Periconceptional antibiotic use and spontaneous abortion: A prospective cohort study.

BACKGROUND: Many reproductive-aged North Americans use antibiotics in the weeks preceding conception or during early pregnancy. Antibiotic use may influence risk of spontaneous abortion (SAB) by disrupting the reproductive tract microbiome or treating harmful infections. However, this association has not been extensively studied. OBJECTIVE: To determine the extent to which periconceptional antibiotic use is associated with the risk of SAB. METHODS: We analysed data from an internet-based preconception cohort study of pregnancy planners. Eligible participants self-identified as female, were aged 21-45 years, resided in the USA or Canada, and conceived during 12 months of follow-up (n = 7890). Participants completed an enrolment questionnaire during June 2013-September 2021 and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. Pregnant participants completed questionnaires in early (~8-9 weeks) and late (~32 weeks) gestation. We assessed antibiotic use, including type (penicillins, nitrofurantoin, cephalosporins and macrolides) and indication for use, during the previous 4 weeks on preconception questionnaires. Participants reported pregnancies and SAB on follow-up and pregnancy questionnaires. We used Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between periconceptional antibiotic use and SAB, controlling for potential demographic, medical, and lifestyle confounders. RESULTS: Nineteen percent (n = 1537) of pregnancies ended in SAB. Participants reported periconceptional antibiotic use in 8% of pregnancies ending in SAB and 7% not ending in SAB. Periconceptional antibiotic use was not appreciably associated with SAB (adjusted HR 1.06, 95% CI 0.88, 1.28). We observed no strong associations between antibiotic type, indication for use, or recency of exposure and SAB risk. CONCLUSIONS: Periconceptional antibiotic use was not appreciably associated with SAB in this study. This association is likely complicated by antibiotic type and dosage, timing of conception, and the individual's overall health.

Antibiotics and fecundability among female pregnancy planners: a prospective cohort study.

STUDY QUESTION: To what extent is female preconception antibiotic use associated with fecundability? SUMMARY ANSWER: Preconception antibiotic use overall was not appreciably associated with fecundability. WHAT IS KNOWN ALREADY: Antibiotics are commonly used by women and are generally thought to be safe for use during pregnancy. However, little is known about possible effects of antibiotic use on fecundability, the per-cycle probability of conception. Previous research on this question has been limited to occupational rather than therapeutic exposure. STUDY DESIGN, SIZE, DURATION: We analyzed data from an Internet-based preconception cohort study of 9524 female pregnancy planners aged 21-45 years residing in the USA and Canada who had been attempting to conceive for six or fewer cycles at study entry. Participants enrolled between June 2013 and September 2020 and completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. The questions pertaining to antibiotic type and indication were added to the PRESTO questionnaires in March 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: We assessed antibiotic use in the previous 4 weeks at baseline and on each follow-up questionnaire. Participants provided the name of the specific antibiotic and the indication for use. Antibiotics were classified based on active ingredient (penicillins, macrolides, nitrofurantoin, nitroimidazole, cephalosporins, sulfonamides, quinolones, tetracyclines, lincosamides), and indications were classified by type of infection (respiratory, urinary tract, skin, vaginal, pelvic, and surgical). Participants reported pregnancy status on follow-up questionnaires. We used proportional probabilities regression to estimate fecundability ratios (FR), the per-cycle probability of conception comparing exposed with unexposed individuals, and 95% confidence intervals (CI), adjusting for sociodemographics, lifestyle factors, and reproductive history. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, women who used antibiotics in the past 4 weeks at baseline had similar fecundability to those who had not used antibiotics (FR: 0.98, 95% CI: 0.89-1.07). Sulfonamides and lincosamides were associated with slightly increased fecundability (FR: 1.39, 95% CI: 0.90-2.15, and FR: 1.58 95% CI: 0.96-2.60, respectively), while macrolides were associated with slightly reduced fecundability (FR: 0.70, 95% CI: 0.47-1.04). Analyses of the indication for antibiotic use suggest that there is likely some confounding by indication. LIMITATIONS, REASONS FOR CAUTION: Findings were imprecise for some antibiotic classes and indications for use owing to small numbers of antibiotic users in these categories. There are likely heterogeneous effects of different combinations of indications and treatments, which may be obscured in the overall null results, but cannot be further elucidated in this analysis. WIDER IMPLICATIONS OF THE FINDINGS: There is little evidence that use of most antibiotics is associated with reduced fecundability. Antibiotics and the infections they treat are likely associated with fecundability through differing mechanisms, resulting in their association with increased fecundability in some circumstances and decreased fecundability in others. STUDY FUNDING/COMPETING INTEREST(S): This study was supported through funds provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (R01-HD086742, R21-HD072326). L.A.W. has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, Fertility Friend, and Kindara for primary data collection in PRESTO. The other authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Preconception use of antibiotics and fecundability: a Danish prospective cohort study.

