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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 -
Environmental Pollution (Barking, Essex... Jun 2024Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air...
Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM), and nitrogen dioxide (NO). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM, NO, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM concentration (3.20 μg/m) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2 (-7.99%, 95% CI: -13.8%, -2.23%) or 3 trimester (-2.81%, 95% CI: -10.0%, 4.38%). The average cumulative PM exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.
PubMed: 38942277
DOI: 10.1016/j.envpol.2024.124463 -
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 -
JAMA Network Open Jun 2024Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations....
IMPORTANCE
Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations. Consequently, professional bodies advise against the use of varenicline and bupropion and recommend caution with nicotine replacement therapy (NRT). Contemporary estimates of the use of smoking cessation pharmacotherapies during pregnancy are lacking.
OBJECTIVE
To quantify the proportion of individuals using prescribed smoking cessation pharmacotherapies during pregnancy and during the first trimester specifically, in 4 countries.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study used linked birth records, hospital admission records, and dispensing records of prescribed medications from all pregnancies resulting in birth between 2015 and 2020 in New South Wales, Australia; New Zealand; Norway; and Sweden. Data analyses were conducted in October and November 2023.
EXPOSURE
Prescribed smoking cessation pharmacotherapy use (varenicline, NRT, and bupropion) during pregnancy was defined as days' supply overlapping the period from date of conception to childbirth.
MAIN OUTCOMES AND MEASURES
Prevalence of use among all pregnancies and pregnancies with maternal smoking were calculated. Among women who used a pharmacotherapy, the proportion of women with use during the first trimester of pregnancy was also calculated.
RESULTS
Among 1 700 638 pregnancies in 4 countries, 138 033 (8.1%) had maternal smoking and 729 498 (42.9%) were younger than 30 years. The prevalences ranged from 0.02% to 0.14% for varenicline, less than 0.01% to 1.86% for prescribed NRT, and less than 0.01% to 0.07% for bupropion. Among pregnant individuals who smoked, use of pharmacotherapies was up to 10 times higher, with maximum prevalences of 1.25% for varenicline in New South Wales, 11.39% for NRT in New Zealand, and 0.39% for bupropion in New Zealand. Use in the first trimester occurred among more than 90% of individuals using varenicline, approximately 60% among those using NRT, and 80% to 90% among those using bupropion.
CONCLUSIONS AND RELEVANCE
In this cohort study of pregnant individuals in 4 high-income countries, the low prevalence of varenicline and bupropion use during pregnancy and higher prevalence of NRT use aligned with current clinical guidelines. As most use occurred in the first trimester, there is a need for evidence on the risk of congenital malformations for these medications.
Topics: Humans; Female; Pregnancy; Smoking Cessation; Adult; Retrospective Studies; Smoking Cessation Agents; Varenicline; Bupropion; New Zealand; Tobacco Use Cessation Devices; Pregnancy Complications; Sweden; New South Wales; Norway; Young Adult; Smoking; Pregnancy Trimester, First
PubMed: 38941092
DOI: 10.1001/jamanetworkopen.2024.19245 -
International Journal of Gynaecology... Jun 2024With inconsistencies regarding the possible effect of hyperemesis gravidarum on the course of pregnancy, this research aimed to study the association between hyperemesis...
OBJECTIVE
With inconsistencies regarding the possible effect of hyperemesis gravidarum on the course of pregnancy, this research aimed to study the association between hyperemesis gravidarum and pregnancy outcomes, while also addressing the trimester of diagnosis and severity.
METHODS
A retrospective cohort study was performed, including all singleton deliveries of mothers from the largest health maintenance organization in the country, in a single tertiary hospital between 1991 and 2021. The incidence of adverse pregnancy outcomes was compared between pregnancies with and without hyperemesis gravidarum diagnosis. Multivariable generalized estimation equation binary models were used to study the association between maternal hyperemesis gravidarum, trimester of diagnosis and hyperemesis gravidarum severity and the studied outcomes.
RESULTS
The study population included 232 476 pregnancies, of which 3227 (1.4%) were complicated with hyperemesis gravidarum. Women with hyperemesis gravidarum were more likely to deliver preterm (adj. OR = 1.33, 95% CI: 1.18-1.50), a newborn with low birthweight (adj. OR = 1.52, 95% CI: 1.16-1.98, only if diagnosed in the second trimester), and to have a cesarean delivery (adj. OR = 1.20, 95% CI: 1.09-1.32). They were less likely to deliver small gestational age newborn (adj. OR = 0.82, 95% CI: 0.69-0.99) and their offspring to experience perinatal mortality (adj. OR = 0.54, 95% CI: 0.31-0.93, among mild cases only). A dose-response association was observed between preterm birth and hyperemesis gravidarum (adj. OR = 1.26; 95% CI: 1.11-1.44, for mild cases and adj. OR = 2.04; 95% CI: 1.31-3.19, for severe cases).
CONCLUSIONS
Hyperemesis gravidarum is associated with an increased risk for adverse pregnancy outcomes including mainly preterm delivery in a dose-response manner and when diagnosed during the second trimester.
