Dataset Information

Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss.

ABSTRACT: Objectives To prospectively estimate the association of preconception antiphospholipid antibodies (aPL) with subsequent pregnancy loss using a cohort design. aPL have been associated with recurrent early pregnancy loss (EPL) prior to 10 weeks in previous case-control studies. Prospective ascertainment of pregnancy loss is challenging, as most women do not seek care prior to EPL. Methods Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial of preconception low-dose aspirin. Preconception anticardiolipin (aCL) and anti-?2-glycoprotein-I (a-?2-I) were assessed in 1208 women with one or two prior pregnancy losses and no more than two prior live births. Comparison cohorts were defined by positive aPL (+aPL) or negative aPL (-aPL) status. All women were followed for six menstrual cycles while trying to conceive; if successful, they underwent an ultrasound at 6-7 weeks' gestation. EPL was defined as loss prior to 10 weeks' gestation; embryonic loss was loss after visualization of an embryo but prior to 10 weeks; clinical loss was any loss after visualization of an embryo (with or without fetal cardiac activity detected). Results In total, 14/1208 (1%) tested positive for +aPL. 786/1208 (65%) women had positive human chorionic gonadotropin during the study period, of which 9/786 (1%) had +aPL. Of the 786 pregnant women, 589 (75%) had live births and 24% had pregnancy losses. Women with +aPL experienced EPL at similar rates as women with -aPL, 44% vs 21% (aRR 2.4, 95% confidence interval (CI) 0.5-10.9). Embryonic loss was more common in women with +aCL IgM (aRR 4.8, 95% CI 1.0-23.0) and in women with two positive aPL. Clinical pregnancy loss was more common in women with positive a-?2-I IgM (50% vs 16.5%, aRR 3.7, 95% CI 1.3-10.8). Conclusion Positive levels of aPL are rare in women with one or two prior pregnancy losses and are not clearly associated with an increased rate of subsequent loss. Clinical trial registration The original source study was registered at ClinicalTrials.gov (#NCT00467363).

SUBMITTER: Gibbins KJ

PROVIDER: S-EPMC6027606 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss.

Gibbins K J KJ Mumford S L SL Sjaarda L A LA Branch D W DW Perkins N J NJ Ye A A Schisterman E F EF Silver R M RM

Lupus 20180517 9

Objectives To prospectively estimate the association of preconception antiphospholipid antibodies (aPL) with subsequent pregnancy loss using a cohort design. aPL have been associated with recurrent early pregnancy loss (EPL) prior to 10 weeks in previous case-control studies. Prospective ascertainment of pregnancy loss is challenging, as most women do not seek care prior to EPL. Methods Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial of preconception low-dose asp ...[more]

PMID: 29771194

Similar Datasets

Project description:BackgroundAlthough redox stress likely plays an important role in reproductive health, the utility of peripheral biomarkers of oxidative stress, such as isoprostanes, during the periconception period remains underexplored. We evaluated the relationship between isoprostanes during preconception and gestational week 4 and women's reproductive health outcomes.MethodsThe Effects of Aspirin in Gestation and Reproduction trial (2007-2011) enrolled 1228 women attempting pregnancy and followed them for up to 6 menstrual cycles and throughout pregnancy if they became pregnant. We measured creatinine-adjusted, log-transformed isoprostanes 8-iso-prostaglandin F 2α (8-iso-PGF2α), its metabolite 2,3-dinor-iPF2α-III, and stereoisomers 5-iso-PGF2α-VI and 8,12-iso-iPF2α-VI in urine during preconception and 4 weeks gestation. We evaluated pregnancy among participants in each menstrual cycle using human chorionic gonadotropin (hCG) and defined pregnancy loss as observed loss following positive hCG. We calculated fecundability odds ratios (FOR) and 95% confidence intervals (CI) using discrete-time Cox proportional hazards models and relative risk of pregnancy loss using adjusted log-binomial models.ResultsHigher preconception isoprostane levels were associated with lower fecundability [e.g., FOR = 0.89; 95% CI = 0.81, 0.97 per interquartile range (IQR) increase in 8-iso-PGF2α]. Among 797 pregnancies, isoprostane levels increased from preconception to 4 weeks gestation (e.g., mean difference = 0.12; 95% CI = 0.10, 0.14 ng/mL for 8-iso-PGF2α) and higher isoprostanes at 4 weeks gestation were associated with lower risk of pregnancy loss (e.g., RR = 0.79; 95% CI = 0.62, 1.00 per IQR increase in 8-iso-PGF2α).ConclusionsPreconception urinary isoprostanes may identify redox stress pathways associated with lower fecundability. However, the increase in isoprostanes into gestational week 4 and the associated lower risk of pregnancy loss may suggest confounding by latent factors in early pregnancy.

