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ABSTRACT: BACKGROUND: Childhood lead exposure has been associated with growth delay. However, the association between blood lead levels (BLLs) and IGF-1 has not been characterized in a large cohort with low-level lead exposure. METHODS: We recruited 394 boys aged 8-9 years from an industrial Russian town in 2003-2005 and followed them annually thereafter. We used linear regression models to estimate the association of baseline BLLs with serum IGF-1 concentration at two follow-up visits (ages 10-11 and 12-13 years), adjusting for demographic and socioeconomic covariates. RESULTS: At study entry, median BLL was 3 μg/dL (range: <0.5-31 μg/dL), most boys (86%) were prepubertal, and mean ± SD height and BMI Z-scores were 0.14 ± 1.0 and -0.2 ± 1.3, respectively. After adjustment for covariates, the mean follow-up IGF-1 concentration was 29.2 ng/mL lower (95% CI: -43.9, -14.6) for boys with high versus low BLL (≥ 5μg/dL or < 5μg/dL); this difference persisted after further adjustment for pubertal status. The association of BLL with IGF-1 was stronger for mid-pubertal than prepubertal boys (p=0.04). Relative to boys with BLLs < 2 μg/dL, adjusted mean IGF-1 concentrations decreased by 12.8 ng/mL (95% CI: -29.9, 4.4) for boys with BLLs of 3-4 μg/dL, 34.5 ng/mL (95% CI: -53.1, -16.0) for BLLs 5-9 μg/dL, and 60.4 ng/mL (95% CI: -90.9, -29.9) for BLLs ≥ 10 μg/dL. CONCLUSIONS: In peripubertal boys with low-level lead exposure, higher BLLs were associated with lower serum IGF-1. Inhibition of the hypothalamic-pituitary-growth axis may be one possible pathway by which lead exposure leads to growth delay.
Environmental Health Perspectives 04/2013; · 7.04 Impact Factor
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ABSTRACT: BACKGROUND:: This study evaluated effects of perinatal exposure to antiretroviral (ARV) medications on neurodevelopment of HIV-exposed, uninfected infants. METHODS:: HIV-exposed, uninfected infants (age 9-15 months) enrolled in SMARTT, a multisite prospective surveillance study, completed the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), assessing cognition, language, motor skills, social-emotional development, and adaptive behavior. Linear regression models were used to evaluate associations between Bayley-III outcomes in infants with and without perinatal and neonatal ARV exposure, by regimen (combination ARV [cARV] versus non-cARV), type of regimen (defined by drug class), and individual ARVs (for infants with cARV exposure), adjusting for maternal and infant health and demographic covariates. RESULTS:: As of May 2010, 374 infants had valid Bayley-III evaluations. Median age at testing was 12.7 months; 49% male, 79% black, 16% Hispanic. Seventy-nine percent were exposed to regimens containing protease inhibitors (PIs; 9% of PI-containing regimens also included non-nucleoside reverse transcriptase inhibitors [NNRTIs]), 5% to regimens containing NNRTIs (without PI), and 14% to regimens containing only nucleoside reverse transcriptase inhibitors (NRTIs). Overall, 83% were exposed to cARV. No Bayley-III outcome was significantly associated with overall exposure to cARV, ARV regimen, or neonatal prophylaxis. For individual ARVs, following sensitivity analyses, the adjusted group mean on the Language domain was within age expectations but significantly lower for infants with perinatal exposure to atazanavir (p=0.01). CONCLUSIONS:: These results support the safety of perinatal ARV use. Continued monitoring for adverse neurodevelopmental outcomes in older children is warranted, and the safety of atazanavir merits further study.
