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Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.Human Reproduction (Oxford, England) Jun 2024What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course...
STUDY QUESTION
What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?
SUMMARY ANSWER
In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.
WHAT IS KNOWN ALREADY
Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.
STUDY DESIGN, SIZE, DURATION
The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.
WIDER IMPLICATIONS OF THE FINDINGS
Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.
STUDY FUNDING/COMPETING INTEREST(S)
The research received no specific funding, and the authors declare no competing interests.
TRIAL REGISTRATION NUMBER
clinicaltrial.gov NCT05557201.
PubMed: 38942601
DOI: 10.1093/humrep/deae146 -
The American Journal of Clinical... Jun 2024The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some...
BACKGROUND
The current Institute of Medicine pregnancy weight gain guidelines were developed using the best available evidence, but were limited by substantial knowledge gaps. Some have raised concern that the guidelines for individuals affected by overweight or obesity are too high and contribute to short- and long-term complications for the mother and child.
OBJECTIVE
To determine the association between pregnancy weight gain below the lower limit of the current Institute of Medicine (IOM) recommendations and risk of 10 adverse maternal and child health outcomes among individuals with overweight and obesity.
METHODS
We used data from a prospective cohort study of US nulliparae with prepregnancy overweight (n=955) or obesity (n=897) followed from the first trimester to 2-7 years postpartum. We used multivariable Poisson regression to relate pregnancy weight gain z-scores with a severity-weighted composite outcome consisting of ≥1 of 10 adverse outcomes (gestational diabetes, preeclampsia, unplanned cesarean delivery, maternal postpartum weight increase >10kg, maternal postpartum metabolic syndrome, infant death, stillbirth, preterm birth, small-for-gestational age birth, and childhood obesity).
RESULTS
Pregnancy weight gain z-scores below, within, and above the IOM-recommended ranges occurred in 5%, 13%, and 80% of pregnancies with overweight and 17%, 13%, and 70% of pregnancies with obesity. There was a positive association between pregnancy weight gain z-scores and all adverse maternal outcomes, childhood obesity, and the composite outcome. Pregnancy weight gain z-scores below the lower limit of the recommended ranges (<6.8 kg for overweight, <5 kg for obesity) were not associated with the severity-weighted composite outcome. For example, compared with the lower limit, adjusted rate ratios (95% confidence interval) for z-scores of -2 standard deviations in pregnancies with overweight (equivalent to 3.6kg at 40 weeks) and obesity (-2.8kg at 40 weeks) were 0.99 (0.91, 1.06) and 0.97 (0.87, 1.07).
CONCLUSIONS
These findings support arguments to decrease the lower limit of recommended weight gain ranges in these prepregnancy BMI groups.
PubMed: 38942117
DOI: 10.1016/j.ajcnut.2024.06.011 -
Reproductive Biology Jun 2024Mesenchymal cells within theplacental villi play a crucial role in shaping the morphology of branching structures and driving the development of blood vessels. However,...
Mesenchymal cells within theplacental villi play a crucial role in shaping the morphology of branching structures and driving the development of blood vessels. However, the markers and functions of placental villous pericytes (PVPs) as distinct subgroups of placental villous mesenchymal cells, remain unclear. Therefore, in this study, the markers and functions of PVPs were investigated. Single-cell sequencing data from the first-trimester placental villi was obtained and the Seurat tool was used to identify PVP markers. Gene Ontology (GO) analysis of specific genes was performed using the DAVID database. The Cellchat tool was employed to investigate the interaction signals between the PVPs and other cells. Expression of the PVP markers was confirmed using immunofluorescence. Presence of extracellular vesicles in the placental villous mesenchyme and PVPs was examined by transmission electron microscopy. Our findings revealed that renin (REN) and amphiregulin (AREG)-positive fibroblasts in the placental villi specifically expressed several classic pericyte markers. In the first trimester, certain conserved functions of pericytes were observed and they displayed tissue-specific functions such as in the integrin-mediated signaling pathway and extracellular exosomes. Moreover, the placental villous mesenchyme was found to be rich in extracellular vesicles. AREG is specifically transcribed in the first trimester PVPs, however, its protein was located in syncytiotrophoblasts. These insights contribute to a comprehensive understanding of early placental development and offer new therapeutic targets for placenta-derived pregnancy complications.
