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Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown., Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US., Design, Setting, and Participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024., Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure., Main Outcomes and Measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted., Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02)., Conclusions and Relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

Adequate iodine nutrition is fundamental for all humans and is critical during pregnancy and lactation due to iodine forms part of the structure of thyroid hormones (THs) and it is required for THs function. Iodine is a scarce micronutrient that must be obtained from the diet. Sufficient iodine can be found in the nature from seafood and given it is not frequently consumed by Chileans, public health policies state that table salt in Chile must be iodized. Health plans must be monitored to determine if the intake of iodine is being appropriated and the population has not fallen in deficiency or excess. The aim of this work was to evaluate iodine intake in 26 women at the third trimester of pregnancy. Pregnant women are resident from El Bosque a low-income County located in Santiago de Chile. These Chilean pregnant women were recruited by nutritionist at the Centros de Salud familiar (CESFAM). A 24 h dietary recall (24 h-DR) was applied to them to evaluate iodine intake. Samples of urine and blood were taken by health professionals to analyze parameters of thyroid function and to measure urine iodine concentration (UIC). The survey analysis showed that the iodine consumption in these pregnant women derived mainly from salt, bread and milk and not from seafood. The survey analysis indicated that iodine intake was above the requirements for pregnant women. However, the average UIC indicated that iodine intake was adequate, suggesting the need to find a better parameter to determine iodine intake in pregnant women., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Inorganic phosphate (P i ) is an essential nutrient that fulfills critical roles in human health. It enables skeletal ossification, supports cellular structure and organelle function, and serves key biochemical roles in energetics and molecular signaling. P i homeostasis is modulated through diet, intestinal uptake, renal reabsorption, and mobilization of stores in bone and extracellular compartments. Disrupted P i homeostasis is associated with phosphate wasting, mineral and bone disorders, and vascular calcification. Mechanisms of Pi homeostasis in pregnancy remain incompletely understood. The study presented herein examined biological fluid Pi characteristics over the course of gestation. Correlations with gestation age, pregnancy number, preterm birth, preeclampsia, diabetes mellitus, and placental calcification were evaluated during the last trimester. The results support that maternal urinary P i levels increased during the third trimester of pregnancy. Reduced levels were observed with previous pregnancy. Amniotic fluid P i levels decreased with gestation while low second trimester levels associated with preterm birth. No significant difference in urinary P i levels was observed between preeclampsia and controls (8.50 ± 2.74 vs. 11.52 ± 2.90 mmol/L). Moreover, increased maternal urinary P i was associated with preexisting diabetes mellitus in preeclampsia. Potential confounding factors in this study are maternal age at delivery and body mass index (BMI)-information which we do not have access to for this cohort. In conclusion, P i levels provide clinical information regarding the pathogenesis of pregnancy-related complications, supporting that phosphate should be examined more closely and in larger populations.

Introduction: Pregnancy-induced increases in nicotine metabolism may contribute to difficulties in quitting smoking during pregnancy. However, the time course of changes in nicotine metabolism during early and late pregnancy is unclear. This study investigated how pregnancy alters the nicotine metabolite ratio (NMR), a common biomarker of nicotine metabolism among nonpregnant smokers., Methods: Urinary NMR (trans-3'-hydroxycotinine [3HC]/cotinine [COT]) was assessed using total (free + glucuronide) and free compounds among women (N = 47) from a randomized controlled trial for smoking cessation who self-reported smoking and provided a urine sample during early pregnancy (M ± SD = 12.5 ± 4.5 weeks' gestation), late pregnancy (28.9 ± 2.0 weeks' gestation), and 6 months postpartum (24.7 ± 1.2 weeks since childbirth). Urine samples were analyzed using liquid chromatography-tandem mass spectrometry and NMR were calculated as Total 3HC/Free COT, Free 3HC/Free COT, and Total 3HC/Total COT., Results: NMR was significantly higher during early and late pregnancy compared to postpartum and significantly increased from early to late pregnancy as measured by Total 3HC/Free COT (0.76, 0.89, 0.60; all p's < .05) and Free 3HC/Free COT (0.68, 0.80, 0.51; all p's < .05). Total 3HC/Total COT did not vary over time (p = .81)., Conclusions: Total 3HC/Free COT and Free 3HC/Free COT increased in the first trimester and continued to increase throughout pregnancy, suggesting a considerable increase in nicotine metabolism over gestation. Future analyses are needed to interpret the changes in NMR in the context of nicotine pharmacokinetics, as well as its impact on changes in smoking behavior and cessation outcomes., Implications: We observed that the NMR was significantly higher as early as 12 weeks' gestation and increased further as a function of gestational age. Among nonpregnant smokers, elevated NMR is associated with smoking phenotypes such as smoking more cigarettes per day and poorer response to nicotine patch; therefore, pregnancy-induced increases in the NMR may contribute to smoking during the first trimester of pregnancy and reducing or quitting smoking may become more challenging as the rate of nicotine metabolism accelerates over the course of pregnancy., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There has been significant research on the genetic and environmental factors of congenital heart defects (CHDs), but few causes of teratogenicity, especially teratogenic mechanisms, can be clearly identified. Metabolomics has a potential advantage in researching the relationship between external factors and CHD., Objective: To find and identify the urinary potential biomarkers of pregnancy (including in the second and third trimesters) for fetuses with CHD based on modified gas chromatograph-mass spectrometer (GC-MS), which could reveal the possibility of high-risk factors for CHD and lay the foundation for early intervention, treatment, and prevention., Methods: Using a case-control design, we measured the urinary potential biomarkers of maternal urine metabolomics based on GC-MS in a population-based sample of women whose infants were diagnosed with CHD (70 case subjects) or were healthy (70 control subjects). SIMCA-P 13.0 software, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), Wilcoxon-Mann-Whitney test, and logistics regression were used to find significant potential biomarkers., Result: The 3D score graph of the OPLS-DA showed that the CHD and control groups were fully separated. The fitting parameters were R 2 x=0.78 and R 2 y=0.69, and the forecast rate was Q 2 =0.61, indicating a high forecast ability. According to the ranking of VIPs from the OPLS-DA models, we found 34 potential metabolic markers with a VIP > 1, and after two pairwise rank sum tests, we found 20 significant potential biomarkers, which were further used in multifactor logistic regressions. Significant substances, including 4-hydroxybenzeneacetic acid ( OR =4.74, 95% CI: 1.06-21.06), 5-trimethylsilyloxy-n-valeric acid ( OR =15.78, 95% CI: 2.33-106.67), propanedioic acid ( OR =5.37, 95% CI: 1.87-15.45), hydracrylic acid ( OR =6.23, 95% CI: 1.07-36.21), and uric acid ( OR =5.23, 95% CI: 1.23-22.32), were associated with CHD., Conclusion: The major potential biomarkers in maternal urine associated with CHD were 4-hydroxybenzeneacetic acid, 5-trimethylsilyloxy-n-valeric acid, propanedioic acid, hydracrylic acid, and uric acid, respectively. These results indicated that the short chain fatty acids (SCFAs) and aromatic amino acid metabolism may be relevant with CHD.

