicate that maternal inflammation and insulin resistance might affect birth and breastfeeding outcomes. Furthermore, hormones in human milk (HM) may influence infant appetite-regulation and thereby milk intake, but the associations are less understood. (1) To investigate associations between maternal inflammatory, lipid and metabolic markers and birth and breastfeeding outcomes, and (2) to assess predictors of maternal inflammatory, lipid and metabolic markers in pregnancy. Seventy-one mother-infant dyads participating in the Mothers, Infants and Lactation Quality (MILQ) study were included in the present study. Fasting blood samples were collected around 28th gestational week, and HM samples at three time points from 1.0 to 8.5 months, where milk intake was assessed using 24-h test weighing. Maternal plasma inflammatory, lipid and metabolic markers included high-sensitive C-reactive protein (hs-CRP), tumor-necrosis factor-α (TNFα), interferon-γ (IFNγ), Interleukin (IL)-6, IL-8, high-, low-, and very-low-density lipoprotein (HDL, LDL, VLDL), total-cholesterol, triglycerides, leptin, adiponectin, insulin, C-peptide, the homeostasis model assessment of insulin resistance (HOMA-IR) and glucose concentration at t = 120 min following an oral glucose tolerance test. Of these, TNFα, IFNγ, IL-6, IL-8, leptin, adiponectin and insulin were also measured in HM samples. HDL in pregnancy was inversely associated with gestational age (GA) at birth and GA-adjusted birthweight z-score, whereas triglycerides and glucose (t = 120) were positively associated with GA-adjusted birthweight z-score. Higher hs-CRP, VLDL and triglycerides were associated with a higher placental weight. Furthermore, higher HDL, insulin, leptin and HOMA-IR were associated with longer duration of exclusive breastfeeding (EBF). Higher pre-pregnancy BMI was the main predictor of higher levels of hs-CRP, log-TNFα, leptin, insulin, C-peptide, and HOMA-IR. Maternal lipid and metabolic markers influenced birthweight z-score and placental weight as well as duration of EBF. Furthermore, pre-pregnancy BMI and maternal age predicted levels of several inflammatory and metabolic markers during pregnancy. Our findings indicate that maternal lipid and metabolic profiles in pregnancy may influence fetal growth and breastfeeding, possibly explained by overweight and/or higher placental weight. https://clinicaltrials.gov/, identifier NCT03254329.

The Association of Inflammatory Markers with Maternal-Neonatal Outcome After Cervical Cerclage

Cervical cerclage is effective in prolonging the number of weeks gestation in patients with cervical insufficiency(CI). However, valuable predictors with successful cervical cerclage remain limited. It aimed to evaluate the value of the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) to predict the outcomes of cervical cerclage. This study analyzed 374 participants. Inflammatory markers were calculated using maternal peripheral blood. The association of inflammatory markers and the outcome of cervical cerclage were analyzed. And the optimal cut-off values of inflammatory markers were calculated. Also, the Chi-square test and logistic and linear regression analyses were performed to evaluate inflammatory markers with the maternal outcome and neonatal outcomes. 374 pregnancies were included in this study. Finally, 268 (71.7%) participants suffered successful cervical cerclage. This study demonstrated that the baseline BMI (cm2/kg), the bulging membrane, cervical dilation (≥2cm), the amniotic sac herniation, the neutrophils counts, the systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were significant difference between the successful and unsuccessful groups (all P<0.05). Additionally, maternal blood inflammatory markers, such as WBC, lymphocyte, neutrophils, monocyte, platelet counts, SII, and SIRI, were significantly associated with maternal-neonatal outcomes. Furthermore, the results demonstrated that the SII level had the highest OR (OR=4.626; 95% CI (2.500-8.560)), as well as the following: SIRI level (OR = 3.795; 95% CI (1.989-7.242)), cervical dilation (≥2cm) (OR =3.477; 95% CI (1.458-10.844)), and amniotic sac herniation (OR = 1.796; 95% (0.473-4.975)). This study demonstrated that the baseline SII level and SIRI level are important biochemical markers for predicting the outcome of cervical cerclage and maternal-neonatal outcomes with non-invasive procedures. They can help to provide personalized treatment before surgery and enhance postoperative surveillance.

The Influence of Exercise, Lifestyle Behavior Components, and Physical Fitness on Maternal Weight Gain, Postpartum Weight Retention, and Excessive Gestational Weight Gain.