The Pediatric Infectious Disease Journal 01/2013; · 3.58 Impact Factor
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James D Wilkinson, Paige L Williams,
Erin Leister,
Bret Zeldow,
William T Shearer,
Steven D Colan,
George K Siberry,
Laurie B Dooley,
Gwendolyn B Scott,
Kenneth C Rich,
Steven E Lipshultz
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ABSTRACT: OBJECTIVES:: To evaluate associations of cardiac biomarkers with in utero antiretroviral (ARV) drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children. DESIGN AND METHODS:: We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal ARV exposures, maternal-child characteristics, and echocardiographic parameters. RESULTS:: Among 338 HEU children (mean age = 4.3 years), 51% had at least 1 elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP (adjusted odds ratio [aOR] = 2.28, P = 0.02). Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR = 3.56, P = 0.01 and aOR = 2.33, P = 0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left ventricular (LV) thickness-to-dimension ratio (r = 0.21, P = 0.04); and elevated cTnT was associated with higher mean LV end-diastolic (ED) posterior wall thickness (P = 0.04). hsCRP measurements were negatively correlated with septal thickness (r = -0.22, P = 0.03) and elevated hsCRP was associated with lower mean LV contractility Z-scores (P = 0.04). NT-proBNP measurements were correlated with increased LVED dimension (r = 0.20, P = 0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P = 0.03). CONCLUSION:: Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of pre-natal abacavir exposure in this population need further investigation.
AIDS (London, England) 12/2012; · 4.91 Impact Factor
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ABSTRACT: Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth.Methods. The PHACS Surveillance Monitoring of ART Toxicities study is a US-based cohort of HIV-exposed uninfected children. We evaluated maternal ARV use during pregnancy and risk of total and spontaneous (occurring after preterm labor or membrane rupture without other complications) preterm birth (<37 weeks gestation), and small for gestational age (< 10(th) percentile) (SGA). Multivariable logistic regression models were used to evaluate association of ARVs and timing of exposure while adjusting for maternal characteristics.Results. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, both preterm and spontaneous preterm birth were increased with 1(st) trimester use of protease inhibitors (adjusted odds ratios [aOR's]=1.55 and 1.59 respectively) but not with non-nucleoside reverse transcriptase inhibitor or triple nucleoside regimens. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens.Conclusions. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.
The Journal of Infectious Diseases 11/2012; · 6.41 Impact Factor
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Olivier Humblet,
Susan A Korrick, Paige L Williams,
Oleg Sergeyev,
Claude Emond,
Linda S Birnbaum,
Jane S Burns,
Larisa M Altshul,
Donald Jr G Patterson,
Wayman E Turner,
Mary M Lee,
Boris Revich,
Russ Hauser
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ABSTRACT: BACKGROUND: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. OBJECTIVES: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. METHODS: In this prospective cohort of Russian adolescent boys, we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and 2 intergenic regions among 392 boys. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were utilized, both with and without pre-screening for marginal genetic associations. RESULTS: After accounting for multiple testing, 2 tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and 1 in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only those with marginal genetic associations. CONCLUSIONS: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.
Environmental Health Perspectives 10/2012; · 7.04 Impact Factor
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ABSTRACT: STUDY QUESTION: In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? SUMMARY ANSWER: Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. WHAT IS KNOWN ALREADY: Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E(2)) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. STUDY DESIGN, SIZE AND DURATION: Prospective preconception cohort study. One hundred and seventy-four women aged 18-45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. PARTICIPANTS/MATERIALS, SETTINGAND METHODS: Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE: The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear dose-response association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E(2) levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend = 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27%, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P < 0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value = 0.08). LIMITATIONS AND REASONS FOR CAUTION: Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample. WIDER IMPLICATIONS OF THE FINDINGS: The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative dose-response association between urinary BPA concentrations and serum peak E(2) and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. None of the authors has actual or potential competing financial interests. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
Human Reproduction 09/2012; · 4.47 Impact Factor
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ABSTRACT: Cross-sectional research indicates high rates of mental health concerns among youth with perinatal HIV infection (PHIV), but few studies have examined emerging psychiatric symptoms over time.
