Kenneth J Rothman

Massachusetts Department of Public Health, Boston, Massachusetts, United States

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Publications (306)2470.11 Total impact

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    ABSTRACT: Background Epidemiologic studies of fecundability often use retrospectively measured time-to-pregnancy (TTP), thereby introducing potential for recall error. Little is known about how recall error affects the bias and precision of the fecundability odds ratio (FOR) in such studies.Methods Using data from the Danish Snart-Gravid Study (2007–12), we quantified error for TTP recalled in the first trimester of pregnancy relative to prospectively measured TTP among 421 women who enrolled at the start of their pregnancy attempt and became pregnant within 12 months. We defined recall error as retrospectively measured TTP minus prospectively measured TTP. Using linear regression, we assessed mean differences in recall error by maternal characteristics. We evaluated the resulting bias in the FOR and 95% confidence interval (CI) using simulation analyses that compared corrected and uncorrected retrospectively measured TTP values.ResultsRecall error (mean = −0.11 months, 95% CI −0.25, 0.04) was not appreciably associated with maternal age, gravidity, or recent oral contraceptive use. Women with TTP > 2 months were more likely to underestimate their TTP than women with TTP ≤ 2 months (unadjusted mean difference in error: −0.40 months, 95% CI −0.71, −0.09). FORs of recent oral contraceptive use calculated from prospectively measured, retrospectively measured, and corrected TTPs were 0.82 (95% CI 0.67, 0.99), 0.74 (95% CI 0.61, 0.90), and 0.77 (95% CI 0.62, 0.96), respectively.Conclusions Recall error was small on average among pregnancy planners who became pregnant within 12 months. Recall error biased the FOR of recent oral contraceptive use away from the null by 10%. Quantitative bias analysis of the FOR can help researchers quantify the bias from recall error.
    Paediatric and Perinatal Epidemiology 11/2015; 29(6):576-588. DOI:10.1111/ppe.12245 · 3.13 Impact Factor
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    ABSTRACT: 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 through 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 (RR) and 95% confidence intervals (CI) 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.
    Epidemiology (Cambridge, Mass.) 10/2015; DOI:10.1097/EDE.0000000000000400 · 6.20 Impact Factor
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    ABSTRACT: Introduction: Epidemiological studies have linked domperidone use with serious cardiac arrhythmias, including sudden cardiac death, but data on age, dose, and duration of use are limited. Objectives: The aim of this study was to assess the risk of out-of-hospital sudden cardiac death associated with domperidone use versus proton pump inhibitors (PPIs), metoclopramide, or non-use of all three medications, and to evaluate the risk of sudden cardiac death in relation to age and domperidone dose. Methods: This was a population-based case-control study nested in a cohort of subjects aged ≥2 years in the Clinical Practice Research Datalink with one or more prescriptions for domperidone, any PPI, or metoclopramide from 2005 to 2011. Out-of-hospital sudden cardiac death was assessed by linkage with Hospital Episode Statistics and death certificates. Controls were matched on age, sex, and medical practice. The risk of sudden cardiac death in domperidone users versus risk in users of PPIs or metoclopramide was evaluated with multivariable conditional logistic regression; case-crossover analysis addressed possible residual confounding. Results: From the study cohort (n = 681,104), 3239 sudden cardiac death cases were matched to 12,572 controls. The adjusted odds ratio (95 % confidence interval) for sudden cardiac death with current use of domperidone alone was 1.71 (0.92-3.18) versus non-use of study medications, 1.26 (0.68-2.34) versus current PPI use, and 0.40 (0.17-0.94) current metoclopramide use. The adjusted odds ratio (95 % confidence interval) relative to exposure to no study drug for domperidone >30 mg/day (eight cases, five controls) was 3.20 (0.59-17.3) and 1.65 (0.89-3.07) for age ≥61 years (27 cases, 49 controls). The odds ratio (95 % confidence interval) was 3.17 (1.72-5.83) for within-person periods of domperidone use versus non-use in the case-crossover analysis. Conclusions: Compared with non-use of any study drug, current domperidone use was associated with sudden cardiac death in nested case-control and case-crossover analyses, with a suggestion of higher risk in older persons and users of higher daily doses.
    Drug Safety 09/2015; DOI:10.1007/s40264-015-0338-0 · 2.82 Impact Factor
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    ABSTRACT: 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.
