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1. Preconception contraceptive use and miscarriage: prospective cohort study

   https://doi.org/10.1136/bmjmed-2023-000569  

   Yland, Jennifer J; Wesselink, Amelia K; Hernandez-Diaz, Sonia; Huybrechts, Krista; Hatch, Elizabeth E; Wang, Tanran R; Savitz, David; Kuohung, Wendy; Rothman, Kenneth J; Wise, Lauren A (September 2023, BMJ Medicine)

   ObjectivesTo evaluate the association between preconception contraceptive use and miscarriage. DesignProspective cohort study. SettingResidents of the United States of America or Canada, recruited from 2013 until the end of 2022. Participants13 460 female identified participants aged 21-45 years who were planning a pregnancy were included, of whom 8899 conceived. Participants reported data for contraceptive history, early pregnancy, miscarriage, and potential confounders during preconception and pregnancy. Main outcome measureMiscarriage, defined as pregnancy loss before 20 weeks of gestation. ResultsPreconception use of combined and progestin-only oral contraceptives, hormonal intrauterine devices, copper intrauterine devices, rings, implants, or natural methods was not associated with miscarriage compared with use of barrier methods. Participants who most recently used patch (incidence rate ratios 1.34 (95% confidence interval 0.81 to 2.21)) or injectable contraceptives (1.44 (0.99 to 2.12)) had higher rates of miscarriage compared with recent users of barrier methods, although results were imprecise due to the small numbers of participants who used patch and injectable contraceptives. ConclusionsUse of most contraceptives before conception was not appreciably associated with miscarriage rate. Individuals who used patch and injectable contraceptives had higher rates of miscarriage relative to users of barrier methods, although these results were imprecise and residual confounding was possible. 

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2. Physical activity and heat stress shape water needs in pregnant endurance athletes

   https://doi.org/10.1093/emph/eoaf003  

   Sadhir, Srishti; McGrosky, Amanda; Swanson, Zane_S; Tavormina, Anna; Tomechko, Keri; Pontzer, Herman (February 2025, Evolution, Medicine, and Public Health)

   Abstract Background and objectivesPregnancy, heat stress, and physical activity (PA) are all known to independently increase human water requirements. We hypothesize that climate conditions and behavioral strategies interact to shape water needs in highly active pregnancies. MethodologyWe recruited 20 female endurance runners who were pregnant (8–16 weeks gestational age; n = 13) or planning to be pregnant (n = 7) for an observational, prospective cohort study. At three timepoints in the study (preconception, 8–16 weeks, and 32–35 weeks), we measured water turnover (WT) using the deuterium dilution and elimination technique, PA using ActiGraph wGT3X-BT accelerometers, and heat index (HI) using historical temperature and humidity data. We also compared athletes to nonathletes from a previously published study. ResultsAthletes maintained high WT from preconception through the end of pregnancy. PA was positively associated with WT among athletes for preconception and early pregnancy time periods but not for the third trimester. HI weakly moderated the relationship between PA and WT in predicting a more positive slope in hotter and more humid weather conditions. WT in athletes was higher than in nonathletes, but this difference attenuated during the third trimester, as nonathletes increased their WT. Conclusions and implicationsAthletes experience higher WT with greater levels of PA, and this relationship is somewhat stronger in higher HI conditions. With the threat of climate change expected to exacerbate extreme heat conditions, evidence-based, global policies are required for particularly vulnerable populations. 

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3. Brain responses to food viewing in women during pregnancy and post partum and their relationship with metabolic health: study protocol for the FOODY Brain Study, a prospective observational study

   https://doi.org/10.1136/bmjopen-2022-067013  

   Lesniara-Stachon, Anna; Quansah, Dan Yedu; Schenk, Sybille; Retsa, Chrysa; Halter, Ryan J; Murray, Micah M; Lacroix, Alain; Horsch, Antje; Toepel, Ulrike; Puder, Jardena J (April 2023, BMJ Open)

   IntroductionFood cravings are common in pregnancy and along with emotional eating and eating in the absence of hunger, they are associated with excessive weight gain and adverse effects on metabolic health including gestational diabetes mellitus (GDM). Women with GDM also show poorer mental health, which further can contribute to dysregulated eating behaviour. Food cravings can lead to greater activity in brain centres known to be involved in food ‘wanting’ and reward valuation as well as emotional eating. They are also related to gestational weight gain. Thus, there is a great need to link implicit brain responses to food with explicit measures of food intake behaviour, especially in the perinatal period. The aim of this study is to investigate the spatiotemporal brain dynamics to visual presentations of food in women during pregnancy and in the post partum, and link these brain responses to the eating behaviour and metabolic health outcomes in women with and without GDM. Methods and analysisThis prospective observational study will include 20 women with and 20 without GDM, that have valid data for the primary outcomes. Data will be assessed at 24–36 weeks gestational age and at 6 months post partum. The primary outcomes are brain responses to food pictures of varying carbohydrate and fat content during pregnancy and in the post partum using electroencephalography. Secondary outcomes including depressive symptoms, current mood and eating behaviours will be assessed with questionnaires, objective eating behaviours will be measured using Auracle and stress will be measured with heart rate and heart rate variability (Actiheart). Other secondary outcome measures include body composition and glycaemic control parameters. Ethics and disseminationThe Human Research Ethics Committee of the Canton de Vaud approved the study protocol (2021-01976). Study results will be presented at public and scientific conferences and in peer-reviewed journals. 

