Linda G Kahn | New York University (original) (raw)

Papers by Linda G Kahn

Human Reproduction Update

BACKGROUND: Exposure to non-persistent chemicals in consumer products is ubiquitous and associate... more BACKGROUND: Exposure to non-persistent chemicals in consumer products is ubiquitous and associated with endocrine-disrupting effects. These effects have been linked to infertility and adverse pregnancy outcomes in some studies and could affect couple fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP). OBJECTIVE AND RATIONALE: Few epidemiologic studies have examined the impact of non-persistent chemicals specifically on TTP, and the results of these studies have not been synthesized. We undertook a systematic review to summarize the strength of evidence for associations of common non-persistent chemicals with couple fecundability and to identify gaps and limitations in the literature, with the aim of informing policy decisions and future research. SEARCH METHODS: We performed an electronic search of English language literature published between 1 January 2007 and 25 August 2017 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE, POPLINE and DESTAF. We included human retrospective and prospective cohort, cross-sectional and case-control studies that examined phthalates, bisphenol A, triclosan, triclocarban, benzophenones, parabens and glycol ethers in consumer products, and considered TTP or fecundability as an outcome among women, men and couples conceiving without medical assistance. We excluded editorials, opinion pieces, introductions to special sections, articles that described only lifestyle (e.g. caffeine, stress) or clinical factors (e.g. semen parameters, IVF success). Standardized forms for screening, data extraction and study quality were developed using DistillerSR software and completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies. OUTCOMES: The search returned 3456 articles. There were 15 papers from 12 studies which met inclusion criteria, of which eight included biomarkers of chemical exposure. Studies varied widely in terms of exposure characterization, precluding a meta-analytic approach. Among the studies that measured exposure using biospecimens, results were equivocal for associations between either male or female phthalate exposure and TTP. There was preliminary support for associations of female exposure to some parabens and glycol ethers and of male exposure to benzophenone with longer TTP, but further research and replication of these results are needed. The results provided little to no indication that bisphenol A, triclocarban or triclosan exposure was associated with TTP. WIDER IMPLICATIONS: Despite a growing literature on couple exposure to non-persistent endocrine-disrupting chemicals and fecundability, evidence for associations between biologically measured exposures and TTP is limited. Equivocal results with different nonpersistent chemical compounds and metabolites complicate the interpretation of our findings with respect to TTP, but do not preclude action, given the documented endocrine disrupting effects on other reproductive outcomes as well as fetal development. We therefore advocate for common-sense lifestyle changes in which both females and males seeking to conceive minimize their exposure to nonpersistent chemicals.

Many studies have described an inverse relationship between birth weight and blood pressure (BP).... more Many studies have described an inverse relationship between birth weight and blood pressure (BP). Debate continues, however, over the magnitude and validity of the association. This analysis draws on the Early Determinants of Adult Health study (2005)(2006)(2007)(2008), a cohort of 393 US adults (mean age 43 years; 47% male), including 114 samesex sibling pairs deliberately sampled to be discordant on sex-specific birth weight for gestational age (BW/GA) in order to minimize confounding in studies of fetal growth and midlife health outcomes. Every quintile increment in BW/GA percentile was associated with a 1.04−mm Hg decrement in adult systolic BP (95% confidence interval (CI): −2.14, 0.06) and a 0.63−mm Hg decrement in diastolic BP (95% CI: −1.35, 0.09), controlling for sex, age, site, smoking, and race/ethnicity. The relationship was strongest among those in the lowest decile of BW/GA. Adding adult body mass index to the models attenuated the estimates (e.g., to −0.90 mm Hg (95% CI: −1.94, 0.14) for systolic BP). In the sibling-pair subgroup, associations were slightly stronger but with wider confidence intervals (e.g., −1.22 mm Hg (95% CI: −5.20, 2.75) for systolic BP). In conclusion, we found a small inverse relationship between BW/GA and BP in cohort and sibling-pair analyses, but the clinical or public health significance is likely limited. birth weight; blood pressure; cohort studies; gestational age; longitudinal studies; siblings Abbreviations: BMI, body mass index; BP, blood pressure; BW, birth weight; BW/GA, sex-specific birth weight for gestational age; CI, confidence interval.

