Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond
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ABSTRACT:
SUBMITTER: Jarmund A
PROVIDER: S-EPMC8552528 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveWe hypothesized that the origins of abruption may extend to the stages of placental implantation; however, there are no reliable markers to predict its development. Based on this hypothesis, we sought to evaluate whether first-trimester and second-trimester serum analytes predict placental abruption.MethodsWe performed a secondary analysis of data of 35,307 women (250 abruption cases) enrolled in the First and Second Trimester Evaluation of Risk cohort (1999-2003), a multicenter, prospective cohort study. Percentiles (based on multiples of the median) of first-trimester (pregnancy-associated plasma protein A and total and free β-hCG) and second-trimester (maternal serum alpha-fetoprotein, unconjugated estriol, and inhibin-A) serum analytes were examined in relation to abruption. Associations are based on risk ratio (RR) and 95% confidence interval (CI).ResultsWomen with an abnormally low pregnancy-associated plasma protein A (fifth percentile or less) were at increased risk of abruption compared with those without abruption (9.6% compared with 5.3%; RR 1.9, 95% CI, 1.2-2.8). Maternal serum alpha-fetoprotein 95th percentile or greater was more common among abruption (9.6%) than nonabruption (5.1%) pregnancies (RR 1.9, 95% CI 1.3-3.0). Inhibin-A fifth percentile or less (8.0% compared with 5.1%; RR 1.8, 95% CI 1.1-2.9), and 95th percentile or greater (9.6% compared with 5.0%; RR 2.0, 95% CI 1.3-3.1) were associated with abruption. Women with all three abnormal pregnancy-associated plasma protein A, maternal serum alpha-fetoprotein, and inhibin-A analytes were at 8.8-fold (95% CI 2.3-34.3) risk of abruption. No associations were seen with other analytes.ConclusionThese data provide support for our hypothesis that the origins of placental abruption may extend to the early stages of pregnancy.
| S-EPMC5367463 | biostudies-literature
Project description:BackgroundPlacental growth factor (PGF), soluble fms-like tyrosine kinase 1 (sFLT1) and asymmetric dimethylarginine (ADMA) are involved in the pathogenesis of preeclampsia. Abnormal maternal sFLT1, PGF and ADMA levels are detectable weeks before the onset of preeclampsia.ObjectiveTo investigate sFLT1, PGF and ADMA in the first trimester of pregnancy as predictors of preeclampsia.MethodsIn this prospective nested case-control study, 740 pregnant women enrolled at 12-16 weeks of gestation and followed up until 6 weeks after delivery at the Shanghai First Maternity and Infant Health Hospital of Tongji University between January 2010 and December 2012. Forty-four women developed preeclampsia. Urinary proteins were measured using 24-hour collection or dipsticks. sFLT1, PGF and ADMA were measured by ELISA in the first trimester. Pulsatility index (PI) was measured by Doppler ultrasound in the second trimester.ResultsFirst-trimester serum sFLT1 and ADMA levels of women who developed preeclampsia were significantly higher compared with women with normal pregnancies (sFLT1: 0.321 ± 0.023 vs. 0.308 ± 0.019 ng/ml, P = 0.001; ADMA: 0.86 ± 0.16 vs. 0.68 ± 0.20 μM, P < 0.001). First-trimester serum PGF levels of women who developed preeclampsia were significantly lower than in women with normal pregnancies (115.72 ± 32.55 vs. 217.30 ± 74.48 pg/ml, P < 0.001). Multiple logistic regression and receiver-operating characteristic curves identified first-trimester PGF and ADMA to be sensitive and selective predictors of preeclampsia (area under the curve [AUC]: 0.902), as well as second-trimester uterine artery pulse index (AUC: 0.836).ConclusionIn the first trimester, maternal serum sFLT1, PGF and ADMA levels, as well as second-trimester uterine artery PI, could predict preeclampsia.