    Annals of epidemiology 09/2015; DOI:10.1016/j.annepidem.2015.09.001 · 2.00 Impact Factor
  • K.A. Hahn · L.A. Wise · E.E. Hatch · K.J. Rothman ·

  • L.A. Wise · E.E. Hatch · J. Stanford · C.J. McKinnon · A. Wesselink · K.J. Rothman ·

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    ABSTRACT: Psoriasis is associated with risk of malignancy. Some psoriasis treatments may increase risk of hospitalised infectious events (HIEs). To evaluate rates of malignancies and HIEs in psoriasis patients. This retrospective cohort study utilised data from MarketScan(®) databases. Cohorts included: adult general population (GP), psoriasis patients, and psoriasis patients treated with nonbiologics, adalimumab, etanercept, infliximab, or phototherapy. Outcomes included incidence rates (IRs) per 10,000 person-years observation (PYO) for all malignancies excluding nonmelanoma skin cancer (NMSC), lymphoma, NMSC, and per 10,000 person-years exposure (PYE) for HIEs. IRs (95% confidence interval [CI]) for all malignancies except NMSC were 129 (127, 130) and 142 (135, 149) for GP (PYO=51,071,587) and psoriasis (PYO=119,432) cohorts, respectively; 10.9 (10.5, 11.3) and 12.9 (10.9, 14.8) for lymphoma; and 145 (144, 147) and 180 (173, 188) for NMSC. Rates for all malignancies excluding NMSC were similar among treatments but variable for lymphoma and NMSC. IRs (95% CI) for HIEs were 332 (256, 408) for the nonbiologic cohort (PYE=3,528); 288 (206, 370) for etanercept (PYE=6,563); 325 (196, 455) for adalimumab (PYE=2,772); 521 (278, 765) for infliximab (PYE=1,058); and 334 (242, 427) for phototherapy (PYE=1,797). IRs for HIEs were lowest for etanercept and higher in patients on baseline systemic corticosteroids across treatment cohorts. Malignancy rates were higher in psoriasis patients than the GP, but these treatments did not appear to increase malignancy risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 08/2015; DOI:10.1111/bjd.14068 · 4.28 Impact Factor
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    ABSTRACT: The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) was designed to provide prospectively collected information on patients with newly diagnosed non-valvular atrial fibrillation at risk of stroke, with the aim of addressing treatment patterns and questions of effectiveness and safety. In this predefined analysis from GLORIA-AF, the baseline characteristics and initial antithrombotic management of the first 10 000 patients in Phase II of this large Registry Program are presented. Overall, 32.3% of patients received VKAs and 47.7% received NOACs, whilst 12.3% received antiplatelet treatment and 7.6 % did not receive any antithrombotic treatment. Amongst patients with CHA2DS2VASc score ≥2, 6.7 % received no antithrombotic treatment and 10.0% received aspirin. In Europe, treatment with dabigatran was as common as treatment with VKAs (38.8% and 37.8%, respectively). More than half of the patients were treated with NOACs (52.4%), whilst antiplatelet treatment was given to 5.7 %, and 4.1% did not receive any antithrombotic treatment. In North America, treatment with dabigatran (25.0%) was as common as with VKAs (26.1%), but overall NOAC use was more common (52.1%) than with VKAs (26.1%); however, 14.1% received antiplatelet treatment, while 7.6 % received no antithrombotic treatment. In Asia, treatment with VKAs (31.9%) was more prevalent than NOACs (25.5 %), but antiplatelet treatment was given to 25.8% and 16.9% did not receive any antithrombotic treatment. In Asia, only 60.7% of patients with high stroke risk received oral anticoagulants (OACs). Paroxysmal atrial fibrillation and minimally symptomatic (or asymptomatic) patients were often undertreated with OACs. In this analysis, OAC use was high in Europe and North America, with overall NOAC use higher than VKA use. A considerable percentage of high-risk patients in North America still received antiplatelet treatment or were untreated, whilst Asian patients had a high proportion of aspirin use and non-treatment. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American journal of medicine 07/2015; DOI:10.1016/j.amjmed.2015.07.013 · 5.00 Impact Factor
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    ABSTRACT: 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. 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 (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. 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 enrolment, 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. Use of the Internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective. © 2015 John Wiley & Sons Ltd.
