Migraine and risk of hypertensive disorders of pregnancy: A population-based cohort study.

BACKGROUND: Migraine is associated with hypertensive disorders of pregnancy through common pathophysiological features. This study evaluates the association between migraine diagnosis and treatment, and risk of hypertensive disorders of pregnancy. METHODS: We conducted a prospective cohort study in the Clinical Practice Research Datalink GOLD, a large longitudinal database of patient records in the UK. We analyzed data from liveborn or stillborn singleton deliveries from 1993-2020 with at least 24 months of medical history and no history of cardiovascular disease (n = 1,049,839). We ascertained migraine through diagnosis or prescription codes before 20 weeks of gestation and hypertensive disorders of pregnancy through diagnosis codes between 20 weeks of pregnancy and delivery. We used log-binomial regression models to estimate the risk ratio and 95% confidence intervals, comparing risk of hypertensive disorders of pregnancy among individuals with migraine to those without migraine, adjusting for confounders. CONCLUSIONS: A history of migraine prior to pregnancy was associated with an increased risk of hypertensive disorders of pregnancy (RR = 1.17, 95% CI: 1.09-1.26). The greatest risk was among those with pre-pregnancy migraine that persisted into the first trimester (RR = 1.84, 95% CI: 1.35-2.50). Use of migraine medication was associated with a higher risk of hypertensive disorders of pregnancy compared to non-migraineurs (RR = 1.50, 95% CI: 1.15-1.97). Results from this study indicate that migraine is a potential risk factor for hypertensive disorders of pregnancy.

Pre-pregnancy migraine diagnosis, medication use, and spontaneous abortion: a prospective cohort study.

BACKGROUND: Migraine is common among females of reproductive age (estimated prevalence:17-24%) and may be associated with reproductive health through underlying central nervous system excitability, autoimmune conditions, and autonomic dysfunction. We evaluated the extent to which pre-pregnancy migraine diagnosis and medication use are associated with risk of spontaneous abortion (SAB). METHODS: We analyzed data from a preconception study of pregnancy planners (2013-2021). Eligible participants self-identified as female, were aged 21-45 years, resided in the USA or Canada, and conceived during follow-up (n = 7890). Participants completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever occurred first. Pregnant participants then completed questionnaires during early (~ 8-9 weeks) and late (~ 32 weeks) gestation. We defined migraineurs as participants who reported a migraine diagnosis or use of a medication to treat migraine. Preconception questionnaires elicited migraine medication use during the past 4 weeks, and SAB on follow-up and pregnancy questionnaires. We used Cox regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations among preconception migraine, migraine medication use, and SAB, controlling for potential demographic, medical, and lifestyle confounders. RESULTS: Nineteen percent of study pregnancies ended in SAB. History of migraine before conception was not appreciably associated with SAB risk (HR = 1.03, 95% CI: 0.91-1.06). Use of any migraine medication was associated with a modest increase in SAB risk overall (HR = 1.14, 95% CI: 0.96-1.36). We observed the greatest increase in risk among those taking migraine medications daily (HR = 1.38, 95% CI: 0.81-2.35) and those taking prescription migraine prophylaxis (HR = 1.43, 95% CI: 0.72-2.84) or combination analgesic and caffeine medications (HR = 1.42, 95% CI: 0.99-2.04). CONCLUSIONS: Migraine medication use patterns suggesting greater underlying migraine severity were associated with increased risk of SAB. This research adds to the limited information available on the reproductive effects of migraine.

The association between time-to-pregnancy and postpartum depressive symptoms in a North American prospective cohort study.

PURPOSE: To prospectively examine the association between time-to-pregnancy (TTP) and postpartum depression (PPD) and determine whether perceived stress during early pregnancy mediated this association. METHODS: In Pregnancy Study Online, an internet-based preconception cohort study of pregnancy planners, participants completed questionnaires every 8 weeks for up to 12 months or conception, during pregnancy, and at postpartum. A total of 2643 women provided information on sociodemographic factors, reproductive history, and stress (i.e., Perceived Stress Scale [PSS]) during preconception and early pregnancy (completed at ∼4-12 weeks' gestation) and on postpartum depressive symptoms (i.e., Edinburgh Postnatal Depression Scale [EPDS]) at ∼6 months postpartum. We used multivariable modified Poisson regression models to estimate risk ratios and 95% confidence intervals (CIs) for the association between TTP (<3, 3-5, 6-11, ≥12 menstrual cycles) and PPD (EPDS score ≥13). Causal mediation analyses assessed the mediating role of early pregnancy PSS scores. RESULTS: 10.6% of women had EPDS scores indicating possible PPD (≥13). Compared with women who took less than 3 cycles to conceive, risk ratios for those who took 3-5, 6-11, and greater than or equal to 12 were 1.06 (95% CI: 0.77, 1.45), 1.24 (95% CI: 0.90, 1.70), and 1.31 (95% CI: 0.87, 1.99), respectively. Approximately 30% of the association between infertility (TTP ≥ 12) and PPD was mediated by early pregnancy PSS. CONCLUSIONS: There was a modest positive dose-response association between delayed conception and PPD. Perceived stress in early pregnancy explained a small proportion of this association. However, given the width of the CIs, chance cannot be ruled out as an explanation for the observed association.