Project description:BackgroundPregnancy-related cardiovascular conditions are associated with both poorer pregnancy outcomes and cardiovascular disease later in life. Little is known about the relationship between preconception cardiovascular risk factor levels and pregnancy complications.MethodsData from the Cardiovascular Risk in Young Finns Study were linked with birth registry data for 1142 primiparous women. Age-standardized levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, insulin, and glucose from the study visit prior to last menstrual period were calculated. These factors were examined as predictors of gestational age, preterm birth (<37 weeks), birthweight, low birthweight (<2500 g), small-for-gestational-age (weight <10th percentile for gestational age), hypertensive disorders of pregnancy, and gestational diabetes, using linear and Poisson regression with adjustment for age, body mass index, smoking, and socioeconomic status.ResultsHigher triglycerides were associated with a higher risk of hypertensive disorders (adjusted risk ratio [aRR] = 1.42 [95% confidence interval (CI) = 0.90-2.23]), preeclampsia (1.70 [1.08-2.65]), and gestational diabetes (1.68 [1.25-2.25]). After removing women with pregnancy complications (n = 30), the estimated aRR for the association between systolic blood pressure and preterm birth was 1.23 (95% CI = 0.99-1.54); for HDL-c and low birthweight, 0.97 (0.73-1.28); for diastolic blood pressure and small-for-gestational-age, 0.98 (0.81-1.20); and for systolic blood pressure and small-for-gestational-age, 1.18 (0.97-1.45).ConclusionsHigh lipid levels before pregnancy predict an increased risk of preeclampsia and gestational diabetes. Reported associations between these pregnancy complications and later cardiovascular disease of the mother are probably explained, at least in part, by maternal conditions that precede pregnancy. Interventions to improve cardiovascular health before pregnancy may reduce risk of pregnancy complications.

Project description:Preeclampsia and gestational hypertension are common complications of pregnancy associated with significant maternal and infant morbidity. Despite extensive research evaluating risk factors during pregnancy, most women who develop a hypertensive disorder of pregnancy are not considered high-risk and strategies for prevention remain elusive. We evaluated preconception blood pressure and its change into early pregnancy as novel risk markers for development of a hypertensive disorder of pregnancy. The EAGeR (Effects of Aspirin in Gestation and Reproduction) trial (2007-2011) randomized 1228 healthy women with a history of pregnancy loss to preconception-initiated low-dose aspirin versus placebo and followed participants for up to 6 menstrual cycles attempting pregnancy and throughout pregnancy if they became pregnant. Blood pressure was measured during preconception and throughout early gestation. The primary outcomes, preterm preeclampsia, term preeclampsia, and gestational hypertension, were abstracted from medical records. Among 586 women with a pregnancy >20 weeks' gestation, preconception blood pressure levels were higher for preterm preeclampsia (87.3±6.7 mm Hg mean arterial pressure), term preeclampsia (88.3±9.8 mm Hg), and gestational hypertension (87.9±9.1 mm Hg) as compared with no hypertensive disorder of pregnancy (83.9±8.6 mm Hg). Change in blood pressure from preconception into very early pregnancy was associated with development of preeclampsia (relative risk, 1.13 [95% CI, 1.02-1.25] per 2 mm Hg increase in mean arterial pressure at 4 weeks' gestation), particularly preterm preeclampsia (relative risk, 1.21 [95% CI, 1.01-1.45]). Randomization to aspirin did not alter blood pressure trajectory or risk of hypertension in pregnancy. Preconception blood pressure and longitudinal changes during early pregnancy are underexplored but crucial windows in the detection and prevention of hypertensive disorders of pregnancy. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00467363.

