Association of systemic chronic inflammation during pregnancy in different periods and its trajectories with preterm birth.

PROBLEM: Systemic chronic inflammation (SCI) is a prevalent characteristic observed in various diseases originating from different tissues, while the association of SCI with preterm birth (PTB) remains uncertain. This study aimed to analyze the association between a nonspecific biomarker of SCI and PTB, while also exploring the trajectories of SCI in pregnant women at risk of PTB. METHOD OF STUDY: The study used data from the Electronic Medical Record System (EMRS) of a hospital in Zhejiang, China and 9226 pregnant women were included. The duration of pregnancy was categorized into four distinct periods: the first, early-second, late-second, and third trimester. Latent class trajectory modeling (LCTM) was used to identify the trajectories of SCI during pregnancy. RESULTS: The elevated WBC counts in the late-second (OR = 1.14, 95% CI: 1.06-1.23) and third (OR = 1.16, 95% CI: 1.09-1.24) trimester were both positively associated with an evaluated risk of PTB. Moreover, significant dose-response relationships were observed. There were three distinct SCI trajectories found: progressing SCI (2.89%), high SCI (7.13%), and low SCI (89.98%). Pregnant women with progressive SCI had the highest risk of PTB (OR = 3.03, 95% CI: 1.47-6.25). CONCLUSIONS: In conclusion, elevated SCI after 23 weeks was a risk factor for PTB in healthy women, even if the SCI indicator was within normal range. Pregnant women with progressive SCI during pregnancy had the highest risk of PTB.

Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy.

Pregnancy is a remarkable event where the semi-allogeneic fetus develops in the mother's uterus, despite genetic and immunological differences. The antigen handling and processing at the maternal-fetal interface during pregnancy appear to be crucial for the adaptation of the maternal immune system and for tolerance to the developing fetus and placenta. Maternal antigen-presenting cells (APCs), such as macrophages (Mφs) and dendritic cells (DCs), are present at the maternal-fetal interface throughout pregnancy and are believed to play a crucial role in this process. Despite numerous studies focusing on the significance of Mφs, there is limited knowledge regarding the contribution of DCs in fetomaternal tolerance during pregnancy, making it a relatively new and growing field of research. This review focuses on how the behavior of DCs at the maternal-fetal interface adapts to pregnancy's unique demands. Moreover, it discusses how DCs interact with other cells in the decidual leukocyte network to regulate uterine and placental homeostasis and the local maternal immune responses to the fetus. The review particularly examines the different cell lineages of DCs with specific surface markers, which have not been critically reviewed in previous publications. Additionally, it emphasizes the impact that even minor disruptions in DC functions can have on pregnancy-related complications and proposes further research into the potential therapeutic benefits of targeting DCs to manage these complications.

Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Pregnancy and the Autoimmune Patient.

PURPOSE OF REVIEW: This article will review the current understanding of the immunologic changes that occur during pregnancy. It will discuss the impact of pregnancy on the disease activity of autoimmune or inflammatory rheumatic diseases (AIRD). Lastly, it will highlight the most recent data on pre-conception and pregnancy management practices that can improve pregnancy outcomes in autoimmune patients. RECENT FINDINGS: Pregnancy is an immunologically complex and dynamic state that may affect the activity of AIRDs, with more patients having active disease during pregnancy than previously thought. Uncontrolled inflammatory diseases are associated with poor pregnancy outcomes such as preeclampsia, small for gestational age infants, and prematurity. Pre-conception counseling and early pregnancy planning discussions can help ensure optimal disease control and medication management prior to attempting conception. Adequate control of AIRDs on pregnancy-compatible medications during the pre-conception, pregnancy, and postpartum periods is required for optimal pregnancy outcomes.

Pharmacokinetics of Monoclonal Antibodies Throughout Pregnancy: A Systematic Literature Review.

BACKGROUND AND OBJECTIVE: Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy. METHODS: A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available. RESULTS: A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state. CONCLUSION: Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.