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4. Association of male fatty acid intake with fecundability among couples planning pregnancy

   https://doi.org/10.1093/humrep/dead100  

   Geller, Ruth J; Wesselink, Amelia K; Koenig, Martha R; Eisenberg, Michael L; Tucker, Katherine L; Hatch, Elizabeth E; Wise, Lauren A (May 2023, Human Reproduction)

   Abstract STUDY QUESTIONTo what extent is male fatty acid intake associated with fecundability among couples planning pregnancy? SUMMARY ANSWERWe observed weak positive associations of male dietary intakes of total and saturated fatty acids with fecundability; no other fatty acid subtypes were appreciably associated with fecundability. WHAT IS KNOWN ALREADYMale fatty acid intake has been associated with semen quality in previous studies. However, little is known about the extent to which male fatty acid intake is associated with fecundability among couples attempting spontaneous conception. STUDY DESIGN, SIZE, DURATIONWe conducted an internet-based preconception prospective cohort study of 697 couples who enrolled during 2015–2022. During 12 cycles of observation, 53 couples (7.6%) were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants were residents of the USA or Canada, aged 21–45 years, and not using fertility treatment at enrollment. At baseline, male participants completed a food frequency questionnaire from which we estimated intakes of total fat and fatty acid subtypes. We ascertained time to pregnancy using questionnaires completed every 8 weeks by female participants until conception or up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs for the associations of fat intakes with fecundability, adjusting for male and female partner characteristics. We used the multivariate nutrient density method to account for energy intake, allowing for interpretation of results as fat intake replacing carbohydrate intake. We conducted several sensitivity analyses to assess the potential for confounding, selection bias, and reverse causation. MAIN RESULTS AND THE ROLE OF CHANCEAmong 697 couples, we observed 465 pregnancies during 2970 menstrual cycles of follow-up. The cumulative incidence of pregnancy during 12 cycles of follow-up after accounting for censoring was 76%. Intakes of total and saturated fatty acids were weakly, positively associated with fecundability. Fully adjusted FRs for quartiles of total fat intake were 1.32 (95% CI 1.01–1.71), 1.16 (95% CI 0.88–1.51), and 1.43 (95% CI 1.09–1.88) for the second, third, and fourth vs the first quartile, respectively. Fully adjusted FRs for saturated fatty acid intake were 1.21 (95% CI 0.94–1.55), 1.16 (95% CI 0.89–1.51), and 1.23 (95% CI 0.94–1.62) for the second, third, and fourth vs the first quartile, respectively. Intakes of monounsaturated, polyunsaturated, trans-, omega-3, and omega-6 fatty acids were not strongly associated with fecundability. Results were similar after adjustment for the female partner’s intakes of trans- and omega-3 fats. LIMITATIONS, REASONS FOR CAUTIONDietary intakes estimated from the food frequency questionnaire may be subject to non-differential misclassification, which is expected to bias results toward the null in the extreme categories when exposures are modeled as quartiles. There may be residual confounding by unmeasured dietary, lifestyle, or environmental factors. Sample size was limited, especially in subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGSOur results do not support a strong causal effect of male fatty acid intakes on fecundability among couples attempting to conceive spontaneously. The weak positive associations we observed between male dietary fat intakes and fecundability may reflect a combination of causal associations, measurement error, chance, and residual confounding. STUDY FUNDING/COMPETING INTEREST(S)The study was funded by the National Institutes of Health, grant numbers R01HD086742 and R01HD105863. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility app). L.A.W. is a consultant for AbbVie, Inc. M.L.E. is an advisor to Sandstone, Ro, Underdog, Dadi, Hannah, Doveras, and VSeat. The other authors have no competing interests to report. TRIAL REGISTRATION NUMBERN/A. 

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

   https://doi.org/10.1093/humrep/deab173  

   Crowe, Holly Michelle; Wesselink, Amelia Kent; Wise, Lauren Anne; Wang, Tanran R; Horsburgh, Charles Robert; Mikkelsen, Ellen Margrethe; Hatch, Elizabeth Elliott (July 2021, Human Reproduction)

   Abstract 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. 

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