Phthalate exposure among US women, NHANES 1999--2002: Relationship to serum gonadotropin levels

Phthalates are industrial chemicals used primarily as plasticizers though they and are found in a myriad of consumer goods such as children's toys, food packaging, dental sealants, cosmetics, pharmaceuticals, perfumes, and building materials. US biomonitoring data show more than 75% of the population have exposure to mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl) hexyl phthalate (MEHP), and mono-benzyl phthalate (MBZP). Reproductive toxicity from phthalate exposure in animal models has raised concerns about similar effects on fertility in humans. This dissertation research focuses on phthalate exposures in the US population and investigates the plausibility of an exposure-response relationship between phthalates and endocrine hormones essential for ovulation among US women. The objective of this research is to determine the relationship between levels of gonadotropins, follicle stimulating hormone (FSH) and leutinizing hormone (LH), and urinary phthalate monoester metabolites: MBP, MEP, MEHP, MBZP among National Health and Nutrition Examination Survey (NHANES) 1999-2002 women aged 35 to 60 years. Using biomarker data from a one-third sub-sample of NHANES participants, log transformed serum FSH and serum LH, respectively were regressed on phthalates controlling for age, body mass index, smoking, and creatinine taking into consideration the complex survey design (n=385). Models were stratified by reproductive status: reproductive (n=185), menopause transition (n=49) and post-menopausal (n=125). A decrease in FSH associated with increasing MBzP (beta=-0.094, p<0.05) was observed for all participants but no statistical association between log FSH and MBP, MEP, or MEHP was seen. A decrease in LH (beta=-0.125, p<0.05) was also observed with increasing MBzP for all participants though there was no relationship between levels of LH and MBP, MEP, or MEHP. The observed associations between FSH, LH and MBzP did not persist when stratified by reproductive status. Thus, the present study shows a change in endocrine hormones related to ovulation with increasing urinary MBzP among a representative sample of US women from 1999-2002 though this observed exposure-response relationship does not remain after stratification by reproductive status. ^

Epidemiology of isolated obstructive genitourinary defect in Texas: 1999--2003

Background. Obstructive genitourinary defects include all anomalies causing obstruction anywhere along the urinary tract. Previous studies have noted a large excess of males among infants affected by these types of defects. This is the first epidemiologic study focused solely on obstructive genitourinary defects (OGD). ^ Methods. Data on 1,683 mild and 302 severe cases of isolated OGD born between 1999 and 2003 and ascertained by the Texas Birth Defects Registry were compared to all births in Texas during the same time period. Adjusted prevalence odds ratios (POR) were calculated for infant sex, birth weight, gestational age, mother’s race/ethnicity, mother’s age, mother’s education, parity, birth year, start of prenatal care, multiple birth, and public health region of birth. Severe cases were defined as those cases that died prior to birth, died after birth, or underwent surgery for OGD in the first year of life. Cases of OGD that had other major birth defects besides OGD were excluded from this study. ^ Results. Severe cases of OGD were more likely than mild cases to have multiple obstructive genitourinary anomalies (37.8% vs. 18.9%) and bilateral defects (40.9% vs. 31.3%). Males had a significantly greater risk of OGD than females for both severe and mild cases: adjusted POR = 3.26 (95% CI = 2.45-4.33) and adjusted POR = 2.60 (95% CI = 2.33-2.90), respectively. Infants with both severe and mild OGD were more likely to be very preterm birth at birth compared with infants without OGD: crude POR of 16.19 (95% CI = 10.60-24.74) and 4.75 (95% CI = 3.54-6.37), respectively. Among the severe group, minority races had a decreased risk of OGD with an adjusted POR of 0.74 (95% CI = 0.55-0.98) compared with whites. Among the mild cases, increased rates of OGD were found in older mothers (adjusted POR = 1.10, 95% CI = 1.05-1.15), college/higher educated mothers (adjusted POR = 1.07, 95% CI = 1.01-1.13) and multiple births (adjusted POR = 1.28, 95% CI = 1.01-1.62). There was also a decreased risk of mild cases among black mothers compared to whites (adjusted POR = 0.63, 95% CI = 0.52-0.76). Compared to 1999, the prevalence of mild cases of OGD increased significantly over the 5 year study period with an adjusted POR of 1.10 (95% CI = 1.06-1.15) by 2003. ^ Conclusion. Risk factors of OGD for both severe and mild forms were male sex and preterm birth. Severe cases were more likely to have multiple OGD defects and be affected bilaterally. An increase in prevalence of mild cases of OGD over time and differences in rates of black, older, and higher educated mothers in mild cases may be attributed to ultrasound use. ^