    Paediatric and Perinatal Epidemiology 07/2015; 29(4):360-71. DOI:10.1111/ppe.12201 · 3.13 Impact Factor
  • H T Cueto · A H Riis · E E Hatch · L A Wise · K J Rothman · H T Sørensen · E M Mikkelsen ·
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    ABSTRACT: Periconceptional folic acid (FA) supplementation reduces the risk of neural tube defects and has been associated with ovulatory function. However, only two studies have associated supplementation with multivitamins (MVs) that contained FA with increased pregnancy rates. We aimed to examine the association between FA supplementation (obtained either through single FA tablets or through MVs) and fecundability. A prospective cohort study of 3895 Danish women who were planning a pregnancy between 2007 and 2011. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) in relation to FA supplementation (either through single FA tablets or MV) using a proportional probabilities regression model, with adjustment for potential socio-demographic, reproductive and lifestyle confounders. In stratified analyses, we also estimated FR with 95% CI in relation to FA supplementation for women with regular and irregular cycles, respectively, and for women with short (<27 days), medium (27-29 days) and long cycles (⩾30 days), respectively. FA supplementation was associated with increased fecundability (FR=1.15, 95% CI=1.06-1.25), compared with non-use. The adjusted FRs for FA supplement use relative to non-use were 1.35 (95% CI=1.12-1.65) and 1.11 (95% CI=1.01-1.22) for women with irregular and regular cycles, respectively, and 1.36 (95% CI=0.95-1.95), 1.10 (95% CI=0.98-1.22) and 1.24 (95% CI=1.10-1.41) for women with short (<27 days), medium (27-29 days) and long cycles (⩾30 days), respectively. FA supplementation was associated with increased fecundability, and this association appeared to be stronger among women with irregular cycles and among women with either short or long cycle length.European Journal of Clinical Nutrition advance online publication, 17 June 2015; doi:10.1038/ejcn.2015.94.
    European journal of clinical nutrition 06/2015; DOI:10.1038/ejcn.2015.94 · 2.71 Impact Factor
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    ABSTRACT: 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.
    European Journal of Epidemiology 06/2015; DOI:10.1007/s10654-015-0053-2 · 5.34 Impact Factor
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    ABSTRACT: To examine the association between folic acid (FA) supplementation obtained through either single FA tablets or multivitamins (MVs) and menstrual cycle characteristics among 5386 women aged 18-40 years, enrolled in an Internet-based study of Danish women attempting pregnancy during 2007-2011. In a cross-sectional study, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of FA supplementation with menstrual cycle regularity; short (<27 days), long (30-33 days), and very long (≥34 days) cycle lengths; and duration and intensity of menstrual bleeding. Compared with nonuse, FA supplementation was associated with reduced odds of short cycle length (OR = 0.80, 95% CI: 0.68-0.94) and a trend toward increased odds of very long cycle length (OR = 1.21, 95% CI: 0.87-1.68) compared with cycle length of 27-29 days. The inverse association with short cycle length was stronger among 18- to 30-year-old women (OR = 0.68, 95% CI: 0.53-0.87), nulliparous women (OR = 0.66, 95% CI: 0.52-0.84), and women who used both FA and MVs (OR = 0.75, 95% CI: 0.60-0.95). We found no clear association between FA supplementation and cycle regularity and duration and intensity of menstrual bleeding. FA supplementation was inversely associated with short menstrual cycle length. This association was strongest among women aged 18-30 years, nulliparous women, and women who used both FA and MVs. Copyright © 2015 Elsevier Inc. All rights reserved.