OBJECTIVE: To assess the association between preconception antibiotic use and fecundability, the per menstrual cycle probability of conception. DESIGN: SnartForaeldre.dk, a Danish prospective cohort study of women trying to conceive (2007-2020). SETTING: Not applicable. SUBJECT(S): 9462 female participants, median age 29 years at enrollment. EXPOSURE: Antibiotic use was defined by filled prescriptions retrieved from the Danish National Prescription Registry, using Anatomical Therapeutic Chemical codes, and modeled as time-varying (menstrual cycle-varying) exposure. MAIN OUTCOME MEASURE(S): Pregnancy status was reported on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Fecundability ratios (FR) and 95% confidence intervals (CI) were computed using proportional probabilities regression models, with adjustment for age, partner age, education, smoking, folic acid supplementation, body mass index, parity, cycle regularity, timing of intercourse, and sexually transmitted infections. RESULT(S): During all cycles of observation, the percentage of participants filing at least 1 antibiotic prescription was 11.9%; 8.6% had a prescription for penicillins, 2.1% for sulfonamides, and 1.8% for macrolides. Based on life-table methods, 86.5% of participants conceived within 12 cycles of follow-up. Recent preconception antibiotic use was associated with reduced fecundability (≥1 prescription vs. none: adjusted FR = 0.86; 95% CI, 0.76-0.99). For participants using penicillins, sulfonamides, or macrolides, the adjusted FRs were 0.97 (95% CI, 0.83-1.12), 0.68 (95% CI, 0.47-0.98), and 0.59 (95% CI, 0.37-0.93), respectively. CONCLUSION(S): Preconception use of antibiotics, specifically sulfonamides and macrolides, was associated with decreased fecundability compared with no use. The observed associations may be explained plausibly by confounding by indication, as we lacked data on indications for the prescribed antibiotics. Consequently, we cannot separate the effect of the medication from the effect of the underlying infection.

Association of Asthma Diagnosis and Medication Use with Fecundability: A Prospective Cohort Study.

PURPOSE: Asthma has been positively associated with irregular menses and infertility in some studies, but data are limited on the relation between asthma medication use and fecundability (i.e., average per-cycle probability of conception among non-contracepting couples). This study examines the extent to which a history of asthma, asthma medication use, and age at first asthma diagnosis are associated with fecundability among female pregnancy planners. PARTICIPANTS AND METHODS: Pregnancy Study Online (PRESTO) is an ongoing, web-based preconception cohort study of couples aged 21-45 years from North America. Between July 2013 and July 2019, a total of 10,436 participants enrolled in PRESTO, and 8286 were included in the present analysis. At study enrollment, women reported whether they had ever been diagnosed with asthma and, if so, the year they were first diagnosed. Women who reported ever being diagnosed with asthma were asked about medication use, including medication type and frequency of use. Participants completed follow-up questionnaires every 8 weeks for up to 12 months or until pregnancy. Proportional probabilities regression models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Fecundability ratios below 1.00 indicate reduced probability of conception. RESULTS: There was little association between a history of asthma diagnosis or asthma medication use and fecundability. Compared with no history of asthma, the FR for ever-diagnosis of asthma with medication use was 1.02 (95% CI: 0.91-1.15) and for ever-diagnosis of asthma without medication use was 1.00 (95% CI: 0.91-1.09). Highest intensity asthma medication use (daily plus extra dosing for symptoms), combination inhaled corticosteroid and long-acting beta-agonist inhaler use, and a first diagnosis of asthma after age 17 years were associated with small reductions in fecundability. CONCLUSION: The present study provides little evidence that asthma or asthma medication use is adversely associated with fecundability.