Background: Phthalates are common plasticizer chemicals that have been linked to glucose intolerance in the general population, but there is only limited research on their association with gestational diabetes (GDM)., Objective: We evaluated the association between 11 urinary phthalate metabolites and GDM, impaired glucose tolerance (IGT), and continuous blood glucose concentration during pregnancy in The Infant Development and Environment Study (TIDES). Based on prior study results, our primary analyses focused on monoethyl phthalate (MEP) in relation to our outcomes of interest., Study Design: We used multi-variable logistic regression to examine the odds of GDM and IGT in relation to an interquartile-range (IQR) increase in natural log (ln)-transformed, specific gravity (SG)-adjusted first trimester (T1) and average of T1 and third trimester (T3) ("T1T3avg") phthalate metabolite concentrations. We fit linear regression models to examine the percent change in blood glucose per IQR increase in ln-transformed, SG-adjusted T1 and T1T3avg phthalates. In sensitivity analyses, we examined interactions between exposure and race. We adjusted for maternal age, maternal body mass index, study center, race/ethnicity, parity, and gestational age at glucose testing., Results: In our sample of 705 pregnant women, we observed 60 cases of GDM, 90 cases of IGT, and an average GLT blood glucose of 113.6 ± 27.7 mg/dL. In our primary analysis, T1T3avg MEP was positively associated with GDM ([OR (95% CI) per IQR increase] T1T3avg MEP: 1.61 (1.10, 2.36)). In secondary analyses, most other phthalates were not found to be related to study outcomes, though some associations were noted. Sensitivity analyses indicated possible strong race-specific associations in Asians, though these results are based on a small sample size (n = 35)., Conclusion: In alignment with our a priori selection, we documented an association between T1T3avg MEP and GDM. Additional phthalate metabolites were also found to be linked to glucose intolerance, with possible stronger associations in certain racial/ethnic subgroups. Given the prevalence of phthalate exposures and the growing evidence of associations with metabolic outcomes, future studies should continue to examine this question in diverse cohorts of pregnant women, particularly in those who may be at higher risk for GDM and IGT., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Oxidative stress has been implicated in numerous birth outcomes, including spontaneous preterm birth. However, the relationship with presentation at delivery has been less well studied. We assessed the relationship between oxidative stress biomarkers and gestational duration with a focus on spontaneous presentation for delivery., Methods: Our sample included 740 women from a multi-center prospective cohort study, recruited from 2010 to 2012. Resultant measures of oxidative stress in pregnancy prostaglandin F 2α (PGF 2α ), 8-iso-prostaglandin F 2α (8-iso-PGF 2α ), and the primary 8-iso-PGF 2α metabolite were measured in third trimester urine samples. Information on presentation for delivery was abstracted from medical records. We examined associations with preterm birth using adjusted logistic models. Time to event (overall delivery and spontaneous delivery) was examined using adjusted accelerated failure time models., Results: The 8-iso-PGF 2α metabolite was associated with increased odds of overall preterm birth (OR: 1.44 [95% CI: 1.00, 2.06]), and the association with spontaneous preterm birth was similar in magnitude but not statistically significant (OR: 1.45 [95% CI: 0.96, 2.20]). We did not detect associations between other biomarkers and preterm birth, or between biomarkers and timing of overall or spontaneous delivery in accelerated failure time models., Conclusions: Our data suggest that increased oxidative stress, as indicated by the 8-iso-PGF 2α metabolite, may be associated with preterm birth. In contrast to previous studies, associations were similar among individuals with spontaneous versus non-spontaneous presentation for delivery., (Published by Elsevier Inc.)

Background: Evidence from experimental and observational studies suggests that prenatal phthalate exposures may be associated with autism spectrum disorder (ASD). We examined whether prenatal phthalate exposures were associated with an increased risk of ASD., Methods: We quantified 14 metabolites of eight phthalates in 636 multiple maternal urine samples collected during 2nd and 3rd trimesters of pregnancy from 201 mother-child pairs in MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD longitudinal cohort. At 3 years old, children were clinically assessed for ASD and classified into three diagnostic categories: ASD (n = 46), non-typical development (Non-TD, n = 55), and typical development (TD, n = 100). We used multinomial logistic regression to evaluate the association of phthalate metabolite concentrations with ASD and Non-TD., Results: Most associations of phthalate biomarkers with both ASD and Non-TD were null, with the exception that monoethyl phthalate (MEP) was significantly associated with an increased risk of Non-TD (per 2.72-fold relative increase in concentration: Relative risk ratio (RRR) = 1.38; 95% confidence interval (CI): 1.01, 1.90). When stratified by prenatal vitamin use during the first month of pregnancy, among mothers who took vitamins, ASD risk was inversely associated with mono-isobutyl phthalate (MiBP, RRR = 0.44; 95% CI: 0.21, 0.88), mono(3-carboxypropyl) phthalate (MCPP, RRR = 0.41; 95% CI: 0.20, 0.83) and mono-carboxyisooctyl phthalate (MCOP, RRR = 0.49; 95% CI: 0.27, 0.88), but among mothers who did not take prenatal vitamins, Non-TD risk was positively associated with MCPP (RRR = 5.09; 95% CI: 2.05, 12.6), MCOP (RRR = 1.86; 95% CI: 1.01, 3.39), and mono-carboxyisononyl phthalate (MCNP, RRR = 3.67; 95% CI: 1.80, 7.48). When stratified by sex, among boys, MEP, monobenzyl phthalate, MCPP, MCNP, and sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) were positively associated with Non-TD risk, but associations with ASD were null. Among girls, associations with both ASD and Non-TD were null., Conclusions: Our study showed that phthalate exposures in mid- to late pregnancy were not associated with ASD in children from this high-risk ASD cohort. Further studies should be conducted in the general population without high-risk genes to confirm our findings.

The objective of this study was to determine the effectiveness of routine iodine supplementation among pregnant women in areas of high prevalence of an iodine insufficiency, using WHO criteria to determine the iodine status. A longitudinal study was conducted on pregnant women attending antenatal care at a tertiary hospital. The urine iodine concentration was measured in the first trimester and after 150 μg of iodine supplementation in the third trimester. A total of 327 pregnant women met the inclusion criteria with a complete follow-up. The prevalence of an iodine insufficiency was significantly lower in the third trimester, when compared to the first trimester (21.41% vs 55.35%, p < .001). However, 21.4% of cases still had an iodine insufficiency and 35.17% had an 'above-requirement' in the third trimester. In the areas of high prevalence of iodine insufficiency, an iodine supplementation significantly reduces the number of women with insufficiency; however, it was associated with unnecessarily high UICs, leading to the risk of excess iodine. Impact statement What is already known on this subject: Iodine insufficiency is highly prevalent in many geographical areas. Half of the pregnant women in the northern part of Thailand had an iodine insufficiency in the first trimester. What do the results of this study add: Iodine supplementation (daily 150-mcg of potassium iodide) could significantly reduce the number of women with the insufficiency. About one-fifth of women still had an iodine insufficiency in spite of iodine supplementation. Universal supplementation could be associated with unnecessarily high UICs, potentially at risk of iodine excess. What are the implications of these findings for clinical practice and/or further research: Physicians should guard against the occurrence of adverse effect from an iodine excess when there is routine iodine supplementation for pregnant women. Further study is required to establish the best strategy for an iodine supplementation in pregnancy.

Background: Iodine deficiency occurs in West European countries. Iodine is important for brain development of the foetus and infant. The current iodine status of pregnant and lactating Dutch women is unknown., Methods: In a pilot study we examined the iodine status of 36 women. From 20 gestational weeks (GW) until 4 weeks postpartum, they ingested 150 μg iodine/day in the form of a multivitamin supplement for pregnant and lactating women. Twenty-four hour urine samples were collected at 20 and 36 GW and at 4 weeks postpartum. A breast milk sample was collected at 4 weeks postpartum. Iodine concentrations were analysed by inductively coupled plasma-mass spectrometry. Cut-off values for the urinary iodine concentration (UIC) for pregnant and lactating women are 150 and 100 μg/l, respectively. Adequate intakes (AI) of iodine for infants aged 0-6 months are 1.1 μmol/l (Institute of Medicine recommendations) or 0.5 μmol/l (Nordic Councilrecommendations)., Results: The median UICs (percentages below cut-off) were 102 μg/l (83%) at 20 GW, 144 μg/l (56%) at 36 GW and 112 μg/l (40%) at 4 weeks postpartum. The median breast milk iodine concentration was 1.2 μmol/l (range 0.5-3.0); 33% and 0% of the infants had estimated iodine intakes below the IOM-AI and Nordic-AI, respectively., Conclusion: This pilot study suggested a high prevalence of iodine deficiency during pregnancy. Daily supplementation of 150 μg iodine from 20 GW might be insufficient to reach maternal iodine adequacy. The median breast milk iodine concentration seems adequate. Further studies, using a representative sample of the Dutch population, are needed to establish the current Dutch iodine status of pregnant and lactating women.