A prospective study of preconception asthma and spontaneous abortion.

PURPOSE: To evaluate the relationships among history of asthma, asthma severity, and spontaneous abortion (SAB). METHODS: Pregnancy Study Online is a preconception cohort study of North American couples. During the preconception period, female participants reported their history of physician-diagnosed asthma, age at first diagnosis, and use of asthma medications in the previous 4 weeks. Asthma severity was classified by medication use proximal to conception, from level 0 to 3 in increasing severity. Pregnancy and SAB were identified using data from follow-up questionnaires. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 6325 participants who conceived, 19% experienced SAB and 17% reported a history of asthma. There was no appreciable association between asthma history and SAB incidence (HR = 0.98; 95% CI: 0.84, 1.14). HRs comparing severity levels 0, 1, and 2-3 with no asthma were 0.82 (95% CI: 0.67, 1.01), 1.20 (95% CI: 0.91, 1.60), and 1.31 (95% CI: 0.97, 1.78), respectively. Among women who conceived without the use of fertility treatment, level 2-3 severity was associated with SAB (HR = 1.39; 95% CI: 1.02, 1.89). CONCLUSIONS: While history of asthma diagnosis was not materially associated with SAB, having severe asthma (based on medication use) was associated with greater SAB risk.

A Prospective Cohort Study of COVID-19 Vaccination, SARS-CoV-2 Infection, and Fertility.

Some reproductive-aged individuals remain unvaccinated against coronavirus disease 2019 (COVID-19) because of concerns about potential adverse effects on fertility. Using data from an internet-based preconception cohort study, we examined the associations of COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with fertility among couples trying to conceive spontaneously. We enrolled 2,126 self-identified female participants aged 21-45 year residing in the United States or Canada during December 2020-September 2021 and followed them through November 2021. Participants completed questionnaires every 8 weeks on sociodemographics, lifestyle, medical factors, and partner information. We fit proportional probabilities regression models to estimate associations between self-reported COVID-19 vaccination and SARS-CoV-2 infection in both partners with fecundability (i.e., the per-cycle probability of conception), adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female fecundability ratio (FR) = 1.08, 95% confidence interval (CI): 0.95, 1.23; male FR = 0.95, 95% CI: 0.83, 1.10). Female SARS-CoV-2 infection was not strongly associated with fecundability (FR = 1.07, 95% CI: 0.87, 1.31). Male infection was associated with a transient reduction in fecundability (for infection within 60 days, FR = 0.82, 95% CI: 0.47, 1.45; for infection after 60 days, FR = 1.16, 95% CI: 0.92, 1.47). These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner.

A prospective study of treatments for cervical intraepithelial neoplasia and fecundability.

BACKGROUND: Treatments for cervical intraepithelial neoplasia remove precancerous cells from the cervix by excising or ablating the transformation zone. Most studies show no association between cervical intraepithelial neoplasia treatments and fertility outcomes. However, only 2 studies have examined time to pregnancy, both using retrospective study designs, with 1 study showing no association and the other showing a 2-fold increased risk of infertility (time to pregnancy >12 months) following excisional or ablative treatment. OBJECTIVE: We examined the association between cervical intraepithelial neoplasia treatments and fecundability. MATERIALS AND METHODS: We analyzed data from Pregnancy Study Online (PRESTO), a prospective cohort study of North American pregnancy planners enrolled during 2013-2019. At baseline, women reported whether they ever had an abnormal Papanicolaou test result, the number of abnormal Papanicolaou test results, and their age at first abnormal Papanicolaou test result. They also reported whether they underwent diagnostic (colposcopy) or treatment (excisional or ablative) procedures, and their age at each procedure. We restricted analyses to 8017 women with 6 or fewer cycles of attempt time at enrollment who reported receiving a Papanicolaou test in the previous 3 years. We estimated fecundability ratios and 95% confidence intervals using proportional probabilities models adjusted for sociodemographics, healthcare use, smoking, number of sexual partners, history of sexually transmitted infections, and human papillomavirus vaccination. RESULTS: A history of abnormal Papanicolaou test results showed little association with fecundability (fecundability ratio, 1.00; 95% confidence interval, 0.95-1.06). Likewise, receipt of colposcopy or treatment procedures, and time since treatment were not materially associated with fecundability. Results were similar when stratified by age and smoking status. CONCLUSION: We observed no appreciable association of self-reported history of abnormal Papanicolaou test results, colposcopy, treatments for cervical intraepithelial neoplasia, or recency of treatment with fecundability. These results agree with the majority of previous studies in indicating little effect of cervical intraepithelial neoplasia treatments on future fertility.