Iodine monitoring models contribute to avoid adverse birth outcomes related more than adequate iodine intake.

BACKGROUND: Iodine plays an important role in pregnancy. How to maintain adequate iodine intake amongst pregnant women in each trimester of pregnancy to prevent adverse birth outcomes in central China is a challenge for clinical practice. METHODS: 870 pregnant women and their infants were enrolled in the study. Urinary iodine concentration (UIC) was measured using an inductively coupled plasma mass spectrometry (ICP-MS). Maternal and newborn information were obtained during follow-up. Multinomial logistic regression models were established. RESULTS: Median UIC of pregnant women was 172 ± 135 µg/L which is currently considered to be sufficient. Multivitamin supplements containing iodine, iodized salt intake and frequent milk intake were significantly associated with higher UIC. Multivariate logistic regression analysis showed that multivitamin supplements containing iodine and milk consumption were risk factors for more than adequate iodine (UIC ≥ 250 µg/L). Iodine-rich diet was significantly related to heavier birthweight, larger head circumference and longer femur length of the newborns while more than adequate iodine intake (UIC ≥ 250 µg/L) was a risk factor for macrosomia. Logistic regression models based on potential risk factors involving iodine containing supplements and iodine-rich diet were established to predict and screen pregnant women with high risk of more than adequate iodine intake among local pregnant women in different trimesters and guide them to supplement iodine reasonably to prevent the risk. CONCLUSIONS: Multivitamin supplements containing iodine and milk consumption were risk factors for maternal UIC ≥ 250 µg/L which was a risk factor for macrosomia. Iodine monitoring models were established to provide guidance for pregnant women to reduce the risk of more than adequate iodine intake, thereby contributing to reduce the risk of having a macrosomia.

Trimester-Specific Thyroid Function in Pregnant Women with Different Iodine Statuses.

OBJECTIVES: To explore trimester-specific thyroid function changes under different iodine statuses throughout pregnancy. METHODS: A cross-sectional study was conducted to assess the pregnancy iodine status, and 2,378 healthy pregnant women covering all 3 trimesters were recruited. Urinary iodine concentration (UIC) was measured by collecting spot urine samples. Blood samples were collected to evaluate thyroid function. Thyroid B-ultrasonography was conducted to measure the thyroid volume (Tvol). RESULTS: The median UIC was 168 µg/L (111-263 µg/L). The UIC, free triiodothyronine (FT3), and free thyroxine (FT4) were significantly decreased as the pregnancy progressed (p < 0.001, p for trend <0.001), while Tvol increased (p < 0.001, p for trend <0.001). Thyrotropin (TSH) was significantly different between the 3 trimesters and showed an upward trend (p < 0.001), but the p for trend was not significant (p for trend = 0.88). After stratification by UIC, there were no significant differences in serum TSH, FT4, or FT3 level between UIC groups. Tvol was significantly higher in the UIC ≥500 µg/L group in the first trimester (ß: 2.41, 95% CI: 1.09-3.72, p <0.001), as well as in the 250 ≤ UIC < 500 µg/L group (ß: 1.65, 95% CI: 0.61-2.70, p < 0.001) and UIC ≥500 µg/L group (ß: 3.35, 95% CI: 1.96-4.74, p < 0.001) in the third trimester. CONCLUSIONS: No difference was observed in TSH, FT3, or FT4 among the different iodine status groups throughout pregnancy. Tvol increased as the pregnancy progressed, and it was especially higher in the UIC ≥500 µg/L group in the first and third trimesters.

Relationship of household cooking salt and eating out on iodine status of pregnant women in environmental iodine-deficient coastal areas of China.

As city residents eat out more frequently, it is unknown that if iodised salt is still required in home cooking. We analysed the relationship of household salt and eating out on urinary iodine concentration (UIC) in pregnant women. A household condiment weighing method was implemented to collect salt data for a week. A household salt sample was collected. A urine sample was taken at the end of the week. Totally, 4640 participants were investigated. The median UIC was 139·1 µg/l in pregnant women and 148·7, 140·0 and 122·9 µg/l in the first, second and third trimesters. Median UIC in the third trimester was lower than in the other trimesters (P < 0·001). The usage rates of iodised (an iodine content ≥ 5·0 mg/kg) and qualified-iodised (an iodine content ≥ 21·0 mg/kg) salt were 73·9 and 59·3 %. The median UIC in the qualified-iodised salt group was higher than in the non-iodised group (P = 0·037). The median UIC in the non-iodised group who did not eat out was lower than in qualified-salt groups who both did and did not eat out (P = 0·007, <0·001). The proportion of qualified-iodised salt used in home cooking is low, but foods eaten out have universal salt iodisation according to the national compulsory policy. Household iodised salt did not play a decisive role in the iodine status of pregnant women. Pregnant women in their third trimester who are not eating out and using non-iodised salt at home require extra iodine.

