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.

Iron Consumption Is Not Consistently Associated with Fecundability among North American and Danish Pregnancy Planners.

BACKGROUND: Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements. OBJECTIVES: The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with fecundability. METHODS: We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n = 1693) and North America (PRESTO; n = 2969) during 2013-2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for confounders. RESULTS: We found little association between dietary heme iron intake and fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles. CONCLUSIONS: Overall, dietary intake of iron was not consistently associated with fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and fecundability among North American, but not Danish, pregnancy planners.

Neonatal Outcomes in a Medicaid Population With Opioid Dependence.

Confounding may account for the apparently improved infant outcomes after prenatal exposure to buprenorphine versus methadone. We used Massachusetts Medicaid Analytic eXtract (MAX) data to identify a cohort of opioid-dependent mother-infant pairs (2006-2011), supplemented with confounder data from an external Boston, Massachusetts, cohort (2015-2016). Associations between prenatal buprenorphine exposure versus methadone exposure and infant outcomes in the MAX cohort were adjusted for measured MAX confounders and were additionally adjusted for unmeasured confounders with bias analysis using external cohort data. A total of 477 women in MAX were treated with methadone and 543 with buprenorphine. More buprenorphine users than methadone users were white and used psychotropic medications. After adjustment for MAX confounders, risk ratios among infants exposed to buprenorphine versus those exposed to methadone were 0.45 (95% confidence interval (CI): 0.34, 0.61) for preterm birth (birth at <37 weeks) and 0.75 (95% CI: 0.51, 1.11) for low birth weight for gestational age. The mean difference in infant hospitalization was -7.35 days (95% CI: -9.16, -5.55). After further adjustment with bias analysis, the risk ratios were 0.53 (95% CI: 0.39, 0.71) for preterm birth and 1.14 (95% CI: 0.77, 1.69) for low birth weight for gestational age, and the mean difference in infant hospitalization was -3.66 days (95% CI: -5.46, -1.87). External confounder data can be used to adjust for unmeasured confounding in studies of prenatal outcomes among women on opioid agonist therapy based on administrative databases.

Dietary Fat Intake and Fecundability in 2 Preconception Cohort Studies.

The association between dietary fat and fertility is not well studied. We evaluated intakes of total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, trans fatty acids (TFA), ω-3 fatty acids, and ω-6 fatty acids in relation to fecundability in Danish and North American preconception cohort studies. Women who were attempting to become pregnant completed a validated food frequency questionnaire at baseline. Pregnancy status was updated bimonthly for 12 months or until pregnancy. Fecundability ratios (FR) and 95% confidence intervals were estimated using multivariable proportional probabilities regression. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and ω-6 fatty acids were not appreciably associated with fecundability. TFA intake was associated with reduced fecundability in North American women (for the fourth quartile vs. the first, FR = 0.86, 95% confidence interval (CI): 0.71, 1.04) but not Danish women (for the fourth quartile vs. the first, FR = 1.04, 95% CI: 0.86, 1.25), though intake among Danish women was low. In North America, ω-3 fatty acid intake was associated with higher fecundability, but there was no dose-response relationship (among persons who did not use fish oil supplements: for the fourth quartile vs. the first, FR = 1.40, 95% CI: 1.13, 1.73); no association was found in Danish women, among whom low intake was rare. In the present study, high TFA intake and low ω-3 fatty acid intake were associated with reduced fecundity.

Intake of Sugar-sweetened Beverages and Fecundability in a North American Preconception Cohort.

BACKGROUND: Dietary factors, including sugar-sweetened beverages, may have adverse effects on fertility. Sugar-sweetened beverages were associated with poor semen quality in cross-sectional studies, and female soda intake has been associated with lower fecundability in some studies. METHODS: We evaluated the association of female and male sugar-sweetened beverage intake with fecundability among 3,828 women planning pregnancy and 1,045 of their male partners in a North American prospective cohort study. We followed participants until pregnancy or for up to 12 menstrual cycles. Eligible women were aged 21-45 (male partners ≥21), attempting conception for ≤6 cycles, and not using fertility treatments. Participants completed a comprehensive baseline questionnaire, including questions on sugar-sweetened beverage consumption during the previous 4 weeks. We estimated time-to-pregnancy from follow-up questionnaires completed every 2 months by the female partner. We calculated adjusted fecundability ratios (FR) and 95% confidence intervals (CIs) according to intake of sugar- sweetened beverages using proportional probabilities regression. RESULTS: Both female and male intakes of sugar-sweetened beverages were associated with reduced fecundability (FR = 0.81; 95% CI = 0.70, 0.94 and 0.78; 95% CI = 0.63, 0.95 for ≥7 sugar-sweetened beverages per week compared with none, for females and males, respectively). Fecundability was further reduced among those who drank ≥7 servings per week of sugar-sweetened sodas (FR = 0.75, 95% CI = 0.59, 0.95 for females and 0.67, 95% CI = 0.51, 0.89 for males). CONCLUSIONS: Sugar-sweetened beverages, particularly sodas and energy drinks, were associated with lower fecundability, but diet soda and fruit juice had little association.

The Role of Professional Journals and Societies in the Future of a Field: A Reflection on the Partnership Between the American Journal of Epidemiology and the Society for Epidemiologic Research.

On this, the 100th anniversary of Johns Hopkins Bloomberg School of Public Health, we take the opportunity to reflect on the ties between the School, the American Journal of Epidemiology, and the Society for Epidemiologic Research. We discuss briefly the intersection of the School, the Journal, and the Society throughout their histories, with the aim of providing some insight into how the Journal and the Society have contributed to the evolution of the field. In so doing, we articulate the challenges that the Journal and the Society jointly face today, with an eye to finding opportunities in these challenges that can be helpful in coming decades.

Evaluation of Selection Bias in an Internet-based Study of Pregnancy Planners.

Selection bias is a potential concern in all epidemiologic studies, but it is usually difficult to assess. Recently, concerns have been raised that internet-based prospective cohort studies may be particularly prone to selection bias. Although use of the internet is efficient and facilitates recruitment of subjects that are otherwise difficult to enroll, any compromise in internal validity would be of great concern. Few studies have evaluated selection bias in internet-based prospective cohort studies. Using data from the Danish Medical Birth Registry from 2008 to 2012, we compared six well-known perinatal associations (e.g., smoking and birth weight) in an internet-based preconception cohort (Snart Gravid n = 4,801) with the total population of singleton live births in the registry (n = 239,791). We used log-binomial models to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for each association. We found that most results in both populations were very similar. For example, maternal obesity was associated with an increased risk of delivering a macrosomic infant in Snart Gravid (RR = 1.5; 95% CI: 1.2, 1.7) and the total population (RR = 1.5; 95% CI: 1.45, 1.53), and maternal smoking of >10 cigarettes per day was associated with a higher risk of low birth weight (RR = 2.7; 95% CI: 1.2, 5.9 vs. RR = 2.9; 95% CI: 2.6, 3.1) in Snart Gravid and the total population, respectively. We cannot be certain that our results would apply to other associations or different populations. Nevertheless, our results suggest that recruitment of reproductive aged women via the internet may be no more prone to selection bias than traditional methods of recruitment.

Comparison of Neonatal Abstinence Syndrome Manifestations in Preterm Versus Term Opioid-Exposed Infants.

BACKGROUND: Twenty percent to 40% of infants exposed to in utero opioid were delivered preterm. There is currently no neonatal abstinence syndrome (NAS) scoring tool known to accurately evaluate preterm opioid-exposed infants. This can lead to difficulties in titrating pharmacotherapy in this population. PURPOSE: To describe NAS symptoms in preterm opioid-exposed infants in comparison with matched full-term controls. METHODS: This was a retrospective cohort study from a single tertiary care center of methadone-exposed infants born between 2006 and 2010. Using modified Finnegan scale scores recorded every 3 to 4 hours beginning at 6 hours of life until 24 to 48 hours after medication discontinuation, NAS symptoms was compared between 45 preterm infants and 49 full-term matched controls. Concurrent neonatal medical diagnoses were also compared. RESULTS: The median gestational age in the preterm group was 35 weeks (interquartile range [IQR] = 33-36) versus 39 weeks (IQR = 38-40) in the term group. Preterm infants scored less frequently for many items including sleep disturbance (24.4% vs 46.2%), tremors (77.9% vs 89.7%), muscle tone (87.9% vs 97.4%), sweating (2.1% vs 9.4%), nasal stuffiness (11.9% vs 20.5%), and loose stools (7.0% vs 14.3%) than full-term controls. Preterm infants scored more frequently for hyperactive moro reflex (26.4% vs 5.5%), tachypnea (19.3% vs 16.1%), and poor feeding (24.6% vs 11.8%). IMPLICATIONS FOR PRACTICE: Provider awareness of differences in manifestations of preterm and term infants with NAS, as well as concurrent prematurity diagnoses that can influence NAS scoring, is needed. These findings mandate the development of a modified NAS scoring tool for the preterm NAS population. IMPLICATIONS FOR RESEARCH: A preterm NAS scoring tool needs to be developed and validated to more accurately evaluate and treat preterm opioid-exposed infants.

Design and Conduct of an Internet-Based Preconception Cohort Study in North America: Pregnancy Study Online.

BACKGROUND: We launched the Boston University Pregnancy Study Online (PRESTO) to assess the feasibility of carrying out an Internet-based preconception cohort study in the US and Canada. METHODS: We recruited female participants age 21-45 and their male partners through Internet advertisements, word of mouth, and flyers. Female participants were randomised with 50% probability to receive a subscription to FertilityFriend.com (FF), a web-based programme that collects real-time data on menstrual characteristics. We compared recruitment methods within PRESTO, assessed the cost-efficiency of PRESTO relative to its Danish counterpart (Snart-Gravid), and validated retrospectively reported date of last menstrual period (LMP) against the FF data. RESULTS: After 99 weeks of recruitment (2013-15), 2421 women enrolled; 1384 (57%) invited their male partners to participate, of whom 693 (50%) enrolled. Baseline characteristics were balanced across randomisation groups. Cohort retention was similar among those randomised vs. not randomised to FF (84% vs. 81%). At study enrollment, 56%, 22%, and 22% couples had been trying to conceive for < 3, 3-5, and ≥ 6 months, respectively. The cost per subject enrolled was $146 (2013 US$), which was similar to our companion Danish study and half that of a traditional cohort study. Among FF users who conceived, > 97% reported their LMP on the PRESTO questionnaire within 1 day of the LMP recorded via FF. CONCLUSIONS: Use of the Internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective.

Pre-gravid oral contraceptive use in relation to birth weight: a prospective cohort study.

Few studies have evaluated the association between pregravid oral contraceptive (OC) use and birth weight, and findings have been conflicting. We conducted a prospective cohort study of 5921 pregnancy planners in Denmark to evaluate recency, duration, and type of OC used before conception in relation to infant birth weight. Participants completed online questionnaires and reported detailed information on contraceptive history and covariates at baseline. Participants completed bimonthly follow-up questionnaires to update their pregnancy status for up to 12 months or until conception occurred. Birth weight data were ascertained from the Danish Medical Birth Registry for 4046 live births delivered by study participants between 2008 and 2010. We used multivariable linear and log-binomial regression analyses to control for confounding. Mean birth weight was higher among women who had used OCs within 0-1 months (mean difference = 97 g, CI 26, 168) or 2-6 months (mean difference = 40 g, CI -5, 85) before conception, compared with more than 12 months before conception. Mean birth weight was lower among women who had used OCs for long durations (mean difference comparing ≥12 with <4 years of OC use = -85 g, CI -158, -11). Our findings indicate that pregravid OC use within 6 months of conception may be associated with a small increase in birth weight, but that long duration of use may have the opposite effect. Results were stronger among male infants, among 2nd and 4th generation OC users, and among users of OCs with a higher estrogen dose.

Body size and risk of spontaneous abortion among danish pregnancy planners.

