Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis

BackgroundHigh rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling.ObjectivesTo assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy.MethodsThis study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied.ResultsDuring the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p<0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs.ConclusionsMaternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.

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Maternal Serum and Cord Blood Leptin Concentrations at Delivery in Normal Pregnancies and in Pregnancies Complicated by Intrauterine Growth Restriction

Obesity Facts ◽

10.1159/000519609 ◽

2021 ◽

pp. 1-8

Author(s):

Małgorzata Stefaniak ◽

Ewa Dmoch-Gajzlerska

Keyword(s):

Birth Weight ◽

Cord Blood ◽

Pregnant Women ◽

Fetal Growth ◽

Intrauterine Growth Restriction ◽

Maternal Serum ◽

Serum Leptin ◽

Intrauterine Growth ◽

The Mean ◽

Maternal Bmi

Introduction: Leptin is a polypeptide hormone, and in pregnancy, it is secreted by the placenta and maternal and fetal adipose tissues. Normal leptin production is a factor responsible for uncomplicated gestation, embryo development, and fetal growth. The study compared maternal serum and cord blood leptin concentrations at delivery in normal pregnancies and in pregnancies complicated by intrauterine growth restriction (IUGR). Methods: The study was performed in 25 pregnant women with isolated IUGR and in 194 pregnant women without any complications. Leptin concentrations in maternal serum and in cord blood samples collected at delivery were measured by ELISA and subsequently analyzed by maternal body mass index (BMI), mode of delivery, and infant gender and birth weight. For comparative analyses of normally distributed variables, parametric tests were used, that is, the Student t test and a one-way ANOVA. The nonparametric Mann-Whitney test was used when the distribution was not normal. The Pearson correlation coefficient was calculated to assess the correlation between normally distributed variables (p < 0.05). Results: In pregnancies complicated by IUGR, the mean maternal serum leptin concentration at delivery was significantly higher (52.73 ± 30.49 ng/mL) than in normal pregnancies (37.17 ± 28.07 ng/mL) (p = 0.01). The mean cord blood leptin concentration in pregnancies complicated by IUGR was 7.97 ± 4.46 ng/mL and significantly lower than in normal pregnancies (14.78 ± 15.97 ng/mL) (p = 0.04). In normal pregnancies, but not in pregnancies complicated by IUGR, a statistically significant correlation was established between maternal serum leptin concentrations and maternal BMI at delivery (r = 0.22; p = 0.00). No statistically significant correlation was found between cord blood leptin concentrations and maternal BMI in either study subjects or controls. In normal pregnancies, but not in pregnancies complicated by IUGR, a strong correlation was observed between cord blood leptin concentrations and birth weight (r = 0.23; p = 0.00). Conclusions: Elevated maternal blood leptin concentrations in pregnancies complicated by IUGR may indicate a significant adverse effect of elevated leptin on fetal growth. The differences in leptin concentrations, measured in maternal serum and in cord blood, between the study subjects and controls suggest that deregulated leptin levels may increase the risk of obstetric complications associated with placental insufficiency.

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Association of higher rheumatoid arthritis disease activity during pregnancy with lower birth weight: Results of a national prospective study

Arthritis & Rheumatism ◽

10.1002/art.24914 ◽

2009 ◽

Vol 60 (11) ◽

pp. 3196-3206 ◽

Cited By ~ 166

Author(s):

Ya��l A. de Man ◽

Johanna M. W. Hazes ◽

Hugo van der Heide ◽

Sten P. Willemsen ◽

Christianne J. M. de Groot ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Birth Weight ◽

Prospective Study ◽

Disease Activity ◽

Lower Birth Weight ◽

Rheumatoid Arthritis Disease Activity ◽

Rheumatoid Arthritis Disease

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Cohort profile: effect of malaria in early pregnancy on fetal growth in Benin (RECIPAL preconceptional cohort)

BMJ Open ◽

10.1136/bmjopen-2017-019014 ◽

2018 ◽

Vol 8 (1) ◽

pp. e019014 ◽

Cited By ~ 17

Author(s):

Manfred Accrombessi ◽

Emmanuel Yovo ◽

Gilles Cottrell ◽

Gino Agbota ◽

Agnès Gartner ◽

...