PubMed: 38941941
DOI: 10.1016/j.repbio.2024.100919 -
Journal of Reproductive Immunology Jun 2024Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor... (Review)
Review
Chronic Intervillositis of Unknown Etiology (CIUE) is a rare idiopathic inflammatory disorder of the placenta. The evidence suggests an increased risk for poor obstetrical outcomes and a risk of recurrence as high as 100 %. This meta-analysis examined CIUE prevalence, recurrence, association with autoimmune disorders, reproductive outcomes, pregnancy complications, and the benefits of medical treatments. A systematic review, following PRISMA guidelines, involved a thorough search across multiple databases including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Evidence Based Medical Reviews, and Scopus. Out of 590 initially identified studies, 19 studies were included for both qualitative synthesis and meta-analysis after full-text review. Risk of bias was assessed using appropriate tools: The Risk Of Bias In Non-randomized Studies of Interventions tool was applied to twelve studies, while the Joanna Briggs Institute case series critical appraisal tool was used for seven studies. Our findings confirm that CIUE is a rare condition (0.7 %). CIUE is associated with decreased live birth rates (53 %), increased recurrent pregnancy loss (23 %), fetal loss beyond 22 weeks gestation (25 %), a higher prevalence of autoimmune diseases (14 %), and a recurrence rate of 30 % in subsequent pregnancies. Moreover, individuals with CIUE had higher rates of pregnancy complications, including gestational hypertension (19 %), intrauterine growth restriction (45 %), and preterm births (43 %). No significant improvement in live birth rate was observed among treated CIUE patients; however, caution is warranted when interpreting these findings due to the limited sample size. Future research in CIUE is crucial given its rarity and complexity.
PubMed: 38941926
DOI: 10.1016/j.jri.2024.104285 -
Psychiatry Research Jun 2024This study examined the association of clinical factors, independent of sex and high psychosocial adversity (HPAd), with the presence of ADHD or other mental disorders,...
This study examined the association of clinical factors, independent of sex and high psychosocial adversity (HPAd), with the presence of ADHD or other mental disorders, specifically within a middle-income country with a non-Caucasian population. A multi-centric cross-sectional study was conducted in three sites in Colombia. Our study recruited trios of an ADHD proband, one sibling, and one parent. We used valid instruments for assessing parents and siblings. The sample included 223 siblings, an average age of 12.3 (SD 3.9), and 51.1% Females. The ADHD recurrence risk ratio (λ) was 12. The clinical factors mainly associated with the presence of ADHD, independent of sex and HPAd, were 1) Pregnancy and childbirth complications, 2) Delayed psychomotor development, 3) Temperament, and 4) Sleep disturbances. Our research showed that, independently of HPAd and the male sex, there were other clinical factors associated with ADHD and other psychiatric disorders in this population. These findings need to be replicated in similar populations globally.
PubMed: 38941862
DOI: 10.1016/j.psychres.2024.115997 -
Midwifery Jun 2024Unnecessary cesarean delivery increases the risk of complications for birthing people and infants.
PROBLEM
Unnecessary cesarean delivery increases the risk of complications for birthing people and infants.
BACKGROUND
Examining the intersectionality of rural and racial disparities in low-risk cesarean delivery is necessary to improve equity in quality obstetrics care.
AIM
To evaluate rural and racial/ethnic differences in Nulliparous, Term, Singleton, Vertex (NTSV) and primary cesarean delivery rates before and during the COVID-19 pandemic in South Carolina.