Pregnancy and reproductive health in women with multiple sclerosis: an update.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, neuro-degenerative disease of the central nervous system, prevalent in women of reproductive age. Today, many women want to start a family after MS diagnosis. There are over 20 treatments for MS, and safely navigating family planning is important. We review updated information on family planning, preconception, and peri-partum considerations, and reproductive concerns in special populations with MS. RECENT FINDINGS: There are no MS-related restrictions on any available and appropriate contraceptive method in women with MS. The question of MS and pregnancy outcomes following assisted reproduction, remains somewhat unsettled. In many studies, no elevated relapse risk is confirmed regardless of the type of fertility treatment. MRI status may offer better assessment of postpartum disease stability than relapse rate alone. Ongoing effective MS treatments during fertility assistance and before pregnancy, can further reduce the relapse risk. B-cell depleting therapies are emerging as safe and effective treatments for peripartum MS patients. SUMMARY: Patients with MS should receive accurate support and counseling related to their reproductive options. The general outlook on pregnancy and MS remains positive. The ever-increasing therapeutic complexity of MS calls for ongoing education and updated guidance for neuroimmunology and obstetrics healthcare providers.

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms.

Importance: Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. Objective: To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. Design, Setting, and Participants: This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Exposures: Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Main Outcomes and Measures: Self-reported depressive symptoms at adolescent follow-up. Results: A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). Conclusions and Relevance: In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Association between a Mixture of Per- and Polyfluoroalkyl Substances (PFAS) and Inflammatory Biomarkers in the Atlanta African American Maternal-Child Cohort.

Per- and polyfluoroalkyl substances (PFAS) have been identified as environmental contributors to adverse birth outcomes. One potential mechanistic pathway could be through PFAS-related inflammation and cytokine production. Here, we examined associations between a PFAS mixture and inflammatory biomarkers during early and late pregnancy from participants enrolled in the Atlanta African American Maternal-Child Cohort (N = 425). Serum concentrations of multiple PFAS were detected in >90% samples at 8-14 weeks gestation. Serum concentrations of interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at up to two time points (8-14 weeks and 24-30 weeks gestation). The effect of the PFAS mixture on each inflammatory biomarker was examined using quantile g-computation, Bayesian kernel machine regression (BKMR), Bayesian Weighted Sums (BWS), and weighted quantile sum (WQS) regression. Across all models, the PFAS mixture was associated with increased IFN-γ, IL-10, and TNF-α at both time points, with the strongest effects being observed at 24-30 weeks. Using quantile g-computation, increasing concentrations of a PFAS mixture were associated with a 29% (95% confidence interval = 18.0%, 40.7%) increase in TNF-α at 24-30 weeks. Similarly, using BWS, the PFAS mixture was associated with increased TNF-α at 24-30 weeks (summed effect = 0.29, 95% highest posterior density = 0.17, 0.41). The PFAS mixture was also positively associated with TNF-α at 24-30 weeks using BKMR [75th vs 50th percentile: 17.1% (95% credible interval = 7.7%, 27.4%)]. Meanwhile, PFOS was consistently the main drivers of overall mixture effect across four methods. Our findings indicated an increase in prenatal PFAS exposure is associated with an increase in multiple pro-inflammatory cytokines, potentially contributing to adverse pregnancy outcomes.

Transplacental transfer of anti-SARS-CoV-2 neutralizing antibodies in comparison to other pathogens total antibodies.