Personal care product use is a potential source of metals exposure among children, but studies have been limited. We measured urinary concentrations of 10 metals (aluminum, arsenic [As], barium [Ba], cadmium, cobalt [Co], lead [Pb], manganese [Mn], molybdenum [Mo], nickel, and zinc [Zn]) in third trimester pregnant women (n = 212) and their children at 8-14 years of age (n = 250). Demographic factors (child sex, age, socioeconomic status, and maternal education), body mass index (BMI) z-score, and child personal care product use in the 24 h prior to urine collection were examined as predictors of urinary metal concentrations. Metals were detected in 80-100% of urine samples, with significant differences in maternal versus childhood levels. However, metal concentrations were not strongly correlated within or between time points. In linear regression models including all demographic characteristics, BMI z-score, and specific gravity, age was associated with higher Co (6% [95% CI: 2, 10]), while BMI z-score was associated with lower Mo (-6% [95% CI: -11, -1). In addition, significantly higher metal concentrations were observed among users of colored cosmetics (Mo: 42% [95% CI: 1, 99]), deodorant (Ba: 28% [3, 58]), hair spray/hair gel (Mn: 22% [3, 45]), and other toiletries (As: 50% [9, 108]), as well as with an increasing number of personal care products used (As: 7% [3, 11]) after adjustment for child sex, age, total number of products used, and specific gravity. However, significantly lower metal concentrations were noted for users of hair cream (As and Zn: -20% [-36, -2] and -21% [-35, -2], respectively), shampoo (Pb: -40% [-62, -7]), and other hair products (Pb: -44% [-65, -9]). We found that personal care product use may be a predictor of exposure to multiple metals among children. Further research is recommended to inform product-specific exposure source identification and related child health risk assessment efforts., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Most pre-eclampsia (PE) studies have used cross-sectional data to derive conclusions regarding the pathophysiology of the condition. This has led to the concept that there exists early (<34 weeks) and late-onset (>34 weeks) disease according to gestational age at diagnosis. Survival time models have predicted that if the pregnancy was to continue indefinitely, all women would develop PE. In this study we have performed a longitudinal analysis of the urinary biomarker, inositol phosphoglycan (IPG), in a cohort of women giving birth in Mauritius (n-920). We have analysed the PE data in the traditional cross-sectional manner for n = 77 women who developed PE and also then looked at the longitudinal data for 71/77 of the same women. The data allows us to use longitudinal values to calculate a date of onset (first presence of biomarker in urine) and compare that to date of clinical diagnosis (cross sectional). We find two populations for both analysis consistent with an early and late stage subgroup. The calculated date of onset had subgroups (early and late) at 28.4 ± 0.41 weeks and 35.37 ± 0.26 weeks and for clinical date of diagnosis, 32.3 ± 0.59 weeks and 37.04 ± 0.62 weeks, respectively. The presence of the same biomarker in both subgroups and its ability to predict clinical onset 2-4 weeks prior to clinical diagnosis suggest that both groups may have similar aetiology., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Tobacco use during pregnancy is the most modifiable risk factor associated with poor pregnancy outcomes. Self-reported tobacco use has been demonstrated to have high misclassification rates. The aims were to examine misclassification rates of perinatal tobacco use during each trimester of pregnancy and 8 weeks postpartum, and to evaluate characteristics associated with misclassification of tobacco use status., Methods: This is secondary analysis of a prospective, multicenter trial of pregnant women, and it includes participants who were biochemically identified as tobacco users during their first trimester (N = 103). Each trimester and once postpartum, tobacco use was assessed via self-report and validated using a cutoff of 100 ng/mL for urine cotinine via NicAlert test strips to indicate current use. Those who self-reported as nonusers but were identified as users via urine cotinine were considered misclassified; misclassification rates were determined for each time period. Logistic regression assessed maternal factors associated with misclassification status., Results: Misclassification rates declined from 35.0% at first trimester to 31.9% and 26.6% at the second and third; the postpartum rate was 30.4%. These rates did not differ significantly from each other at the 0.05 level. Race/ethnicity was associated with misclassification status; white/non-Hispanic women were 87% less likely to be misclassified (p < .001)., Conclusion: Misclassification of prenatal smoking status decreases as pregnancy progresses, though the observed rate change was not significant. Minority women may be at particular risk for non-disclosure of tobacco use. Biochemical validation should be considered when assessing perinatal tobacco use via self-report, given high misclassification rates throughout the perinatal period., Implications: These results demonstrate that regardless of trimester, more than one-quarter of tobacco-using pregnant women may not disclose tobacco use throughout pregnancy and early postpartum. Although the rate of misclassification decreased from first to third trimester and then increased in the immediate postpartum, these changes in misclassification rates were not significant. Minority groups may be at particular risk of misclassification compared with white/non-Hispanic women. Biochemical validation is warranted throughout pregnancy to encourage cessation as tobacco use is one of the most easily-modified risk factors for poor birth outcomes., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15μg/L, 20μg/L, or 24.5μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198μg/kg/day). We determined that a daily intake of 0.45 to 0.50μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25-0.3μg/kg/day. Assuming a drinking water intake rate of 0.033L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6-9.2μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher., (Published by Elsevier Inc.)

Objective: To examine the association between the phthalate exposure in the first trimester and fasting blood glucose level or gestational diabetes mellitus (GDM) in the third trimester in pregnant women. Methods: A total of 3 474 pregnant women, receiving their prenatal examination in Ma' anshan Maternal and Child Health-Care Hospital of Anhui province, were selected from May 2013 to September 2014. Questionnaires were used to collect the information about their socio-demographic characteristics, clinical characteristics and GDM diagnostic results in the first, second and third trimesters. Urine samples and fasting venous blood samples were collected. Concentrations of 7 kinds of phthalate metabolites in urine samples were detected by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS), and multiple linear regression model was used for statistical analyses. Logistic regression analysis on the risk of the first trimester phthalate exposure for GDM in the third trimester was conducted. Results: The prevalence of GDM in this study was 12.8%, monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEHHP) exposure levels were positively correlated with the fasting blood glucose level in the third trimester ( P <0.05), but mono-(2-ethylhexyl) phthalate (MEHP) and mono-(2-ethyl-5-hydroxylhexyl) phthalate (MEOHP) exposure levels were negatively correlated with the fasting blood glucose level in the third trimester ( P <0.05). Stratified analysis showed a positive correlation between MEHHP exposure and the third trimester fasting blood glucose level in both normal group and GDM group. However, MMP, MEP, MBP, MBzP, MEHP and MEOHP exposure levels had influences on the third trimester fasting blood glucose level in normal group but not in GDM group. MMP and MBP exposure might increase the risk of GDM, but MEOHP exposure might reduce the risk of GDM. Conclusion: The phthalate exposure in the first trimester might be associated with the fasting blood glucose level in the third trimester, MMP, MEP, MBP, MBzP and MEHHP concentrations were positively associated with the third trimester blood glucose level, MEHP and MEOHP concentrations were negatively associated with the third trimester blood glucose level. Moreover, the effects of different kinds of phthalates might be different.

Purpose: The aim of this study was to evaluate serum and urinary nephrin levels of normal pregnancy to establish a standard reference value and to compare them with patients who subsequently developed preeclampsia (PE)., Materials and Methods: In this prospective study, 117 healthy singleton pregnancies were enrolled between 6 to 20 weeks of gestation at 2 participating medical centers during October 2010 to March 2012. Urine and serum samples were collected at the time of enrollment, each trimester, and at 4 to 6 weeks postpartum. Enzyme-linked immunosorbent assay for nephrin was performed and samples from patients who subsequently developed PE were compared to the normal patients., Results: Of 117 patients initially enrolled, 99 patients delivered at the study centers and of those patients, 12 (12.1%) developed PE at a median gestational age of 34⁺⁴ weeks (range 29⁺⁵-36⁺⁶). In the normal patients (n=68), serum nephrin level decreased and urinary nephrin level increased during the latter of pregnancy. In 12 patients who subsequently developed PE, a significant rise in the 3rd trimester serum and urinary nephrin levels, compared to the controls, was observed (p<0.001), and this increase occurred 9 days prior to the onset of clinical disease., Conclusion: As the onset of PE was preceded by the rise in the serum and urinary nephrin in comparison to normal pregnancy, serum and urinary nephrin may be a useful predictive marker of PE., Competing Interests: The authors have no financial conflicts of interest.

Objective: The objective of this study was to evaluate the prevalence of late pregnancy nicotine exposures, including secondhand smoke exposures, and to evaluate the associated risk of exposure to drugs of abuse., Study Design: The study was a retrospective single-center cohort analysis of more than 18 months. We compared self-reported smoking status from vital birth records with mass spectrometry laboratory results of maternal urine using a chi-square test. Logistic regression estimated adjusted odds for detection of drugs of abuse based on nicotine detection., Results: Compared with 8.6% self-reporting cigarette use, mass spectrometry detected high-level nicotine exposures for 16.5% of 708 women (P<0.001) and an additional 7.5% with low-level exposures. We identified an increased likelihood of exposure to drugs of abuse, presented as adjusted odds ratios, (95% confidence interval (CI), for both low-level (5.69, CI: 2.09 to 15.46) and high-level (13.93, CI: 7.06 to 27.49) nicotine exposures., Conclusion: Improved measurement tactics are critically needed to capture late pregnancy primary and passive nicotine exposures from all potential sources.