METHODS
This retrospective cohort study used birth certificates linked to all-payer hospital discharge data for South Carolina childbirths from 2018 to 2021. Multilevel logistic regressions examined differences in cesarean outcomes by rural/urban hospital location and race/ethnicity of birthing people during pre-pandemic (January 2018-February 2020) and peri-pandemic periods (March 2020-December 2021), adjusting for maternal, infant, and hospital characteristics among two low-risk pregnancy cohorts: 1) Nulliparous, Term, Singleton, Vertex (NTSV, n = 65,974) and 2) those without prior cesarean (primary, n = 167,928).
FINDINGS
Black vs. White disparities remained for NTSV cesarean in adjusted models (urban pre-pandemic aOR = 1.34, 95 %CI 1.23-1.46) but were not significantly different for primary cesarean, apart from rural settings peri-pandemic (aOR = 0.87, 95 %CI 0.79-0.96). Hispanic individuals had higher adjusted odds of NTSV cesarean only for rural settings pre-pandemic (aOR = 1.28, 95 %CI 1.05-1.56), but this disparity was not significant during the pandemic (aOR = 1.13, 95 %CI 0.93-1.37).
DISCUSSION AND CONCLUSION
Observed rural and racial/ethnic disparities in cesarean delivery outcomes were present before and during the COVID-19 pandemic. Strategies effective in reducing racial disparities in primary cesarean may be useful in also reducing Black vs. White NTSV cesarean disparities.
PubMed: 38941782
DOI: 10.1016/j.midw.2024.104075 -
Blood Advances Jun 2024Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in...
Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. While studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in preeclampsia remains controversial. LMWH may convey beneficial effects in preeclampsia independent of their anti-coagulant activity, possibly by inhibiting inflammation. Here we evaluated whether LMWH inhibit placental thrombo-inflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle (EV)-induced and platelet-dependent preeclampsia-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation and improves trophoblast proliferation in-vivo and in-vitro. Moreover, LMWH inhibits platelet independent trophoblast NLRP3 inflammasome activation. Mechanistically, LWMH activates via Heparin binding epidermal growth factor (HBEGF) signaling the PI3-Kinase-AKT pathway in trophoblasts thus preventing inflammasome activation. In human preeclampsia placental explants, inflammasome activation and PI3-Kinase-AKT signaling events were reduced with LMWH treatment compared to those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates preeclampsia-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in preeclampsia and identify a signaling mechanism through which LMWH ameliorates preeclampsia, thus providing a rationale for the use of LMWH in preeclampsia.
PubMed: 38941535
DOI: 10.1182/bloodadvances.2023011895 -
Medicine Jun 2024This study aimed to investigate immune score and stromal score-related signatures associated with preeclampsia (PE) and identify key genes for diagnosing PE using...
This study aimed to investigate immune score and stromal score-related signatures associated with preeclampsia (PE) and identify key genes for diagnosing PE using bioinformatics analysis. Four microarray datasets, GSE75010, GSE25906, GSE44711, and GSE10588 were obtained from the Gene Expression Omnibus database. GSE75010 was utilized for differential expressed gene (DEGs) analysis. Subsequently, bioinformatic tools such as gene ontology, Kyoto Encyclopedia of Genes and Genomes, weighted gene correlation network analysis, and gene set enrichment analysis were employed to functionally characterize candidate target genes involved in the pathogenesis of PE. The least absolute shrinkage and selection operator regression approach was employed to identify crucial genes and develop a predictive model. This method also facilitated the creation of receiver operating characteristic (ROC) curves, enabling the evaluation of the model's precision. Furthermore, the model underwent external validation through the other three datasets. A total of 3286 DEGs were identified between normal and PE tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed enrichments in functions related to cell chemotaxis, cytokine binding, and cytokine-cytokine receptor interaction. weighted gene correlation network analysis identified 2 color modules strongly correlated with immune and stromal scores. After intersecting DEGs with immune and stromal-related genes, 13 genes were selected and added to the least absolute shrinkage and selection operator regression. Ultimately, 7 genes were screened out to establish the risk model for discriminating preeclampsia from controls, with each gene having an area under the ROC curve >0.70. The constructed risk model demonstrated that the area under the ROC curves in internal and the other three external datasets were all greater than 0.80. A 7-gene risk signature was identified to build a potential diagnostic model and performed well in the external validation group for PE patients. These findings illustrated that immune and stromal cells played essential roles in PE during its progression.