A cross-sectional research of iodine status of pregnant women in Chongqing, south-west China.

OBJECTIVE: To investigate whether implementation of a universal salt iodization (USI) programme has sufficient effects on pregnant women in Chongqing, the present study evaluated the iodine nutritional status of pregnant women living in Chongqing by spot urinary iodine concentration (UIC), to provide scientific suggestions to better meet the specific iodine needs of this vulnerable group. DESIGN: Cross-sectional design. SETTING: A random spot urine sample and household table salt sample were provided by each participant. PARTICIPANTS: A total of 2607 pregnant women from twenty-six of thirty-nine districts/counties in Chongqing participated. RESULTS: The overall median UIC of pregnant women was 171·80 µg/l (interquartile range (IQR) = 113·85-247·00 µg/l) and 40·97 % (n 1057) of participants were iodine insufficient. The median iodine in table salt samples was 25·40 mg/kg (IQR = 23·10-28·30 mg/kg); 93·26 % (n 2406) of samples examined were found to be adequately iodized. Iodine nutritional status was not significantly different according to table salt iodization category. Trimester was identified to be statistically associated with UIC (P < 0·01). Seven districts/counties had median UIC below 150 µg/l and one district had median UIC of 277·40 µg/l. CONCLUSIONS: The USI programme in Chongqing prevents iodine deficiency generally, but does not maintain iodine status within adequate and recommended ranges throughout pregnancy. Usage of non-iodized or unqualified iodized salt and the slight change of dietary habits of iodized salt in Chongqing may present a substantial challenge to fight iodine-deficiency disorders; more efforts are needed to ensure adequate iodine intake during pregnancy besides the USI programme.

Reference Intervals for Urine Sediment Analysis of Healthy Pregnant Women.

BACKGROUND: Urine sediment parameters of pregnant women are different from those of non-pregnant women, and it is necessary to establish reference intervals for pregnant women. The aim of this study was to establish reference intervals of white blood cell (WBC), red blood cell (RBC), bacteria (BACT), squamous epithelial cell (EC), small round epithelial cell (SRC), and mucous strands (MUS) for urine sediment test of pregnant women using a UF-1000i analyzer as the detection device. The differences between pregnant women and non-pregnant women in terms of the aforementioned parameters as well as the differences of such parameters in different trimesters of pregnancy were clarified. METHODS: The experimental subjects were divided into two groups: the experiment group (612 healthy pregnant women) and the control group (582 healthy non-pregnant women). Subjects of both groups are women between the age of 22 and 46. The urine specimens were analyzed using the Sysmex UF-1000i analyzer, followed by manual correction. A statistical analysis was performed by SPSS 22.0. Results were considered significant at p < 0.01. RESULTS: The pregnancy reference intervals of WBC, RBC, BACT, EC, SRC, and MUS were 0 ~ 30/µL, 0 ~ 23/µL, 0 ~ 698/µL, 0 ~ 28/µL, 0 ~ 8/µL, and 0 ~ 3/µL, respectively. In the experiment group, the concentrations of WBC, BACT, EC, and SRC were significantly higher than those of the control group (p < 0.01), while the concentrations of RBC and MUS were significantly lower than those of the control group (p < 0.01). The inter-trimester differences in terms of the concentrations of WBC, BACT, EC, and SRC were statistically indistinguishable (p > 0.05). However, the concentration of RBC was significantly lower with the increase of trimester of pregnancy (the comparison between the first trimester with the second trimester: p = 0.000 < 0.01; the comparison between the second trimester and the third trimester: p = 0.004 < 0.01). The WBC, BACT, EC, and SRC had moderate intercorrelations (0.569 ~ 0.681, p < 0.01). CONCLUSIONS: There were significant differences in the aforementioned parameters between the two groups. The intervals of WBC, RBC, BACT, EC, SRC, and MUS for urine sediment analysis of healthy pregnant women using a UF-1000i should be established.

Iodine deficiency among pregnant women living in Northern Ireland.

