Guidance for design and analysis of observational studies of fetal and newborn outcomes following COVID-19 vaccination during pregnancy
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SUBMITTER: Fell D
PROVIDER: S-EPMC7923848 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Project description:ImportanceThe study team previously showed that maternal mRNA COVID-19 vaccination during pregnancy confers protection against SARS-CoV-2 infection and COVID-19-related hospital admission in newborns and young infants. In this study, the study team evaluated newborn and early infant safety outcomes following maternal messenger RNA (mRNA) COVID-19 vaccination during pregnancy, for which there is limited comparative epidemiological evidence.ObjectiveTo determine if maternal mRNA COVID-19 vaccination during pregnancy is associated with adverse newborn and early infant outcomes.Design, setting, and participantsThis population-based retrospective cohort study took place in Ontario, Canada, using multiple linked health administrative databases. Singleton live births with an expected delivery date between May 1, 2021, and September 2, 2022, were included. Data were analyzed from January 2023 through March 2023.ExposureMaternal mRNA COVID-19 vaccination (1 or more doses) during pregnancy.Main outcomes and measuresSevere neonatal morbidity (SNM), neonatal death, neonatal intensive care unit (NICU) admission, neonatal readmission, and hospital admission up to 6 months of age. The study team calculated inverse probability of treatment weighted risk ratios (RRs) and fit weighted Cox proportional hazards regression models comparing outcomes in infants of mothers who received COVID-19 vaccination during pregnancy with those who received no COVID-19 vaccine doses before delivery.ResultsIn total, 142 006 infants (72 595 male [51%]; mean [SD] gestational age at birth, 38.7 [1.7] weeks) were included; 85 670 were exposed to 1 or more COVID-19 vaccine doses in utero (60%). Infants of vaccinated mothers had lower risks of SNM (vaccine exposed 7.3% vs vaccine unexposed 8.3%; adjusted RR [aRR], 0.86; 95% CI, 0.83-0.90), neonatal death (0.09% vs 0.16%; aRR, 0.47; 95% CI, 0.33-0.65), and NICU admission (11.4% vs 13.1%; aRR, 0.86; 95% CI, 0.83-0.89). There was no association between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted hazard ratio, 1.03; 95% CI, 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; adjusted hazard ratio, 1.01; 95% CI, 0.96-1.05).Conclusions and relevanceIn this population-based cohort study in Ontario, Canada, maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of SNM, neonatal death, and NICU admission. In addition, neonatal and 6-month readmissions were not increased in infants of mothers vaccinated during pregnancy.
| S-EPMC10594175 | biostudies-literature
Project description:OBJECTIVE:To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. DESIGN:Cohort study nested in the Medicaid Analytic eXtract for 2004-13. SETTING:Publicly insured pregnancies in the United States. PARTICIPANTS:Pregnant women 18 to 55 years of age and their liveborn infants. INTERVENTIONS:Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. MAIN OUTCOME MEASURES:Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. RESULTS:Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. CONCLUSIONS:On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. TRIAL REGISTRATION:EUPAS 15946.