Keyword(s):

Birth Weight ◽

Pregnant Women ◽

Fetal Growth ◽

Early Pregnancy ◽

First Trimester ◽

Reproductive Age ◽

Health Determinants ◽

Women Of Reproductive Age ◽

High Prevalence ◽

First Trimester Of Pregnancy

PurposeREtard de Croissance Intra-uterin et PALudisme (RECIPAL) is an original preconceptional cohort designed to assess the consequences of malaria during the first trimester of pregnancy, which is a poorly investigated period in Africa and during which malaria may be detrimental to the fetus.ParticipantsFor this purpose, a total of 1214 women of reproductive age living in Sô-Ava and Akassato districts (south Benin) were followed up monthly from June 2014 to December 2016 until 411 of them became pregnant. A large range of health determinants was collected both before and during pregnancy from the first weeks of gestation to delivery. Five Doppler ultrasound scans were performed for early dating of the pregnancy and longitudinal fetal growth assessment.Findings to datePregnant women were identified at a mean of 6.9 weeks of gestation (wg). Preliminary results confirmed the high prevalence of malaria in the first trimester of pregnancy, with more than 25.4% of women presenting at least one microscopic malarial infection during this period. Most infections occurred before six wg. The prevalence of low birth weight, small birth weight for gestational age (according to INTERGROWTH-21st charts) and preterm birth was 9.3%, 18.3% and 12.6%, respectively.Future plansREtard de Croissance Intra-uterin et PALudisme (RECIPAL) represents at this time a unique resource that will provide information on multiple infectious (including malaria), biological, nutritional and environmental determinants in relation to health outcomes in women of reproductive age, pregnant women and their newborns. It will contribute to better define future recommendations for the prevention of malaria in early pregnancy and maternal malnutrition in Africa. It confirms that it is possible to constitute a preconceptional pregnancy cohort in Africa and provides valuable information for researchers starting cohorts in the future.

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The sFlt-1 to PlGF Ratio in Pregnant Women with Rheumatoid Arthritis: Impact of Disease Activity and Sulfasalazine Use

Rheumatology ◽

10.1093/rheumatology/keab372 ◽

2021 ◽

Author(s):

Rugina I Neuman ◽

Hieronymus T W Smeele ◽

A H Jan Danser ◽

Radboud J E M Dolhain ◽

Willy Visser

Keyword(s):

Rheumatoid Arthritis ◽

Cohort Study ◽

Disease Activity ◽

Pregnant Women ◽

Gestational Age ◽

Third Trimester ◽

Low Disease Activity ◽

The Third ◽

Observational Prospective Cohort Study ◽

Plgf Ratio

Abstract Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). Conclusion Our study shows that in pregnant women with RA, the sFlt-1/PlGF-ratio is not altered due to disease activity and a cut-off ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.

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POS0997 PERFORMANCE OF ASDAS VERSUS BASDAI DURING PREGNANCY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2859 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 767.1-767

Author(s):

P. Fischer ◽

A. Zbinden ◽

F. Foerger

Keyword(s):

Disease Activity ◽

Pregnant Women ◽

Global Assessment ◽

Signs And Symptoms ◽

First Trimester ◽

Point Estimation ◽

High Disease Activity ◽

Physician Global Assessment ◽

Pregnancy And Postpartum ◽

Pregnant State

Background:Disease activity in patients with axial spondyloarthritis (axSpA) can be measured by BASDAI and ASDAS. Both instruments were validated in non-pregnant patients with cutoff values for active diseases. In pregnant women with axSpA, however, BASDAI and ASDAS scores might be biased by signs and symptoms of pregnancy itself.Objectives:To compare the performance of ASDAS and BASDAI during pregnancyMethods:Patients with axSpA were prospectively followed before pregnancy, at each trimester and 6 to 12 weeks postpartum. Disease activity was assessed by BASDAI, ASDAS, patient global assessment (PGA) and physician global assessment (PhGA). We analysed the disease course throughout pregnancy and postpartum, the correlation between BASDAI and ASDAS and the agreement in the classification of active disease. We applied receiver operating curves (ROC) to evaluate the cut-off points in pregnant patients.Results:The study involved 40 women with axSpA. Disease activity scores were higher during pregnancy (median ASDAS score: 2.5, median BASDAI score 3.1) than during a non-pregnant state (median ASDAS score 2.3, median BASDAI score 2.1). Median BASDAI scores were highest at the first trimester, median ASDAS scores were highest at the second trimester. ASDAS strongly correlated with BASDAI, both in the pregnant and in the non-pregnant state (r=0.796, r=0.727). However, there was a discordance when analysing the proportion of patients with high disease activity using the common cut-off values (ASDAS >2.1, BASDAS >4). More patients had high disease activity when measured by ASDAS (1st trimester (T): 63%, 2nd T: 76%, 3rd T: 61%) compared to those measured by BASDAI (1st T 43%, 2nd T: 39%, 3rd T: 34%). The κ coefficient showed only fair agreement (κ=0.39). ROC analysis among pregnant patients showed that the cut-off point estimation for high disease activity using ASDAS >2.75 corresponded to a BASDAI >4. The ASDAS >2.75 cut-off for high disease activity had a good agreement with BASDAI >4 (κ=0.657). When ASDAS >2.75 was applied in pregnant women with axSpA, about 40% experienced high disease activity.Conclusion:During pregnancy, the majority of women with axSpA experience ongoing disease activity. However, the cut-off values defining low and high disease activity might differ between pregnant and non-pregnant individuals since BASDAI and ASDAS are biased by pregnancy related symptoms like fatigue and mechanical back pain.Disclosure of Interests:None declared.