OBJECTIVE: Mild iodine deficiency has re-emerged among school girls in the UK. We wished to study a contemporaneous pregnant population because a relationship between maternal iodine deficiency and offspring cognitive scores has recently been reported. The WHO has set a median population urinary iodine concentration (UIC) of ≥100 and ≥150 µg/L to define adequacy outside of and during pregnancy, respectively. Iodine creatinine ratio (ICR) is also used to correct for dilution effects (sufficiency ≥150 µg/g creatinine in pregnancy). DESIGN AND METHODS: A total of 241 women were followed across trimesters (T) into the postpartum period (PPP) along with 80 offspring with spot urine sampling and food frequency questionnaires. RESULTS: Median UIC was 73 µg/L in the 1st T (ICR 102 µg/g creatinine) despite 55% taking iodine-containing supplements. Median UICs were 94, 117 and 90 µg/L in the 2nd T, 3rd T and PPP, respectively. Corresponding ICRs were 120, 126 and 60 µg/g creatinine. ICR was associated with volume of milk consumed throughout pregnancy. Median UIC among the offspring was 148 µg/L, with no difference between the breast- and formula-fed babies. CONCLUSIONS: Pregnant women living in Northern Ireland may be at risk of iodine deficiency across pregnancy and into the PPP while the offspring are iodine sufficient. This is the first study of its kind in the UK with data for pregnant women and their offspring. The UK does not provide an iodine fortification programme nor offer routine iodine dietary advice in pregnancy and this requires consideration by public health agencies.

Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data.

CONTEXT: Although the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established. OBJECTIVE: To study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability. DESIGN: Meta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively. SETTING: General community. PARTICIPANTS: 6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancies, fertility treatment, medication affecting the thyroid, and preexisting thyroid disease. MAIN OUTCOME MEASURE: Child nonverbal and verbal IQ assessed at 1.5 to 8 years of age. RESULTS: There was a positive curvilinear association of urinary iodine/creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat <150 µg/g was not associated with lower nonverbal IQ (-0.6 point; 95% CI: -1.7 to 0.4 points; P = 0.246) or lower verbal IQ (-0.6 point; 95% CI: -1.3 to 0.1 points; P = 0.082). Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation. CONCLUSIONS: Fetal brain development is vulnerable to mild to moderate iodine deficiency, particularly in the first trimester. Our results show that potential randomized controlled trials investigating the effect of iodine supplementation in women with mild to moderate iodine deficiency on child neurodevelopment should begin supplementation not later than the first trimester.

Early pregnancy bisphenol and phthalate metabolite levels, maternal hemodynamics and gestational hypertensive disorders.

