Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study

Hedman, Anna M.; Lundholm, Cecilia; Andolf, Ellika; Pershagen, Göran; Fall, Tove; Almqvist, Catarina

doi:10.1038/s41598-020-74722-5

Cited by 21 publications

(22 citation statements)

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“…IL-7 also peaked in the second trimester and has been suggested important for maintaining fetal tolerance through the induction of δγ T cells and uterine NK cells ( 61 ). Previously, increasing ( 4 ) or stable ( 15 , 62 ) levels of IL-7 have been reported, but then measured at different time points in pregnancy. Special attention must be drawn to the strong expression of the chemokine eotaxin in early pregnancy and the marked decrease towards term, as supported by others ( 4 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, increasing ( 4 ) or stable ( 15 , 62 ) levels of IL-7 have been reported, but then measured at different time points in pregnancy. Special attention must be drawn to the strong expression of the chemokine eotaxin in early pregnancy and the marked decrease towards term, as supported by others ( 4 , 15 ). The role of eotaxin in pregnancy is largely unknown, but in vitro experiments support importance of eotaxin in first trimester by its involvement in extravillous trophoblast invasion and migration ( 63 ).…”

Section: Discussionmentioning

confidence: 99%

“…Earlier attempts have shown strong impact of pregnancy on serum cytokine levels but resulted in conflicting conclusions, as reviewed by Spence et al (14). While analysis of few or single cytokines has dominated the literature (14), broad cytokine profiling in pregnancy is feasible (4,13,(15)(16)(17)(18)(19)(20)(21) but these studies have typically employed small study samples or examined only parts of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

“…Pregnancy is a complex and dynamic process during which the immune system must balance tolerance towards the fetus and maternal immunological integrity ( 1 ), and serves as a key player for timing and orchestrating normal gestation ( 2 , 3 ). Studies suggest that the maternal immune system is sensitive to factors such as obesity ( 4 ) and fetal sex ( 5 ). Aberrant immunological status has been associated with infertility, spontaneous abortions, preterm delivery ( 6 ) and a variety of pregnancy-related conditions ranging from perinatal depression ( 7 ) to preeclampsia ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

“…( 14 ). While analysis of few or single cytokines has dominated the literature ( 14 ), broad cytokine profiling in pregnancy is feasible ( 4 , 13 , 15 – 21 ) but these studies have typically employed small study samples or examined only parts of pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

et al. 2021

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Pregnancy implies delicate immunological balance between two individuals, with constant changes and adaptions in response to maternal capacity and fetal demands. We performed cytokine profiling of 1149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum levels of 22 cytokines and C-reactive protein (CRP) followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptions. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus. These findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

et al. 2021

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Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories

Van Pee,

Martens,

Alfano

et al. 2024

JAMA Netw Open

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ImportanceThe cord blood proteome, a repository of proteins derived from both mother and fetus, might offer valuable insights into the physiological and pathological state of the fetus. However, its association with birth weight and growth trajectories early in life remains unexplored.ObjectiveTo identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories.Design, Setting, and ParticipantsThis cohort study included 288 mother-child pairs from the ongoing prospective Environmental Influence on Early Aging birth cohort study. Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages 4 to 6 years. Data were analyzed from February 2022 to September 2023.Main Outcomes and MeasuresThe outcome of interest was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age 4-6 years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins.ResultsThe sample included 288 infants (125 [43.4%] male; mean [SD] gestation age, 277.2 [11.6] days). The mean (SD) age of the child at the follow-up examination was 4.6 (0.4) years old. After multiple testing correction, there were significant associations of birth weight and BWR with 7 proteins: 2 positive associations: afamin (birth weight: coefficient, 341.16 [95% CI, 192.76 to 489.50]) and secreted frizzled-related protein 4 (SFRP4; birth weight: coefficient, 242.60 [95% CI, 142.77 to 342.43]; BWR: coefficient, 0.07 [95% CI, 0.04 to 0.10]) and 5 negative associations: cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2; birth weight: coefficient, −237.52 [95% CI, −343.15 to −131.89]), ephrin type-A receptor 4 (EPHA4; birth weight: coefficient, −342.78 [95% CI, −463.10 to −222.47]; BWR: coefficient, −0.11 [95% CI, −0.14 to −0.07]), SLIT and NTRK-like protein 1 (SLITRK1; birth weight: coefficient, −366.32 [95% CI, −476.66 to −255.97]; BWR: coefficient, −0.11 [95% CI, −0.15 to −0.08]), transcobalamin-1 (TCN1; birth weight: coefficient, −208.75 [95% CI, −305.23 to −112.26]), and unc-5 netrin receptor D (UNC5D; birth weight: coefficient, −209.27 [95% CI, −295.14 to −123.40]; BWR: coefficient, −0.07 [95% CI, −0.09 to −0.04]). Further evaluation showed that 2 proteins were still associated with rapid growth at age 12 months (afamin: OR, 0.32 [95% CI, 0.11-0.88]; TCN1: OR, 2.44 [95% CI, 1.26-4.80]). At age 4 to 6 years, CELSR2, EPHA4, SLITRK1, and UNC5D were negatively associated with weight (coefficients, −1.33 to −0.68 kg) and body mass index z score (coefficients, −0.41 to −0.23), and EPHA4, SLITRK1, and UNC5D were negatively associated with waist circumference (coefficients, −1.98 to −0.87 cm). At ages 4 to 6 years, afamin (OR, 0.19 [95% CI, 0.05-0.70]) and SLITRK1 (OR, 0.32 [95% CI, 0.10-0.99]) were associated with lower odds for overweight.Conclusions and RelevanceThis cohort study found 7 cord blood proteins associated with birth weight and growth trajectories early in life. Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics.

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Evaluation of the predictive values of elevated serum l-homoarginine and dimethylarginines in preeclampsia

Yuan

Cai

Hu³

et al. 2022

Amino Acids

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Abstractl-homoarginine (hARG) is involved in nitric oxide biosynthesis, but its role and concentration in preeclampsia (PE) have not been fully revealed. The purpose of this study was to develop and validate a feasible clinical assay to quantify serum hARG, arginine (ARG), asymmetric (ADMA) and symmetric dimethylarginines (SDMA) levels by LC–MS/MS and investigate their differences at different stages of pregnancy with or without preeclampsia. Serum samples were collected from 84 pregnant women without complications (controls), 84 with mild preeclampsia (MPE), and 81 with severe preeclampsia (SPE) at various gestation stages (before the 20th week, during the 20th–28th week or after the 28th week of gestation). No significant difference in ARG levels was observed between PE and controls at any stage (P > 0.05). The serum hARG levels and hARG/ADMA ratios of MPE before the 20th week were higher than those of controls (P < 0.001). ADMA levels of MPE were higher than those of controls during the 20th–28th week (P < 0.01). SDMA levels of SPE were higher than those of MPE (P < 0.01) and controls (P < 0.05) after the 28th week. Elevated serum hARG before the 20th week was identified as an independent predictor for PE (OR = 1.478, 95% CI 1.120–1.950). ROC curve analysis showed serum hARG before the 20th week had a good potential to predict MPE (AUC = 0.875, 95% CI 0.759–0.948). In conclusion, our study indicated that elevated serum hARG and dimethylarginine levels detected by LC–MS/MS might serve as potential biomarkers for the early prediction of PE.

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Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study

Cited by 21 publications

References 56 publications

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories

Evaluation of the predictive values of elevated serum l-homoarginine and dimethylarginines in preeclampsia

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