Birth prevalence of isolated congenital limb reduction defects in Texas 1999--2001

Objective. Congenital limb defects are common birth defects occurring in approximately 2-7/10,000 live births. Because congenital limb defects are pervasive throughout all populations, and the conditions profoundly affect quality of life, they represent a significant public health concern. Currently there is a paucity of etiologic information in the literature regarding congenital limb reduction defects which represents a major limitation in developing treatment strategies as well as identifying high risk pregnancies. ^ Additionally, despite the fact that the majority of congenital limb reduction defects are isolated, most previous studies have not separated them from those occurring as part of a known syndrome or with multiple additional congenital anomalies of unknown etiology. It stands to reason that factors responsible for multiple congenital anomalies that happen to include congenital limb reduction defects may be quite different from those factors leading to an isolated congenital limb reduction defect. ^ As a first step toward gaining etiologic understanding, this cross-sectional study was undertaken to determine the birth prevalence and obtain demographic information about non-syndromic (isolated) congenital limb reduction defects that occurred in Texas from 1999-2001. ^ Methods. The study population included all infants/fetuses with isolated congenital limb reduction defects born in Texas during 1999-2001; the comparison population was all infants who were born to mothers who were residents of Texas during the same period of time. The overall birth prevalence of limb reduction defects was determined and adjusted for ethnicity, gender, site of defect (upper limb versus lower limb), county of residence, maternal age and maternal education. ^ Results. In Texas, the overall birth prevalence of isolated CLRDs was 2.1/10,000 live births (1.5 and 0.6/10,000 live births for upper limb and lower limb, respectively). ^ The risk of isolated lower limb CLRDs in Texas was significantly lower in females when gender was examined individually (crude prevalence odds ratio of 0.57, 95% CI of 0.36-0.91) as well as in relation to all other variables used in the analysis (adjusted prevalence odds ratio of 0.58, 95% CI of 0.36-0.93). ^ Harris County (which includes the Houston metropolitan area) had significantly lower risks of all (upper limb and lower limb combined) isolated CLRDs when examined in relation to other counties in Texas, with a crude prevalence odds ratio of 0.4 (95% CI: 0.29-0.72) and an adjusted prevalence odds ratio of 0.50 (95% CI: 0.31-0.80). The risk of isolated upper limb CLRDs was significantly lower in Harris County (crude prevalence odds ratio of 0.45, CI of 0.26-0.76 and adjusted prevalence odds ratio of 0.49, CI of 0.28-0.84). This trend toward decreased risk in Harris County was not observed for isolated lower limb reduction defects (adjusted prevalence odds ratio of 0.50, 95% confidence interval: 0.22-1.12). ^ Conclusions. The birth prevalence of isolated congenital limb reduction defects in Texas is in the lower limits of the range of rates that have been reported by other authors for other states (Alabama, Arkansas, California, Georgia, Hawaii, Iowa, Maryland, Massachusetts, North Carolina, Oklahoma, Utah, Washington) and other countries (Argentina, Australia, Austria, Bolivia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Croatia, Denmark, Ecuador, England, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Lithuania, Mexico, Norway, Paraguay, Peru, Spain, Scotland, Sweden, Switzerland, Uruguay, and Venezuela). In Texas, the birth prevalence of isolated congenital lower limb reduction defects was greater for males than females, while the birth prevalence of isolated congenital upper limb reduction defects was not significantly different between males and females. The reduced rates of limb reduction defects in Harris County warrant further investigation. This study has provided an important first step toward gaining etiologic understanding in the study of isolated congenital limb reduction defects. ^

Survey analysis on dental infection control & occupational safety from India---1999 & 2010

The objective was to study knowledge, attitudes, practice (KAP) and needs regarding infection control measures using two cross-sectional surveys from 1999 and 2010 conducted in India. Both data collection instruments had only about 35 comparable variables in common. In 1999, there were 456 respondents (dentists) who completed a self-administered survey instrument compared to 272 respondents in 2010. Both the 1999 and 2010 samples were mutually independent with no overlap, had regional differences, and therefore, were not completely comparable for changes in KAP over time. While almost all respondents from both surveys felt that education in dental safety was needed and wanted mandatory dental safety curriculum in dental schools, severe inadequacies in dental safety knowledge, protection against immunizable diseases, and practice of universal precaution were noted. Data from the study demonstrated that there is a substantial opportunity to improve the knowledge, attitude and practice of dental infection control and occupational safety in India. Few respondents (27%) reported that the infectious disease status of a patient is always known and a significant number reported that they had the right to refuse care for patients of known infectious disease status. This indicates that Stigma in treating HIV/AIDS patients remains a concern, which in turn suggests that a stronger focus on educating dentists about dental safety and on stigma and infectious disease is needed. Information obtained from this study could be utilized for developing policies oriented towards increasing dental safety educational efforts, in both dental schools as curriculum, and for practicing dentists through professional updates or continuing dental education.^

