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Journal of Reproductive Immunology Sep 2023Extracellular vesicles (EVs) are cell-derived particles released during different pathophysiological processes and emerging as relevant players in inter-cellular... (Observational Study)
Observational Study
OBJECTIVES
Extracellular vesicles (EVs) are cell-derived particles released during different pathophysiological processes and emerging as relevant players in inter-cellular crosstalk. Previous studies have highlighted the role of EVs as potential biomarkers for several pregnancy complications, including miscarriage, pre-eclampsia and gestational diabetes. Despite that, the actual distribution of EVs through gestation has not been reported yet. The aim of this study was to report the concentration of different sub-types of EVs in the first, second and third trimester of pregnancy and to correlate them with different pregnancy and ultrasound characteristics.
STUDY DESIGNS
Prospective observational study including uncomplicated pregnancies in the first, second and third trimester of pregnancy. The first aim of the study was to report the concentration of the EVs derived from endothelial, epithelial, platelet and leukocyte cells of maternal peripheral blood samples in the first, second and third trimester pregnancy using polychromatic flow cytometry. The secondary aim was to correlate EVs with neonatal birthweight and fetal Dopplers, including uterine and umbilical arteries. Un and multivariate analyses were used to compute the data.
RESULTS
64 women (20 in the first, 22 in the second and 22 in the third trimester of pregnancies) were included in the analysis. There was no difference in the median concentration of either platelet, leukocyte and endothelial EVs between the first, second and third trimester of pregnancy. The concentration of epithelial derived EVs was higher in the third compared to first and second trimester of pregnancy. When analyzing the percentage of EV vesicles through gestation, there was no difference in the percentage of either leukocyte or endothelial EVs through gestation. Conversely, the median percentage of platelet derived vesicles was higher in the first (48.7 %, IQR 34.1-58.5) compared to second (34.0 %, IQR 22.7-44.9) and third (9.13 %, IQR 5.01-12.1) trimester of pregnancy, while the median percentage of third trimester (6.01, IQR 2.42-7.34) epithelial derived vesicles was higher than that of the second (1.53 %, IQR 0.65-2.98), but not of the first (4.45 %, IQR 1.44-6.07) trimester. Finally, we found no association between the median concentration or percentage of endothelial, epithelial, leukocyte vesicles, neonatal birthweight and fetal or maternal Dopplers.
CONCLUSIONS
Distribution of EVs examined does not change during the three trimesters of pregnancy and is not influenced by neonatal birthweight or maternal and fetal Dopplers. The findings from this study allows a more objective interpretation of studies comparing EVs in pregnancies with compared to those without obstetric complication. EVs in future can be used for "liquid biopsy" for the early diagnosis of pathological pregnancies up to the development of possible screening protocols.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Birth Weight; Pregnancy Trimesters; Pregnancy Trimester, Third; Diabetes, Gestational; Extracellular Vesicles
PubMed: 37454539
DOI: 10.1016/j.jri.2023.103987 -
The Journal of Maternal-fetal &... Dec 2023The majority of expectant mothers report sleep alterations during pregnancy and almost 40% report poor sleep quality. There is growing evidence that sleep quality (SQ)... (Review)
Review
BACKGROUND
The majority of expectant mothers report sleep alterations during pregnancy and almost 40% report poor sleep quality. There is growing evidence that sleep quality (SQ) during pregnancy influences maternal health. This review focuses on how SQ during pregnancy relates to maternal health-related quality of life (HRQoL). The review also aims to identify whether this relation varies between pregnancy trimesters, and for different subdomains of HRQoL.
METHODS
A systematic review was performed according to PRISMA guidelines and registered on Prospero in August 2021 with ID no: CRD42021264707. Pubmed, Psychinfo, Embase, Cochrane, and trial registries were searched up to June 2021. Studies with any design that investigated the relation between SQ and quality of life/HRQoL in pregnant women, published in English, and peer-reviewed, were included. Two independent reviewers screened titles, abstracts, and full texts, and extracted data from the included papers. The quality of the studies was evaluated using the Newcastle-Ottawa Scale.