BACKGROUNDS: Due to immaturity of their immune system, passive maternal immunization is essential for newborns during their first months of life. Therefore, in the current context of intense circulation of SARS-CoV-2, identifying factors influencing the transfer ratio (TR) of neutralizing antibodies against SARS-CoV-2 (NAb) appears important. METHODS: Our study nested in the COVIPREG cohort (NCT04355234), included mothers who had a SARS-CoV-2 PCR positive during their pregnancy and their newborns. Maternal and neonatal NAb levels were measured with the automated iFlash system. RESULTS: For the 173 mother-infant pairs included in our study, the median gestational age (GA) at delivery was 39.4 weeks of gestation (WG), and 29.7 WG at maternal SARS-CoV-2 infection. Using a multivariate logistic model, having a NAb TR above 1 was positively associated with a longer delay from maternal positive SARS-CoV-2 PCR to delivery (aOR 1.09, 95% CI: 1.03 - 1.17) and with a later GA at delivery (aOR = 1.58, 95% CI: 1.09 - 2.52). It was negatively associated with being a male newborn (aOR 0.21, 95% CI: 0.07 - 0.59). In 3rd trimester SARS-CoV-2 infected mothers, NAb TR was inferior to VZV, toxoplasmosis, CMV, measle and rubella's TR. However, in 1st or 2nd trimester infected mothers, only measle TR was different from NAb TR. CONCLUSION: Male newborn of mothers infected by SARS-CoV-2 during their pregnancy appear to have less protection against SARS-CoV-2 in their first months of life than female newborns. Measle TR was superior to NAb TR even in case of 1st or 2nd trimester maternal SARS-CoV-2 infection. Future studies are needed to investigate possible differences in transmission of NAb following infection vs vaccination and its impact on TR.

VPAC1 and VPAC2 receptor deficiencies negatively influence pregnancy outcome through distinct and overlapping modulations of immune, trophoblast and vascular functions.

Pregnancy outcome relies on the maintenance of immune and metabolic homeostasis at the maternal fetal interface. Maternal and perinatal morbidity and mortality is associated with impaired placental development. Multiple regulatory effects of the endogenous-produced vasoactive intestinal peptide (VIP) on vascular, metabolic and immune functions at the maternal-fetal interface have been reported. Here we studied the involvement of the two primary high affinity receptors for VIP (VPAC1 and VPAC2) on maternal immune response, placental homeostasis and pregnancy outcome. Targeted disruption of each receptor gene led to altered placental structure, vascular and trophoblast functional markers and shaped the functional profiles of macrophages and neutrophils towards a proinflammatory state. Several changes in pregnant mice were receptor specific: ROS production elicited by VIP on neutrophils was selectively dependent on the presence of VPAC1 whereas apoptosis rate was associated with the VPAC2 deletion. In peritoneal macrophages from pregnant mice, levels of MHC-II, TLR2, and IL-10 were selectively altered in VPAC2 receptor-deficient mice, whereas IL-6 gene expression was reduced only in mice lacking VPAC1 receptors. Additionally, MMP9 mRNA in isolated TGCs was reduced in VPAC2 receptor deleted mice, while the percentage of IL-12 cells in post-phagocytosis macrophage cultures was selectively reduced in VPAC2 receptor deficient mice. The results indicate that manipulation of VPAC1 and VPAC2 receptor affects immune, vascular and metabolic environment at the maternal fetal interface. These mouse models offer new approaches to study pregnancy complications adding new perspectives to the development of VPAC receptor-selective drugs.

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice.

Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.

Role of Natural Killer Cells during Pregnancy and Related Complications.

A high number of leucocytes reside in the human endometrium and are distributed differentially during the menstrual cycle and pregnancy. During early pregnancy, decidual natural killer (dNK) cells are the most common type of natural killer (NK) cells in the uterus. The increase in the number of uterine NK (uNK) cells during the mid-secretory phase of the menstrual cycle, followed by further increase of dNK cells in early pregnancy, has heightened interest in their involvement during pregnancy. Extensive research has revealed various roles of dNK cells during pregnancy including the formation of new blood vessels, migration of trophoblasts, and immunological tolerance. The present review article is focused on the significance of NK cells during pregnancy and their role in pregnancy-related diseases. The article will provide an in-depth review of cellular and molecular interactions during pregnancy and related disorders, with NK cells playing a pivotal role. Moreover, this study will help researchers to understand the physiology of normal pregnancy and related complications with respect to NK cells, so that future research work can be designed to alleviate the complications.