Youth with PHIV and peer comparisons who were HIV-exposed but uninfected or living in households with HIV-infected family members (HIV-affected) and primary caregivers participated in a prospective, multisite, longitudinal cohort study. Groups were compared for differences in the incidence of emerging psychiatric symptoms during 2 years of follow-up and for differences in psychotropic drug therapy. Logistic regression models were used to evaluate the association of emerging symptoms with HIV status and psychosocial risk factors.
Of 573 youth with study entry assessments, 92% attended at least 1 annual follow-up visit (PHIV: 296; comparisons: 229). A substantial percentage of youth who did not meet symptom criteria for a psychiatric disorder at study entry did so during follow-up (PHIV = 36%; comparisons = 42%). In addition, those who met criteria at study entry often met criteria during follow-up (PHIV = 41%; comparisons = 43%). Asymptomatic youth with PHIV were significantly more likely to receive psychotropic medication during follow-up than comparisons. Youth with greater HIV disease severity (entry CD4% <25% vs 25% or more) had higher probability of depression symptoms (19% vs 8%, respectively).
Many youth in families affected by HIV are at risk for development of psychiatric symptoms.
Journal of developmental and behavioral pediatrics: JDBP 07/2012; 33(6):456-68. · 2.27 Impact Factor
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Kristen W Smith,
Joe M Braun, Paige L Williams,
Shelley Ehrlich,
Katharine F Correia,
Antonia M Calafat,
Xiaoyun Ye,
Jennifer Ford,
Myra Keller,
John D Meeker,
Russ Hauser
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ABSTRACT: Background: Parabens are suspected endocrine disruptors and ubiquitous preservatives used in personal care products, pharmaceuticals, and foods. No studies have assessed the variability of parabens in women, including during pregnancy. Objective: Evaluate predictors and variability of urinary paraben concentrations. Methods: We measured urinary concentrations of methyl- (MP), propyl- (PP), and butyl-paraben (BP) among couples from a fertility center. Mixed-effects regression models were fit to examine demographic predictors of paraben concentrations and to calculate intraclass correlation coefficients (ICCs). Results: Between 2005 and 2010, we collected 2,721 spot urine samples from 245 men and 408 women. The median concentrations were 112 µg/L (MP), 24.2 µg/L (PP), and 0.70 µg/L (BP). Urinary MP and PP concentrations were 4.6- and 7.8-times higher in women than men, respectively, and concentrations of both MP and PP were 3.8-times higher in African Americans than Caucasians. MP and PP concentrations were slightly more variable in women (ICC=0.42, 0.43) than men (ICC=0.54, 0.51), and were weakly correlated between partners (r=0.27-0.32). Among 129 pregnant women, urinary paraben concentrations were 25-45% lower during pregnancy than before pregnancy, and MP and PP concentrations were more variable (ICCs of 0.38 and 0.36 compared with 0.46 and 0.44, respectively). Conclusions: Urinary paraben concentrations were more variable in women compared to men, and during pregnancy compared to before pregnancy. However, results for this study population suggest that a single urine sample may reasonably represent an individual's exposure over several months, and that a single sample collected during pregnancy may reasonably classify gestational exposure.
Environmental Health Perspectives 06/2012; · 7.04 Impact Factor
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Renee Smith,
Miriam Chernoff, Paige L Williams,
Kathleen M Malee,
Patricia A Sirois,
Betsy Kammerer,
Megan Wilkins,
Sharon Nichols,
Claude Mellins,
Ann Usitalo,
Patricia Garvie,
Richard Rutstein
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ABSTRACT: The influence of disease severity on cognitive and adaptive functioning in perinatally HIV-infected youth with (PHIV+/C) and without (PHIV+/NoC) a previous AIDS-defining illness (Centers for Disease Control and Prevention Class C event), compared with perinatally HIV-exposed but uninfected youth (PHEU) is not well understood.
This was a cross-sectional analysis of cognitive and adaptive functioning in PHIV+/C (n = 88), PHIV+/NoC (n = 270) and PHEU (n = 200) youth aged 7-16 years, from a multisite prospective cohort study. Youth and caregivers completed the Wechsler Intelligence Scale for Children, Fourth Edition and the Adaptive Behavior Assessment System, Second Edition, respectively. We compared means and rates of impairment between groups, and examined associations with other psychosocial factors.