| S-EPMC4408038 | biostudies-literature
Project description:Characterization of normal changes in the serum proteome during pregnancy may enhance understanding of maternal physiology and lead to the development of new gestational biomarkers. In 23 Nepalese pregnant women who delivered at term, two-dimensional difference in-gel electrophoresis (DIGE) was used to assess changes in relative protein abundance between paired serum samples collected in the first and third trimesters. One-hundred and forty-five of over 700 protein spots in DIGE gels (pI 4.2-6.8) exhibited nominally significant (p < 0.05) differences in abundance across trimesters. Additional filtering using a Bonferroni correction reduced the number of significant (p < 0.00019) spots to 61. Mass spectrometric analysis detected 38 proteins associated with gestational age, cytoskeletal remodeling, blood pressure regulation, lipid and nutrient transport, and inflammation. One new protein, pregnancy-specific ?-glycoprotein 4 was detected. A follow-up isotope tagging for relative and absolute quantitation (iTRAQ) experiment of six mothers from the DIGE study revealed 111 proteins, of which 11 exhibited significant (p < 0.05) differences between trimesters. Four of these proteins: gelsolin, complement C1r subcomponent, ?-1-acid glycoprotein, and ?-1B-glycoprotein also changed in the DIGE analysis. Although not previously associated with normal pregnancy, gelsolin decreased in abundance by the third trimester (p < 0.01) in DIGE, iTRAQ and Western analyses. Changes in abundance of proteins in serum that are associated with syncytiotrophoblasts (gelsolin, pregnancy-specific ?-1 glycoprotein 1 and ?-2-glycoprotein I) probably reflect dynamics of a placental proteome shed into maternal circulation during pregnancy. Measurement of changes in the maternal serum proteome, when linked with birth outcomes, may yield biomarkers for tracking reproductive health in resource poor settings in future studies.
| S-EPMC4703092 | biostudies-literature
Project description:ObjectiveThe objective of the study was to combine early, direct assessment of the placenta with indirect markers of placental development to identify pregnancies at greatest risk of delivering small-for-gestational age infants (SGA10).Study designWe prospectively collected 3-dimensional ultrasound volume sets, uterine artery pulsatility index, and maternal serum of singleton pregnancies at 11-14 weeks. Placental volume (PV), quotient (placental quotient [PQ] = PV/gestational age), mean placental diameter (MPD) and chorionic diameters, and the placental morphology index (PMI = MPD/PQ and adjusts the lateral placental dimensions for quotient) were measured offline. Maternal serum was assayed for placental growth factor and placental protein-13. These variables were evaluated as predictors of SGA10.ResultsOf the 578 pregnancies included in the study, 56 (9.7%) delivered SGA10. SGA10 pregnancies had a significantly smaller PV, PQ, MPD, and mean placental diameter and higher PMI compared with normal pregnancies (P < .001 for each). Each placental measure remained significantly associated with SGA10 after adjusting for confounders and significantly improved the performance of the model using clinical variables alone (P < .04 for each) with adjusted areas under the curve ranging from 0.71 to 0.74. Uterine artery pulsatility index did not remain significantly associated with SGA10 after adjusting for confounders (P = .06). Placental growth factor was significantly lower in SGA10 pregnancies (P = .02) and remained significant in adjusted models but failed to significantly improve the predictive performance of the models as measured by area under the curve (P > .3). Placental protein-13 was not associated with SGA10 (P = .99).ConclusionDirect assessment of placental size and shape with 3-dimensional ultrasound can serve as the foundation upon which to build a multivariable model for the early prediction of SGA.
| S-EPMC4149853 | biostudies-literature
Project description:BackgroundMonochorionic twin pregnancies are at high risk of adverse outcomes, but it is not possible to predict which pregnancies will develop complications. The aim of the study was to evaluate, in monochorionic twin pregnancies, whether first-trimester ultrasound (nuchal translucency [NT], crown-rump length [CRL]), and maternal serum biomarkers (alpha-fetoprotein [AFP], soluble fms-like tyrosine kinase-1 [sFlt-1] and placental growth factor [PlGF]), are prognostic factors for fetal adverse outcome composite, twin-twin transfusion syndrome (TTTS), growth restriction, and intrauterine fetal death (IUFD).MethodsA cohort study of 177 monochorionic diamniotic twin pregnancies. Independent prognostic ability of each factor was assessed by multivariable logistic regression, adjusting for standard prognostic factors. Factors were analysed as continuous data; thus, the reported ORs relate to either 1% change in NT or CRL inter-twin percentage discordance or one unit of measure in each serum biomarker.ResultsThe odds of the fetal adverse outcome composite were significantly associated with increased NT inter-twin percentage discordance (adjusted OR 1.03 [95% CI 1.01, 1.06]) and CRL inter-twin percentage discordance (adjusted OR 1.17 [95% CI 1.07, 1.29]). TTTS was significantly associated with increased NT discordance (adjusted OR 1.06 [95% CI 1.03, 1.10]) and decreased PlGF (adjusted OR 0.42 [95% CI 0.19, 0.93]). Antenatal growth restriction was significantly associated with increased CRL discordance (adjusted OR 1.20 [95% CI 1.08, 1.34]). Single and double IUFD were associated with decreased PlGF (adjusted OR 0.34 [95% CI 0.12, 0.98]) and (adjusted OR 0.18 [95%CI 0.05, 0.58]) respectively.ConclusionsThis study has identified potential individual prognostic factors in the first trimester (fetal biometric and maternal serum biomarkers) that show promise but require further robust evaluation in a larger, prospective series of MC twin pregnancies, so that their usefulness both individually and in combination can be defined.Trial registrationISRCTN 13114861 (retrospectively registered).