A B S T R A C T Background: The collapse of the World Trade Center (WTC) on September 11, 2001 re... more A B S T R A C T Background: The collapse of the World Trade Center (WTC) on September 11, 2001 released a dust cloud containing numerous environmental contaminants, including polychlorinated dibenzo-para-dioxins and poly-chlorinated dibenzofurans (PCDD/Fs). PCDD/Fs are toxic and are associated with numerous adverse health outcomes including cancer, diabetes, and impaired reproductive and immunologic function. Prior studies have found adults exposed to the WTC disaster to have elevated levels of PCDD/Fs. This is the first study to assess PCDD/F levels in WTC-exposed children. Methods: This analysis includes 110 participants, a subset of the 2014–2016 WTC Adolescent Health Study, a group of both exposed youths who lived, attended school, or were present in lower Manhattan on 9/11 recruited from the WTC Health Registry (WTCHR) and unexposed youths frequency matched on age, sex, race, ethnicity, and income. Our sample was selected to maximize the contrast in their exposure to dust from the WTC collapse. Questionnaire data, including items about chronic home dust and acute dust cloud exposure, anthropometric measures, and biologic specimens were collected during a clinic visit. Serum PCDD/F concentrations were measured according to a standardized procedure at the New York State Department of Health Organic Analytical Laboratory. We used multivariable linear regression to assess differences in PCCD/Fs between WTCHR and non-WTCHR participants. We also compared mean and median PCDD/F and toxic equivalency (TEQ) concentrations in our cohort to 2003–4 National Health and Nutrition Examination Survey (NHANES) levels for youths age 12–19. Results: Median PCDD/F levels were statistically significantly higher among WTCHR participants compared to non-WTCHR participants for 16 out of 17 congeners. Mean and median TEQ concentrations in WTCHR participants were > 7 times those in non-WTCHR participants (72.5 vs. 10.1 and 25. 3 vs. 3.39 pg/g lipid, respectively). Among WTCHR participants, median concentrations of several PCDD/Fs were higher than the NHANES 95th percentiles. After controlling for dust cloud exposure, home dust exposure was significantly associated with higher PCDD/F level. Conclusions: Adolescents in lower Manhattan on the day of the WTC attack and exposed to particulate contamination from the WTC collapse had significantly elevated PCDD/F levels > 12 years later compared to a matched comparison group, driven by chronic home dust exposure rather than acute dust cloud exposure. PCDD/F and TEQ levels substantially exceeded those in similar-aged NHANES participants. Future studies are

Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is,... more Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is, therefore, fundamental for understanding human health at the population level. Given the absence of a population (bio)marker, fecundity is assessed indirectly by various individual-based (e.g. semen quality, ovulation) or couple-based (e.g. time-to-pregnancy) endpoints. Population monitoring of fecundity is challenging, and often defaults to relying on rates of births (fertility) or adverse outcomes such as genitourinary malformations and reproductive site cancers. In light of reported declines in semen quality and fertility rates in some global regions among other changes, the question as to whether human fecundity is changing needs investigation. We review existing data and novel methodological approaches aimed at answering this question from a transdisciplinary perspective. The existing literature is insufficient for answering this question; we provide an overview of currently available resources and novel methods suitable for delineating temporal patterns in human fecundity in future research.

The authors examined the relationship of prepregnancy body mass index (BMI) and gestational weigh... more The authors examined the relationship of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with child neurodevelopment. Mother–child dyads were a subgroup (n = 2,084) of the Child Health and Development Studies from the Oakland, California, area enrolled during pregnancy from 1959 to 1966 and followed at child age 9 years. Linear regression was used to examine associations between prepregnancy BMI, GWG, and standardized Peabody Picture Vocabulary Test and Raven Progressive Matrices scores and to evaluate effect modification of GWG by prepregnancy BMI. Before pregnancy, 77% of women were normal weight, 8% were underweight, 11% were overweight, and 3% were obese. Associations between GWG and child outcomes did not vary by prepregnancy BMI, suggesting no evidence for interaction.