| S-EPMC7190016 | biostudies-literature
Project description:IntroductionWomen with a prior stillbirth or a history of recurrent first trimester miscarriages are at increased risk of adverse pregnancy outcomes. However, little is known about the impact of a second trimester pregnancy loss on subsequent pregnancy outcome. This review investigated if second trimester miscarriage or termination for medical reason or fetal anomaly (TFMR/TOPFA) is associated with future adverse pregnancy outcomes.Material and methodsA systematic review of observational studies was conducted. Eligible studies included women with a history of a second trimester miscarriage or termination for medical reasons and their pregnancy outcomes in the subsequent pregnancy. Where comparative studies were identified, studies which compared subsequent pregnancy outcomes for women with and without a history of second trimester loss or TFMR/TOPFA were included. The primary outcome was livebirth, and secondary outcomes included: miscarriage (first and second trimester), termination of pregnancy, fetal growth restriction, cesarean section, preterm birth, pre-eclampsia, antepartum hemorrhage, stillbirth and neonatal death. Studies were excluded if exposure was nonmedical termination or if related to twins or higher multiple pregnancies. Electronic searches were conducted using the online databases (MEDLINE, Embase, PubMed and The Cochrane Library) and searches were last updated on June 16, 2023. Risk of bias was assessed using the Newcastle-Ottawa scale. Where possible, meta-analysis was undertaken. PROSPERO registration: CRD42023375033.ResultsTen studies were included, reporting on 12 004 subsequent pregnancies after a second trimester pregnancy miscarriage. No studies were found on outcomes after second trimester TFMR/TOPFA. Overall, available data were of "very low quality" using GRADE assessment. Meta-analysis of cohort studies generated estimated outcome frequencies for women with a previous second trimester loss as follows: live birth 81% (95% CI: 64-94), miscarriage 15% (95% CI: 4-30, preterm birth 13% [95% CI: 6-23]).The pooled odds ratio for preterm birth in subsequent pregnancy after second trimester loss in case-control studies was OR 4.52 (95% CI: 3.03-6.74).ConclusionsVery low certainty evidence suggests there may be an increased risk of preterm birth in a subsequent pregnancy after a late miscarriage. However, evidence is limited. Larger, higher quality cohort studies are needed to investigate this potential association.
| S-EPMC10867354 | biostudies-literature
Project description:Recent studies on the role of epigenetics in complex disease have focused primarily on DNA methylation. As genome-wide patterns of DNA methylation are largely determined by cell type, analyses of bulk tissues, composed of a heterogeneous mix of cell types, limits the ability to identify both the specific loci affected by disease associated differences and the cell type within which these changes occur. Cell-specific datasets now make it possible to identify DNA methylation differences associated with disease in specific cell types. Critically, the analytical framework for these differ from the traditional bulk tissue approach, as the statistical method needs to characterise whether the difference affects multiple cell types or is specific to a particular cell-type. In this manuscript, we evaluate the effects on study design, data preprocessing and statistical analysis for cell-specific studies of DNAm, particularly for scenarios where multiple cell types are considered. For this study we take advantage of a large set of DNA methylation profiles (n = 751) obtained from five different purified cell populations isolated from human prefrontal cortex nuclei samples.
2024-11-06 | GSE279509 | GEO
Project description:BACKGROUND:Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking. OBJECTIVE:The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders. STUDY DESIGN:This is a study based on data from a prospective longitudinal cohort study of fetal growth performed at 12 US sites (2009-2013). Project gestational age was confirmed by ultrasound between 8 weeks 0 days and 13 weels 6 days, and up to 6 ultrasounds were performed across gestation. Hypertensive disorders were diagnosed based on 2002 American College of Obstetricians and Gynecologists guidelines and grouped hierarchically as severe preeclampsia (including eclampsia or HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome), mild preeclampsia, severe gestational hypertension, mild gestational hypertension, or unspecified hypertension. Women without any hypertensive disorder constituted the normotensive group. Growth curves for estimated fetal weight and individual biometric parameters including biparietal diameter, head circumference, abdominal circumference, and femur and humerus length were calculated for each group using linear mixed models with cubic splines. Global and weekly pairwise comparisons were performed between women with a hypertensive disorder compared with normotensive women to analyze differences while adjusting for confounding variables. Delivery gestational age and birthweights were compared among groups. RESULTS:Of 2462 women analyzed, 2296 (93.3%) were normotensive, 63 (2.6%) had mild gestational hypertension, 54 (2.2%) mild preeclampsia, 32 (1.3%) severe preeclampsia, and 17 (0.7%) unspecified hypertension. Compared with normotensive women, those with severe preeclampsia had estimated fetal weights that were reduced between 22 and 38 weeks (all weekly pairwise values of P < .008). Women with severe preeclampsia compared with those without hypertension also had significantly smaller fetal abdominal circumference between 23-31 and 33-37 weeks' gestation (weekly pairwise values of P < .04). Scattered weekly growth differences were noted on other biometric parameters between these 2 groups. The consistent differences in estimated fetal weight and abdominal circumference were not observed between women with other hypertensive disorders and those who were normotensive. Women with severe preeclampsia delivered significantly earlier (mean gestational age 35.9 ± 3.2 weeks) than the other groups (global P < .0001). Birthweights in the severe preeclampsia group were also significantly lower (mean -949.5 g [95% confidence interval, -1117.7 to -781.2 g]; P < .0001) than in the normotensive group. CONCLUSION:Among women with pregnancy-associated hypertensive disorders, only those destined to develop severe preeclampsia demonstrated a significant and consistent difference in fetal growth (ie, smaller estimated fetal weight and abdominal circumference) when compared with normotensive women.