RESULTS
Three hundred and thirteen papers were identified in the initial search, of which 10 met the inclusion criteria. Data included 7330 participants from six different countries. The studies had longitudinal ( = 1) or cross-sectional designs ( = 9). In nine studies SQ was reported subjectively by self-report questionnaires. Actigraphic data was available from two studies. HRQoL was assessed by validated questionnaires in all studies. Due to high levels of clinical and methodological heterogeneity in included studies, a narrative synthesis was employed. Nine studies found that poor sleep quality was related to a lower overall HRQoL during pregnancy. Effect sizes were low to medium. This relation was reported most during the third trimester. Especially sleep disturbances and subjective low SQ seemed to be related consistently to lower HRQoL. Furthermore, an indication was found that SQ might have a relation with the mental and physical domain of HRQoL. The social and environmental domain may also be associated with overall SQ.
CONCLUSION
Despite the scarcity of studies available, this systematic review found evidence that low SQ is related to low HRQoL during pregnancy. An indication was found that the relationship between SQ and HRQoL during the second trimester might be less prominent.
Topics: Humans; Female; Pregnancy; Quality of Life; Sleep Quality; Cross-Sectional Studies; Pregnant Women; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 37197986
DOI: 10.1080/14767058.2023.2212829 -
Autoimmunity Reviews Dec 2023Complement levels have been proposed as candidate biomarkers of disease activity and obstetric risk in systemic lupus erythematosus (SLE) pregnancies, but their... (Meta-Analysis)
Meta-Analysis Review
Complement levels during the first trimester predict disease flare and adverse pregnancy outcomes in systemic lupus erythematosus: A network meta-analysis on 532 pregnancies.
BACKGROUND
Complement levels have been proposed as candidate biomarkers of disease activity and obstetric risk in systemic lupus erythematosus (SLE) pregnancies, but their reliability has been questioned due to the physiologic fluctuations of complement during gestation. Thus, this network meta-analysis aimed at assessing the clinical significance of complement fluctuations in lupus pregnant women.
METHODS
Corresponding authors of 19 studies meeting inclusion criteria were invited to contribute with additional data including C3 and C4 levels [before pregnancy, at conception, in every trimester (T) and 3 months after delivery]; data were pooled together in a network meta-analysis.
RESULTS
A total of 532 lupus women from four studies were included in the analysis. In SLE women, C3 and C4 increased progressively during gestation: levels remained stable during T1 and peaked in T2 to decrease in T3. Patients with previous lupus nephritis (LN) and those who experienced flares during pregnancy had significantly lower mean levels of C3 and C4 at all timepoints. The lowest levels of complement were observed, particularly during T1, in patients with LN and gestational flare. Both reduction and the lack of increase of C3 and C4 levels at T1 versus conception were associated with gestational flares, particularly in LN patients. Pregnancies with flare had a statistically significant higher rate of maternal and fetal complications(60% versus 50.3%; p = 0.03).
CONCLUSIONS
Low complement levels, particularly in T1, were associated with a higher frequency of gestational flare. Either reduction or smaller increase of C3 and/or C4 levels, even within normal range, might predict flares especially in early gestation.
Topics: Humans; Female; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Network Meta-Analysis; Reproducibility of Results; Symptom Flare Up; Pregnancy Complications; Lupus Erythematosus, Systemic; Lupus Nephritis; Complement System Proteins; Retrospective Studies
PubMed: 37852515
DOI: 10.1016/j.autrev.2023.103467 -
International Journal of Molecular... Jun 2024The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early... (Review)
Review
The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.