Changes in Serum Cytokines Throughout Pregnancy in Women With Polycystic Ovary Syndrome.

CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with low-grade inflammation and increased incidence of pregnancy complications, but its influence on the maternal immune system in pregnancy is unknown. Longitudinal serum cytokine profiling is a sensitive measure of the complex immunological dynamics of pregnancy. OBJECTIVE: This work aimed to determine the immunological dynamics of serum cytokines throughout pregnancy in women with PCOS and compare it to pregnancy in women without PCOS. METHODS: A post hoc analysis was conducted of longitudinal serum samples from 2 randomized, placebo-controlled multicenter studies of pregnant women with PCOS and 2 studies of pregnant women without PCOS. Pregnant women with PCOS (n = 358) and without PCOS (n = 258, controls) provided 1752 serum samples from 4 time points in pregnancy (weeks 10, 19, 32, and 36). Main outcome measures included maternal serum levels of 22 cytokines and C-reactive protein (CRP) at 4 time points in pregnancy. RESULTS: Women with PCOS showed marked immunological changes in serum cytokines throughout pregnancy. Compared to controls, women with PCOS showed higher levels of 17 cytokines and CRP at week 10 of pregnancy and a distinct cytokine development throughout pregnancy. The immunological dynamics in women with PCOS was significantly affected by maternal body mass index, smoking, and fetal sex. CONCLUSION: Pregnancy in women with PCOS was associated with a strong early mobilization of inflammatory and other serum cytokines persisting throughout pregnancy, indicating a more activated immune status. These findings provide a novel basis for further study of PCOS and pregnancy complications.

Characteristics of purified anti-ß2GPI IgG N-glycosylation associate with thrombotic, obstetric and catastrophic antiphospholipid syndrome.

OBJECTIVE: Anti-ß-2 glycoprotein I (anti-ß2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-ß2GP1 IgG with clinical features of APS. METHODS: We purify anti-ß2GPI IgG and total IgG from 82 APS patients including nine catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyse all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry. RESULTS: Both purified anti-ß2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with healthy control (HC) IgG. Anti-ß2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aß2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aß2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-ß2GPI IgG subclasses, increased bisection and core fucosylation of anti-ß2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs). CONCLUSION: We comprehensively characterize the N-Glycans landscape of both anti-ß2GP1 and total IgG in APS. Altered N-glycan profiles of anti-ß2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-ß2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments.

Effects of anti-beta 2-glycoprotein 1 antibodies and its association with pregnancy-related morbidity in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by venous, arterial, or small-vessel thrombosis and/or pregnancy-related morbidity, associated with persistent positivity of antiphospholipid antibodies (aPL). Pregnancy-related morbidity in APS patients is characterized by unexplained fetal deaths, premature birth of morphologically normal newborns, and/or consecutive pregnancy losses before the 10th week of gestation. Beta 2-glycoprotein 1 (ß2GP1) is the main antigen recognized by aPL and plays an essential role in the pathogenesis of APS. Antibodies against ß2GP1 (aß2GP1) are involved in damage-generating mechanisms in APS due to their interaction with trophoblasts, decidua, and endothelial cells. aß2GP1 might be used as a prognostic tool for obstetric risk stratification and ß2GP1 could be a target for molecular-targeted treatment to prevent pregnancy morbidity in APS. This review describes these aspects of aß2GP1, including effects on different cellular targets, its association with the severity of obstetric manifestations and the potential of ß2GP1-targeted therapies for APS.

Targeting TBK1 Attenuates LPS-Induced NLRP3 Inflammasome Activation by Regulating of mTORC1 Pathways in Trophoblasts.