| S-EPMC6888945 | biostudies-literature
Project description: Not available
| S-EPMC8427483 | biostudies-literature
Project description:PURPOSE:To evaluate pregnancy outcomes following onabotulinumtoxinA (US Food and Drug Administration pregnancy category C product) exposure using the Allergan safety database. METHODS:The Allergan Global Safety Database contains reports of onabotulinumtoxinA administration before/during pregnancy, including both prospective (reported before outcome) and retrospective (outcome already known) cases. The database was searched from 1/1/90 to 12/31/13 for eligible cases where treatment occurred during pregnancy or ?3?months before conception. To minimize reporting bias, prevalence rates were focused on prospective cases. RESULTS:Of 574 pregnancies with maternal onabotulinumtoxinA exposure, 232 were eligible with known outcomes. Patients received onabotulinumtoxinA most frequently for cosmetic indications (50.5%), movement disorders (16.8%), and pain disorders (14.2%). Of the 137 with dose information, 40.1% received <50U, 14.6% 50U to <100U, 27.7% 100U to <200U, and 17.5% ?200U. Among 146 cases with known maternal age, 47.9% were ?35?years. Most (96.0%) fetal exposures occurred during/before the first trimester. Of the 137 prospective cases (139 fetuses), 110 (79.1%) were live births; 29 (20.9%; 95% CI, 14.0-30.0%) ended in fetal loss (21 spontaneous, 8 induced abortions). Among live births, 106 (96.4%) were normal, with four abnormal birth outcomes (1 major fetal defect, 2 minor fetal malformations, 1 birth complication), giving a 2.7% (3/110; 95% CI, 0.6-8.0%) prevalence rate for overall fetal defects. CONCLUSIONS:A 24-year retrospective review of the Allergan safety database shows that the prevalence of fetal defects in onabotulinumtoxinA-exposed mothers before/during pregnancy (2.7%) is comparable with background rates in the general population. Pregnancy outcome monitoring in onabotulinumtoxinA-exposed women continues.
| S-EPMC5063122 | biostudies-literature
Project description:ContextFindings from studies evaluating adverse pregnancy outcomes in pregnant women with subclinical hyperthyroidism are conflicting and inconclusive.ObjectivesIn this systematic review and meta-analysis, our aim was to evaluate the pooled odds ratio (OR) of adverse pregnancy outcomes in women with subclinical hyperthyroidism, compared to euthyroid women.Data sourcesScopus, PubMed (including Medline), and Web of Science databases were systemically searched for regaining published studies to January 2022 examining adverse pregnancy outcomes in women with subclinical hyperthyroidism.Study selectionOutcomes of interest were classified into seven composite outcomes, including hypertensive disorders, preterm delivery, macrosomia/large for gestational age (LGA), pregnancy loss, adverse maternal outcomes, adverse neonatal outcomes, and adverse fetal outcomes.Data extractionIn this meta-analysis, both fixed and random effect models were used. Publication bias was also evaluated by Egger test and the funnel plot, and the trim and fill method was conducted in case of a significant result, to adjust the bias.ResultsOf 202 records retrieved through searching databases, 11 studies were selected for the final analyses. There were no significant differences in pooled ORs of hypertensive disorders, preterm delivery, macrosomia/LGA, and pregnancy loss in pregnant women with subclinical hyperthyroidism, compared to the euthyroid controls. The pooled OR of adverse maternal, neonatal, and fetal outcomes in pregnant women with subclinical hyperthyroidism was not statistically significantly different from that of the euthyroid control group.ConclusionsThe current meta-analysis demonstrated that subclinical hyperthyroidism in pregnancy is not related with adverse maternal and fetal outcomes. Therefore, clinicians should be avoided unnecessary treatments for pregnant women with subclinical hyperthyroidism.
