Uterine fibroids and risk of preterm birth by clinical subtypes: a prospective cohort study.

BACKGROUND: Fibroids are present in approximately one in ten pregnancies and are inconsistently linked with preterm birth. We sought to determine the association between fibroids and preterm birth in a prospective cohort with standardized research ultrasounds for characterizing fibroids in early pregnancy while accounting for the clinical paths that precede preterm birth. METHODS: Participants who were pregnant or planning a pregnancy were recruited from communities in three states between 2000 and 2012. Members of this prospective cohort had a research ultrasound in the first trimester to establish pregnancy dating and to record detailed information about the presence, size, number, and location of fibroids. Baseline information from time of enrollment and a detailed first trimester interview contributed key information about candidate confounders. Birth outcomes, including clinical classification of type of preterm birth (preterm labor, preterm premature rupture of membranes, and medically indicated preterm birth) were cross-validated from participant report, labor and delivery records, and birth certificate data. RESULTS: Among 4,622 women with singleton pregnancies, 475 had at least one fibroid (10.3%) and 352 pregnancies resulted in preterm birth (7.6%). Prevalence of fibroids was similar for women with preterm and term births (10.2% vs. 10.3%). Fibroids were not associated with increased risk of preterm birth after taking into account confounding (risk ratio adjusted for race/ethnicity and maternal age, 0.88; 95% confidence interval, 0.62-1.24) nor any clinical subtype of preterm birth. No fibroid characteristic or combination of characteristics was associated with risk. CONCLUSIONS: If fibroids increase risk of preterm birth, the effect is substantially smaller than previous estimates. Given lack of effect in a large population of women from the general population, rather than higher risk academic tertiary populations previously most studied, we encourage a reconsideration of the clinical impression that presence of fibroids is a major risk factor for preterm birth.

First-trimester antihistamine exposure and risk of spontaneous abortion or preterm birth.

PURPOSE: We tested whether antihistamine exposure during early pregnancy is associated with spontaneous abortion (SAB) or preterm birth (PTB). METHODS: Women were enrolled in Right from the Start (2004-2010), a prospective pregnancy cohort. Data about first-trimester antihistamine use were obtained from screening and first-trimester interviews. Self-reported outcomes included SAB and PTB and were verified by medical records. Cox proportional hazards models were used to test for an association between antihistamine use and each outcome, both performed adjusting for confounders. RESULTS: Among the 2685 pregnancies analyzed, 14% (n = 377) reported use of antihistamines. Among antihistamine users, 12% (n = 44) experienced SABs, and 6% (n = 21) had PTBs. Antihistamine exposure was not associated with SAB (adjusted hazard ratio [aHR] = 0.88, 95% confidence interval [CI] 0.64, 1.21) or PTB, which was modified by maternal race (aHR = 1.03, 95%CI 0.61, 1.72 among White women and aHR = 0.43, 95%CI 0.14, 1.34 among Black women). CONCLUSIONS: Despite the biologic plausibility that antihistamine use may influence pregnancy outcomes, we did not detect evidence of an association with SAB or PTB. These data demonstrate the utility of large prospective cohorts for evaluating drug safety in pregnancy when concerns are raised from animal models.

Periconceptional over-the-counter nonsteroidal anti-inflammatory drug exposure and risk for spontaneous abortion.

OBJECTIVE: To estimate the association between over-the-counter nonsteroidal anti-inflammatory drug (NSAID) exposure during the early first trimester and risk for spontaneous abortion (gestation before 20 weeks of gestation) in a prospective cohort. METHODS: Women were enrolled in the Right from the Start study (2004-2010). Exposure data regarding over-the-counter NSAID use from the last menstrual period (LMP) through the sixth week of pregnancy were obtained from intake and first-trimester interviews. Pregnancy outcomes were self-reported and verified by medical records. Gestational age was determined from the LMP. Stage of development before loss was determined from study ultrasonography. Cox proportional hazards regression models were used to estimate the association between NSAID exposure and pregnancy outcome taking into account candidate confounders. RESULTS: Among 2,780 pregnancies, 367 women (13%) experienced a spontaneous abortion. NSAID exposure was reported by 1,185 (43%) women. NSAID exposure was not associated with spontaneous abortion risk in unadjusted models (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.82-1.24) or models adjusted for maternal age (adjusted HR 1.00, 95% CI 0.81-1.23). CONCLUSION: Our findings suggest that use of nonprescription over-the-counter NSAIDs in early pregnancy does not put women at increased risk of spontaneous abortion.