Background and Objective: Angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) play a key role in the pathogenesis of preeclampsia. Uterine artery (UA) blood flow is important for preeclamptic pregnancy outcome, but small amount of evidence suggests UA dopplerometry for preeclampsia diagnostics and management. The aim of our study was to compare the value of angiogenic factors and UA dopplerometry in preeclampsia diagnosis and determine cut-off values to obtain the highest sensitivity and specificity of the parameter., Materials and Methods: We performed a case controlled study of 72 pregnant women with preeclampsia and 72 healthy matched controls. SFlt-1 and PlGF were measured in serum samples, the sFlt-1/PlGF ratio was calculated and UA pulsatility (PI) and resistance (RI) indexes were registered., Results: Significantly higher levels of sFlt-1, sFlt-1/PlGF ratio and mean UAPI and UARI and lower levels of PlGF were found in preeclampsia group when compared to controls. The highest sensitivity and specificity for preeclampsia had SFlt-1/PlGF and PlGF with the cut-off values of ≥35 (sensitivity of 95.8% and specificity of 96.2%, respectively) and ≤138.6pg/mL (sensitivity of 95.8% and specificity of 93.7%, respectively). For diagnostics of early-onset preeclampsia, all factors sFlt-1, PlGF and sFlt-1/PlGF had equal significance with the cut-off values of ≥7572pg/mL (specificity of 97.5%, sensitivity 92.3%), ≤100.5pg/mL (specificity 96.2%, sensitivity of 100%) and ≥54.6 (specificity 97.5%, sensitivity 97.5%) respectively., Conclusions: The sFlt-1/PlGF ratio and PlGF are superior to sFlt-1, UAPI and UARI for preeclampsia diagnosis. For early-onset preeclampsia diagnostics either sFlt-1 or PlGF is sufficient., (Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background: Arsenic has immunomodulatory properties and may have the potential to alter susceptibility to infection in humans., Objectives: We aimed to assess the relation of arsenic exposure during pregnancy with immune function and hepatitis E virus (HEV) infection, defined as seroconversion during pregnancy and postpartum., Methods: We assessed IgG seroconversion to HEV between 1st and 3rd trimester (TM) and 3 months postpartum (PP) among 1100 pregnancies in a multiple micronutrient supplementation trial in rural Bangladesh. Forty women seroconverted to HEV and were matched with 40 non-seroconverting women (controls) by age, parity and intervention. We assessed urinary inorganic arsenic plus methylated species (∑As) (µg/L) at 1st and 3rd TM and plasma cytokines (pg/mL) at 1st and 3rd TM and 3 months PP., Results: HEV seroconverters' urinary ∑As was elevated throughout pregnancy. Non-seroconverters' urinary ∑As was similar to HEV seroconverters at 1st TM but declined at 3rd TM. The adjusted odds ratio (95% confidence interval) of HEV seroconversion was 2.17 (1.07, 4.39) per interquartile range (IQR) increase in average-pregnancy urinary ∑As. Increased urinary ∑As was associated with increased concentrations of IL-2 during the 1st and 3rd TM and 3 months PP among HEV seroconverters but not non-seroconverters., Conclusions: The relation of urinary arsenic during pregnancy with incident HEV seroconversion and with IL-2 levels among HEV-seroconverting pregnant women suggests arsenic exposure during pregnancy may enhance susceptibility to HEV infection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There is inconsistent evidence regarding the effects of prenatal phthalate exposure on children's neuropsychological development. We evaluate the association between prenatal phthalate exposure and the cognitive, psychomotor and behavioral development of 367 children at repeated ages in a prospective birth cohort study. We measured phthalate metabolites (sum of four DEHP metabolites - Σ4DEHP, MBzP, MEP, MiBP and MnBP) in urine samples collected during the 1st and 3rd trimesters of pregnancy in women participating in the INMA-Sabadell birth cohort study. We assessed cognitive and psychomotor development of their children at 1 and 4 years, and social competence, ADHD symptoms and other behavioral problems at 4 and 7 years. No associations were observed between prenatal phthalate exposure and cognitive and psychomotor scores at the age of 1 year and at the age of 4 years, except for an association between MBzP and lower psychomotor scores (β=-1.49 [95% confidence interval (CI)=-2.78, -0.21]). Σ4DEHP concentrations were associated with increased social competence scores at 4 years and with reduced ADHD symptoms at age 4 and 7 years. Increasing MEP concentrations were associated with a reduced risk of inattention symptoms at 4 years. No associations were observed for MBzP, MiBP or MnBP in relation to behavioral problems. This study, with multiple phthalate exposure measurements and measures of neuropsychological domains at different ages, suggest that prenatal phthalate exposure does not adversely affect children's cognitive, psychomotor or behavioral development., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: The purpose of this study was to examine the relationship of phthalates exposure with thyroid function in pregnant women and their newborns., Methods: One hundred and forty-eight Taiwanese maternal and infant pairs were recruited from E-Da hospital in southern Taiwan between 2009 and 2010 for analysis. One-spot urine samples and blood samples in the third trimester of pregnant women and their cord blood samples at delivery were collected. Nine phthalate metabolites in urine were determined by triple quadrupole liquid chromatography tandem mass spectrometry, whereas serum from pregnant women and their cord blood were used to measure thyroid profiles (thyroid-stimulating hormone [TSH], thyroxine, free thyroxine, and triiodothyronine) by radioimmunoassay., Results: Median levels of urinary mono-n-butyl phthalate, mono-ethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate (μg/g creatinine) were the three highest phthalate metabolites, which were 37.81, 34.51, and 21.73, respectively. Using Bonferroni correction at a significance of < 0.006, we found that urinary mono-benzyl phthalate (MBzP) levels were significantly and negatively associated with serum TSH in cord blood (β = -2.644, p = 0.003)., Conclusions: Maternal urinary MBzP, of which the parental compound is butylbenzyl phthalate, may affect TSH activity in newborns. The alteration of thyroid homeostasis by certain phthalates in the early life, a critical period for neurodevelopment, is an urgent concern.

Multiple sclerosis (MScl) frequently is remitted during the third trimester of pregnancy but exacerbated in the first postpartum period. In this context, we investigated protein identification, its abundance, and its change in urine related to these two periods. Using mass spectrometry (LTQ Orbitrap), we identified 1699 tryptic peptides (related to 402 proteins) in urine from 31 MScl and 8 control at these two periods. Pregnancy-related peptides were significantly elevated (p < 0.01) in MScl patients compared with controls (Analysis 1: 531 peptides in MScl and 36 peptides in controls higher abundant in the third trimester compared to postpartum). When comparing the longitudinal differences (Analysis 2), we identified 43 (related to 35 proteins) MScl disease-associated peptides (p < 0.01) with increased or decreased difference ratio in MScl compared with controls. The most discriminating peptides identified were trefoil factor 3 and lysosomal-associated membrane protein 2. Both proteins have a role in the innate immune system. Three proteins with a significant decreased ratio were plasma glutamate carboxypeptidase, Ig mu chain C region, and osteoclast associated immune like receptor. Our results indicate that the protein expression pattern in urine of MScl patients contains information about remote CNS and brain disease processes.

Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed.