Overall mean scores on measures of cognitive and adaptive functioning were in the low average range for all 3 groups. After adjustment for covariates, mean full-scale intelligence quotient scores were significantly lower for the PHIV+/C group than the PHIV+/NoC and PHEU groups (mean = 77.8 versus 83.4 and 83.3, respectively), whereas no significant differences were observed between the PHEU and PHIV+/NoC groups in any domain. Lower cognitive performance for the PHIV+/C group was primarily attributable to a prior diagnosis of encephalopathy. No significant differences between groups were observed in adaptive functioning. Conclusion: For long-term survivors, youth with HIV infection and a prior Centers for Disease Control and Prevention Class C event have higher risk for cognitive but not adaptive impairment regardless of current health status; this finding appears attributable to a previous diagnosis of encephalopathy. Early preventive therapy may be critical in reducing risk of later neurodevelopmental impairments.
The Pediatric Infectious Disease Journal 06/2012; 31(6):592-8. · 3.58 Impact Factor
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Jorge Lujan-Zilbermann,
Meredith G Warshaw, Paige L Williams,
Stephen A Spector,
Michael D Decker,
Mark J Abzug,
Barb Heckman,
Adam Manzella,
Bill Kabat,
Patrick Jean-Philippe,
Sharon Nachman,
George K Siberry
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ABSTRACT: To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV).
P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥15.
Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72.
In youth infected with HIV with a CD4% ≥15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.
The Journal of pediatrics 05/2012; 161(4):676-681.e2. · 4.02 Impact Factor
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ABSTRACT: Little is known about hearing loss in children with HIV infection (HIV+). We examined the prevalence of hearing loss in perinatally HIV+ and HIV-exposed but uninfected (HEU) children, compared these with the percentage with hearing loss in the general population and evaluated possible risk factors for hearing loss in HIV+ and HEU children.
Audiometric examinations were completed in children who met any prespecified criteria for possible hearing loss. The hearing examination consisted of a tympanogram in each ear and pure-tone air-conduction threshold testing from 500 through 4000 Hz. Hearing loss was defined as the pure-tone average over these frequencies ≥ 20 dB hearing level. The associations of demographic variables, parent/caregiver, HIV disease and HIV treatment with hearing loss were evaluated with univariate and multivariable logistic regression models.
Hearing testing was completed in 231 children (145 HIV+ and 86 HEU). Hearing loss occurred in 20.0% of HIV+ children and 10.5% of HEU children. After adjusting for caregiver education level, HIV infection was associated with increased odds of hearing loss (adjusted odds ratio = 2.13, 95% confidence interval: 0.95-4.76, P = 0.07). Among HIV+ children, those with a Centers for Disease Control and Prevention class C diagnosis had over twice the odds of hearing loss (adjusted odds ratio = 2.47, 95% confidence interval: 1.04-5.87, P = 0.04). The prevalence of hearing loss was higher in both HIV+ and HEU children compared with National Health and Nutrition Examination Survey III children.
Hearing loss was more common in both HIV+ and HEU children than in children from a US population sample. More advanced HIV illness increased the risk of hearing loss in HIV+ children.
The Pediatric Infectious Disease Journal 04/2012; 31(8):835-41. · 3.58 Impact Factor
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Paige L Williams,
George R Seage,
Russell B Van Dyke,
George K Siberry,
Raymond Griner,
Katherine Tassiopoulos,
Cenk Yildirim,
Jennifer S Read,
Yanling Huo,
Rohan Hazra,
Denise L Jacobson,
Lynne M Mofenson,
Kenneth Rich
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ABSTRACT: The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a "trigger-based" design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or "triggers" undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios.
American journal of epidemiology 04/2012; 175(9):950-61. · 5.59 Impact Factor
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ABSTRACT: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size.
We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF).
We used online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-hCG < 6 IU/L) 17 days after egg retrieval.
Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) µg/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06).
There was a positive linear dose-response association between BPA urinary concentrations and implantation failure.
Environmental Health Perspectives 04/2012; 120(7):978-83. · 7.04 Impact Factor
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Renee Smith,
Miriam Chernoff, Paige L Williams,
Kathleen M Malee,
Patricia A Sirois,
Betsy Kammerer,
Megan Wilkins,
Sharon Nichols,
Claude Mellins,
Ann Usitalo,
Patricia Garvie,
Richard Rutstein
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ABSTRACT: BACKGROUND:: The influence of disease severity on cognitive and adaptive functioning in perinatally infected youth with (PHIV+/C) and without (PHIV+/NoC) a previous AIDS-defining illness (CDC Class C event), compared to perinatally exposed but uninfected youth (PHEU) is not well understood. METHODS:: This was a cross-sectional analysis of cognitive and adaptive functioning in PHIV+/C (n=88), PHIV+/NoC (n=270), and PHEU (n=200) youth aged 7 to 16 years, from a multi-site prospective cohort study. Youth and caregivers completed the Wechsler Intelligence Scale for Children (WISC-IV) and the Adaptive Behavior Assessment System (ABAS-II) respectively. We compared means and rates of impairment between groups, and examined associations with other psychosocial factors. RESULTS:: Overall mean scores on measures of cognitive and adaptive functioning were in the low average range for all three groups. After adjustment for covariates, mean full scale IQ (FSIQ) scores were significantly lower for the PHIV+/C group than the PHIV+/NoC and PHEU groups (mean=77.8 vs 83.4 and 83.3, respectively), while no significant differences were observed between the PHEU and PHIV+/NoC groups in any domain. Lower cognitive performance for the PHIV+/C group was primarily attributable to a prior diagnosis of encephalopathy. No significant differences between groups were observed in adaptive functioning. CONCLUSION:: For long-term survivors, youth with HIV infection and a prior CDC class C event have higher risk for cognitive but not adaptive impairment regardless of current health status; this finding appears attributable to a previous diagnosis of encephalopathy. Early preventive therapy may be critical in reducing risk of later neurodevelopmental impairments.
The Pediatric Infectious Disease Journal 03/2012; · 3.58 Impact Factor
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George K Siberry, Paige L Williams,
Hermann Mendez,
George R Seage,
Denise L Jacobson,
Rohan Hazra,
Kenneth C Rich,
Raymond Griner,
Katherine Tassiopoulos,
Deborah Kacanek,
Lynne M Mofenson,
Tracie Miller,
Linda A DiMeglio,
D Heather Watts
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ABSTRACT: To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants.
US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure.
We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW, <2.5 kg); weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF exposure.
Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age 1 year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: -0.17 vs. -0.03, P=0.04; HCAZ: 0.17 vs. 0.42, P=0.02).
TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.
AIDS (London, England) 02/2012; 26(9):1151-9. · 4.91 Impact Factor
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Jane S Burns, Paige L Williams,
Oleg Sergeyev,
Susan A Korrick,
Mary M Lee,
Boris Revich,
Larisa Altshul,
Julie T Del Prato,
Olivier Humblet,
Donald G Patterson,
Wayman E Turner,
Mikhail Starovoytov,
Russ Hauser
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ABSTRACT: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth.
We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels.
A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders.
Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), β-hexachlorocyclohexane (βHCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, βHCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile.
Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.