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The Effect of Down Syndrome Biochemical Markers on Predicting Severity of Preeclampsia

10.21203/rs.3.rs-132123/v1 ◽

2020 ◽

Author(s):

AYSE OZBAN

Keyword(s):

Down Syndrome ◽

Pregnant Women ◽

Biochemical Markers ◽

First Trimester ◽

Maternal Serum ◽

Screening Tests ◽

Second Trimester ◽

Study Results ◽

Second Trimester Screening ◽

Trimester Screening

Abstract Objective: This study aims to determine whether it is possible to predict preeclampsia by comparing postpartum results and test results of the pregnant women diagnosed with preeclampsia, whose first and/or second trimester screening tests were accessible, and to demonstrate the predictability of severity and week of onset.Background: 204 patients underwent renal transplantation in our center and 84 of them were female. Five of our patients (one of them had two births) gave birth to a total of 6 pregnancies.Method: 135 patients were diagnosed with preeclampsia and their first and/or second trimester screening tests were accessible, and 366 control participants gave birth to a healthy baby between 37-41 weeks after standard follow-up period for pregnancy and their screening tests were also accessible.Results: The study results show that the first trimester maternal serum PAPP-A level is significantly low in preeclamptic pregnant women, and that the second trimester maternal serum AFP and hCG levels are significantly high and uE3 levels are significantly low The results also suggest that the first and second trimester Down syndrome biochemical markers can be used in preeclampsia screening.Conclusion: Among these markers, uE3 is the parameter which affects the possibility of preeclampsia the most. However, the first and second trimester Down syndrome biochemical markers are not effective in predicting the severity and onset week of preeclampsia.

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P45 Frequency of cytokine secreting T cells and plasma cytokine levels at baseline: Do they correlate with disease activity or response to MTX in rheumatoid arthritis?

Indian Journal of Rheumatology ◽

10.1016/s0973-3698(09)60063-7 ◽

2009 ◽

Vol 4 (3) ◽

pp. S16

Author(s):

Padmanabha Shenoy ◽

Rajni Srivastava ◽

Veena V Nair ◽

Sushma Singh ◽

Amita Aggarwal

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Disease Activity ◽

Plasma Cytokine ◽

Cytokine Levels

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M20. CYTOKINE LEVELS THROUGHOUT PREGNANCY AND RISK FOR PSYCHOSIS IN ADULT OFFSPRING: EARLY PREGNANCY MATTERS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.332 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S141-S141

Author(s):

Dana Allswede ◽

Robert Yolken ◽

Stephen Buka ◽

Tyrone Cannon

Keyword(s):

Psychotic Disorder ◽

Early Pregnancy ◽

Serum Levels ◽

First Trimester ◽

Underlying Mechanism ◽

Maternal Serum ◽

Serum Samples ◽

Birth Complications ◽

Cytokine Levels ◽

Pregnancy And Birth

Abstract Background Schizophrenia has been associated with pregnancy and birth complications, and fetal exposure to inflammation is thought to be a common underlying mechanism. However, it is unclear whether the risk associated with inflammation is specific to particular phases of pregnancy, as no prior studies have examined maternal serum samples across multiple assessments from the first trimester onward. This study examined differences in longitudinal patterns of maternal serum levels of TNFa, IL-1b, IL-5, IL-6, IL-8, IL-10, and IL-17a across pregnancy for offspring who were later ascertained as having a psychotic disorder diagnosis, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls. Methods Participants included 90 offspring, 79 siblings, and 273 matched controls from the Philadelphia cohort of the National Collaborative Perinatal Project. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Cytokine levels were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth. Results Levels of pro-inflammatory TNFa, IL-1b, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis relative to maternal serum of non-psychotic siblings and matched controls. These differences were maximal in first half of pregnancy (7–20 weeks), tapering to non-significant during the second half of pregnancy. Discussion These findings elucidate the importance of exposure to elevated maternal pro-inflammatory cytokine levels in early pregnancy to the etiology of psychosis.

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