Background: Kisspeptin is an arginine-phenylalanine amide peptide hormone critical for reproductive function. Kisspeptin is also abundantly expressed in the placenta, where it has an important physiological role in regulating placental invasion. Accordingly, plasma kisspeptin concentrations rise dramatically during normal pregnancy. However, lower plasma concentrations of kisspeptin are associated with obstetric complications such as pre-eclampsia. It is not currently known whether kisspeptin-immunoreactivity (IR) can be detected in bodily fluids not requiring invasive collection such as saliva or urine., Aim: To determine the clinical utility of urinary and salivary kisspeptin measurement in healthy pregnant women., Methods: Forty-nine healthy third trimester pregnant women (gestational age 34 ± 0.6 w) from a single maternity unit and 50 healthy non-pregnant women were recruited. Urine, saliva and blood were simultaneously collected from all volunteers. Kisspeptin concentrations were determined by in-house manual radioimmunoassay., Results: Mean concentrations of plasma kisspeptin-IR were over 200-fold greater in third trimester pregnant women compared with non-pregnant women (13,783 ± 864 pmol/L, pregnant; 65 ± 13 pmol/L, non-pregnant; p < 0.0001). The urine kisspeptin:creatinine ratio was greater in pregnant women when compared with non-pregnant women (urine kisspeptin:creatinine: 37 ± 6 pmol/µmol, pregnant; 7 ± 1 pmol/µmol, non-pregnant; p < 0.0001). Mean concentrations of salivary kisspeptin-IR were not statistically different between pregnant and non-pregnant women (123 ± 34 pmol/L, pregnant; 83 ± 33 pmol/L, non-pregnant; p = 0.2)., Conclusion: We demonstrate for the first time that kisspeptin-IR is elevated in urine during pregnancy. Urinary measurement of kisspeptin-IR may, therefore, offer a non-invasive and simple method of screening for pregnancy and obstetric complications., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Developmental exposure to phthalates may be associated with adverse health outcomes but information on the variability and predictors of urinary phthalate metabolite concentrations during pregnancy is limited. We evaluated in Spanish pregnant women (n=391) the reproducibility of urinary phthalate metabolite concentrations and predictors of exposure. We measured mono-(4-methyl-7-hydroxyoctyl) phthalate (7-OHMMeOP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-carboxyhexyl) phthalate (MCMHP), mono-benzyl phthalate (MBzP), mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) in two spot urine samples collected in the first and third pregnancy trimesters. Questionnaires on predictors and food-frequency questionnaires were administered in the first and/or third pregnancy trimesters. Using creatinine-adjusted phthalate metabolite concentrations (log10-trasformed) we calculated intraclass correlation coefficients (ICCs). Linear mixed and regression models assessed the associations between predictors and phthalate metabolites. The ICCs ranged from 0.24 to 0.07 and were higher for MBzP, MEP, MiBP, and lower for MEOHP and MEHHP. Overweight, lower education and social class, and less frequent consumption of organic food were associated with higher levels of some phthalate metabolites. The use of household cleaning products (bleach, ammonia, glass cleaners, oven cleaning sprays and degreasing products) at least once per week during pregnancy was associated with 10-44% higher urinary phthalate metabolites. Bottled-water consumption, consumption of food groups usually stored in plastic containers or cans, use of plastic containers for heating food and cosmetic use were not associated with increased concentrations of phthalate metabolites. This large study with repeated phthalate measurements suggests that, in this Spanish setting, sociodemographic and lifestyle factors and household cleaning product use are better predictors of phthalate exposure levels in pregnant women than average water and food consumption and use of plastic containers and cosmetics., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Background: Few studies have shown an association between prenatal phthalate exposure and adverse effects on neurodevelopment and behavior in young children., Objectives: We aimed to assess the relationship between prenatal exposure to phthalate esters and behavior syndromes in children at 8 years of age., Methods: A total of 122 mother-child pairs from the general population in central Taiwan were studied from 2000 to 2009. Mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three di-(2-ethylhexyl) phthalate (DEHP) metabolites-mono-2-ethylhexyl, mono-2-ethyl-5-hydroxyhexyl, and mono-2-ethyl-5-oxohexyl phthalates (MEHP, MEHHP, and MEOHP)--were measured in maternal urine collected during the third trimester of pregnancy using liquid chromatography-electrospray ionization-tandem mass spectrometry. Behavioral syndromes of children at 8 years of age were evaluated using the Child Behavior Checklist (CBCL). Associations between log10-transformed creatinine-corrected phthalate concentrations and standardized scores of the CBCL were estimated using linear regression models or multinomial logistic regressions with adjustments for potential confounders., Results: Externalizing problem scores were significantly higher in association with a 1-unit increase in log10-transformed creatinine-corrected concentrations of maternal MBP (β = 4.29; 95% CI: 0.59, 7.99), MEOHP (β = 3.74; 95% CI: 1.33, 6.15), and MEHP (β = 4.28 ; 95% CI: 0.03, 8.26) after adjusting for the child's sex, intelligence, and family income. Meanwhile, MBP and MEOHP were significantly associated with Delinquent Behavior and Aggressive Behavior scores. The same pattern was found for borderline and/or clinical ranges., Conclusions: Our findings suggest positive associations between maternal DEHP and dibutyl phthalate (DBP) exposure and externalizing domain behavior problems in 8-year-old children.

Background: Pregnancy and postpartum have been associated to several physiological changes; however, empirical evidence was almost exclusively obtained in primiparous women and few studies focus on hormonal changes in men and second-time parents. The main aim of this study is to examine 24-h urinary free cortisol from mid-pregnancy to 3-months postpartum, comparing women/men and first/second-time parents., Methods: Twenty-six women and 22 men (N=48) were recruited from an antenatal obstetric unit in Porto, Portugal. 24-h urinary free cortisol was measured at the 2nd and 3rd trimester and at 3-months postpartum. Repeated measures analyses of variance were conducted, in order to analyze 24-h urinary free cortisol patterns of change over this period. Gender and parity were included in the analyses as potential modifiers, in order to compare women and men, and first- and second-time parents., Results: An increase from the 2nd to the 3rd trimester (p=.006) and a decrease from the 3rd trimester to 3-months postpartum (p=.005) were reported in all parents' 24-h urinary free cortisol. The interaction effects for Time*Gender (p=.03) and Time*Parity (p=.02) were found. Women and first-time parents revealed higher levels, while men and second-time parents showed lower 24-h urinary free cortisol levels at the 2nd trimester than at 3-months postpartum., Conclusions: Findings appear to clarify the direction, as well as, the timing, gender and parity extension of 24-h urinary free cortisol changes from mid-pregnancy to 3-months postpartum. The same pattern of change in all parents' 24-h urinary free cortisol from mid-pregnancy to 3-months postpartum is consistent with the proposed role of hormones in preparation to parenting. Gender and parity differences and effects on 24-h urinary free cortisol are also consistent with cortisol as a stress biomarker for higher challenges associated to pregnancy and childbirth in women and first-time parents versus higher demands related to after childbirth parenting in men and second-time parents., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Seafood consumption provides a significant amount of arsenic, although in its organic, nontoxic forms. Mediterranean populations may incorporate high levels of this metalloid as a consequence of seafood consumption. In the present study, the significance of this input among pregnant women from a Mediterranean city (Sabadell, Catalonia, Spain) is assessed. Total urinary arsenic was analyzed in 489 pairs of urine samples, corresponding to the 12th and 32 th weeks of pregnancy. Association of arsenic content with seafood and other dietary items were studied. Geometric mean concentrations were 34 and 37 μg/g creatinine during the first and third trimesters, respectively. The observed concentrations were similar to those reported in studies from other Mediterranean countries. The differences between both periods were not statistically significant. The only dietary factor significantly and positively associated with total urinary arsenic in both series of samples was seafood, particularly lean fish. Moreover, lean fish consumption during both periods was found to be the main determinant for differences in levels of arsenic between the first and third trimesters, which confirms the association between high levels of total urinary arsenic and seafood consumption.