Environmental Health Perspectives 02/2012; 120(2):303-8. · 7.04 Impact Factor
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Mabel L. Rice,
Ashley L. Buchanan,
George K. Siberry,
Kathleen M. Malee,
Bret Zeldow,
Toni Frederick,
Murli U. Purswani,
Howard J. Hoffman,
Patricia A. Sirois,
Renee Smith,
Peter III Torre,
Susannah M. Allison, Paige L. Williams
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ABSTRACT: Objective: To investigate the risk for language impairment (LI) in children perinatally infected or exposed to HIV. Methods: We evaluated the prevalence of LI in 7- to 16-year-old children with perinatal HIV infection (HIV+) compared with HIV-exposed and uninfected children, using a comprehensive standardized language test (Clinical Evaluation of Language Functioning-Fourth Edition [CELF-4]). LI was classified as primary LI (Pri-LI) (monolingual English exposure and no cognitive or hearing impairment), concurrent LI (Con-LI) (cognitive or hearing impairment), or no LI. Associations of demographic, caregiver, HIV disease, and antiretroviral treatment factors with LI category were evaluated using univariate and multivariable logistic regression models. Results: Of the 468 children with language assessments, 184 (39%) had LI. No difference was observed by HIV infection status for overall LI or for Pri-LI or Con-LI; mean (SD) CELF-4 scores were 88.5 (18.4) for HIV+ versus 87.5 (17.9) for HIV-exposed and uninfected children. After adjustment, black children had higher odds of Pri-LI versus no LI (adjusted odds ratio [aOR] = 2.43, p = .03). Children who were black, Hispanic, had a caregiver with low education or low intelligence quotient, or a nonbiological parent as caregiver had higher odds of Con-LI versus no LI. Among HIV+ children, viral load >400 copies/mL (aOR = 3.04, p < .001), Centers for Disease Control and Prevention Class C (aOR = 2.19, p = .02), and antiretroviral treatment initiation <6 months of age (aOR = 2.12, p = .02) were associated with higher odds of Con-LI versus no LI. Conclusions: Children perinatally exposed to HIV are at high risk for LI, but such risk was not increased for youth with HIV. Risk factors differed for Pri-LI and Con-LI.
Journal of Developmental & Behavioral Pediatrics 01/2012; 33(2):112–123. · 2.13 Impact Factor
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ABSTRACT: Gestational phthalate and bisphenol A (BPA) exposure may increase the risk of adverse maternal/child health outcomes, but there are few data on the variability of urinary biomarkers before and during pregnancy.
We characterized the variability of urinary phthalate metabolite and BPA concentrations before and during pregnancy and the ability of a single spot urine sample to classify average gestational exposure.
We collected 1,001 urine samples before and during pregnancy from 137 women who were partners in couples attending a Boston fertility clinic and who had a live birth. Women provided spot urine samples before (n ≥ 2) and during (n ≥ 2) pregnancy. We measured urinary concentrations of monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate, monobenzyl phthalate (MBzP), four metabolites of di-(2-ethylhexyl) phthalate (DEHP), and BPA. After adjusting for specific gravity, we characterized biomarker variability using intraclass correlation coefficients (ICCs) and conducted several surrogate category analyses to determine whether a single spot urine sample could adequately classify average gestational exposure.
Absolute concentrations of phthalate metabolites and BPA were similar before and during pregnancy. Variability was higher during pregnancy than before pregnancy for BPA and MBzP, but similar during and before pregnancy for MBP, MEP, and ΣDEHP. During pregnancy, MEP (ICC = 0.50) and MBP (ICC = 0.45) were less variable than BPA (ICC = 0.12), MBzP (ICC = 0.25), and ΣDEHP metabolites (ICC = 0.08). Surrogate analyses suggested that a single spot urine sample may reasonably classify MEP and MBP concentrations during pregnancy, but more than one sample may be necessary for MBzP, DEHP, and BPA.
Urinary phthalate metabolites and BPA concentrations were variable before and during pregnancy, but the magnitude of variability was biomarker specific. A single spot urine sample adequately classified MBP and MEP concentrations during pregnancy. The present results may be related to unique features of the women studied, and replication in other pregnancy cohorts is recommended.