    Annals of Epidemiology 06/2015; 25(10). DOI:10.1016/j.annepidem.2015.05.008 · 2.00 Impact Factor
  • Casper Roed · Henrik Toft Sørensen · Kenneth J Rothman · Peter Skinhøj · Niels Obel ·
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    ABSTRACT: In this nationwide population-based cohort study using national Danish registries, in the period 1980-2008, our aim was to study employment and receipt of disability pension after central nervous system infections. All patients diagnosed between 20 and 55 years of age with meningococcal (n = 451), pneumococcal (n = 553), or viral (n = 1,433) meningitis or with herpes simplex encephalitis (n = 115), who were alive 1 year after diagnosis, were identified. Comparison cohorts were drawn from the general population, and their members were individually matched on age and sex to patients. Five years after diagnosis, the differences in probability of being employed as a former patient with pneumococcal meningitis or herpes simplex encephalitis versus being a member of the comparison cohorts were -19.9% (95% confidence interval (CI): -24.7, -15.1) and -21.1% (95% CI: -33.0, -9.3), respectively, and the corresponding differences in probability of receiving disability pension were 20.2% (95% CI: 13.7, 26.7) and 16.2% (95% CI: 6.2, 26.3). The differences in probability of being employed or receiving disability pension in former meningococcal or viral meningitis patients versus members of the comparison cohorts were small. In conclusion, pneumococcal meningitis and herpes simplex encephalitis were associated with substantially decreased employment and increased need for disability pension. These associations did not seem to apply to meningococcal meningitis or viral meningitis. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail:
    American journal of epidemiology 04/2015; 181(10). DOI:10.1093/aje/kwu359 · 5.23 Impact Factor
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    ABSTRACT: Is caffeine and caffeinated beverage consumption associated with the risk of spontaneous abortion (SAB)? While preconceptional caffeine consumption was not materially associated with an increased risk of SAB, consumption during early pregnancy was associated with a small increased risk of SAB, although the relation was not linear. Caffeine has been hypothesized as a risk factor for SAB since the 1980s; however, results from previous studies have been conflicting. This prospective cohort study included 5132 Danish women planning pregnancy and enrolled from 2007 to 2010. Participants were women who conceived after entry into the Snart-Gravid cohort and who were aged 18-40, in a stable relationship with a male partner, and did not use fertility treatments to conceive. Women reported their daily caffeine and caffeinated beverage consumption on questionnaires before conception and during early pregnancy. All exposure measurements were prospective with respect to outcome ascertainment. We estimated hazard ratios (HRs) of SAB for categories of caffeine consumption in milligrams (mg) per day and the corresponding 95% confidence intervals (CIs) using Cox proportional hazards regression models with gestational weeks as the time scale. There were 732 women (14.3%) who were identified as having a SAB. In the preconceptional period, caffeine consumption was not materially associated with SAB risk (HR comparing ≥300 with <100 mg/day: 1.09; 95% CI: 0.89, 1.33). In early pregnancy, the HRs for 100-199, 200-299 and ≥300 mg/day of caffeine consumption were 1.62 (95% CI: 1.19, 2.22), 1.48 (95% CI: 1.03, 2.13) and 1.23 (95% CI: 0.61, 2.46), respectively, compared with that for <100 mg/day. The observed results may be affected by non-differential exposure misclassification, reverse causation and residual confounding. This is the largest study to date of prospectively measured, preconception caffeine consumption and risk of SAB. We were able to reduce the likelihood of differential left truncation bias and recall bias present in other analyses. Snart-Gravid was funded by the NICHD (R21-050264). Dr. Hahn's work was funded in part by the BU Reproductive, Perinatal, and Pediatric Epidemiology Training Grant NIH #T32HD052458. There are no competing interests. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
    Human Reproduction 03/2015; 30(5). DOI:10.1093/humrep/dev063 · 4.57 Impact Factor
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    ABSTRACT: We measured birth prevalence of major congenital malformations (MCMs) after topiramate use during pregnancy to screen for a possible signal of increased risk. Using four healthcare databases, we identified three cohorts of pregnant women: cohort 1, used topiramate during the first trimester; cohort 2, used topiramate or another antiepileptic drug previously but not during pregnancy; and cohort 3, were pregnant and did not use topiramate but had indications for use individually matched to those of users. Cohort 1 was compared with cohorts 2 and 3. MCMs were a code for any major congenital malformation dated within 30 days of the delivery date on the mother's claims or within 365 days after infant birth date, excluding a genetic or syndromic basis, and with procedure or healthcare usage consistent with the MCM diagnosis code in the 365 days after infant birth. Of the 10 specific common MCMs evaluated, 1 (conotruncal heart defects) had a prevalence ratio greater than 1.5 for both primary comparisons, and 4 (ventricular septal defect, atrial septal defect, hypospadias, coarctation of the aorta) had a prevalence ratio greater than 1.5 for one of the two comparisons. Following screening of organ systems with elevated MCMs, the prevalence ratio was greater than 1.5 for patent ductus arteriosus in both comparisons and for obstructive genitourinary defects in one comparison. To evaluate a large number of MCMs across many pregnancies, we used crude methods for detecting potential signals. Therefore, these results should be seen as potential signals, not causal. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 03/2015; 103(4). DOI:10.1002/bdra.23357 · 2.09 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1520. DOI:10.1016/S0735-1097(15)61520-0 · 16.50 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1518. DOI:10.1016/S0735-1097(15)61518-2 · 16.50 Impact Factor