| S-EPMC6507122 | biostudies-literature
Project description:Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) are known to be associated with the development of pregnancy-related complications like small for gestational age infants, intrauterine fetal demise, gestational diabetes and preeclampsia. The study aims to find possible long-term correlations with the development of metabolic and cardiovascular complications in the mothers and their progeny in later life. This is a retrospective cohort study conducted on consecutive unselected women screened for chromosomal anomalies in the first trimester of pregnancy between 2004 and 2010. PAPP-A values as well as clinical data collected at childbirth were considered. A maternal and neonatal follow-up was performed through a telephone interview with the mother during 2015. The body-mass-index and the presence of cardiovascular diseases, dyslipidaemia and diabetes mellitus were evaluated. The analysis included 988 patients. The median time of follow-up was 7 years (IQR 6-9). Lower first trimester maternal blood PAPP-A quartiles were associated with small stature of the offspring (z-score 1st-2nd quartile 0.37 IQR -0.42 and 1.17 vs 3rd-4th quartile 0.67 IQR -0.17 and 1.36, p?<?0.05). Furthermore, low first trimester PAPP-A in pregnancy without other gestations following the index one, in Kaplan-Meier analysis was associated to a significant increase of hypoglycemic agents use at 7 and 10 years (respectively 1.12% CI.95 0-2.38% and 5.45% CI.95 0-10.82%) compared to the control group of high first trimester PAPP-A values (0% CI.95 0-0%) (p?<?0.05). Low PAPP-A serum levels in the first trimester of pregnancy are associated with short stature in offspring and de-novo development of maternal diabetes mellitus in later life.
| S-EPMC7083850 | biostudies-literature
Project description:Evidence suggests that maternal metabolome may be associated with child health outcomes. We analyzed the association between the maternal metabolome between 28-35 gestational weeks and child growth and development during the first year. A prospective cohort of 98 mother-child dyads was followed at birth, 1, 6, and 12 months. Maternal serum samples were collected for targeted LC-MS/MS analysis, which measured 132 metabolites. The child's growth and development were assessed at each time-point. Z-scores were calculated based on WHO growth standards, and the domains of development were assessed using the Ages and Stages Questionnaires (ASQ-3). Multiple linear mixed-effects models were performed and confounders were identified using a Diagram Acyclic Graph. The Benjamini-Hochberg correction was used for multiple comparison adjustments. We found a positive association between lysophosphatidylcholines (14:0; 16:0; 16:1; 17:0; 18:0; 18:1; 18:2; 20:4) with the z-score of weight-for-age, and lysophosphatidylcholines (14:0; 16:0; 16:1; 18:0) and taurine with the z-score of weight-for-length, and lysophosphatidylcholines (14:0; 16:0; 16:1; 17:0; 18:0; 18:1; 18:2; 20:4) and glycine with the z-score of BMI-for-age. The leucine, methionine, tryptophan, and valine were negatively associated with the fine motor skills domain. We observed an association between maternal metabolome and the growth and child's development throughout the first year.
| S-EPMC11306240 | biostudies-literature
Project description:ObjectiveTo explore noninvasively the complex interactions of the maternal hemodynamic system throughout pregnancy and the resulting after-effect six weeks postpartum.MethodsEighteen women were tested beginning at the 12th week of gestation at six time-points throughout pregnancy and six weeks postpartum. Heart rate, heart rate variability, blood pressure, pulse transit time (PTT), respiration, and baroreceptor sensitivity were analyzed in resting conditions. Additionally, hemoglobin, asymmetric and symmetric dimethylarginine and Endothelin (ET-1) were obtained.ResultsHeart rate and sympathovagal balance favoring sympathetic drive increased, the vagal tone and the baroreflex sensitivity decreased during pregnancy. Relative sympathetic drive (sympathovagal balance) reached a maximum at 6 weeks postpartum whereas the other variables did not differ compared to first trimester levels. Postpartum diastolic blood pressure was higher compared to first and second trimester. Pulse transit time and endothelial markers showed no difference throughout gestation. However, opposing variables PTT and asymmetric dimethylarginine (ADMA) were both higher six weeks postpartum.ConclusionsThe sympathetic up regulation throughout pregnancy goes hand in hand with a decreased baroreflex sensitivity. In the postpartum period, the autonomic nervous system, biochemical endothelial reactions and PTT show significant and opposing changes compared to pregnancy findings, indicating the complex aftermath of the increase of blood volume, the changes in perfusion strategies and blood pressure regulation that occur in pregnancy.