The application of principal component analysis on human development indicators: Temporal approach from 1999 to 2010

Background and Objective. Ever since the human development index was published in 1990 by the United Nations Development Programme (UNDP), many researchers started searching and corporative studying for more effective methods to measure the human development. Published in 1999, Lai’s “Temporal analysis of human development indicators: principal component approach” provided a valuable statistical way on human developmental analysis. This study presented in the thesis is the extension of Lai’s 1999 research. ^ Methods. I used the weighted principal component method on the human development indicators to measure and analyze the progress of human development in about 180 countries around the world from the year 1999 to 2010. The association of the main principal component obtained from the study and the human development index reported by the UNDP was estimated by the Spearman’s rank correlation coefficient. The main principal component was then further applied to quantify the temporal changes of the human development of selected countries by the proposed Z-test. ^ Results. The weighted means of all three human development indicators, health, knowledge, and standard of living, were increased from 1999 to 2010. The weighted standard deviation for GDP per capita was also increased across years indicated the rising inequality of standard of living among countries. The ranking of low development countries by the main principal component (MPC) is very similar to that by the human development index (HDI). Considerable discrepancy between MPC and HDI ranking was found among high development countries with high GDP per capita shifted to higher ranks. The Spearman’s rank correlation coefficient between the main principal component and the human development index were all around 0.99. All the above results were very close to outcomes in Lai’s 1999 report. The Z test result on temporal analysis of main principal components from 1999 to 2010 on Qatar was statistically significant, but not on other selected countries, such as Brazil, Russia, India, China, and U.S.A.^ Conclusion. To synthesize the multi-dimensional measurement of human development into a single index, the weighted principal component method provides a good model by using the statistical tool on a comprehensive ranking and measurement. Since the weighted main principle component index is more objective because of using population of nations as weight, more effective when the analysis is across time and space, and more flexible when the countries reported to the system has been changed year after year. Thus, in conclusion, the index generated by using weighted main principle component has some advantage over the human development index created in UNDP reports.^

A descriptive study of syphilis infection in Houston, Texas, 1999--2008

The rate of syphilis nationally has been on the rise since 2001. Syphilis, if left untreated can facilitate the transmission of HIV infection. An epidemiologic study describing the trends of syphilis is important to the public health community to lay the foundation for the development and implementation of programs to prevent and eliminate syphilis in the United States. ^ The objective of this study was to describe the trends of syphilis among the population in Houston/Harris County, Texas. ^ We reviewed surveillance data that included 11,605 unique cases from the Houston Department of Human and Health Service from 1999 through 2008. The rates were calculated per 100,000 population. ^ We show the prevalence of syphilis at testing (excluding congenital) increased 40% in Houston/Harris County, Texas from 2001 through 2008, and the ratio of syphilis comparing men to women was 2:1. The 18–29 years age group had the highest percentage of cases of syphilis among all age groups in Houston/Harris County. Primary and Secondary (P&S) syphilis, the most infectious stage, had an 85% increase in rate among males from 1999 through 2008. ^ Between 1999 and 2000, 71% of cases were identified through public facilities compared to private facilities. However, after 2001 rates shifted over more to the private facilities. By 2008, private facilities identified 54.7% of cases, compared to 45.3% identified through public facilities. This may be due to an increase among individuals who have a higher socio-economic status with access to health care insurance. ^ In conclusion, syphilis rates from 1999 through 2008 increased among all race ethnicities, age groups, and genders in Houston/Harris County. Blacks still are disproportionally affected by syphilis infections, and for the first time, White males displayed a significant increase in cases among males. It is vital to Houston public health professionals to have improved surveillance techniques to track syphilis trends and engage high risk groups to better understand their risks in hope of treating and preventing syphilis.^

The epidemiology of dengue among children less than 18 months of age in Puerto Rico, 1999--2011