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    ABSTRACT: To investigate the association between time to pregnancy (TTP) and adverse birth outcomes. Prospective cohort study. Not applicable. A total of 3,521 singletons born to women aged 18-40 years at cohort entry. None. Selected birth outcomes, including preterm birth (PTB, <37 weeks' gestation), low birth weight (<2,500 g), small for gestational age, large for gestational age, and placental disorders, ascertained from the Danish Medical Birth Registry and Danish National Registry of Patients. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using log-binomial regression, with adjustment for potential confounders and fertility treatment. Multivariable RRs for PTB in relation to TTP of 3-5, 6-11, and ≥12 vs. <3 cycles were 1.59 (95% CI 0.94-2.69), 0.85 (95% CI 0.48-1.50), and 1.57 (95% CI 0.93-2.65). The association was slightly stronger for spontaneous PTB (TTP ≥12 vs. <3 cycles: RR 1.69, 95% CI 0.84-3.42) than for medically indicated PTB (RR 1.39, 95% CI 0.62-3.12). Longer TTPs (≥12 cycles) were associated with increased risks of low birth weight (RR 1.80, 95% CI 0.97-3.35), cesarean delivery (RR 1.64, 95% CI 1.27-2.12), placental disorders (RR 2.21, 95% CI 1.07-4.56), ischemic placental disease (RR 1.56, 95% CI 0.99-2.44), pre-eclampsia (RR 1.45, 95% CI 0.79-2.65), and postpartum hemorrhage (RR 1.58, CI 1.14-2.19), and decreased risks of macrosomia (≥4,500 g; RR 0.63, 95% CI 0.35-1.13) and large for gestational age (RR 0.76, 95% CI 0.58-1.00). Longer TTP showed little association with small for gestational age. In a prospective cohort study of Danish pregnancy planners, delayed conception was a marker for adverse birth outcomes, after accounting for fertility treatment. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Fertility and Sterility 02/2015; 103(4). DOI:10.1016/j.fertnstert.2015.01.024 · 4.59 Impact Factor
  • L A Wise · R Troisi · E E Hatch · L J Titus · K J Rothman · B L Harlow ·
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    ABSTRACT: Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (β), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (β=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (β=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (β=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (β=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml - indicators of low ovarian reserve - were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.
    Journal of Developmental Origins of Health and Disease 02/2015; 6(03):1-9. DOI:10.1017/S2040174415000082 · 0.75 Impact Factor

Publication Stats

10k Citations
2,470.11 Total Impact Points


  • 2015
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 2006-2015
    • RTI International
      Durham, North Carolina, United States
  • 1989-2015
    • Boston University
      • • Department of Epidemiology
      • • School of Public Health
      • • Department of Medicine
      • • Section of Preventive Medicine and Epidemiology
      • • Center for Human Genetics
      Boston, Massachusetts, United States
    • University of Massachusetts Amherst
      Amherst Center, Massachusetts, United States
  • 2007-2014
    • RTI Health Solutions
      Durham, North Carolina, United States
  • 2013
    • Cardiff University
      Cardiff, Wales, United Kingdom
  • 2012
    • Denver Health and Hospital Authority
      Denver, Colorado, United States
    • The University of Manchester
      • School of Translational Medicine
      Manchester, ENG, United Kingdom
  • 2001-2012
    • Aarhus University Hospital
      • Department of Clinical Epidemiology
      Aarhus, Central Jutland, Denmark
  • 1994-2012
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2011
    • Health Effects Institute
      Boston, Massachusetts, United States
  • 1980-2011
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2009
    • University of Chichester
      Chichester, England, United Kingdom
    • Brigham and Women's Hospital
      Boston, Massachusetts, United States
  • 2008
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Ángeles, California, United States
  • 1978-2006
    • University of Massachusetts Boston
      • Clinical Epidemiology Research and Training Unit
      Boston, Massachusetts, United States
  • 2005
    • Aalborg University Hospital
      Ålborg, North Denmark, Denmark
  • 1978-2004
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 1999-2002
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
    • Oulu University Hospital
      Uleoborg, Oulu, Finland
  • 1998
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      Chapel Hill, NC, United States
  • 1986-1987
    • University of Massachusetts Medical School
      • Department of Family Medicine and Community Health
      Worcester, Massachusetts, United States
  • 1981
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States