Topics: Humans; Pregnancy; Female; Biomarkers; Pregnancy Trimester, First; Placenta; Pregnancy Outcome; Pre-Eclampsia; MicroRNAs; Pregnancy-Associated Plasma Protein-A; Diabetes, Gestational
PubMed: 38892323
DOI: 10.3390/ijms25116136 -
Physiology & Behavior Jan 2024Pregnancy is a transformative phase marked by significant behavioral and physiological changes. Substantial changes in pregnancy-related hormones are thought to induce... (Meta-Analysis)
Meta-Analysis Review
Pregnancy is a transformative phase marked by significant behavioral and physiological changes. Substantial changes in pregnancy-related hormones are thought to induce changes in chemosensory perception, as often observed in non-human animals. However, empirical behavioral research on pregnancy-related olfactory or gustatory changes has not yet reached a consensus. This PROSPERO pre-registered systematic review and meta-analysis evaluated published data of olfactory and gustatory changes in pregnant individuals, across the three pregnancy trimesters and postpartum period. Our comprehensive search strategy identified 20 relevant studies, for inclusion in the meta-analysis. The meta-analysis revealed that pregnant individuals, regardless of trimester, performed significantly poorer in terms of odour identification, however, no difference was detected between non-pregnant controls and women postpartum. Additionally, pregnant women in the second and third trimester rated olfactory stimuli to be more intense. A slight decline in odour pleasantness ratings was observed amongst those in the second trimester. No major difference was observed between pregnant and non-pregnant subjects in terms of gustatory functions, except the first trimester appeared to be associated with increased pleasantness for the sweet taste. Post-hoc meta-regression analyses revealed that pregnancy stage was a significant predictor for observed effect size for odour intensity ratings, but not for odour identification scores. These findings provide valuable insights into the interplay between pregnancy and chemosensory perception, highlighting systematic physiological changes due to pregnancy. Healthcare providers can also utilize the knowledge of sensory shifts to better support pregnant women in making appropriate dietary choices, managing sense-related discomfort, and leading to potential sensory interventions. Overall, this research enhances our comprehension of sensory shifts during pregnancy, benefiting maternal health and pregnancy-related care.
Topics: Pregnancy; Female; Humans; Postpartum Period; Smell; Taste Perception; Diet; Odorants
PubMed: 37890603
DOI: 10.1016/j.physbeh.2023.114388 -
Science (New York, N.Y.) Oct 2023The thalamus plays a central coordinating role in the brain. Thalamic neurons are organized into spatially distinct nuclei, but the molecular architecture of thalamic...
The thalamus plays a central coordinating role in the brain. Thalamic neurons are organized into spatially distinct nuclei, but the molecular architecture of thalamic development is poorly understood, especially in humans. To begin to delineate the molecular trajectories of cell fate specification and organization in the developing human thalamus, we used single-cell and multiplexed spatial transcriptomics. We show that molecularly defined thalamic neurons differentiate in the second trimester of human development and that these neurons organize into spatially and molecularly distinct nuclei. We identified major subtypes of glutamatergic neuron subtypes that are differentially enriched in anatomically distinct nuclei and six subtypes of γ-aminobutyric acid-mediated (GABAergic) neurons that are shared and distinct across thalamic nuclei.
Topics: Humans; Thalamic Nuclei; Thalamus; GABAergic Neurons; Female; Pregnancy; Single-Cell Analysis; Neurogenesis; Pregnancy Trimester, Second
PubMed: 37824646
DOI: 10.1126/science.adf9941 -
JAMA Network Open Sep 2023Prenatal cardiac screening of the first and second trimesters has had a major impact on postnatal prevalence of congenital heart defects (CHDs), rates of termination of...
IMPORTANCE
Prenatal cardiac screening of the first and second trimesters has had a major impact on postnatal prevalence of congenital heart defects (CHDs), rates of termination of pregnancy (TOP), and outcomes among children born alive with CHDs.
OBJECTIVE
To examine the prenatal and postnatal incidence of major CHDs (ie, necessitating intervention within the first year of life), detection rate trends, rates of TOP, and the association of cardiac screening with postnatal outcomes.
DESIGN, SETTINGS, AND PARTICIPANTS
In this cross-sectional study, 3827 fetuses with antenatally diagnosed major CHDs in the Czech Republic (population 10.7 million) between 1991 and 2021 were prospectively evaluated with known outcomes and associated comorbidities. Prenatal and postnatal prevalence of CHD in an unselected population was assessed by comparison with a retrospective analysis of all children born alive with major CHDs in the same period (5454 children), using national data registry. Data analysis was conducted from January 1991 to December 2021.
MAIN OUTCOMES AND MEASURES
Prenatal detection and postnatal prevalence of major CHDs and rate of TOPs in a setting with a centralized health care system over 31 years.