| S-EPMC9675093 | biostudies-literature
Project description:BackgroundSARS-CoV-2 infection during pregnancy is associated with significant maternal morbidity and increased rates of preterm birth. For this reason, COVID-19 vaccination in pregnancy has been endorsed by multiple professional societies, including the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, despite the exclusion of pregnant women from initial clinical trials of vaccine safety and efficacy. However, to date, little data exist regarding the outcomes of pregnant patients after COVID-19 vaccination.ObjectiveTo assess the safety and efficacy of COVID-19 vaccines in pregnant patients.Study designA comprehensive vaccine registry was combined with a delivery database for an integrated healthcare system to create a delivery cohort that included vaccinated patients. Maternal sociodemographic data were examined to identify factors associated with COVID-19 vaccination. Pregnancy and birth outcomes were analyzed, including a composite measure of maternal and neonatal pregnancy complications, the Adverse Outcome Index.ResultsOf 2002 patients in the delivery cohort, 140 (7.0%) received a COVID-19 vaccine during pregnancy, and 212 (10.6%) experienced a COVID-19 infection during pregnancy. The median gestational age at first vaccination was 32 weeks (range, 13 6/7-40 4/7 weeks), and patients vaccinated during pregnancy were less likely than unvaccinated patients to experience COVID-19 infection before delivery (2/140 [1.4%] vs 210/1862 [11.3%]; P<.001). No maternal COVID-19 infection occurred after the vaccination of pregnant patients. Factors significantly associated with increased likelihood of vaccination in a multivariable logistic regression model included older age, higher level of maternal education, being a nonsmoker, use of infertility treatment for the current pregnancy, and lower gravidity. Compared with unvaccinated patients, no significant difference in the composite adverse outcome (7/140 [5.0%] vs 91/1862 [4.9%]; P=.95) or other maternal or neonatal complications, including thromboembolic events and preterm birth, was observed in vaccinated patients.ConclusionIn this birth cohort, vaccinated pregnant women were less likely than unvaccinated pregnant patients to experience COVID-19 infection, and COVID-19 vaccination during pregnancy was not associated with increased pregnancy or delivery complications. The cohort was skewed toward late pregnancy vaccination, and thus, findings may not be generalizable to vaccination during early pregnancy.
| S-EPMC8378017 | biostudies-literature
Project description:Pregnancy in kidney disease is considered high risk, but the degree of this risk is unclear. We tested the hypothesis that kidney disease in pregnancy is associated with adverse maternal and fetal outcomes.Retrospective study comparing pregnant women with and without kidney disease.Using data from an integrated health care delivery system from 2000 through 2013, a total of 778 women met the criteria for kidney disease. Using a pool of 74,105 women without kidney disease, we selected 778 women to use for matches for the women with kidney disease. These women were matched 1:1 by age, race, and history of diabetes, chronic hypertension, liver disease, and connective tissue disease.Kidney disease was defined using the NKF-KDOQI definition for chronic kidney disease or International Classification of Diseases, Ninth Revision codes prior to pregnancy or serum creatinine level > 1.2mg/dL and/or proteinuria in the first trimester.Maternal outcomes included preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, length of stay at hospital (>3 days), and maternal death. Fetal outcomes included low birth weight (weight < 2,500g), small for gestational age, number of admissions to neonatal intensive care unit, and infant death.Compared with women without kidney disease, those with kidney disease had 52% increased odds of preterm delivery (OR, 1.52; 95% CI, 1.16-1.99) and 33% increased odds of delivery by cesarean section (OR, 1.33; 95% CI, 1.06-1.66). Infants born to women with kidney disease had 71% increased odds of admission to the neonatal intensive care unit or infant death compared with infants born to women without kidney disease (OR, 1.71; 95% CI, 1.17-2.51). Kidney disease also was associated with 2-fold increased odds of low birth weight (OR, 2.38; 95% CI, 1.64-3.44). Kidney disease was not associated with increased risk of maternal death.Data for level of kidney function and cause of death not available.Kidney disease in pregnancy is associated independently with adverse maternal and fetal outcomes when other comorbid conditions are controlled by matching.
| S-EPMC4485539 | biostudies-literature