Project description:BackgroundPhthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation-reduction reaction stress and endocrine disruption, evidence for the impact of women's phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive.ObjectivesWe aimed to determine the relationship of preconception phthalate metabolite exposure with a) fecundability and pregnancy loss and b) markers of potential biological mechanisms, including reproductive hormones, inflammation, and oxidative stress.MethodsData were collected from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a preconception study following 1,228 women who were attempting pregnancy, for up to six menstrual cycles and throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured in a consecutive 3-d pooled urine sample at enrollment. Pregnancy was determined through urinary human chorionic gonadotropin (hCG) at the expected date of menses during each cycle and pregnancy loss as an observed loss following positive hCG. Highly sensitive C-reactive protein (hsCRP) and isoprostanes were measured at enrollment, and reproductive hormones were measured during the follicular phase, ovulation, and luteal phase. Discrete-time Cox proportional hazards models evaluated the relationship of phthalate metabolites with fecundability and weighted Poisson models with robust variance evaluated the risk of pregnancy loss.ResultsAn interquartile range (IQR) higher mono-(2-ethylhexyl) phthalate [fecundability odds ratio (FOR)=0.88; 95% confidence interval (CI): 0.78, 1.00], mono-butyl phthalate (FOR=0.82; 95% CI: 0.70, 0.96), and mono-benzyl phthalate (FOR=0.85; 95% CI: 0.74, 0.98) was associated with lower fecundability. No consistent associations were observed with pregnancy loss. Preconception phthalates were consistently associated with higher hsCRP and isoprostanes, as well as lower estradiol and higher follicle-stimulating hormone across the menstrual cycle.DiscussionWomen's preconception exposure to phthalates was associated with lower fecundability, changes in reproductive hormones, and increased inflammation and oxidative stress. The pre- and periconception periods may represent sensitive windows for intervening to limit the reproductive toxicity of phthalate exposure. https://doi.org/10.1289/EHP12287.

Project description:BackgroundPreterm birth (PTB) remains a leading cause of neonatal mortality and long-term morbidity. Individual factors have been linked to PTB risk. The impact of a healthy lifestyle, with multiple modifiable prenatal factors, remains unknown.ObjectivesWe aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk.MethodsThis prospective cohort study included 2449 women with singleton pregnancies in the Pregnancy Environment and Lifestyle Study. PTB was defined as ultrasound-confirmed obstetric estimate-based gestational age at delivery <37 wk. A set of low-risk modifiable factors were identified: healthy weight (prepregnancy BMI: 18.5-24.9 kg/m2) based on clinical measurements and high-quality diet (Alternate Healthy Eating Index-Pregnancy score ≥75th percentile) and low-to-moderate stress during early pregnancy (Perceived Stress Scale score <75th percentile) assessed at gestational weeks 10-13. Poisson regression estimated adjusted relative risk (aRR) of PTB in association with individual and combined low-risk modifiable prenatal factors, adjusting for sociodemographic, clinical, and other prenatal factors.ResultsOne hundred and sixty women (6.5%) delivered preterm. Risk of PTB was lower among women who had a healthy weight (aRR: 0.58; 95% CI: 0.39, 0.86), high-quality diet (aRR: 0.68; 95% CI: 0.39, 0.99), and low-to-moderate stress (aRR: 0.60; 95% CI: 0.41, 0.88). Women with 1, 2, or 3 low-risk modifiable prenatal factors compared with none had a 38% (aRR: 0.72; 95% CI: 0.45, 1.16), 51% (aRR: 0.49; 95% CI: 0.29, 0.84), or 70% (aRR: 0.30; 95% CI: 0.13, 0.70) lower PTB risk, respectively. Associations of having ≥1 low-risk factor with PTB risk were more pronounced for medically indicated than for spontaneous PTB and for late than for early or moderate PTB. Associations also varied by race or ethnicity, although with overlapping 95% CIs.ConclusionsA healthy prenatal lifestyle with multiple low-risk modifiable factors was associated with lower risk of PTB. Our findings may inform multicomponent preconceptional or early-pregnancy prevention strategies to mitigate PTB risk.