RESULTS
A total of 3 300 068 children were born alive during the study period. Major CHD was diagnosed in 3827 fetuses, of whom 1646 (43.0%) were born, 2069 (54.1%) resulted in TOP, and 112 (2.9%) died prenatally. The prenatal detection rate increased from 6.2% in 1991 to 82.8% in 2021 (P < .001). Termination of pregnancy decreased from 70% in 1991 to 43% (P < .001) in 2021. Of 627 fetuses diagnosed in the first trimester (introduced in 2007), 460 were terminated (73.3%). Since 2007, of 2066 fetuses diagnosed in the second trimester, 880 (42.6%) were terminated, resulting in an odds ratio of 3.6 (95% CI, 2.8-4.6; P < .001) for TOP in the first trimester compared with the second trimester. Postnatal prevalence of major CHDs declined from 0.21% to 0.14% (P < .001). The total incidence (combining prenatal detection of terminated fetuses with postnatal prevalence) of major CHD remained at 0.23% during the study period.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, the total incidence of major CHD did not change significantly during the 31-year study period. The prenatal detection of major CHD approached 83% in the current era. Postnatal prevalence of major CHD decreased significantly due to early TOPs and intrauterine deaths. The introduction of first trimester screening resulted in a higher termination rate in the first trimester but did not revert the overall decreasing trend of termination for CHDs in general.
Topics: Child; Female; Pregnancy; Humans; Cross-Sectional Studies; Prevalence; Retrospective Studies; Heart Defects, Congenital; Abortion, Induced
PubMed: 37713196
DOI: 10.1001/jamanetworkopen.2023.34069 -
Environment International Apr 2024Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine...
BACKGROUND
Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes.
OBJECTIVES
To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity.
METHODS
In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity.
RESULTS
We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories.
CONCLUSION
Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.
Topics: Humans; Female; Pregnancy; Adult; Fluorocarbons; Blood Pressure; Environmental Pollutants; Pregnancy Trimester, Third; Pregnancy Trimester, First; Pregnancy Trimester, Second; Young Adult; Maternal Exposure; Alkanesulfonic Acids
PubMed: 38583297
DOI: 10.1016/j.envint.2024.108628 -
Journal of Clinical Medicine Dec 2023Data on the real long-term influences of in utero drug exposure in pregnant women on childhood development are scarce and remain not well determined and depend on the... (Review)
Review
Data on the real long-term influences of in utero drug exposure in pregnant women on childhood development are scarce and remain not well determined and depend on the duration of in utero drug exposure and maternal drug levels. Therapeutic drug monitoring (TDM) during pregnancy may help limit fetal drug exposure while maintaining an effective dose for the treatment of the underlying inflammatory bowel disease (IBD) in women. Most antibody therapies used in patients with IBD are IgG molecules which are actively transported across the placenta, especially during the third trimester of the pregnancy. Here, we propose an up-to-date clinical review to summarize the available findings of serum drug levels in maternal blood during pregnancy, in the cord blood, infants at delivery and in breast milk of patients with IBD treated with biologics. Conversely, in comparison to adalimumab (ADA) levels, which are relatively stable during pregnancy, infliximab (IFX) drug clearance decreased significantly during the last two trimesters of the pregnancy, leading to increasing drug concentrations in the blood of the pregnant women. As most guidelines recommend using live vaccines in infants at the age of one or earlier in case of negative serum drug levels in newborns, statistical models could help clinicians in making a decision to adjust the last dose of the biologic during pregnancy and to determine the optimal date to vaccinate. Altogether, data from the literature offers strong reassurance in terms of safety for anti-TNFα therapies during pregnancy not only for IBD patients who intend to conceive, but also for pregnant women and for the physicians taking care of these patients. ADA and IFX levels in breast milk are detectable, but at very low levels, and therefore, it is recommended to pursue breast feeding under anti-TNFα therapy. Our knowledge on ustekinumab or vedolizumab levels in pregnant women remains unclear and scarce. These drugs are currently not recommended for patients with IBD in clinical practice. Therefore, TDM and proactive dose adjustment are not necessary during pregnancy since its impact on making a clinical decision have not yet been clearly demonstrated in routine practice. Overall, drug concentrations in the cord blood, an infant at birth and postpartum serum concentrations in infants, due to active placental drug transfer, may have a greater impact than the limited drug transfer in breast milk during lactation on the risk of infection and developmental outcomes. Ustekinumab and vedolizumab exposure during pregnancy and lactation are both considered low risk by the recent ECCO guidelines despite the limited data that are currently available.
PubMed: 38068547
DOI: 10.3390/jcm12237495