Background: Preterm birth is a significant public health problem, affecting over 1 in 10 live births and contributing largely to infant mortality and morbidity. Everyday exposure to environmental chemicals such as phthalates could contribute to prematurity, and may be modifiable. In the present study we examine variability in phthalate exposure across gestation and identify windows of susceptibility for the relationship with preterm birth., Methods: Women were recruited early in pregnancy as part of a prospective, longitudinal birth cohort at the Brigham and Women's Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points during gestation for phthalate measurement, and birth outcomes were recorded at delivery. From this population we selected all 130 cases of preterm birth, defined as delivery before 37 weeks of completed gestation, as well as 352 random controls., Results: Urinary phthalate metabolite levels were moderately variable over pregnancy, but levels measured at multiple time points were associated with increased odds of preterm birth. Adjusted odds ratios (aOR) for spontaneous preterm birth were strongest in association with phthalate metabolite concentrations measured at the beginning of the third trimester (aOR for summed di-2-ethylhexyl phthalate metabolites [∑DEHP]=1.33, 95% confidence interval [CI]=1.02, 1.73). Odds ratios for placental preterm birth, defined as delivery with presentation of preeclampsia or intrauterine growth restriction, were slightly elevated in the first trimester for DEHP metabolites (aOR for ∑DEHP=1.33, 95% CI=0.99, 1.78)., Conclusions: Pregnant women with exposure to phthalates both early and late in pregnancy are at an increased risk of delivering preterm, but mechanisms may differ based on etiology., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Prenatal exposure to organophosphate pesticides (OPs) has been associated with adverse neurodevelopmental outcomes in childhood, including low IQ, pervasive developmental disorder (PDD), attention problems and ADHD. Many of these disorders involve impairments in social functioning. Thus, we investigated the relationship between biomarkers of prenatal OP exposure and impaired reciprocal social behavior in childhood, as measured by the Social Responsiveness Scale (SRS). Using a multi-ethnic urban prospective cohort of mother-infant pairs in New York City recruited between 1998 and 2002 (n=404) we examined the relation between third trimester maternal urinary levels of dialkylphosphate (ΣDAP) OP metabolites and SRS scores among 136 children who returned for the 7-9year visit. Overall, there was no association between OPs and SRS scores, although in multivariate adjusted models, associations were heterogeneous by race and by sex. Among blacks, each 10-fold increase in total diethylphosphates (ΣDEP) was associated with poorer social responsiveness (β=5.1 points, 95% confidence interval (CI) 0.8, 9.4). There was no association among whites or Hispanics, or for total ΣDAP or total dimethylphosphate (ΣDMP) biomarker levels. Additionally, stratum-specific models supported a stronger negative association among boys for ΣDEPs (β=3.5 points, 95% CI 0.2, 6.8), with no notable association among girls. Our results support an association of prenatal OP exposure with deficits in social functioning among blacks and among boys, although this may be in part reflective of differences in exposure patterns., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Phthalates and BPA are known endocrine disruptors and exposure in pregnant mothers and children is ubiquitous. We explored the relationship of prenatal and childhood exposures with pubertal onset and sex hormones in boys (ages 8-14). Phthalate metabolites and BPA were measured in maternal 3rd trimester or childhood urine. Sex hormones DHEAS, estradiol, inhibin B, SHBG, and total testosterone were measured in serum. Adrenarche and puberty were assessed by pediatrician. Prenatal exposure to some phthalates was associated with decreased DHEAS and inhibin B levels, and with increased SHBG. Prenatal exposure to most phthalates and BPA was associated with greatly reduced odds of adrenarche (odds ratios [OR]=0.12-0.65) and slightly reduced odds of puberty (OR=0.50-0.98). Childhood exposure was not associated with adrenarche or puberty, but some phthalates and BPA were associated with increased SHBG levels and decreased total and free testosterone levels., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and studied the predictive ability of these three urinary biomarkers. The subjects were recruited between 15-38 weeks of gestation. Fourteen patients, all in the high-risk obstetric group, developed preeclampsia. The levels of podocyturia, nephrinuria, and albuminuria were variably higher in the high-risk pregnant patients who developed preeclampsia. The sensitivities and specificities for podocyturia were 70% and 43%, for albuminuria were 36% and 96%, and for nephrinuria were 57% and 58%, respectively. Also, abnormal nephrinuria (69%) and podocyturia (38%) were detected in low risk women who had uncomplicated gestations; none of these women exhibited albuminuria. In our study, none of the three urinary markers achieved the minimum predictive values required for clinical testing. The lack of excessive albuminuria, however, may indicate a preeclampsia-free gestation. Given a discrepant literature, further studies with larger sample size should be considered.

Objective: Prenatal exposure to organophosphate pesticides can lead to developmental neurotoxicity. A longitudinal birth cohort was established to investigate pesticide exposures from different agricultural activities. Maternal urinary organophosphate metabolites were measured at 28 weeks of pregnancy (n=86), delivery (n=67) and 2 months postpartum (n=51)., Method: Subjects were interviewed with questionnaires about work, home and behavioral factors potentially associated with pesticide exposures, and spot urine samples were also collected. The urine samples were analyzed for dimethyl phosphate (DMP), diethyl phosphate (DEP), diethyl thiophosphate (DETP) and diethyl dithiophosphate (DEDTP), using gas chromatography-mass spectrometry., Results: The urinary DMP and dialkyl phosphate (DAP) concentrations at 28 weeks of pregnancy and delivery were not significantly different, but the DMP and DAP concentrations at 28 weeks of pregnancy and DAP concentrations at delivery were significantly different (p<0.05) from those at 2 months postpartum. The factors influencing the urinary DAP concentrations at 28 weeks of pregnancy included insecticide used in the home, living close to agricultural farmland, frequency of agricultural field visits during the first and second trimesters of pregnancies, occupation of subjects, pesticide used and other agricultural activities., Conclusions: The urinary organophosphate metabolites, DMP, DEP, DETP, DEDTP, total DEP and DAPs, at 28 weeks of pregnancy, delivery and 2 months postpartum fluctuated depending on their pesticide exposures both at home and in agricultural fields.

Prenatal exposure to trace metals, whether they are essential, non-essential, or toxic, must be assessed for their potential health effects in the offspring. Herein is reported an approach to this end which involved collection of urine samples during the first and third trimesters of pregnancy from 489 mothers from Sabadell (Catalonia, Spain), a highly industrialized town. These samples were analyzed for cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), arsenic (As), molybdenum (Mo), cadmium (Cd), antimonium (Sb), cesium (Cs), thallium (Tl), and lead (Pb). An acid digestion method was developed and validated for inductively coupled plasma quadruple mass spectrometry (Q-ICP-MS) analysis of these 12 metals. The median concentrations of metals ranged from 0.13 to 290 μg/g creatinine, the highest levels were found for Zn and the lowest for Th. The mean concentrations of most metals except As, Ni, Th, and Pb showed statistically significant differences between both trimesters. The concentrations of Mo, Se, Cd, Cs, and Sb were higher in the first than in the third trimester, whereas the opposite was found for Co, Cu, and Zn. The concentrations of all metals in both sampling periods showed statistically significant correlations (p<0.01 for Mo and Cu, p<0.001 for the others). The significant correlations of metal urine concentrations in the first and third trimesters of pregnancy suggest that the observed differences between both periods are related to physiological changes. Accordingly, the measured urine concentrations during either the first or third trimesters can be used as estimates of exposure during pregnancy and can serve as markers for prenatal intake of these metals in the studied cohort.

Low iodine intake during pregnancy may cause thyroid dysfunction in pregnant women and their newborn. In the present study, iodine status among a nation-wide representative sample of Belgian pregnant women in the first and third trimester of pregnancy was determined, and determinants of iodine status were assessed 1 year after the introduction of bread fortified with iodised salt. The women were selected according to a multistage proportionate-to-size sampling design. Urine samples were collected and a general questionnaire was completed face to face with the study nurse. The median urinary iodine concentration (UIC) among pregnant women (n 1311) was 124.1mg/l and 122.6 mg/g creatinine when corrected for urinary creatinine. The median UIC in the first trimester (118.3 mg/l) was significantly lower than that in the third trimester (131.0 mg/l) but significantly higher than among non-pregnant women (84.8 mg/l). Iodine-containing supplement intake was reported by 60.8% of the women and 57.4% of the women took this supplement daily. The risk of iodine deficiency was significantly higher in younger women, in women not taking iodine-containing supplements, with low consumption of milk and dairy drinks and during autumn. Women with a higher BMI had a higher risk of iodine deficiency but the risk was lower in women who reported alcohol consumption. The median UIC during pregnancy indicates iodine deficiency in Belgium and some women are at a higher risk of deficiency. The current low iodine intake in women of childbearing age precludes the correction of iodine deficiency in pregnant women supplemented with multivitamins containing 150 mg iodine as recommended.

Adequate maternal iodine intake is essential during pregnancy for the development of the foetus. To assess the extent of iodine insufficiency and its association with household iodized salt in rural Bangladesh, we measured urinary iodine and household salt iodine content among pregnant women in early (≤16 weeks, n = 1376) and late (≥32 weeks, n = 1114) pregnancy. Salt (∼20 g) and a spot urine sample (∼10 mL) were collected from women participating in a randomized, placebo-controlled trial of vitamin A or beta-carotene supplementation in rural northwestern Bangladesh during home visits in early and late pregnancy. Salt iodine was analyzed by iodometric titration, and urinary iodine by the Ohashi method. Almost all salt samples had some detectable iodine, but over 75% contained <15 ppm. Median (interquartile range) urinary iodine concentrations were 66 (34-133) and 55 (28-110) µg L⁻¹ in early and late pregnancy, respectively; urinary iodine <150 µg L⁻¹ was found in ∼80% of women at both times in pregnancy. Although the risk of iodine insufficiency declined with increasing iodine content of household salt (P for trend <0.05), median urinary iodine did not reach 150 µg L⁻¹ until iodine in household salt was at least 32 ppm and 51 ppm during early and late pregnancy, respectively. Despite a national policy on universal salt iodization, salt iodine content remains insufficient to maintain adequate maternal iodine status throughout pregnancy in rural northern Bangladesh. Alternative measures like direct iodine supplementation during pregnancy could be considered to assure adequate iodine status during this high-risk period of life., (© 2010 Blackwell Publishing Ltd.)