Objectives: To review James Jackson's analysis of bloodletting among pneumonitis patients at the ... more Objectives: To review James Jackson's analysis of bloodletting among pneumonitis patients at the newly founded Massachusetts General Hospital, in which he implemented the numerical method advocated by Pierre-Charles-Alexandre Louis. Study Design and Setting: The study sample included 34 cases of clinically diagnosed pneumonitis admitted to Massachusetts General Hospital between April 19, 1825, and May 10, 1835, and discharged alive. Patient data were extracted from meticulously kept case books. Jackson calculated mean number of venesections, ounces of blood taken, and days of convalescence within groups stratified by day of the disease when first bloodletting occurred. He also calculated average convalescence within groups stratified by age, sex, prior health, ves-ication, and day of the disease when the patients were admitted to the hospital. Results: To Jackson's surprise, it ''seemed to be of less importance, whether our patients were bled or not, than whether they entered the hospital early or late'' after the onset of the pneumonitis. Bloodletting was ineffective. Our multivariate reanalysis of his data confirms his conclusion. Outstandingly for his time, Jackson ruled out unwarranted effects of covariates by tabulating their numerical relations to the duration of pneumonia. Conclusion: Using novel gathering of patient clinical data from hospital records and quantitative analytical methods, Jackson contributed results that challenged conventional wisdom and bridged French therapeutic epistemology and American medical pragma-tism.

Objective: To evaluate associations between work-related stress, stressful life events, and perce... more Objective: To evaluate associations between work-related stress, stressful life events, and perceived stress and semen quality.
Design: Cross-sectional analysis.
Setting: Northern California.
Patient(s): 193 men from the Child Health and Development Studies evaluated between 2005–2008.
Intervention(s): None.
Main Outcome Measure(s): Measures of stress including job strain, perceived stress, and stressful life events; outcome measures of sperm concentration, percentage of motile sperm, and percentage of morphologically normal sperm.
Result(s): We found an inverse association between perceived stress score and sperm concentration (estimated coefficient b=-0.09 x 103/mL; 95% confidence interval [CI] -0.18, -0.01), motility (b=-0.39; 95% CI, -0.79, 0.01), and morphology (b=-0.14; 95% CI, -0.25, -0.04) in covariate-adjusted linear regression analyses. Men who experienced two or more stressful life events in the past year compared with no stressful events had a lower percentage of motile sperm (b=-8.22; 95% CI, -14.31, -2.13) and a lower percentage of morphologically normal sperm (b=-1.66; 95% CI, -3.35, 0.03) but a similar sperm concentration. Job strain was
not associated with semen parameters.
Conclusion(s): In this first study to examine all three domains of stress, perceived stress and stressful life events but not work-related stress were associated with semen quality.

Background: Although maternal hypothyroidism increases the risk of adverse neonatal and obstetric... more Background: Although maternal hypothyroidism increases the risk of adverse neonatal and obstetric outcomes as well as lower IQ in children, the environmental determinants of maternal thyroid dysfunction have yet to be fully explored.
Objectives: We aimed to examine associations between mid-pregnancy blood lead (BPb) and concomitant measures of thyroid function among participants in the Yugoslavia Prospective Study
of Environmental Lead Exposure.
Methods: As part of a population-based prospective study of two towns in Kosovo—one with high levels of environmental lead and one with low—women were recruited during the second trimester
of pregnancy, at which time blood samples and questionnaire data were collected. We measured concentrations of BPb, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid
peroxidase antibodies (TPOAb) in archived serum samples.
Results: Compared with women from the unexposed town, women from the exposed town had lower mean FT4 (0.91 ± 0.17 vs. 1.03 ± 0.16 ng/dL), higher mean TPOAb (15.45 ± 33.08 vs.
5.12 ± 6.38 IU/mL), and higher mean BPb (20.00 ± 6.99 vs. 5.57 ± 2.01 μg/dL). No differences in TSH levels were found. After adjustment for potential confounders, for each natural log unit
increase in BPb, FT4 decreased by 0.074 ng/dL (95% CI: –0.10, –0.046 ng/dL), and the odds ratio for testing positive to TPOAb was 2.41 (95% CI: 1.53, 3.82). We found no association between BPb and TSH.
Conclusions: Prolonged lead exposure may contribute to maternal thyroid dysfunction by stimulating autoimmunity to the thyroid gland.

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Human Reproduction Update

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