Topics: Humans; Pre-Eclampsia; Female; Pregnancy; Computational Biology; Gene Expression Profiling; ROC Curve; Databases, Genetic; Gene Ontology; Gene Regulatory Networks
PubMed: 38941397
DOI: 10.1097/MD.0000000000038638 -
Medicine Jun 2024To analyze maternal and neonatal effects of placental abruption (PA) through a novel classification in the presence of hypertension. Initial hemoglobin parameters were... (Comparative Study)
Comparative Study Observational Study
To analyze maternal and neonatal effects of placental abruption (PA) through a novel classification in the presence of hypertension. Initial hemoglobin parameters were also compared to predict pregnancy outcomes in addition to hypertension. This retrospective cohort designed study was conducted on 115 pregnant women with PA. The main parameters scanned and recorded from the hospital database and patient medical files. Two groups were classified regarding of presence or absence of hypertension (53 hypertensive, 62 normotensive). Maternal demographical and clinical characteristics (abdominal pain, vaginal bleeding) were recorded. APGAR scores below 5 at 1st and 5th minute, fetal or neonatal death, admission and length of stay in Neonatal Intensive Care Unit were also investigated and compared between the groups. Stillborn to live-born ratio and lower APGAR scores < 5 at 5th minute were significantly higher in hypertensive group than normotensive group (P = .006 and 0.047, respectively). Poor maternal outcomes were detected in the hypertensive group than normotensive group regarding rate of blood transfusion (27/53, 50.9%; 18/62, 29%, respectively, P = .017). More abdominal pain and less vaginal bleeding were seen in PA with HT. Higher lymphocyte count, mean platelet volume, and platelet distribution width were reported in hypertensive group. Poorer maternal and neonatal outcomes of hypertensive patients with PA were detected. These patients should deserve greater attention to assess not only the possible risks associated with abruption but also the accompanying complications.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Adult; Abruptio Placentae; Pregnancy Outcome; Infant, Newborn; Apgar Score; Hypertension, Pregnancy-Induced; Hypertension
PubMed: 38941372
DOI: 10.1097/MD.0000000000038633 -
PloS One 2024This cross-sectional study aims to describe doubts regarding the diagnosis and treatment of syphilis in pregnancy among primary care professionals in a telehealth...
This cross-sectional study aims to describe doubts regarding the diagnosis and treatment of syphilis in pregnancy among primary care professionals in a telehealth service. All teleconsultations (TCs) offered through TelessaúdeRS-UFRGS to primary health care (PHC) services in the state of Rio Grande do Sul between 2018 and 2021 involving syphilis in pregnancy were included. A total of 356 (TCs) were analyzed. The main doubts about syphilis during pregnancy raised by primary care professionals were related to the need for retreatment (35%), diagnostic definition (23%) and initial treatment (16%). In addition, 95% of TCs were suitable for diagnosing and treating syphilis based on the 2020 Brazilian Ministry of Health guideline. This study suggests that TCs can identify failures in the diagnosis and treatment of public health problems and support decision making in PHC involving syphilis in pregnancy.
Topics: Humans; Female; Pregnancy; Syphilis; Telemedicine; Primary Health Care; Cross-Sectional Studies; Adult; Pregnancy Complications, Infectious; Brazil; Health Personnel
PubMed: 38941327
DOI: 10.1371/journal.pone.0306192