Sialic acid storage disease (SASD) is an inborn error resulting from defects in the lysosomal membrane protein sialin. The SASD phenotypical spectrum ranges from a severe presentation, infantile sialic acid storage disease (ISSD) which may present as hydrops fetalis, to a relatively mild form, Salla disease. Screening for SASD is performed by determination of free sialic acid (FSA) in urine or amniotic fluid supernatant (AFS). Subsequent diagnosis of SASD is performed by quantification of FSA in cultured fibroblasts and by mutation analysis of the sialin gene, SLC17A5. We describe simple quantitative procedures to determine FSA as well as conjugated sialic acid in AFS, and FSA in cultured fibroblasts, using isotope dilution ((13)C(3)-sialic acid) and multiple reaction monitoring LC-ESI-MS/MS. The whole procedure can be performed in 2-4 h. Reference values in AFS were 0-8.2 μmol/L for 15-25 weeks of gestation and 3.2-12.0 μmol/L for 26-38 weeks of gestation. In AFS samples from five fetuses affected with ISSD FSA was 23.9-58.9 μmol/L demonstrating that this method is able to discriminate ISSD pregnancies from normal ones. The method was also validated for determination of FSA in fibroblast homogenates. FSA in SASD fibroblasts (ISSD; 20-154 nmol/mg protein, intermediate SASD; 12.9-15.1 nmol/mg, Salla disease; 5.9-7.4 nmol/mg) was clearly elevated compared to normal controls (0.3-2.2 nmol/mg). In conclusion, we report simple quantitative procedures to determine FSA in AFS and cultured fibroblasts improving both prenatal diagnostic efficacy for ISSD as well as confirmatory testing in cultured fibroblasts following initial screening in urine or AFS.

Background: Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects., Objectives: To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project., Methods: One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols., Results: Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education., Conclusions: Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Presence of Bisphenol A (BPA) has been documented worldwide in a variety of human biological samples. There is growing evidence that low level BPA exposure may impact placental tissue development and thyroid function in humans. The aim of this present pilot study was to determine urinary concentrations of BPA during the last trimester of pregnancy among a small subset of women in Mexico City, Mexico and relate these concentrations to risk of delivering prematurely., Methods: A nested case-control subset of 60 participants in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study in Mexico City, Mexico were selected based on delivering less than or equal to 37 weeks of gestation and greater than 37 weeks of gestation. Third trimester archived spot urine samples were analyzed by online solid phase extraction coupled with high performance liquid chromatography isotope dilution tandem mass spectrometry., Results: BPA was detected in 80.0% (N = 48) of the urine samples; total concentrations ranged from < 0.4 μg/L to 6.7 μg/L; uncorrected geometric mean was 1.52 μg/L. The adjusted odds ratio of delivering less than or equal to 37 weeks in relation to specific gravity adjusted third trimester BPA concentration was 1.91 (95%CI 0.93, 3.91, p-value = 0.08). When cases were further restricted to births occurring prior to the 37th week (n = 12), the odds ratio for specific-gravity adjusted BPA was larger and statistically significant (p < 0.05)., Conclusions: This is the first study to document measurable levels of BPA in the urine of a population of Mexican women. This study also provides preliminary evidence, based on a single spot urine sample collected during the third trimester, that pregnant women who delivered less than or equal to 37 weeks of gestation and prematurely (< 37 weeks) had higher urinary concentrations of BPA compared to women delivering after 37 weeks.

Pregnancy is associated with increased oxidative stress, and exaggeration of oxidative damage is considered important in pregnancy complications such as preeclampsia. There is, however, only scattered information regarding the longitudinal change of oxidative stress during pregnancy. We surmised that the placenta is the cause of the increased oxidative stress during pregnancy and hypothesized that the amount of placenta-derived cell-free fetal DNA in maternal plasma is correlated with maternal oxidative stress status. Blood and urine samples were collected at different stages of gestation and 6 to 8 weeks postpartum from 105 women with uncomplicated pregnancies. Additionally, 40 healthy women of reproductive age, but not pregnant, were recruited as controls. All oxidative stress markers, including urinary 8-hydroxydeoxyguanosine (8-OHdG), plasma 8-isoprostane, total antioxidant capacity (TAC), and erythrocyte glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, were increased in the third trimester, and most of them returned to nonpregnant levels postpartum. Furthermore, the DYS14 gene of the Y chromosome was quantified from plasma samples obtained at 26 to 30 weeks' gestation in 54 women who later delivered a male infant. Significant associations were noted between plasma concentrations of the DYS14 gene and the levels of urinary 8-OHdG and plasma 8-isoprostane, suggesting an association between the breakdown of syncytiotrophoblast and maternal oxidative stress during pregnancy.

Objective: An adequate iodine intake during pregnancy is essential for normal development of the foetus. The World Health Organization (WHO) recommends that the median urinary iodine concentration (UIC) in a population of pregnant women should range between 150 and 249 microg/l. The aim of this study was to evaluate iodine status and to examine the main sources of iodine in pregnant women from an apparently iodine-sufficient area., Methods: Six hundred pregnant women in the third trimester completed a food frequency questionnaire, and iodine was measured in urine samples. Urinary iodine concentrations were described in the whole population and in subgroups according to their frequency of intake of milk, fish, eggs, bread and iodized salt, as iodine supplements., Results: The median UIC was 104 microg/l (n = 600), however, the median was higher among women who had a high milk intake (117 microg/l), used iodized salt (117 microg/l) or who were supplemented with iodine (141 microg/l). Women receiving iodine supplementation who also consumed more than one cup of milk per day had median UIC higher than 150 microg/l. In multivariate models, women with moderate and high milk intake had lower risk of having UIC below 150 microg/l [OR (95% CI): 0.42 (0.22-0.82) and 0.29 (0.15-0.55) respectively], after adjustment for potential confounders., Conclusions: On the basis of WHO criteria, the iodine status of pregnant women was inadequate in this area. Milk was the most important dietary source of iodine, and iodine supplementation was also an important source of iodine, although not enough to reach the current recommendations.

Objective: To characterise the haemodynamic, renal-electrolyte and hormonal parameters in normal near-term pregnancy., Design: Observational prospective case-series study., Setting and Population: Eleven women with normal pregnancies at 35-39 weeks gestation., Methods: Following baseline laboratory assessments and placement of a right-atrial catheter, serial measurements were obtained for 2 hours in the supine position (SP) followed by a change to the (LLP) and subsequent observations for 2 hours., Main Outcome Measures: Blood pressure (BP), central venous pressure (CVP), atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone (ALDO), diuresis, creatinine clearance, sodium and potassium excretion., Results: In the SP, the subjects' BP remained stable while their CVP decreased. In the LLP, the subjects' systolic and diastolic BP consistently decreased by about 15 mmHg and their CVP increased within the first 60 minutes. ANP levels doubled in the subjects while they rested in the LLP, whereas the subjects' PRA and ALDO levels decreased by half compared with when they rested in the SP. In the LLP, the subjects' creatinine clearance significantly increased by 12% and their sodium excretion and diuresis increased by 38% and 59% respectively., Conclusion: Rest in the LLP induces systemic and intra-renal haemodynamic and hormonal changes that may play a central physiological role in the renal excretory response to restore excessive sodium/water retention in late pregnancy.

We investigated the relationship between prenatal maternal urinary concentrations of phthalate metabolites and neonatal behavior in their 295 children enrolled in a multiethnic birth cohort between 1998 and 2002 at the Mount Sinai School of Medicine in New York City. Trained examiners administered the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) to children within 5 days of delivery. We measured metabolites of 7 phthalate esters in maternal urine that was collected between 25 and 40 weeks' gestation. All but two phthalate metabolites were over 95% detectable. We summed metabolites on a molar basis into low and high molecular weight phthalates. We hypothesized the existence of sex-specific effects from phthalate exposure a priori given the hormonal activity of these chemicals. Overall we found few associations between individual phthalate metabolites or their molar sums and most of the BNBAS domains. However, we observed significant sex-phthalate metabolite interactions (p<0.10) for the Orientation and Motor domains and the overall Quality of Alertness score. Among girls, there was a significant linear decline in adjusted mean Orientation score with increasing urinary concentrations of high molecular weight phthalate metabolites (B=-0.37, p=0.02). Likewise, there was a strong linear decline in their adjusted mean Quality of Alertness score (B=-0.48, p<0.01). In addition, boys and girls demonstrated opposite patterns of association between low and high molecular weight phthalate metabolite concentrations and motor performance, with some indication of improved motor performance with increasing concentration of low molecular weight phthalate metabolites among boys. This is the first study to report an association between prenatal phthalate exposure and neurological effects in humans or animals, and as such requires replication.