Project description:Over 20% of pregnancies in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (APL) result in an adverse pregnancy outcome (APO) related to abnormal placentation. The ability to identify, early in pregnancy, patients who are destined for poor outcomes would significantly impact care of this high-risk population. In nonautoimmune patients, circulating angiogenic factors are dysregulated in disorders of placentation, such as preeclampsia (PE) and fetal growth restriction.We sought to determine whether early dysregulation of circulating angiogenic factors can predict APO in high-risk SLE and/or APL pregnancies.We used data and samples from the Predictors of Pregnancy Outcome: Biomarkers in APL Syndrome and SLE (PROMISSE), a multicenter prospective study that enrolled 492 pregnant women with SLE and/or APL from September 2003 through August 2013. Patients were followed through pregnancy from <12 weeks gestation. Circulating levels of soluble fms-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble endoglin were measured monthly and subjects followed up for APO, classified as severe (PE <34 weeks, fetal/neonatal death, indicated preterm delivery <30 weeks) or moderate (PE ?34 weeks, indicated preterm delivery 30-36 weeks, growth restriction without PE).Severe APOs occurred in 12% and moderate APOs in 10% of patients. By 12-15 weeks, sFlt1, PlGF, and soluble endoglin levels were markedly altered in women who developed severe APO. After adjusting for clinical risk factors, sFlt1 was the strongest predictor of severe APO among 12-15 week measures (odds ratio, 17.3 comparing highest and lowest quartiles; 95% confidence interval [CI], 3.5-84.8; positive predictive value [PPV], 61%; negative predictive value [NPV], 93%). At 16-19 weeks, the combination of sFlt1 and PlGF was most predictive of severe APO, with risk greatest for subjects with both PlGF in lowest quartile (<70.3 pg/mL) and sFlt1 in highest quartile (>1872 pg/mL; odds ratio, 31.1; 95% CI, 8.0-121.9; PPV, 58%; NPV, 95%). Severe APO rate in this high-risk subgroup was 94% (95% CI, 70-99.8%), if lupus anticoagulant or history of high blood pressure was additionally present. In contrast, among patients with both sFlt1 <1872 pg/mL and PlGF >70.3 pg/mL, rate of severe APO was only 4.6% (95% CI, 2.1-8.6%).Circulating angiogenic factors measured during early gestation have a high NPV in ruling out the development of severe adverse outcomes among patients with SLE and/or APL syndrome. Timely risk stratification of patients is important for effective clinical care and optimal allocation of health care resources.

Project description:BackgroundAt present, individualized interventions can be given to patients with a clear etiology of pregnancy loss to improve the subsequent pregnancy outcomes, but the current reproductive status of the patient cannot be changed. The aim of this study was to investigate the association between female reproductive status and subsequence pregnancy outcome in patients with prior pregnancy loss (PL).MethodsA prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to February 2022, a total of 1955 women with at least one previous PL were enrolled. Maternal reproductive status and subsequent reproductive outcomes were recorded through an electronic medical record system and follow-up. Logistic regression was used to evaluate the association between reproductive status and the risk of subsequent reproductive outcomes.ResultsAmong all patients, the rates of subsequent infertility, early PL, late PL, and live birth were 20.82%, 24.33%, 1.69% and 50.77% respectively. In logistic regression, we found that age (OR 1.08, 95% CI 1.04-1.13) and previous cesarean delivery history (OR 2.46, 95% CI 1.27-4.76) were risk factors for subsequent infertility in patients with PL. Age (OR 1.06, 95% CI 1.03-1.10), age at first pregnancy (OR 1.06, 95% CI 1.03-1.10), BMI (OR 1.06, 95% CI 1.02-1.11), previous PL numbers (OR 1.18, 95% CI 1.04-1.57) and without pre-pregnancy intervention (OR 1.77, 95% CI 1.35-2.24) were risk factors for non-live birth. Age (OR 1.06, 95% CI 1.03-1.09), age at first pregnancy (OR 1.06, 95% CI 1.02-1.09), BMI (OR 1.07, 95% CI 1.02-1.11), previous PL numbers (OR 1.15, 95% CI 1.02-1.31) and without pre-pregnancy intervention (OR 2.16, 95% CI 1.65-2.84) were risk factors for PL.ConclusionsThe reproductive status of people with PL is strongly correlated with the outcome of subsequent pregnancies. Active pre-pregnancy intervention can improve the subsequent pregnancy outcome.Trial registrationThis study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

Dataset Information

Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss.

Publications

Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets