Kristen A. Hahn

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

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

146 (2013 US

Correlates of menstrual cycle characteristics among nulliparous Danish women

), 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.

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

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.

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

Objective We examined the association between lifestyle factors and menstrual cycle characteristics among nulliparous Danish women aged 18–40 years who were participating in an Internet-based prospective cohort study of pregnancy planners. Methods We used cross-sectional data collected at baseline to assess the association of age, body mass index (BMI), physical activity, alcohol and caffeine consumption, and smoking with the prevalence of irregular cycles, short (≤25 days) and long (≥33 days) cycles, and duration and amount of menstrual flow. We used log-binomial and multinomial logistic regression to estimate prevalence ratios and 95% confidence intervals. Results Low physical activity and heavy alcohol consumption were associated with an increased prevalence of irregular periods. High BMI, smoking, and caffeine and alcohol consumption were related to an increased prevalence of short menstrual cycles and heavy menstrual bleeding. Women in their mid-to-late thirties had shorter and lighter menstrual flow, but a lower prevalence of irregular cycles, compared with women 18–25 years of age. Discussion In this study, increased age, high BMI, and sedentary behavior were associated with menstrual-pattern irregularities. These factors may influence the balance and level of endogenous hormones conducive to optimal menstrual function.

Confounding of the Comparative Safety of Prenatal Opioid Agonist Therapy.

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.

Dietary Fat Intake and Fecundability in 2 Preconception Cohort Studies

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.

Dairy intake and fecundability in 2 preconception cohort studies.

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.

Neonatal Outcomes in a Medicaid Population With Opioid Dependence

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.

History of oral contraceptive use and risk of spontaneous abortion

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.