STUDY QUESTION: Are early-pregnancy urinary bisphenol and phthalate metabolite concentrations associated with placental function markers, blood pressure (BP) trajectories during pregnancy and risk of gestational hypertensive disorders? SUMMARY ANSWER: Early-pregnancy bisphenols and phthalate metabolites were not consistently associated with maternal BP changes or gestational hypertensive disorders, but subclinical, statistically significant associations with placental angiogenic markers and placental hemodynamics were identified. WHAT IS KNOWN ALREADY: In vitro studies suggest that bisphenols and phthalate metabolites may disrupt early placental development and affect the risk of gestational hypertensive disorders. Previous studies investigating effects of bisphenols and phthalate metabolites on gestational hypertensive disorders reported inconsistent results and did not examine placental function or BP throughout pregnancy. STUDY DESIGN, SIZE, DURATION: In a population-based prospective cohort study, bisphenol and phthalate metabolite concentrations were measured in a spot urine sample in early pregnancy among 1396 women whose children participated in postnatal follow-up measurements. PARTICIPANTS/MATERIALS, SETTING, METHODS: After exclusion of women without any BP measurement or with pre-existing hypertension, 1233 women were included in the analysis. Urinary bisphenol and phthalate metabolite concentrations were measured in early-pregnancy [median gestational age 13.1 weeks, inter-quartile range 12.1-14.5]. Molar sums of total bisphenols and of low molecular weight phthalate, high molecular weight (HMW) phthalate, di-2-ethylhexylphthalate, and di-n-octylphthalate metabolites were calculated. Placental angiogenic markers (placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt)-1), placental hemodynamic function measures (umbilical artery pulsatility index (PI), uterine artery resistance index (RI), notching and placental weight), and maternal BP were measured in different trimesters. Information on gestational hypertensive disorders was obtained from medical records. MAIN RESULTS AND THE ROLE OF CHANCE: Each log unit increase in HMW phthalate metabolites was associated with a 141.72 (95% CI: 29.13, 373.21) higher early pregnancy sFlt-1/PlGF ratio (range in total sample 9-900). This association was driven by mono-[(2-carboxymethyl)hexyl]phthalate. In the repeated measurements regression models, each log unit increase in bisphenol A was associated with a 0.15 SD (95% CI: 0.03, 0.26) higher intercept and -0.01 SD (95% CI: -0.01, -0.00) decreasing slope of the umbilical artery PI Z-score and a -1.28 SD (95% CI: -2.24, -0.33) lower intercept and 0.06 SD (95% CI: 0.02, 0.11) increasing slope of the uterine artery RI Z-score. These associations remained significant after Bonferroni correction. Early-pregnancy bisphenols or phthalate metabolites showed no consistent associations with any other outcome. LIMITATIONS, REASONS FOR CAUTION: Information on a large number of potential confounders was available but was partly self-reported. Bisphenols and phthalate metabolites, which typically have a half-life of 24-48 h, were measured via single spot urine samples in early-pregnancy. In addition, at the current sample size, the study was powered to detect an odds ratio of 1.57 for gestational hypertension and 1.78 for pre-eclampsia, but was underpowered to perform multivariable analyses for these outcomes. Further studies combining data from different cohorts may be necessary to increase power. These limitations are possible sources of non-differential misclassification leading to bias toward the null. WIDER IMPLICATIONS OF THE FINDINGS: Bisphenols and phthalate metabolites were not associated with longitudinal changes in BP in pregnancy in our low-risk population. The observed subclinical associations of phthalates with the sFlt-1/PlGF ratio and of bisphenol A with placental hemodynamics may contribute to adverse pregnancy outcomes. Our results are therefore more supportive of an association of early pregnancy bisphenols and phthalate metabolites with risk for pre-eclampsia than with gestational hypertension. STUDY FUNDING/COMPETING INTEREST(S): This analysis was supported by Grant (ES022972) from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors report no conflicts of interest.

Maternal urinary benzophenones and infant birth size: Identifying critical windows of exposure.

Benzophenones (BPs) are widely used as ultraviolet absorbers and fragrance retention agents. Evidences from animal studies have suggested that exposure to BPs may affect fetal growth, but human data is limited and no study is concerning critical windows of BPs exposure throughout pregnancy in relation to fetal growth. We aimed to investigate the associations of prenatal exposure to BPs with birth size and examine the critical exposure windows of fetus development. We measured BPs (including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-hydroxybenzophenone (4-OH-BP)) in maternal urine samples collected in the first, second, and third trimester from 847 mothers recruited in Wuhan, China. The general estimation equations were used to analyze the relationships between maternal exposure to BPs levels and birth size. In all newborns, we found each log unit increase in maternal urinary concentrations of BP-1 and 4-OH-BP in the 1st trimester were associated with decreases in birth length by 0.06 cm (95% confidence interval (CI): -0.11, -0.01) and 0.08 cm (95% CI: -0.15, -0.01), respectively, but only the association with BP-1 in the boys remained significant in the stratified analysis by infant sex. In girls, urinary concentrations of BP-1 and BP-3 in the 3rd trimester were associated with decreased birth weight (adjusted ß = -27.99 g, 95% CI: -50.66, -5.31 and -19.75 g, 95% CI: -37.31, -2.19, respectively) and length (adjusted ß = -0.08 cm, 95% CI: -0.17, 0.00 and -0.08 cm, 95% CI: -0.15, -0.02) (p for interaction = 0.04). Our findings indicate that maternal urinary levels of BPs in the early and late periods during pregnancy may have impacts on delayed fetal growth, and the effects were more pronounced in girls.

Normal pregnancy induced glucose metabolic stress in a longitudinal cohort of healthy women: Novel insights generated from a urine metabolomics study.