BACKGROUND: Several studies indicate that female obesity increases the risk of spontaneous abortion (SAB). Central adiposity, height, and location of typical weight gain have not been examined as risk factors for SAB. METHODS: We examined the associations between selected anthropometric factors and risk of SAB among 5132 women enrolled in a Danish Internet-based prospective cohort study of pregnancy planners. We used Cox proportional hazards regression models, with gestational weeks as the time scale, to compute hazard ratios (HRs) of SAB and 95% confidence intervals (CIs). RESULTS: After adjustment for potential confounders, the HRs for SAB among underweight (body mass index (BMI, kg/m(2) ) <20), overweight (BMI: 25-29) and obese (BMI ≥30) women were 1.00 [95% CI: 0.81, 1.24], 0.90 [95% CI: 0.73, 1.09] and 1.23 [95% CI: 0.98, 1.54], respectively, compared with normal weight women (BMI 20-24). The association between obesity and SAB was stronger for early SAB (<8 weeks gestation); HR: 1.34 95% CI: 1.01, 1.77. The HR for height ≥174 cm vs. <166 cm was 0.81 [95% CI: 0.66, 1.00]. Increased waist-to-hip ratio (WHR) was inversely associated with risk of SAB (HR: 0.81; 95% CI: 0.63, 1.05). Waist circumference and location of typical weight gain were not appreciably associated with SAB risk. CONCLUSIONS: This study confirms previous studies that have shown a small positive association between obesity and SAB risk. Our results suggest that obesity is a stronger risk factor for early pregnancy losses, and that small stature and low WHR are associated with an increased risk of SAB.

The Impact of Budesonide/Formoterol pMDI Medication Reminders on Adherence in Chronic Obstructive Pulmonary Disease (COPD) Patients: Results of a Randomized, Phase 4, Clinical Study.

PURPOSE: Among patients with chronic obstructive pulmonary disease (COPD), adherence to inhaled medication leads to fewer exacerbations and improved health status. The goal of the present study was to evaluate the effects of medication reminders via the BreatheMate device on adherence in patients with COPD. PATIENTS AND METHODS: A 6-month, phase 4, randomized, multicenter, open-label US study (NCT02864342) enrolled 138 patients aged ≥40 years with moderate to very severe COPD and ≥10 pack-year smoking history. Patients in the intervention (n = 68) and control (n = 70) groups received the BreatheMate device, smartphone application, and vouchers to redeem pressurized metered-dose inhalers (pMDIs) for the prescribed 2 puffs of budesonide/formoterol 160/4.5 µg twice daily. The intervention group also received twice-daily electronic reminders to take budesonide/formoterol. The primary endpoint was the mean number of sets of adherent puffs/day (4 puffs: 2 puffs within 60 minutes, twice daily) over 6 months. Secondary endpoints included adherence by three 60-day intervals, usage days, prescription refills, and Clinical COPD Questionnaire (CCQ) score. Study enrollment terminated early due to issues with inconsistent syncing. RESULTS: A higher mean proportion of adherent days (77.6% vs 60.2%; P <0.001) and sets of adherent puffs/day (1.61 vs 1.33; P <0.001) were recorded for the intervention group versus the control group. Intervention group adherence was higher than that of the control group for each 60-day interval (P <0.001); the intervention group was 3.07 (95% confidence interval: 1.49-6.52) times more likely than the control group to be adherent for ≥80% of study days. Overuse (>2 sets of 2 puffs/day), underuse (<2 sets of 2 puffs/day), and no use days were lower in the intervention group versus control (P <0.05). Patients aged ≥65 years had higher adherence (P <0.001). CONCLUSION: Medication reminders through the BreatheMate device and application produced greater adherence to inhaled therapy in patients with COPD.

Use of a Digital Chronic Obstructive Pulmonary Disease Respiratory Tracker in a Primary Care Setting: A Feasibility Study.

INTRODUCTION: Telemonitoring is a promising self-management strategy to improve health care outcomes. This study evaluated real-world adoption of the chronic obstructive pulmonary disease (COPD) Co-Pilot daily symptom monitoring tool by patients and primary care providers (PCPs). METHODS: An open-label, 6-month, single-arm, multicenter, noninterventional feasibility study enrolled 97 patients aged ≥ 40 years with symptomatic or poorly controlled COPD and ≥ 10 pack-year smoking history. Patients received smartphones and training to use the COPD Co-Pilot application. During the study, patients tracked symptoms daily; an increase in symptom score of ≥ 1.0 point from baseline (symptom alert) prompted patients to contact their PCP via toll-free number. The primary endpoint was time to clinical recommendation (TTCR) from a symptom alert; adherence to completing daily symptom reports through the COPD Co-Pilot application and patient satisfaction were also measured. RESULTS: Overall, 87 of 96 patients (90.6%) received 2142 symptom alerts; 42 alerts (equivalent to 2% of all symptom alerts) resulted in 23 patients contacting their PCP. Median TTCR was 7.1 h (interquartile range [IQR]: 4.0-29.9). Among 15 patients using the toll-free number, median TTCR was 2.1 h (IQR 0.0-7.2) versus 19.6 h (IQR 4.5-45.2) for eight patients using other contact methods. Average COPD Co-Pilot adherence overall was 75.2% (95% CI 74.6-75.9). Patients responded favorably regarding the application's ease of use, functionality, and information provided. CONCLUSIONS: The COPD Co-Pilot tool was associated with relatively high levels of adherence, suggesting patients' willingness to monitor symptoms daily. Although a limited number of patients initiated PCP contact, patients who used the study-provided toll-free number had substantially shorter median TTCR, suggesting that this tool could help empower patients to better manage their COPD.

Early Intervention With Vedolizumab on Longer Term Surgery Rates in Crohn's Disease: Post Hoc Analysis of the GEMINI Phase 3 and Long-term Safety Programs.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disease that, with progression, may require surgical intervention. AIM: To determine whether vedolizumab treatment of CD earlier in the disease course (≤2 or ≤5 years disease duration) influences risk of CD-related surgery after accounting for probability of response. METHODS: Post hoc analyses of data from CD patients treated with vedolizumab in the GEMINI 2, GEMINI 3, and GEMINI LTS trials (N=1253) evaluated CD-related surgery (bowel resection or colectomy) with stratification by probability of response to vedolizumab (low/intermediate or high). Analyses used a previously validated clinical decision support tool and both logistic regression and Cox proportional hazard analyses. RESULTS: In total, 113 (9.0%) vedolizumab-treated patients required CD-related surgery. Surgical rates were 6.1% and 9.8% for the high and low/intermediate probability of response groups, respectively. Risk of surgery was lower for patients with a high probability of response versus those with a low/intermediate probability of response (HR 0.50; 95%CI 0.29 to 0.85). For patients with a low/intermediate probability of vedolizumab response, there was a consistent trend for association between earlier treatment (≤2 or ≤5 years since diagnosis) and a lower risk of surgery relative to later treatment (≤2 years versus >2 years: OR 0.77, 95%CI 0.38 to 1.58; ≤5 years versus >5 years: OR 0.61, 95%CI 0.37 to 1.00). CONCLUSIONS: Earlier intervention with vedolizumab may be associated with lower rates of surgery. Use of the clinical decision support tool may help identify patients most likely to benefit from earlier intervention with vedolizumab.

Comparison of Post-Cesarean Section Opioid Analgesic Requirements in Women With Opioid Use Disorder Treated With Methadone or Buprenorphine.