Between 1999 and 2011, 4,178 suspected dengue cases in children less than 18 months of age were reported to the Centers for Disease Control and Prevention Dengue Branch in Puerto Rico. Of the 4,178, 813 were determined to be laboratory-positive and 737 laboratory-negative. Those remaining were either laboratory-indeterminate, not processed or positive for Leptospira . On average, 63 laboratory-positive cases were reported per year. Laboratory-positive cases had a median age of 8.5 months. Among these cases, the median age for those with dengue fever was 8.7 months and 7.9 months for dengue hemorrhagic fever. Clinical signs and symptoms indicative of dengue were greatest among laboratory-positive cases and included fever, rash, thrombocytopenia, bleeding manifestations, and petechiae. The most common symptoms among patients who were laboratory-negative were fever, nasal congestion, cough, diarrhea, and vomiting. Using the 1997 WHO guidelines, nearly 50% of the laboratory-positive cases met the case definition for dengue fever, and 61 of these were further determined to meet the case definition for dengue hemorrhagic fever. In comparison, 15% of laboratory-negative cases met the case definition for dengue fever and less than 1% for dengue hemorrhagic fever. None of the laboratory-positive or laboratory-negative cases met the criteria for dengue shock syndrome.^

Maternal exposure to hazardous air pollutants and oral clefts among offspring: Texas, 1999-2008

Birth defects are a leading cause of infant mortality in the United States. About one in 33 births in the United States is diagnosed with birth defects. Common birth defects include neural tube defects, Down syndrome and oral clefts. The present study focused on oral clefts. ^ Oral clefts refer to the malformation of lip, mouth or both. Birth prevalence of oral clefts in Texas is about 11 per 10,000 births. Etiologically, oral clefts have been classified into two groups, cleft lip with or without cleft palate (CL±P) and isolated cleft palate (CP). In spite of their high prevalence and clinical significance, the etiology of oral clefts in humans has not been well understood. Though a number of risk factors have been identified in epidemiological studies, most of them do not explain the majority of the cases. The need to identify novel risk factors associated with oral clefts provided the motivation for this study. The present study focused on maternal exposure to several hazardous air pollutants. A common subgroup of hazardous air pollutants is the volatile organic compounds found in petroleum derivatives. Four important hydrocarbons in this group are benzene, toluene, ethyl benzene and xylenes (BTEX). ^ The specific aim of this study was to evaluate the association between maternal exposure to environmental levels of BTEX and oral clefts among offspring in Texas for the period 1999-2008. ^ A case-control study design was used to assess if maternal exposure to BTEX increased the risk of oral clefts. The Texas Birth Defects Registry provided data on cases of non-syndromic oral clefts delivered in Texas during the period 1999-2008. Census tract level maternal exposure to BTEX concentrations were obtained from the Hazardous Air Pollutant Exposure Model (HAPEM) developed by the U.S. Environmental Protection Agency. Unconditional logistic regression was used to assess the relationship between maternal exposure to BTEX levels and risk of oral clefts in offspring. ^ In the selected population, mothers who had high estimated exposure to any of the BTEX compounds were not more likely to deliver an offspring with oral clefts. Future research efforts will focus on additional birth defects and thorough assessment of additional potential confounders.^

Phytoplankton photosynthetic competence, underway data of SOIREE cruise track 1999-02-08 to 1999-02-24

Active fluorescence (fast repetition rate fluorometry, FRRF) was used to follow the photosynthetic response of the phytoplankton community during the 13-day Southern Ocean Iron RElease Experiment (SOIREE). This in situ iron enrichment was conducted in the polar waters of the Australasian-Pacific sector of the Southern Ocean in February 1999. Iron fertilisation of these high nitrate low chlorophyll (HNLC) waters resulted in an increase in the photosynthetic competence (Fv/Fm) of the resident cells from around 0.20 to greater than 0.60 (i.e. close to the theoretical maximum) by 10/11 days after the first enrichment. Although a significant iron-mediated response in Fv/Fm was detected as early as 24 h after the initial fertilisation, the increase in Fv/Fm to double ambient levels took 6 days. This response was five-fold slower than observed in iron enrichments (in situ and in vitro) in the HNLC waters of the subarctic and equatorial Pacific. Although little is known about the relationship between water temperature and Fv/Fm, it is likely that low water temperatures - and possibly the deep mixed layer - were responsible for this slow response time. During SOIREE, the photosynthetic competence of the resident phytoplankton in iron-enriched waters increased at dissolved iron levels above 0.2 nM, suggesting that iron limitation was alleviated at this concentration. Increases in Fv/Fm of cells within four algal size classes suggested that all taxa displayed a photosynthetic response to iron enrichment. Other physiological proxies of algal iron stress (such as flavodoxin levels in diatoms) exhibited different temporal trends to iron-enrichment than Fv/Fm during the time-course of SOIREE. The relationship between Fv/Fm, algal growth rate and such proxies in Southern Ocean waters is discussed.