| S-EPMC5962097 | biostudies-literature
Project description:Maternal iodine (I) status is critical in embryonic and foetal development. We examined the effect of preconception iodine supplementation on maternal iodine status and on birth outcomes. Non-pregnant women in Guatemala, India and Pakistan (n ~ 100 per arm per site) were randomized ≥ 3 months prior to conception to one of three intervention arms: a multimicronutrient-fortified lipid-based nutrient supplement containing 250-μg I per day started immediately after randomization (Arm 1), the same supplement started at ~12 weeks gestation (Arm 2) and no intervention supplement (Arm 3). Urinary I (μg/L) to creatinine (mg/dl) ratios (I/Cr) were determined at 12 weeks for Arm 1 versus Arm 2 (before supplement started) and 34 weeks for all arms. Generalized linear models were used to assess the relationship of I/Cr with arm and with newborn anthropometry. At 12 weeks gestation, adjusted mean I/Cr (μg/g) for all sites combined was significantly higher for Arm 1 versus Arm 2: (203 [95% CI: 189, 217] vs. 163 [95% CI: 152, 175], p < 0.0001). Overall adjusted prevalence of I/Cr < 150 μg/g was also lower in Arm 1 versus Arm 2: 32% (95% CI: 26%, 38%) versus 43% (95% CI: 37%, 49%) (p = 0.0052). At 34 weeks, adjusted mean I/Cr for Arm 1 (235, 95% CI: 220, 252) and Arm 2 (254, 95% CI: 238, 272) did not differ significantly but were significantly higher than Arm 3 (200, 95% CI: 184, 218) (p < 0.0001). Nominally significant positive associations were observed between I/Cr at 12 weeks and birth length and head circumference z-scores (p = 0.028 and p = 0.005, respectively). These findings support the importance of first trimester iodine status and suggest need for preconception supplementation beyond salt iodization alone.
| S-EPMC8476419 | biostudies-literature
Project description:OBJECTIVE:To assess the relationship between first-trimester vaginal bleeding and fetal growth patterns. METHODS:We conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons, a prospective cohort study of low-risk, nonobese women with healthy lifestyles. Duration of bleeding was self-reported at enrollment (10 0/7 to 13 6/7 weeks of gestation) and categorized as 0, 1, or more than 1 day. Longitudinal measures of fetal biometrics were obtained in up to six study visits, and estimated fetal weight was computed. Growth trajectories were created for biometrics and estimated fetal weight. When global tests among groups was significant (P<.05), week-specific global and pairwise differences were tested. Birth weight and risk of a small-for-gestational-age (SGA) neonate were secondary outcomes. All analyses were adjusted for maternal age, weight, height, parity, and racial-ethnic group and neonatal sex in a sensitivity analysis. RESULTS:In 2,307 eligible women, 410 (17.8%) reported first-trimester bleeding, of whom 176 bled for 1 day and 234 bled for more than 1 day. Women with more than 1 day of bleeding demonstrated decreased fetal abdominal circumference from 34 to 39 weeks of gestation compared with women without bleeding. For women with more than 1 day of bleeding, compared with women without bleeding, estimated fetal weight was 68-107 g smaller from 35 to 39 weeks of gestation. Mean birth weight at term was 88 g smaller, confirming differences in calculated fetal weight, and SGA neonates were delivered to 148 (8.5%), 9 (5.7%), and 33 (15.7%) women in the no bleeding, 1 day, and more than 1 day of bleeding groups, respectively. CONCLUSION:More than 1 day of first-trimester vaginal bleeding was associated with smaller estimated fetal weight late in pregnancy driven by smaller abdominal circumference. The magnitude of decrease in birth weight was small, albeit comparable with observed decreases associated with maternal smoking. It remains unknown whether early pregnancy bleeding is associated with short-term or long-term morbidity and whether additional intervention would be of benefit. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT00912132.
| S-EPMC6223322 | biostudies-literature