During normal pregnancy, mothers face a unique physiological challenge in the adaptation of glucose metabolism in preparation for the metabolic stress presented by fetal development. However, the responsible mechanism remains elusive. The purpose of this study is to investigate the mechanism of the metabolic stress of glucose metabolism in pregnant women using metabolomics method.A Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometer-based untargeted metabolomics study was performed to investigate the dynamic urinary signature of the intermediates of glucose metabolism in a longitudinal cohort of 232 healthy pregnant women in their first, second, and third trimesters.Twelve glucose metabolic intermediates were screened out from hundreds of candidate metabolites using partial least squares discriminant analysis models. These 12 markers were mainly involved in the metabolic pathways of insulin resistance, glycolysis/gluconeogenesis, tricarboxylic acid cycle, nonabsorbable carbohydrate metabolism, and N-glycan biosynthesis. In particular, L-acetylcarnitine, a metabolite that is beneficial for the amelioration of insulin resistance, decreased in a time-dependent manner during normal pregnancy. Moreover, thiamine pyrophosphate, an intermediate product of glycolysis/gluconeogenesis, significantly increased in the second trimester, and argininosuccinic acid and oxalosuccinic acid, intermediates involved in the tricarboxylic acid cycle, significantly decreased in the third trimester, suggesting an increased glucose demand in the maternal body during fetal development.These findings provide novel insight into the normal pregnancy-induced elevation of insulin resistance and glycolysis/gluconeogenesis, as well as the observed reduction in the aerobic oxidation of glucose.

Urinary angiotensinogen excretion in Australian Indigenous and non-Indigenous pregnant women.

The intrarenal renin-angiotensin system (iRAS) is implicated in the pathogenesis of hypertension, chronic kidney disease and diabetic nephropathy. Urinary angiotensinogen (uAGT) levels reflect the activity of the iRAS and are altered in women with preeclampsia. Since Indigenous Australians suffer high rates and early onset of renal disease, we hypothesised that Indigenous Australian pregnant women, like non-Indigenous women with pregnancy complications, would have altered uAGT levels. The excretion of RAS proteins was measured in non-Indigenous and Indigenous Australian women with uncomplicated or complicated pregnancies (preeclampsia, diabetes/gestational diabetes, proteinuria/albuminuria, hypertension, small/large for gestational age, preterm birth), and in non-pregnant non-Indigenous women. Non-Indigenous pregnant women with uncomplicated pregnancies, had higher uAGT/creatinine levels than non-Indigenous non-pregnant women (P < 0.01), and levels increased as pregnancy progressed (P < 0.001). In non-Indigenous pregnant women with pregnancy complications, uAGT/creatinine was suppressed in the third trimester (P < 0.01). In Indigenous pregnant women with uncomplicated pregnancies, there was no change in uAGT/creatinine with gestational age and uAGT/creatinine was lower in the 2nd and 3rd trimesters than in non-Indigenous pregnant women with uncomplicated pregnancies (P < 0.03, P < 0.007, respectively). The uAGT/creatinine ratios of Indigenous women with uncomplicated or complicated pregnancies were the same. A decrease in uAGT/creatinine with advancing gestational age was associated with increased urinary albumin/creatinine, as is seen in preeclampsia, but it was not specific for this disorder. The reduced uAGT/creatinine in Indigenous pregnant women may reflect subclinical renal dysfunction which limits the ability of the kidney to maintain sodium balance and could indicate an increased risk of pregnancy complications and/or future renal disease.

Dietary determinants of urinary molybdenum levels in Mexican women: a pilot study.

OBJECTIVE: This study determined the main dietary sources of urinary molybdenum (Mo) concentrations in a sample of 124 pregnant women in Mexico. MATERIALS AND METHODS: Dietary data was collected during pregnancy, through a semi-qualitative food frequency questionnaire, with information of 84 foods. Urine Mo levels were determined by atomic absorption spectrometry, for at least two trimesters of pregnancy. The associations with Mo levels were estimated by generalized mixed effect regression models. RESULTS: Between 5.8 to 12.7% of the samples were above the 95th percentile of urinary Mo distribution reported by National Health and Nutrition Examination Survey (NHANES) 2009-2010 for women (151 µg/L and 148 µg/g creatinine). After bootstrap resampling was conducted, women with high-consumption of hot peppers (ß=1.34µg/g; 95% CI: 1.00-1.80; p= 0.05) had marginally higher urinary Mo concentration levels, creatinine adjusted, compared to women with low-consumption. CONCLUSION.: Hot chili pepper consumption may contribute to body burden Mo levels in this population.

Dietary determinants of urinary molybdenum levels in Mexican women: a pilot study / Determinantes dietéticos de molibdeno urinario en mujeres mexicanas: un estudio piloto

Abstract: Objective: This study determined the main dietary sources of urinary molybdenum (Mo) concentrations in a sample of 124 pregnant women in Mexico. Materials and methods: Dietary data was collected during pregnancy, through a semi-qualitative food frequency questionnaire, with information of 84 foods. Urine Mo levels were determined by atomic absorption spectrometry, for at least two trimesters of pregnancy. The associations with Mo levels were estimated by generalized mixed effect regression models. Results: Between 5.8 to 12.7% of the samples were above the 95th percentile of urinary Mo distribution reported by National Health and Nutrition Examination Survey (NHANES) 2009-2010 for women (151 μg/L and 148 μg/g creatinine). After bootstrap resampling was conducted, women with high-consumption of hot peppers (β=1.34μg/g; 95% CI: 1.00-1.80; p= 0.05) had marginally higher urinary Mo concentration levels, creatinine adjusted, compared to women with low-consumption. Conclusion. Hot chili pepper consumption may contribute to body burden Mo levels in this population.

Resumen: Objetivo: Determinar las fuentes dietéticas de molibdeno (Mo) urinario en 124 mujeres embarazadas residentes en el estado de Morelos, México. Material y métodos: Mediante un cuestionario de frecuencia de consumo de 84 alimentos, se obtuvo información dietética durante el embarazo. Las concentraciones urinarias de Mo se determinaron por espectrometría de absorción atómica, en al menos dos trimestres del embarazo. La asociación se estimó mediante modelos de efectos mixtos generalizados. Resultados: Entre 5.8 y 12.7% de las muestras superaron el P95 (151 µg/L y 148 µg/g creatinina) de la distribución de Mo urinario reportado para mujeres por la Encuesta Nacional de Nutrición y Salud de Estados Unidos (NHANES) 2009-2010. El mayor consumo de chile (β=1.34μg/g; IC95%: 1.00-1.80; p=0.05) se asoció con concentraciones marginalmente mayores de Mo. Conclusión: Probablemente debido a los fertilizantes o el sistema de riego utilizado en su cultivo, el consumo de chile es una posible fuente de exposición a Mo, en esta población.

Effect of urine creatinine level during pregnancy on dipstick test.

AIM: Dipstick results for proteinuria are affected by urine concentration, and thus urine creatinine concentration ([Cr]). This study was performed to determine whether spot urine [Cr] changes significantly during pregnancy, leading to a significantly different false-negative rate (FNR) on dipstick test between trimester. METHODS: The [Cr] and protein concentrations ([P]) were analyzed in 631 spot urine samples with negative/equivocal dipstick from 425 pregnant women. False-negative dipstick was defined as [P] : [Cr] ratio (P/Cr) > 0.27 mg/mg. RESULTS: Median [Cr] was 117 mg/dL (range, 6.5-326 mg/dL), 72 mg/dL (range, 4.3-477 mg/dL), and 73 mg/dL (range, 8.4-396 mg/dL) in the first (n = 96), second (n = 344), and third (n = 191) trimester urine samples, respectively (P = 0.000, Kruskal-Wallis). Both [P] and P/Cr increased significantly with advancing gestation. FNR 9.4% (18/191) in the third trimester was significantly higher than that of 0.0% (0/96) in the second trimester and that of 0.5% (2/344) in the third trimester. In the 20 urine samples with false-negative dipstick, median [Cr] was 47.0 mg/dL (range, 11.0-358 mg/dL) and the proportion of samples with dilute urine, that is, [Cr] <47 mg/dL, was significantly higher than in the remaining 611 urine samples (50%, 10/20 vs 28%, 174/611, respectively, P = 0.046). CONCLUSIONS: Urine samples in the second and third trimesters were more likely to be diluted compared with the first trimester. This was associated with high FNR in third trimester urine samples.

Trimester-Specific Urinary Bisphenol A Concentrations and Blood Glucose Levels Among Pregnant Women From a Fertility Clinic.

Context: Women with a history of infertility are at increased risk of impaired glucose tolerance during pregnancy. Studies suggest higher urinary bisphenol A (BPA) concentrations are associated with diabetes in nonpregnant populations, but the association between BPA and glucose levels among pregnant women is unclear. Objective: To assess trimester-specific urinary BPA concentrations in relation to blood glucose levels among subfertile women. Design: Environment and Reproductive Health Study, an ongoing prospective cohort study. Setting: A fertility center in a teaching hospital. Patients: A total of 245 women contributed at least one urine sample during first and/or second trimesters, delivered a singleton or twin pregnancy, and had available blood glucose data (2005 to 2015). Main Outcome Measure: Blood glucose levels after a nonfasting 50-g glucose challenge test at 24 to 28 weeks of gestation. Results: The specific gravity-adjusted geometric mean urinary BPA concentrations during first and second trimesters were 1.39 and 1.27 µg/L, respectively. Second-trimester BPA concentrations were positively associated with blood glucose (P, trend = 0.01). Specifically, the adjusted mean glucose levels (95% confidence interval) for women in the highest quartile of second-trimester BPA concentrations was 119 (112, 126) mg/dL compared with 106 (100, 112) mg/dL for women in the lowest quartile. No associations were observed between first-trimester BPA concentrations and glucose levels. Conclusions: BPA exposure during the second trimester may have adverse effect on blood glucose levels among subfertile women. As the findings represent the first report suggesting a potential etiologically relevant window for BPA and glucose in humans, further studies are needed.

Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies.

Higher concentrations of certain phthalate metabolites are associated with adverse reproductive and pregnancy outcomes, as well as poor infant/child health outcomes. In non-pregnant populations, phthalate metabolite concentrations vary by race/ethnicity. Few studies have documented racial/ethnic differences between phthalate metabolite concentrations at multiple time points across the full-course of pregnancy. The objective of the study was to characterize the change in phthalate metabolite concentrations by race/ethnicity across multiple pregnancy time points. Women were participants in a prospectively collected pregnancy cohort who delivered at term (≥37 weeks) and had available urinary phthalate metabolite concentrations for ≥3 time points across full-term pregnancies (n=350 women). We assessed urinary concentrations of eight phthalate metabolites that were log-transformed and specific gravity-adjusted. We evaluated the potential racial/ethnic differences in phthalate metabolite concentrations at baseline (median 10 weeks gestation) using ANOVA and across pregnancy using linear mixed models to calculate the percent change and 95% confidence intervals adjusted for sociodemographic and lifestyle factors. Almost 30% of the population were non-Hispanic black or Hispanic. With the exception of mono-(3-carboxypropyl) (MCPP) and di-ethylhexyl phthalate (DEHP) metabolites, baseline levels of phthalate metabolites were significantly higher in non-whites (P<0.05). When evaluating patterns by race/ethnicity, mono-ethyl phthalate (MEP) and MCPP had significant percent changes across pregnancy. MEP was higher in Hispanics at baseline and decreased in mid-pregnancy but increased in late pregnancy for non-Hispanic blacks. MCPP was substantially higher in non-Hispanic blacks at baseline but decreased later in pregnancy. Across pregnancy, non-Hispanic black and Hispanic women had higher concentrations of certain phthalate metabolites. These differences may have implications for racial/ethnic differences in adverse pregnancy and child health outcomes.

Maternal creatine in pregnancy: a retrospective cohort study.

OBJECTIVE: To estimate creatine concentrations in maternal plasma and urine, and establish relationships with maternal characteristics, diet and fetal growth. DESIGN: Retrospective cohort study. SETTING: Lyell McEwin Hospital, Adelaide, Australia. POPULATION: A biobank of plasma and urine samples collected at 13, 18, 30 and 36 weeks' gestation from 287 pregnant women from a prospective cohort of asthmatic and non-asthmatic women. METHODS: Creatine was measured by enzymatic analysis. Change in creatine over pregnancy was assessed using the Friedman test. Linear mixed models regression was used to determine associations between maternal factors and diet with creatine across pregnancy and between creatine with indices of fetal growth at birth. MAIN OUTCOME MEASURES: Maternal creatine concentrations, associations between maternal factors and creatine and between creatine and fetal growth parameters. RESULTS: Maternal smoking, body mass index, asthma and socio-economic status were positively and parity negatively associated with maternal plasma and/or urine creatine. Maternal urine creatine concentration was positively associated with birthweight centile and birth length. After adjustment, each µmol/l increase in maternal urinary creatine was associated with a 1.23 (95% CI 0.44-2.02) unit increase in birthweight centile and a 0.11-cm (95% CI 0.03-0.2) increase in birth length. CONCLUSIONS: Maternal factors and fetal growth measures are associated with maternal plasma and urine creatine concentrations. TWEETABLE ABSTRACT: Maternal creatine is altered by pregnancy; fetal growth measures are associated with maternal creatine concentrations.

Associations of Maternal Urinary Cadmium with Trimester-Specific Blood Pressure in Pregnancy: Role of Dietary Intake of Micronutrients.