OBJECTIVE: Buprenorphine is a highly effective treatment for opioid use disorders, but its continuation in the perioperative setting remains controversial, unlike the accepted practice of perioperative methadone continuation. METHODS: We conducted a retrospective cohort study from 2006 to 2014 comparing post-cesarean section opioid analgesic requirements of women with opioid use disorders treated with methadone or buprenorphine. Preoperative, intraoperative, and postoperative opioid requirements (morphine equivalent dose [MED]), postoperative complications, and length of stay were compared between the methadone and buprenorphine groups. RESULTS: During the 9-year study period, there were 185 women treated with methadone (mean dose 93.7 mg, SD 2.6) and 88 women treated with buprenorphine (mean dose 16.1 mg, SD 7.8). There were no statistically significant differences in MED requirements in the methadone versus buprenorphine groups: preoperative MED (11.4 mg [SD 31.5] vs 20.0 mg [SD 15.1]; mean difference [MD] 8.6, 95% confidence interval [CI] -1.9, 19.1), intraoperative MED (3.5 mg [SD 6.6] vs 5.2 mg [SD 13.7]; MD 1.8, 95% CI -1.1, 4.6), and postoperative MED during hospitalization (97.7 mg [SD 65.6] vs 85.1 mg [SD 73.0]; MD -12.6, 95% CI -31.1, 5.8). There were no statistically significant differences in postoperative complications or length of stay. CONCLUSIONS: Our study suggests that buprenorphine treatment will not interfere more than methadone with pain management after a cesarean section with no significant differences in opioid analgesic requirements, postoperative complications, or length of hospital stay. Future studies should investigate the generalizability to other surgeries.

Dairy intake and fecundability in 2 preconception cohort studies.

BACKGROUND: Animal studies have shown that a high intake of galactose, a breakdown product of lactose, increases ovarian toxicity. Few epidemiologic studies, to our knowledge, have examined the association between dairy intake and fertility, and they have had conflicting findings. OBJECTIVE: We prospectively evaluated dairy intake in relation to fecundability among women who were planning for pregnancy. DESIGN: Data were derived from preconception cohort studies in Denmark (Snart Foraeldre) and North America [PRESTO (Pregnancy Study Online)] in which women completed a validated food-frequency questionnaire 10 d after enrollment. The dietary intake of dairy foods and their constituents was calculated based on reported frequencies, mean serving sizes, and standard recipes for mixed foods. Outcome data were updated every 8 wk for 12 mo or until reported conception. Analyses were restricted to 2426 women attempting pregnancy for ≤6 cycles at study entry. Fecundability ratios (FRs) and 95% CIs were estimated with the use of proportional probabilities regression models adjusted for potential confounders. RESULTS: FRs for total dairy intake (≥18 compared with <7 servings/wk) were 1.37 (95% CI: 1.05, 1.78) among 1126 Snart Foraeldre participants and 1.04 (95% CI: 0.78, 1.38) among 1300 PRESTO participants (pooled FR: 1.11; 95% CI: 0.94, 1.31). The elevated FR for total dairy intake among Snart Foraeldre participants was limited to milk consumption and found only among women aged <30 y. There was no clear association between low- or high-fat dairy intake and fecundability in either cohort. Although there was little evidence of an association between dietary intake of calcium, potassium, magnesium, or vitamin D and fecundability, a greater consumption of phosphorus and lactose was associated with slightly higher fecundability in both cohorts. CONCLUSIONS: Associations between dairy intake and fecundability were generally small and inconsistent across cohorts. Our findings do not support the hypotheses that a greater consumption of high-fat dairy improves fertility or that a greater consumption of lactose or low-fat dairy harms fertility.

Caffeine and caffeinated beverage consumption and fecundability in a preconception cohort.

Caffeine is an adenosine receptor antagonist that may influence fertility by affecting ovulation, menstrual characteristics, or sperm quality. We studied the association between female and male preconception caffeine intake and fecundability in a North American prospective cohort study of 2135 pregnancy planners. Frequency of caffeinated beverage intake was self-reported at baseline. Outcome data were updated every 8 weeks until reported pregnancy; censoring occurred at 12 months. Adjusted fecundability ratios (FR) and 95% confidence intervals (CI) were estimated using proportional probabilities regression. Total caffeine intake among males, but not females, was associated with fecundability (FR for ≥300 vs. <100mg/day caffeine among males=0.72, 95% CI=0.54-0.96), although the association was not monotonic. With respect to individual beverages, caffeinated tea intake was associated with slight reductions in fecundability among females, and caffeinated soda and energy drink intake were associated with reduced fecundability among males.

Body mass index, physical activity and fecundability in a North American preconception cohort study.

