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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 -
The Lancet. Global Health Jun 2024Insufficient physical activity increases the risk of non-communicable diseases, poor physical and cognitive function, weight gain, and mental ill-health. Global...
National, regional, and global trends in insufficient physical activity among adults from 2000 to 2022: a pooled analysis of 507 population-based surveys with 5·7 million participants.
BACKGROUND
Insufficient physical activity increases the risk of non-communicable diseases, poor physical and cognitive function, weight gain, and mental ill-health. Global prevalence of adult insufficient physical activity was last published for 2016, with limited trend data. We aimed to estimate the prevalence of insufficient physical activity for 197 countries and territories, from 2000 to 2022.
METHODS
We collated physical activity reported by adults (aged ≥18 years) in population-based surveys. Insufficient physical activity was defined as not doing 150 minutes of moderate-intensity activity, 75 minutes of vigorous-intensity activity, or an equivalent combination per week. We used a Bayesian hierarchical model to compute estimates of insufficient physical activity by country or territory, year, age, and sex. We assessed whether countries or territories, regions, and the world would meet the global target of a 15% relative reduction of the prevalence of insufficient physical activity by 2030 if 2010-22 trends continue.
FINDINGS
We included 507 surveys across 163 countries and territories. The global age-standardised prevalence of insufficient physical activity was 31·3% (95% uncertainty interval 28·6-34·0) in 2022, an increase from 23·4% (21·1-26·0) in 2000 and 26·4% (24·8-27·9) in 2010. Prevalence was increasing in 103 (52%) of 197 countries and territories and six (67%) of nine regions, and was declining in the remainder. Prevalence was 5 percentage points higher among female (33·8% [29·9-37·7]) than male (28·7% [25·0-32·6]) individuals. Insufficient physical activity increased in people aged 60 years and older in all regions and both sexes, but age patterns differed for those younger than 60 years. If 2010-22 trends continue, the global target of a 15% relative reduction between 2010 and 2030 will not be met (posterior probability <0·01); however, two regions, Oceania and sub-Saharan Africa, were on track with considerable uncertainty (posterior probabilities 0·70-0·74).
INTERPRETATION
Concerted multi-sectoral efforts to reduce insufficient physical activity levels are needed to meet the 2030 target. Physical activity promotion should not exacerbate sex, age, or geographical inequalities.
FUNDING
Ministry of Public Health, Qatar, and World Health Organization.
TRANSLATIONS
For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.
PubMed: 38942042
DOI: 10.1016/S2214-109X(24)00150-5 -
International Journal of Pediatric... Jun 2024There is limited but consistent evidence that suggests prenatal factors, including maternal stress, may contribute to susceptibility for otitis media. We aimed to...
OBJECTIVES
There is limited but consistent evidence that suggests prenatal factors, including maternal stress, may contribute to susceptibility for otitis media. We aimed to determine the effect of multiple life stress events during pregnancy on risk of acute and recurrent otitis media in offspring at three and five years of age.
METHODS
Exposure data on stressful life events were collected from pregnant women in a longitudinal prospective pregnancy cohort study, at 18 and 34 weeks' gestation. We used longitudinal regression models stratified by offspring sex to examine associations between the number, type and timing of maternal prenatal stress events and the likelihood of any OM in addition to recurrent OM infection at age three and five years, adjusting for pre-specified prenatal sociodemographic and environmental confounders.
RESULTS
Each additional stressful life event in pregnancy was associated with increased risk of any OM at both ages (3 years: OR = 1.07, 95%CI = 1.02, 1.12; 5 years: OR = 1.07, 95%CI = 1.02, 1.12), with larger effect sizes for recurrent otitis media (3 years: OR = 1.11, 95%CI = 1.05, 1.17; 5 years: OR = 1.09, 95%CI = 1.04, 1.14). Risk of offspring otitis media did not differ with timing of stress nor by offspring sex. Specific types of stress (pregnancy and relationship problems, issues with other children) were each associated with increased risk of recurrent OM at age three and five years.
CONCLUSIONS
We observed a dose-response relationship between maternal stressful life events in pregnancy and the risk for offspring otitis media in the preschool years, most marked for recurrent otitis media.
PubMed: 38941719
DOI: 10.1016/j.ijporl.2024.112022 -
Neurology(R) Neuroimmunology &... Sep 2024Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw...
BACKGROUND AND OBJECTIVES
Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS).
METHODS
We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests.
RESULTS
In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], 3.82e). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], = 0.04). Compared with raw values with arbitrary cutoffs, applying the score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score).
DISCUSSION
In conclusion, our work demonstrated reference cohort-based scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.
Topics: Humans; Female; Male; Tomography, Optical Coherence; Adult; Middle Aged; Disease Progression; Prognosis; Multiple Sclerosis; Retina; Severity of Illness Index
PubMed: 38941572
DOI: 10.1212/NXI.0000000000200269 -
Ecology of Food and Nutrition Jun 2024Double burden of malnutrition (DBM) is a global public health concern. This study determined the prevalence of DBM and its associated factors among 451 indigenous...
Double burden of malnutrition (DBM) is a global public health concern. This study determined the prevalence of DBM and its associated factors among 451 indigenous households in an urbanized state of Malaysia. Mothers and children were measured for weight and height/length. Mothers were interviewed for socio-demographics and diets of mothers and children. Prevalence of DBM (overweight/obese mother and underweight/stunted child) was 28.8%. Food insecurity, maternal height (<150 cm) and energy intake (>recommendation), child's age (≥24 months) and energy intake (
PubMed: 38941571
DOI: 10.1080/03670244.2024.2373231 -
PloS One 2024Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and...
Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and risk factors remain limited in sub-Saharan Africa. In Ghana, HCV-related deaths are estimated to have increased since 2015. Risk factors associated with HCV infection in Ghana are not well described. The aim of this study was to determine the prevalence of, and risk factors associated with hepatitis C virus infection in the Upper East Region located in the northern part of Ghana. A community-based cross-sectional study was conducted in 9 communities in the Upper East region of Ghana. A total of 1,769 participants aged ≥12 years were screened for HCV antibody (anti-HCV) using rapid diagnostic testing (RDT). Seventy-four participants undertook HCV RNA testing after a positive anti-HCV result. Multivariate logistic regression was used to determine risk factors associated with HCV seropositivity. The anti-HCV prevalence was 8.4%, with 149 out of 1,769 testing anti-HCV positive. Mean age (±SD) of seropositive persons was 45.4 (±16.3) years. The highest anti-HCV seroprevalence was amongst persons aged 60 years and above. Forty-four out of 74 (59.5%) seropositive cases had viremic infection and the estimated viremic prevalence in the screened population was 5.0%. Predictors of HCV seropositivity were age (OR 1.03 95% CI 1.01-1.04), history of female genital mutilation or circumcision (OR 1.63 95% CI 1.04-2.55), sexual activity (OR 2.57 95% CI 1.38-4.79), positive maternal HCV status (OR 10.38 95% CI 4.13-26.05) and positive HIV status (OR 4.03 95% CI 1.35-12.05). In conclusion, the Upper East Region demonstrates a high Hepatitis C antibody prevalence. Almost 60% of individuals have viremic infection, however the cost of RNA testing is a barrier to virological diagnosis. There is a need to educate the population about HCV-associated risk factors to reduce HCV transmission and burden of disease.
Topics: Humans; Ghana; Female; Male; Middle Aged; Cross-Sectional Studies; Risk Factors; Adult; Hepatitis C; Prevalence; Hepacivirus; Young Adult; Seroepidemiologic Studies; Adolescent; Hepatitis C Antibodies; Aged; Child
PubMed: 38941280
DOI: 10.1371/journal.pone.0306292 -
JAMA Network Open Jun 2024Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability.
IMPORTANCE
Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability.
OBJECTIVE
To assess the heritability of obesity by measuring the association between the BMIs of fathers, mothers, and their offspring at the same age.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from population-wide mandatory medical screening before compulsory military service in Israel. The study included participants examined between January 1, 1986, and December 31, 2018, whose both parents had their BMI measurement taken at their own prerecruitment evaluation in the past. Data analysis was performed from May to December 2023.
MAIN OUTCOMES AND MEASURES
Spearman correlation coefficients were calculated for offsprings' BMI and their mothers', fathers', and midparental BMI percentile (the mean of the mothers' and fathers' BMI cohort- and sex-specific BMI percentile) to estimate heritability. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs of obesity compared with healthy BMI, according to parental BMI status.
RESULTS
A total of 447 883 offspring (235 105 male [52.5%]; mean [SD] age, 17.09 [0.34] years) with both parents enrolled and measured for BMI at 17 years of age were enrolled in the study, yielding a total study population of 1 343 649 individuals. Overall, the correlation between midparental BMI percentile at 17 years of age and the offspring's BMI at 17 years of age was moderate (ρ = 0.386). Among female offspring, maternal-offspring BMI correlation (ρ = 0.329) was somewhat higher than the paternal-offspring BMI correlation (ρ = 0.266). Among trios in which both parents had a healthy BMI, the prevalence of overweight or obesity in offspring was 15.4%; this proportion increased to 76.6% when both parents had obesity and decreased to 3.3% when both parents had severe underweight. Compared with healthy weight, maternal (OR, 4.96; 95% CI, 4.63-5.32), paternal (OR, 4.48; 95% CI, 4.26-4.72), and parental (OR, 6.44; 95% CI, 6.22-6.67) obesity (midparent BMI in the ≥95th percentile) at 17 years of age were associated with increased odds of obesity among offspring.
CONCLUSIONS AND RELEVANCE
In this cohort study of military enrollees whose parents also underwent prerecruitment evaluations, the observed correlation between midparental and offspring BMI, coupled with a calculated narrow-sense heritability of 39%, suggested a substantive contribution of genetic factors to BMI variation at 17 years of age.
Topics: Humans; Body Mass Index; Male; Female; Israel; Adolescent; Obesity; Cohort Studies; Adult; Fathers
PubMed: 38941093
DOI: 10.1001/jamanetworkopen.2024.19029 -
Drug Safety Jun 2024While many pregnant individuals use prescription medications, evidence supporting product safety during pregnancy is often inadequate. Existing electronic healthcare...
While many pregnant individuals use prescription medications, evidence supporting product safety during pregnancy is often inadequate. Existing electronic healthcare data sources provide large, diverse samples of health plan members to allow for the study of medical product utilization during pregnancy, as well as pregnancy, maternal, and infant outcomes. The Sentinel System is a national medical product surveillance system that includes administrative claims and electronic health record databases from large national and regional health insurers. In addition to these data sources, Sentinel develops and maintains a sizeable selection of analytic tools to facilitate epidemiologic analyses in a way that protects patient privacy and health system autonomy. In this article, we provide an overview of Sentinel System infrastructure, including the Mother-Infant Linkage Table, parameterizable analytic tools, and algorithms to estimate gestational age and identify pregnancy outcomes. We also describe past and future Sentinel work that contributes to our understanding of the way medical products are used and the safety of these products during pregnancy.
PubMed: 38940904
DOI: 10.1007/s40264-024-01447-z