This study examines (a)the influence of exercise, lifestyle behavior components (sedentary time, physical activity, and sleep and dietary patterns), and physical fitness on maternal weight gain, postpartum weight retention, and excessive gestational weight gain and (b)whether exercise protects against the adverse effects of impaired metabolism and nonoptimal body composition related to excessive gestational weight gain. Subjects were assigned to either a supervised concurrent (aerobic + resistance) exercise program followed 3days/week (n = 47) or a control group (n = 54). Sedentary time, physical activity, sleep and dietary patterns (assessed by accelerometry and questionnaires), muscle strength (handgrip test), and cardiorespiratory fitness (Bruce test) were determined at gestational Weeks 16 and 33 (early-middle and late pregnancy, respectively), and at 6 weeks postpartum. Weight gain and weight retention were calculated using recorded weights at prepregnancy, early-middle, and late pregnancy, and at 6weeks postpartum. Birth complications, maternal postpartum body composition, cardiometabolic, and inflammatory markers in maternal and umbilical cord arterial and venous blood, and in colostrum, and mature milk were also recorded. The exercise intervention reduced late weight gain (B = -2.7, SE = 0.83, p = .003) and weight retention (B = -2.85, SE = 1.3, p = .03), independent of any lifestyle behavior component or physical fitness, but did not prevent excessive weight gain. Increasing cardiorespiratory fitness, muscle strength, and sleep duration were associated with a smaller mean weight gain and lower excessive weight gain values (p < .05). Among the participants who experienced excessive weight gain, those who were exercisers had a lower body mass index and systemic tumor necrosis factor-alpha concentration, lower umbilical cord venous tumor necrosis factor-alpha and arterial interferon gamma levels, higher cord arterial interleukin-10 levels, and improved placental function compared with controls (p < .05). In summary, exercise may help optimize gestational weight gain and weight retention, and may attenuate the impaired phenotype related to excessive weight gain. Increasing cardiorespiratory fitness, muscle strength, and sleep duration might help to prevent excessive weight gain during pregnancy.

Maternal Allergic Asthma Induces Prenatal Neuroinflammation.

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by impaired social interactions and communication skills and repetitive or stereotyped behaviors. Rates of ASD diagnosis continue to rise, with current estimates at 1 in 44 children in the US (Maenner 2021). Epidemiological studies have suggested a link between maternal allergic asthma and an increased likelihood of having a child diagnosed with ASD. However, a lack of robust laboratory models prevents mechanistic research from being carried out. We developed a novel mouse model of maternal asthma-allergy (MAA) and previously reported that offspring from these mothers exhibit behavioral deficits compared to controls. In addition, it was shown that epigenetic regulation of gene expression in microglia was altered in these offspring, including several autism candidate genes. To further elucidate if there is neuroinflammation in the fetus following MAA, we investigated how allergic asthma impacts the maternal environment and inflammatory markers in the placenta and fetal brain during gestation. Female C57Bl/6 mice were primed with ovalbumin (OVA) prior to allergic asthma induction during pregnancy by administering aerosolized ovalbumin or PBS control to pregnant dams at gestational days (GD)9.5, 12.5, and 17.5. Four hours after the final induction, placenta and fetal brains were collected and measured for changes in cytokines using a Luminex bead-based multiplex assay. Placental MAA tissue showed a decrease in interleukin (IL)-17 in male and female offspring. There was a sex-dependent decrease in female monocyte chemoattractant protein 1 (MCP-1). In male placentas, IL-4, C–X–C motif chemokine 10 (CXCL10)—also known as interferon γ-induced protein 10 kDa (IP-10)—and chemokine (C-C motif) ligand 5 (RANTES) were decreased. In fetal brains, elevated inflammatory cytokines were found in MAA offspring when compared to controls. Specifically, interferon-gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1α (IL-1α), IL-6, and tumor necrosis factor α (TNFα) were elevated in both males and females. In contrast, a decrease in the cytokine IL-9 was also observed. There were slight sex differences after OVA exposures. Male fetal brains showed elevated levels of macrophage inflammatory protein-2 (MIP-2), whereas female brains showed increased keratinocytes-derived chemokine (KC). In addition, IL-1𝛽 and IP-10 in male fetal brains were decreased. Together, these data indicate that repeated exposure to allergic asthma during pregnancy alters cytokine expression in the fetal environment in a sex-dependent way, resulting in homeostatic and neuroinflammatory alterations in the fetal brain.