OBJECTIVE: To evaluate the association between adiposity, physical activity (PA), and fecundability. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 2,062 female pregnancy planners from the United States and Canada who were enrolled during the preconception period. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Self-reported pregnancy. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were estimated using proportional probabilities models that adjusted for potential confounders. RESULT(S): Relative to body mass index (BMI) 18.5-24 kg/m(2), FRs for BMI <18.5, 25-29, 30-34, 35-39, 40-44, and ≥45 kg/m(2) were 1.05 (95% CI 0.76-1.46), 1.01 (95% CI 0.89-1.15), 0.98 (95% CI 0.82-1.18), 0.78 (95% CI 0.60-1.02), 0.61 (95% CI 0.42-0.88), and 0.42 (95% CI 0.23-0.76), respectively. Reduced fecundability was observed among women with the largest waist-to-hip ratios (≥0.85 vs. <0.75; FR = 0.87, 95% CI 0.74-1.01) and waist circumferences (≥36 vs. <26 inches [≥90 vs. <66 cm]; FR = 0.80, 95% CI 0.59-1.01). Tendency to gain weight in the chest/shoulders (FR = 0.63, 95% CI 0.36-1.08) and waist/stomach (FR = 0.90, 95% CI 0.79-1.02), relative to hips/thighs, was associated with lower fecundability. Moderate PA was associated with increased fecundability (≥5 vs. <1 h/wk; FR = 1.26, 95% CI 0.96-1.65), but there was no dose-response relation. Among overweight/obese women (BMI ≥25 kg/m(2)), fecundability was 27% higher for vigorous PA of ≥5 versus <1 h/wk (95% CI 1.02-1.57). CONCLUSION(S): Various measures of overall and central adiposity were associated with decreased fertility among pregnancy planners. Vigorous PA was associated with improved fertility among overweight and obese women only; moderate PA was associated with improved fertility among all women.

Confounding of the Comparative Safety of Prenatal Opioid Agonist Therapy.

Prenatal opioid agonist therapy with methadone or buprenorphine prevents maternal illicit opioid use and withdrawal and improves pregnancy outcomes compared to heroin use alone. Historically, methadone has been the first-line opioid agonist therapy for pregnant opioid dependent women; in recent years buprenorphine has become first-line treatment for some opioid dependent pregnant women. While there is some evidence of better outcomes in neonates exposed to buprenorphine vs. methadone, the effect of confounding from differences in women who use buprenorphine and methadone has not been carefully examined in most studies. This review explores mechanisms by which confounding can arise in measuring associations between prenatal buprenorphine vs. methadone exposure on neonatal outcomes using a graphical approach, directed acyclic graphs. The goal of this paper is to facilitate better understanding of the factors influencing neonatal abstinence syndrome and accurate assessment of the comparative safety of opioid agonist therapies on the neonate.

History of oral contraceptive use and risk of spontaneous abortion.

PURPOSE: To examine the association between pregravid oral contraceptive (OC) use and spontaneous abortion (SAB). METHODS: In an Internet-based preconception cohort study of 4862 Danish pregnancy planners, we used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for the association between OC use and SAB. We controlled for maternal age, physical activity, parity, education, alcohol and caffeine consumption, body mass index, and smoking. RESULTS: Compared with women who discontinued OCs >1 year before conception, HRs were 0.95 (95% confidence interval (CI) = 0.77-1.17), 0.99 (95% CI = 0.82-1.19), and 0.80 (95% CI = 0.60-1.06) for women who discontinued OCs 7-12, 2-6, and 0-1 months before conception, respectively. Compared with less than 4 years of OC use, HRs for 4-7, 8-11, and 12 years or more of OC use were 1.05 (95% CI = 0.80-1.37), 0.92 (95% CI = 0.71-1.19), and 0.88 (95% CI = 0.65-1.19), respectively. Dose of estrogen and generation of progestin were not materially associated with SAB risk. CONCLUSIONS: We found no evidence that pregravid OC use is associated with an increase in SAB. Use within 1 month of conception was associated with a slightly lower risk of SAB, but this may be due to increased reproductive fitness in women who conceive quickly after discontinuation of OCs.