Environmental Health Perspectives 01/2012; 120(5):739-45. · 7.04 Impact Factor
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George K Siberry,
Meredith G Warshaw, Paige L Williams,
Stephen A Spector,
Michael D Decker,
Patrick Jean-Philippe,
Ram Yogev,
Barbara E Heckman,
Adam Manzella,
Jhoanna Roa,
Sharon Nachman,
Jorge Lujan-Zilbermann
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ABSTRACT: Human immunodeficiency virus (HIV)-infected children are at increased risk of meningococcal infection and poor response to quadrivalent meningococcal conjugate vaccine (MCV4), but MCV4 has not been studied in preadolescent HIV-infected children.
The P1065 trial enrolled 2- to 10-year-old HIV-infected children with CD4 ≥ 25% to receive MCV4 at entry and at week 24. Rates of response (≥ 4-fold increase in rabbit serum bactericidal antibody) against each meningococcal serogroup (A, C, Y, W-135), geometric mean titers, and rates of seroprotection (rabbit serum bactericidal antibody titer ≥ 1:128) were determined from sera obtained at entry and weeks 4, 24, 28, and 72. Adverse events were assessed for 6 weeks after each MCV4 dose.
At entry, 47% of the 59 participants were male, 56% black, 31% Latino, median age was 6 years, 88% were receiving antiretroviral therapy, and 75% had viral load <400 copies/mL. There were no serious adverse events within 6 weeks after MCV4 doses; all vaccination reactions were mild. Response after a single MCV4 dose was high to serogroup A (92%) and W-135 (98%); responses improved after a second dose for serogroup C (43%-80%) (P < 0.0001) and Y (76%-84%) (P = 0.38). By week 72, seroprotection rates were 93%, 91%, 78%, and 46% for serogroups W-135, Y, A, and C, respectively.
Two doses of MCV4 were safe and immunogenic in 2- to 10-year-old HIV-infected children. The second dose increased the proportion of children who made a response to serogroup C. Seroprotection waned substantially for serogroups A and C within 1 year of last MCV4 dose.
The Pediatric Infectious Disease Journal 01/2012; 31(1):47-52. · 3.58 Impact Factor
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George K. Siberry,
Meredith G. Warshaw, Paige L. Williams,
Stephen A. Spector,
Michael D. Decker,
Patrick Jean-Philippe,
Ram Yogev,
Barbara E. Heckman,
Adam Manzella,
Jhoanna Roa,
Sharon Nachman,
Jorge Lujan-Zilbermann,
for the IMPAACT Protocol Team
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ABSTRACT: Background: Human immunodeficiency virus (HIV)-infected children are at increased risk of meningococcal infection and poor response to quadrivalent meningococcal conjugate vaccine (MCV4), but MCV4 has not been studied in preadolescent HIV-infected children.
Methods: The P1065 trial enrolled 2- to 10-year-old HIV-infected children with CD4 ≥25% to receive MCV4 at entry and at week 24. Rates of response (≥4-fold increase in rabbit serum bactericidal antibody) against each meningococcal serogroup (A, C, Y, W-135), geometric mean titers, and rates of seroprotection (rabbit serum bactericidal antibody titer ≥1:128) were determined from sera obtained at entry and weeks 4, 24, 28, and 72. Adverse events were assessed for 6 weeks after each MCV4 dose.
Results: At entry, 47% of the 59 participants were male, 56% black, 31% Latino, median age was 6 years, 88% were receiving antiretroviral therapy, and 75% had viral load <400 copies/mL. There were no serious adverse events within 6 weeks after MCV4 doses; all vaccination reactions were mild. Response after a single MCV4 dose was high to serogroup A (92%) and W-135 (98%); responses improved after a second dose for serogroup C (43%–80%) (P < 0.0001) and Y (76%–84%) (P = 0.38). By week 72, seroprotection rates were 93%, 91%, 78%, and 46% for serogroups W-135, Y, A, and C, respectively.
Conclusions: Two doses of MCV4 were safe and immunogenic in 2- to 10-year-old HIV-infected children. The second dose increased the proportion of children who made a response to serogroup C. Seroprotection waned substantially for serogroups A and C within 1 year of last MCV4 dose.
The Pediatric Infectious Disease Journal 12/2011; 31(1):47–52. · 3.58 Impact Factor