Female sleep patterns, shift work, and fecundability in a North American preconception cohort study.

OBJECTIVE: To prospectively evaluate the association between female sleep patterns, shift work, and fecundability. DESIGN: Web-based preconception cohort study, Pregnancy Study Online (PRESTO). SETTING: Not applicable. PATIENT(S): North American Women aged 21-45 years attempting pregnancy. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): At baseline, self-reported average sleep duration per 24-hour period in the previous month, the frequency of trouble sleeping within the last 2 weeks (as measured by the Major Depression Inventory), and shift work patterns. Pregnancy status determined by follow-up questionnaires completed every 8 weeks for up to 12 months or until conception. RESULT(S): The analyses were restricted to 6,873 women attempting pregnancy for ≤6 months at enrollment from June 2013 through September 2018. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Relative to 8 hours of sleep per day, FRs for <6, 6, 7, and ≥9 hours of sleep/day were 0.89 (95% CI, 0.75-1.06), 0.95 (95% CI, 0.86-1.04), 0.99 (95% CI, 0.92-1.06), and 0.96 (95% CI, 0.84-1.10), respectively. Compared with no trouble sleeping, FRs for trouble sleeping <50% of the time or trouble sleeping >50% of the time were 0.93 (95% CI, 0.88-1.00) and 0.87 (95% CI, 0.79-0.95), respectively. The results were slightly stronger among women with higher depressive symptoms and perceived stress levels. There was no association between shift work and fecundability. CONCLUSION(S): Trouble sleeping at night was associated with modestly reduced fecundability. A weaker inverse association was observed between shorter sleep duration and fecundability.

Male sleep duration and fecundability in a North American preconception cohort study.

OBJECTIVE: To evaluate prospectively the association between male sleep duration and fecundability. DESIGN: Pregnancy Online Study (PRESTO), a Web-based prospective cohort study of North American couples enrolled during the preconception period (2013-2017). SETTING: Not applicable. PATIENT(S): Male participants were aged ≥21 years; female participants were aged 21-45 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): At enrollment, men reported their average nightly sleep duration in the previous month. Pregnancy status was updated on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Analyses were restricted to 1,176 couples who had been attempting to conceive for up to six cycles at enrollment. Proportional probabilities regression models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULT(S): Relative to 8 hours per night of sleep, multivariable-adjusted FRs for <6, 6, 7, and ≥9 hours per night of sleep were 0.62 (95% CI 0.45-0.87), 1.06 (95% CI 0.87-1.30), 0.97 (95% CI 0.81-1.17), and 0.73 (95% CI 0.46-1.15), respectively. The association between short sleep duration (<6 hours per night) and fecundability was similar among men not working nights or rotating shifts (FR 0.60, 95% CI 0.41-0.88) and among men without a history of infertility (FR 0.62, 95% CI 0.44-0.87) and was stronger among fathers (FR 0.46, 95% CI 0.28-0.76). CONCLUSION(S): Short sleep duration in men was associated with reduced fecundability. Because male factor accounts for 50% of couple infertility, identifying modifiable determinants of infertility could provide alternatives to expensive fertility workups and treatments.