Antenatal maternal depression, early life inflammation and neurodevelopment in a South African birth cohort

BackgroundAntenatal exposure to maternal psychological adversity, including depression, increases the risk of impaired neurodevelopment in children. The underlying biological mechanisms remain unclear, especially in early life during critical windows of development and maturation. This study investigated the association of antenatal maternal depression, maternal and early life inflammatory markers and neurodevelopmental outcomes in children at 2 years of age. MethodsA subgroup of mothers and their children (n = 255) that were enrolled in a South African birth cohort study, the Drakenstein Child Health Study, were followed from the antenatal period through to 2 years of child age. Maternal depressive symptoms were measured by the Beck Depression Inventory (BDI-II) at 26 weeks gestation. Serum inflammatory markers [granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were measured in mothers at enrolment and in their children at 6–10 weeks and at 2 years. Neurodevelopment was assessed at 2 years using the Bayley Scales of Infant and Toddler Development III. ResultsAntenatal depressive symptoms (present in 25% of the mothers) were significantly associated with higher levels of IL-7 (p = 0.008), IL-8 (p = 0.019) and TNF-α (p = 0.031) in the mothers after correcting for sociodemographic and lifestyle factors. Serum IL-1β and NGAL levels were significantly elevated over time in children born to mothers with depressive symptoms compared to those without depression, after controlling for maternal and child health and sociodemographic factors. Elevated infant IL-1β at 6–10 weeks of age partially mediated the association of maternal depressive symptoms with poorer language scores at 2 years. ConclusionAlterations in early life immunity, as reflected by elevated IL-1β, is a potential pathway through which antenatal maternal depressive symptoms may impact language development in young children.

Role of derived neutrophil-to-lymphocyte ratio, uric acid-to-creatinine ratio and Delta neutrophil index for predicting neonatal outcomes in pregnancies with preeclampsia

We aimed to compare the maternal and neonatal systemic inflammatory markers, platelet indices and new indices in biochemical parameters in women with preeclampsia and healthy controls. The secondary aim was to investigate whether there was a relationship between maternal hematological markers and neonatal outcomes. A retrospective case control study was conducted in a tertiary hospital. Maternal demographic and birth characteristics, complete blood count indices, derived neutrophil to lymphocyte ratio (dNLR), Delta neutrophil index (DNI), uric acid-to-creatinine (Cre) ratio and uric acid-to-alanine transaminase ratio, neonatal hematological parameters were compared between the preeclamptic group and control group. The study consisted of 170 cases (84 preeclampsia and 86 control). Neutrophil-to-lymphocyte ratio (NLR), dNLR, blood urea nitrogen (BUN), creatinine (Cre), uric acid, LDH, aspartate transaminase (AST) and alanine aminotransferase (ALT), uric acid-to-Cre ratio and uric acid-to-ALT ratio were higher and statistically significant in the preeclamptic group than in control ones (p: 0.000 – BUN, Cre, uric acid, LDH, p: 0.001 – AST, p: 0.004 – ALT, p: 0.000 – uric acid-to-Cre ratio, p: 0.009 – uric acid-to-ALT ratio, respectively). NLR and platelet-to-lymphocyte (PLR) ratio were significantly higher in newborns of preeclamptic mothers (p: 0.039; p: 0.004, respectively). A low-moderate correlation between maternal uric acid-to-Cre ratio and neonatal PLR was detected (r: 0.193; p: 0.013). Moreover, moderate negative correlations between maternal PLR (r:−0.231, p: 0.002), uric acid (r: 0.332, p:0.000) and adverse neonatal outcomes were found. Uric acid and PLR, which can be easily calculated clinically may predict adverse neonatal outcomes. IMPACT STATEMENT What is already known about this topic? Preeclampsia is known as a significant cause of maternal morbidity and mortality. Haematological indices have been evaluated for the prognosis of many kinds of disease. What do the results of this study add? This study has focussed on new combined haematological–biochemical indices and its relationship with neonatal outcomes. Both higher NLR, derived NLR, DNI and lower PLR were recorded as useful markers for preeclampsia. What are the implications of these findings for clinical practice and/or further research? Some indices that were calculated by assessing basic and simple blood parameters may help clinicians to predict clinical outcomes of preeclampsia.

Maternal serum adipokines and inflammatory markers at late gestation and newborn weight in mothers with and without gestational diabetes mellitus.