Measurement of osmolality of biological liquids is particular importance for value osmoregulation. The aim of our research was measuring osmolality of blood serum and urine by using fundamentally new measuring method of osmolality; method allows decreasing the quantitative data of osmolar gap. The study was conducted on 44 patients with cardiac insufficiency and 77 women in the III term of pregnancy under the test of Zimnicki. Osmolality of biological liquids - blood serum and urine was measured by using fundamentally new method - new conductance-measuring method of osmolality. The method is based on the total specific electroconductivity of available electrolytes in the liquid to be measured. The electrical scheme and methodical rule of this method is based on the two patents about measurement osmolality, those patents are received by G. Gelbakhiani (#1521039 and #4719485/14). This method implies to measure the total sum of electrolytes all dissolved salts in the biological liquids. By this way this method allows to measure blood and urine osmolality with high precision, which reduces osmolar gap.

Background: Post-partum thyroiditis (PPT) is an autoimmune disorder occurring within the first year following delivery. A variable prevalence has been reported in different surveys. We prospectively evaluated PPT prevalence and outcome in a cohort of pregnant women living in a well-defined geographic area., Aim: A subset from a group of healthy women consecutively evaluated for thyroid function and thyroid autoimmunity during pregnancy, referring to the same obstetric unit, were followed up at 4-6 months and 1 yr after delivery., Materials/subjects and Methods: Follow-up for PPT was performed in 258 pregnant women. Control data were obtained in a comparable group of healthy non-pregnant women. Free T3 (fT3), free T4 (fT4), TSH thyroglobulin/thyroid peroxidase autoantibodies (TgAb/TPOAb), and urinary iodine excretion were measured., Results: Autoantibody positivity was observed in 9.3% of pregnant, similar to control women. Forty-three out of 59 autoantibody-positive women were followed up; 23 showed PPT at the first control, 18 had hypothyroidism at 1 yr (5 had not shown PPT at the first control). Among 215 out of 584 autoantibody-negative women followed up, 27 developed PPT (15 of them without thyroid autoantibodies); 16 developed thyroid autoantibodies without PPT. After 1 yr, 9 women had hypothyroidism: only 1 of them was autoantibody-negative at the former control. Urinary iodine was increased in several pregnant women., Conclusions: An overall PPT prevalence of about 18% may be estimated. PPT was also observed in autoantibody- negative women. Differences with other surveys may be related to both study protocol and characteristics of the population studied.

Background: Many phthalates and phenols are hormonally active and are suspected to alter the course of development., Objective: We investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth., Methods: We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth., Results: Median urinary concentrations were > 10 microg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07-1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (-210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys., Conclusions: We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.

Unlabelled: Up to now, little has been known about iodine intake and the prevalence of iodine deficiency (ID), if any, in Kuwait. Urinary iodine excretion (UIE) and changes in thyroid function during pregnancy were thus evaluated., Methods: Urinary iodide level was measured in random urine samples collected from 326 pregnant women at different gestational trimesters. Blood samples were drawn for free T4 (FT4) and TSH level determination., Results: Median UIE levels fall within the normal range during all gestational trimesters i.e. >100 microg/l. However, if the new suggested recommendation for pregnant women <140 microg/l, is applied, median UIE values during trimesters 2 and 3 indicate ID. Mean serum TSH levels increased between trimesters 1 and 3 (p<0.05), whereas serum FT4 decreased between first and second trimesters (p<0.05), and this reduction continued at the third trimester. Furthermore, an increase in TSH levels for subjects with mild and moderate ID (Mi and Mo, respectively) were noticed (p<0.05) during the second trimester. However, FT4 levels dropped in subjects with Mi and Mo ID during the first trimester (p<0.05). In conclusion, these results suggest that 56.8% of pregnant women had median UIE level <145 microg/l, associated with high TSH and low FT4 levels., Conclusion: Data obtained may indicate insufficient iodine intake among pregnant women in Kuwait.

Objective: To assess intertrimester and seasonal variations in urinary iodine concentration (UIC) among pregnant women., Patients and Measurements: Pregnant Tehranian women, with no history of thyroid ablation or consumption of thyroid-affecting medication were selected consecutively from November 2004 to November 2006. Morning spot urine samples were collected from each participant during the first, second and third trimesters of pregnancy. Of 466 participants, 298 completed the study in all three trimesters of pregnancy. UIC < 150, 150-250, and > 250 microg/l indicated low, adequate, and high levels, respectively. UIC was measured using a modified Sandell-Kolthoff digestion method., Results: The pregnant women were aged 25.0 +/- 5.0 (range 16-48) years. Median UIC did not show seasonal fluctuations during pregnancy. However, median (range) UIC was 193 (19-840), 159 (16-640), and 141 (16-400) microg/l in the first, second and third trimesters of pregnancy, respectively (P < 0.0001). Frequency distributions of low, adequate and excessive UIC were 33.2, 31.2 and 35.6% in the first trimester, 46.0, 28.9 and 25.2% in the second trimester, and 53.4, 30.9 and 15.8% in the third trimester of pregnancy, respectively (P < 0.0001). Women with UIC < 150 were more frequently represented in the second vs. the first (P = 0.043; odds ratio 1.49, 95% confidence interval 1.012-2.213) and in the third vs. the first (P = 0.013; odds ratio 1.62, 95% confidence interval 1.108-2.379) trimesters of pregnancy than the 150-250 microg/l group were. UIC decreased throughout pregnancy in all seasons., Conclusions: Iranian national salt iodization may prevent seasonal fluctuations of UIC but does not maintain median UIC within adequate and recommended ranges throughout pregnancy. Extra iodine supplementation during pregnancy is recommended.

Urinary Iodine excretion is a useful and important indicator of the iodine status of a population. This study attempts to determine the urinary iodine concentration of non-pregnant, pregnant and lactating women, resident in the National Capital District of Papua New Guinea, so as to evaluate their status of iodine nutrition. The study population was made up of 56 non-pregnant, 40 lactating and 212 pregnant women. Of the 212 pregnant women, 14 were in the first, 64 in the second, and 134 in the third Trimester of pregnancy. Casual urine samples were collected and analysed for urinary iodine by Sandell-Kolthoff reaction. The median urinary iodine concentration for the non-pregnant, lactating and pregnant women was 163.0 micro g/L, 134.0 micro g/L and 180.0 micro g/L, respectively. Median urinary iodine for the first, second and third trimesters were 165.0 micro g/L, 221.5 micro g/L and 178.0 micro g/L, respectively. The 20th percentile urinary iodine values were higher than 50 micro g/L for all the groups. This indicates adequate intake of dietary iodine and optimal status of iodine nutrition amongst women in the various groups. Mild to severe status of iodine nutrition was found in 30.4% of non-pregnant, 35.0% of lactating, 22.2% of pregnant women, 28.5% of women in the first, 18.8% in the second, and 23.1% in the third trimester of pregnancy. To achieve optimal iodine nutrition in pregnant and lactating women, an increase in their intake of dietary iodine is recommended.

Objectives: We assessed the effect of freezing on fragmentation of fetal DNA in maternal plasma and differences in DNA fragmentation between plasma and urine from pregnant women., Methods: 1. We prepared seven kinds of real-time PCR assays to amplify different-sized amplicons targeting the SRY gene. Fragmentation of fetal DNA in maternal plasma was compared between new (n=10) and 4-year-old samples (n=10). 2. To investigate differences in fragmentation of fetal DNA between plasma and urine from pregnant women, we amplified three different-sized amplicons and compared DNA fragmentation between plasma and urine (n=7)., Results: 1. Relative concentrations of fetal DNA compared to a 63-bp amplicon in new samples were 53.1, 42.0, 9.2 and 2.0% (median) for PCR amplicons of 107, 137, 193 and 313 bp, respectively. Concentrations in 4-year-old samples were 70.4, 40.9, 11.9 and 2.3%, respectively. 2. Although fetal DNA in urine was not detected for 107- and 137-bp amplicons of the SRY sequence, fetal DNA using a 63-bp amplicon was detectable in five of seven cases (71.4%)., Conclusion: Cell-free fetal DNA in maternal plasma is stable under cryopreservation at -20 degrees C for at least 4 years. Approximately, 60% of fetal DNA in maternal plasma was fragmented to <100-bp long, and fetal DNA in urine was further fragmented. Maternal urine may be usable for detection of fetal DNA, although smaller target size is more important for PCR amplification of fetal DNA in urine than in the analysis of plasma from pregnant women., (Copyright (c) 2005 John Wiley & Sons, Ltd.)