PubMed: 38940074
DOI: 10.1002/ijgo.15760 -
Cureus May 2024The management of symptomatic hydronephrosis presents substantial challenges due to the absence of consensus within clinical guidelines concerning pain management,... (Review)
Review
The management of symptomatic hydronephrosis presents substantial challenges due to the absence of consensus within clinical guidelines concerning pain management, diagnostic approaches, therapeutic interventions, and follow-up protocols. This literature review focuses on complexities involving diagnostic challenges that arise from the difficulty in distinguishing physiological from pathological obstruction and treatment complexities that involve deciding on the most appropriate pain management medications and safe interventions while minimizing risks to both the mother and foetus. To address these challenges, a comprehensive search of electronic databases, including PubMed, Embase, and Google Scholar, was conducted for the terms "hydronephrosis", "hydronephrosis in pregnancy", "ionising radiation in pregnancy", and "safe analgesia in pregnancy". Moreover, Mendeley software was used to collect and organize the references. Diagnostic complexities involve selecting the appropriate imaging modality that balances accurate diagnosis with minimal radiation to the foetus. Ultrasound remains the first-line option. However, it has limitations in delineating the underlying aetiology. MRI avoids ionizing radiation but has restricted utility due to foetal movement artifacts. CT provides the highest diagnostic accuracy but raises foetal radiation exposure concerns, though ultra-low dose protocols (<1 mGy) are deemed acceptable by most guidelines. Management includes either a conservative approach, which is a safe option in the majority of cases, or intervention with a percutaneous nephrostomy or ureteric stent insertion, both with comparable symptom control. However, there is no consensus on the optimal frequency for drain changes to prevent rapid encrustation. Definitive procedures like ureteroscopy and percutaneous nephrolithotomies remain controversial. Most guidelines suggest limiting these interventions to specialist centres during the second trimester if required.
PubMed: 38939245
DOI: 10.7759/cureus.61240 -
Journal of Preventive Medicine and... Jun 2024A substantial proportion of women experience mental health challenges during pregnancy or the postpartum period. Common mental disorders (CMDs), including depression,...
OBJECTIVES
A substantial proportion of women experience mental health challenges during pregnancy or the postpartum period. Common mental disorders (CMDs), including depression, anxiety, and obsessive-compulsive disorder, are prevalent. Identifying causes and associated risk factors is imperative for early intervention and the prevention of mental health issues.
METHODS
This study utilized data from the 2018 Basic Health Research, which was conducted nationwide in Indonesia, using a cross-sectional approach. We focused on women aged 13-49 years who were currently or previously married, and had experienced pregnancy, including 8,889 pregnant women and 77,012 women who had delivered between January 1, 2013, and August 31, 2018. The Self-Reporting Questionnaire-20 was employed to assess CMDs. Multivariate logistic regression was performed.
RESULTS
The prevalence of CMDs in pregnant women was 12.6%, while postpartum mothers exhibited a prevalence of 10.1%. Poor health status displayed the strongest impact on CMDs during both pregnancy (Adjusted Odds Ratio [AOR]: 12.23, 95% Confidence Interval [CI]: 9.06-16.60) and the postpartum period (AOR: 16.72, 95% CI: 14.85-18.82). Additional significant factors for both group include young maternal age, lack of education, unemployment, hystory of hypertension, and smoking status. Among pregnant women, CMDs was also associated with first-trimester pregnancy, previous pregnancy complications, and small upper arm circumference. For postpartum mothers, significant factors include history of abortion, unwanted pregnancy, pregnancy complications, lack of antenatal care, spontaneous delivery, postpartum complications and contraceptive use.
CONCLUSIONS
CMDs can impact in pregnant and postpartum women. Early diagnosis and management must be seamlessly integrated into primary healthcare practices.
PubMed: 38938048
DOI: 10.3961/jpmph.24.082 -
Scientific Reports Jun 2024The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show...
The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.
Topics: Humans; Female; Pregnancy; Adult; Proteome; Postpartum Period; Ventricular Remodeling; Prospective Studies; Biomarkers; Vascular Stiffness; Echocardiography; Risk Factors
PubMed: 38937573
DOI: 10.1038/s41598-024-65612-1 -
Current Medical Science Jun 2024After traumatic injury in pregnant women, providing timely and appropriate management for high-risk patients is crucial for both pregnant women and fetuses. This study...
OBJECTIVE
After traumatic injury in pregnant women, providing timely and appropriate management for high-risk patients is crucial for both pregnant women and fetuses. This study aimed to identify risk factors that predict adverse pregnancy outcomes after traumatic injury.
METHODS
A retrospective cohort study including 317 pregnant patients who experienced trauma was conducted. The collected data included general demographics, injury mechanisms and adverse pregnancy outcomes. Patients were divided into two subgroups based on the absence or presence of trauma-related adverse pregnancy outcomes. Univariate and multivariate logistic regressions were conducted to estimate the associations between clinical variables and adverse pregnancy outcomes.
RESULTS
A total of 41 (12.93%) patients experienced adverse pregnancy outcomes within the first 24 h post-trauma. This study revealed that age >35 years (OR=14.995, 95% CI: 5.024-44.755, P<0.001), third trimester trauma (OR=3.878, 95% CI: 1.343-11.204, P=0.012), abdominal pain (OR=3.032, 95% CI: 1.221-7.527, P=0.017), vaginal bleeding (OR=3.226, 95% CI: 1.093-9.523, P=0.034), positive scan in focused assessment with sonography for trauma (FAST) positive (OR=8.496, 95% CI: 2.825-25.555, P<0.001), 9≤ injury severity score (ISS) <16 (OR=3.039, 95% CI: 1.046-8.835, P=0.041) and ISS≥16 (OR=5.553, 95% CI: 1.387-22.225, P=0.015) increased the probability of posttraumatic adverse pregnancy outcomes. Maternal age, gestational age at delivery, vaginal bleeding and positive FAST results were risk factors for abnormal delivery.
CONCLUSION
Advanced maternal age, third trimester, and positive FAST results should alert multidisciplinary trauma teams to closely monitor patients to prevent adverse pregnancy outcomes.
Topics: Humans; Pregnancy; Female; Adult; Pregnancy Outcome; Retrospective Studies; Wounds and Injuries; Risk Factors; Pregnancy Complications
PubMed: 38937397
DOI: 10.1007/s11596-024-2885-z