Maternal obesity increases the risk of gestational diabetes mellitus (GDM) and is positively correlated with neonatal obesity increasing the risk of adiposity in both young and adult offspring. Maternal secreted factors from adipose tissue such as adipokines and inflammatory cytokines may regulate fetal growth. This study investigated associations between maternal adipokines and inflammatory markers at late gestation, and neonatal anthropometric characteristics in mothers with and without GDM. The study included 65 women with GDM and 65 pregnant women with normal glucose tolerance evaluated at the time of term elective Caesarean section. Adiponectin, leptin, resistin, adipsin, neutrophil gelatinase-associated lipocalin (NGAL), nerve growth factor (NGF), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) concentrations were measured in maternal serum by the multiplex immunoassay using Magpix technology. C-reactive protein (CRP) was measured with a particle-enhanced turbidimetric immunoassay and neonatal anthropometric variables were assessed. The association of birthweight with individual biomarkers was analyzed using multivariate logistic regression adjusted for maternal factors. Adiponectin, leptin, resistin, adipsin, NGAL and NGF were not significantly associated with higher birthweight. The maternal factors in association with higher birthweight observed in GDM were CRP, MCP-1 and TNF-alpha levels. Regression analysis showed that TNF-alpha was an independent risk factor for higher birthweight (p = 0.046). These results suggest an involvement of maternal inflammatory markers at late gestation and fetal growth in mothers with GDM, and that TNF-alpha could play a major role.

Gestational stress alters maternal behavior and inflammatory markers in the olfactory bulb of lactating mice.

Inflammatory markers represent important candidates responsible for the altered behavior and physiology observed after stressful experiences. In the maternal brain, the olfactory bulb (OB) is a key constituent of the neural circuit that mediates the reciprocal interaction between mother and infant. This study aimed to investigate the effects of stress during pregnancy on maternal behavior and inflammatory changes in the olfactory bulb of lactating mice. Female Balb/c mice were divided into two groups: control (CT) and restraint stress (RS). Maternal behavior was performed during the first 8days of life of the offspring. On the 10th day after parturition, corticosterone, gene, and protein expression were assessed. Stress during pregnancy decreased the maternal index at postnatal day 4 and the nuclear factor-κB 1 (NFκB1) gene expression in the OB. Moreover, females from the RS group showed increased interleukin (IL-1β) protein expression. In contrast, stressed females exhibited a decreased tumor necrosis factor (TNF-α) protein expression in the OB. In conclusion, exposure to stress during pregnancy was able to induce specific postnatal effects on maternal behavior and balance of inflammatory mediators in the OB.

Maternal Proinflammatory Adipokines Throughout Pregnancy and Neonatal Size and Body Composition: A Prospective Study.

Increased maternal adiposity and inflammation have impacts on fetal growth. The purpose of this prospective study was to investigate the associations of 3 proinflammatory adipokines in pregnancy with neonatal anthropometry. In a sample of 321US pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (NCT00912132), plasma IL-6, fatty acid binding protein-4 (FABP4), and chemerin were measured in plasma samples collected at 10-14, 15-26, 23-31, and 33-39 weeks of gestation. Generalized linear models were used to estimate associations of adipokines with neonatal weight, thigh, and crown-heel length, and skinfolds at birth. Models adjusted for age, race/ethnicity, education, nulliparity, prepregnancy BMI, and weeks of gestation at blood collection. At each time point, higher IL-6 was associated with lower neonatal birthweight and thigh length. At 15-26 weeks of gestation, a 1 SD pg/mL increase in IL-6 was associated with -84.46g lower neonatal birthweight (95% CI: -150.70, -18.22), -0.17cm shorter thigh length (95% CI: -0.27, -0.07), -0.43cm shorter crown-heel length (95% CI: -0.75, -0.10), and -0.75mm smaller sum of skinfolds (95% CI: -1.19, -0.31), with similar associations at 23-31 and 33-39 weeks of gestation. There were no associations of FABP4 and chemerin with neonatal anthropometry. Starting as early as 15 weeks of gestation, higher maternal IL-6 concentrations in pregnancy were associated with lower neonatal birthweight, thigh and crown-heel length, and skinfolds. These data provide insight into the relevance of maternal inflammatory markers with neonatal anthropometry.

Prenatal inflammation as a link between placental expression signature of tryptophan metabolism and preterm birth.

Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here, we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory markers (such as maternal serum C-reactive protein and white blood cell count). We show that preterm birth is associated with significant changes in placental tryptophan metabolism. Multifactorial analysis revealed similarities in expression patterns associated with multiple phenotypes of preterm delivery. Subsequent correlation computations and mediation analyses identified links between intra-amniotic and maternal inflammatory markers and placental serotonin and kynurenine pathways of tryptophan catabolism. Collectively, the findings suggest that a hostile inflammatory environment associated with preterm delivery underlies the mechanisms affecting placental endocrine/transport functions and may contribute to disruption of developmental programming of the fetal brain.