Previous studies revealed associations of urinary Cd (U-Cd), a chronic Cd exposure biomarker, with blood pressure (BP) in non-pregnant adults. However, the evidence regarding trimester-specific blood pressure in pregnancy and U-Cd and effect modification by dietary intake of micronutrients is scarce. We randomly selected 653 women from the Omega Study cohort. U-Cd was quantified by inductively coupled plasma mass spectrometry. Trimester-specific, systolic (SBP) and diastolic blood pressure (DBP) were determined employing standard protocols and mean arterial pressure (MAP) was also calculated. Associations of SBP, DBP, and MAP with U-Cd tertiles (≤0.21; 0.22-0.41; ≥0.42 µg/g Cr) were assessed using multivariable linear regression models. We also explored effect modification by pre-pregnancy BMI (≤25 or >25 kg/m2) or low/high micronutrients intake. After adjusting confounders in women with elevated (upper tertile) as compared with those with low (lowest tertile) U-Cd (≥0.42 vs. ≤0.21 µg/g Cr, respectively) had reduced third trimester MAP (-1.8; 95 % confidence interval (CI) = -3.1, -0.5 mmHg) and second trimester MAP (-1.1; 95 % CI = -2.3, -0.03 mmHg). A significant decrease in third-trimester MAP associated with increased U-Cd was observed only among normal/underweight women (BMI ≤ 25 kg/m2) and women with high dietary intake of micronutrients (calcium, magnesium, zinc, and selenium). Notably, U-Cd concentrations increased with the increased consumption of zinc and non-heme iron food sources. No significant differences in U-Cd concentrations were found in preeclamptic women compared with non-preeclamptic women. Our study provides evidence that dietary intake of micronutrients should be taken into account when assessing the health effects of Cd in pregnant women.

Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolites.

This study sought to assess the pharmacokinetic (PK) changes of caffeine and its CYP1A2 metabolites across the 3 trimesters of pregnancy. A prospective, multicenter PK study was conducted among 59 pregnant women (93.2% white) who were studied once during a trimester. One beverage with 30-95 mg caffeine was consumed, and a blood/urine sample was collected within 1 hour postingestion. Concentrations of caffeine and its primary metabolites were quantified from serum and urine by LC-MS/MS. There was a significant increase in dose-normalized caffeine serum and urine concentrations between the first and third trimesters (P < .05 and P < .01, respectively). Normalized theophylline concentrations also increased significantly in the third trimester in serum (P < .001) and in urine (P < .05). The caffeine urine/serum concentration ratio also increased in the last trimester (P < .05). No significant difference was found in normalized paraxanthine or theobromine concentrations. This study identified decreased caffeine metabolism and an increase in the active metabolite theophylline concentrations during pregnancy, especially in the third trimester, revealing evidence of the large role that pregnancy plays in influencing caffeine metabolism.

No increase in renal iodine excretion during pregnancy: a telling comparison between pregnant women and their spouses.

OBJECTIVE: Adequate dietary iodine intake is necessary for normal thyroid gland function at all times, and most particularly during pregnancy. Increased iodine loss is cited, among other factors, as responsible for the increased iodine demand in this period. Our aim was to compare renal iodine excretion between women during all three pregnancy trimesters with that of their spouses and thereby to estimate the iodine intake in an a large sample of pregnant women in urban areas in Greece. DESIGN: Four hundred twenty-four healthy pregnant women were included prospectively (residents of Athens n=218, residents of Patras n=206). The spouses of 177 of these women following the same diet were also studied. Determinations included serum FT4, TSH and aTPO and urinary iodine excretion (UIE). RESULTS: No difference was found either in median UIE throughout pregnancy or between the UIE of the pregnant women and their spouses during the trimesters. Throughout pregnancy, mild iodine deficiency was noted and was classified as mild in 60%, moderate in 30% and severe in 10% of the women studied. Users of iodized salt had significantly higher median UIE compared with non-users. Serum FT4 levels decreased and TSH increased as pregnancy progressed. CONCLUSIONS: Our study indicates that renal iodine excretion is not increased during pregnancy. This finding needs to be confirmed by further investigation in other populations with different iodine intakes. Thus, increased iodine requirements in pregnancy are possibly due to extra-renal causes. The population of pregnant women in Greek urban areas is mildly-and often moderately and severely-iodopenic and needs to be treated accordingly.