Pathological maternal inflammation and abnormal placentation contribute to several pregnancy-related disorders, including preterm birth, intrauterine growth restriction, and preeclampsia. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, has been implicated in the regulation of various physiological processes, including innate immune response, autophagy, and cell growth. However, the relevance of TBK1 in the placental pro-inflammatory environment has not been investigated. In this study, we assessed the effect of TBK1 inhibition on lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation and its underlying mechanisms in human trophoblast cell lines and mouse placenta. TBK1 phosphorylation was upregulated in the trophoblasts and placenta in response to LPS. Pharmacological and genetic inhibition of TBK1 in trophoblasts ameliorated LPS-induced NLRP3 inflammasome activation, placental inflammation, and subsequent interleukin (IL)-1 production. Moreover, maternal administration of amlexanox, a TBK1 inhibitor, reversed LPS-induced adverse pregnancy outcomes. Notably, TBK1 inhibition prevented LPS-induced NLRP3 inflammasome activation by targeting the mammalian target of rapamycin complex 1 (mTORC1). Thus, this study provides evidence for the biological significance of TBK1 in placental inflammation, suggesting that amlexanox may be a potential therapeutic candidate for treating inflammation-associated pregnancy-related complications.

Chemokine profile in women with moderate to severe anxiety and depression during pregnancy.

BACKGROUND: Cytokine levels have been extensively described in pregnant subjects under normal and pathological conditions, including mood-related disorders. Concerning chemokines, very few studies have reported their association with psychiatric disorders during pregnancy. Therefore, we explored the chemokine profile in women exhibiting anxiety and depression during late pregnancy in the present study. METHODS: One hundred twenty-six pregnant women in the 3rd trimester of pregnancy, displaying moderate to severe anxiety (ANX) alone and women exhibiting moderate to severe anxiety with comorbid depression (ANX + DEP), and 40 control pregnant women without affective disorders (CTRL) were evaluated through the Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS). Serum chemokine levels of MCP-1 (CCL2), RANTES (CCL5), IP-10 (CXCL10), Eotaxin (CCL11), TARC (CCL17), MIP-1α (CCL3), MIP-1ß (CCL4), MIG (CXCL9), MIP-3α (CCL20), ENA-78 (CXCL5), GROα (CXCL1), I-TAC (CXCL11) and IL-8 (CXCL8)] were measured by immunoassay. Clinical, biochemical, and sociodemographic parameters were correlated with HARS and HDRS score values. RESULTS: Serum levels of most chemokines were significantly higher in the ANX and in the ANX + DEP groups, when compared to the CTRL group. Positive correlations were observed between MIP-1α/CCL3, MIP-1ß/CCL4, MCP-1/CCL2, MIP-3α/CCL20, RANTES/CCL5, Eotaxin/CCL11, and I-TAC/CXCL11 with high scores for anxiety (HARS) (p < 0.05) and for depression (HDRS) (p < 0.004). After controlling clinical measures for age + gwk + BMI, chemokines such as IL-8/CXCL8, MCP-1/CCL2 and MIP-1ß/CCL4 were found associated with high scores for anxiety (p < 0.05) in the ANX group. TARC/CCL17 and Eotaxin/CCL11 showed significant associations with high scores for depression (p < 0.04) whereas, MCP-1/CCL2 and MIP-1α/CCL3 were significantly associated with high scores for anxiety (p < 0.05) in the ANX + DEP group. Using a multivariate linear model, high serum levels of MIP-1ß/CCL4 and Eotaxin/CCL11 remained associated with depression (p < 0.01), while, IL-8/CXCL8, MIP-1ß/CCL4, MCP-1/CCL2, and MIP-1α/CCL3 were associated with anxiety (p < 0.05) in the symptomatic groups. CONCLUSIONS: Our data show that serum levels of distinct chemokines are increased in women exhibiting high levels of affective symptoms during late pregnancy. Our results suggest that increased levels of anxiety, depressive symptoms, and mood-related disorders may promote changes in specific functional chemokines associated with a chronic inflammatory process. If not controlled, it may lead to adverse obstetric and negative neonate outcomes, child development and neuropsychiatric alterations in the postnatal life. HIGHLIGHTS: Chemokine levels increase in affective disorders during pregnancy.