Maternal Urinary Levels Research Articles

Maternal urinary levels of PAH metabolites, umbilical cord blood telomere length and anthropometric indices in newborns.

The existing evidence indicating that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with a range of adverse outcomes, including alterations in anthropometric indices, underscores the need for further investigation into the underlying mechanisms. This study aims to examine the effects of prenatal PAH exposure on anthropometric indices and telomere length (TL), as well as to explore whether changes in TL can serve as a predictor of alterations in anthropometric measures. The study was conducted in Shenyang, China, with 2460 pregnant women participating between 2022 and 2023. Maternal urine samples were analyzed for eleven PAH metabolites, and neonatal outcomes, such as birth weight (BW), birth length (BL), and head circumference (HC), were extracted from medical records as anthropometric indices. We employed multiple linear regression (MLR), generalized quantile g-computation (g-comp), Bayesian Kernel Machine Regression (BKMR), and mediation analysis to comprehensively assess the associations between PAH exposure and umbilical TL and neonatal outcomes. Notably, significant negative associations were found between several PAH metabolites and umbilical telomere length (TL). These metabolites included 2-hydroxy naphthalene (2-OH Nap), 1-hydroxy pyrene (1-OH Pyr), 6-hydroxy chrysene (6-OH Chr), 9-hydroxy benzo(a)pyrene (9-OH Bap), and the sum of hydroxylated PAHs (Σ-OH PAHs). Additionally, negative correlations were identified between specific PAH metabolites and HC, although no significant associations were found for BW. Birth weight showed a significant inverse relationship with metabolites such as 1-hydroxy phenanthrene (1-OH Phe), 9-hydroxy phenanthrene (9-OH Phe), and 1-hydroxy naphthalene(1-OH Nap). Results from g-comp analysis and BKMR indicated significant mixture effects of PAHs on umbilical TL and HC, with more heterogeneous effects on BW and BL. Mediation analysis indicated that alterations in umbilical TL partially mediated the associations between PAH exposure and BW and HC. Notably, metabolites such as 2-OH Nap and the Σ-OH PAHs demonstrated substantial mediation effects. Overall, our findings suggest that changes in umbilical TL partially mediate the associations between prenatal PAH exposure and HC and BW, highlighting the complex pathways through which PAH metabolites may influence neonatal development.

Prenatal exposure to pesticide mixtures and the placental transcriptome: Insights from trimester-specific, sex-specific and metabolite-scaled analyses in the SAWASDEE cohort.

We investigated the effect of exposure to pesticide mixtures during pregnancy on the placental transcriptome, to link these exposures and placental functions. The Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) enrolled pregnant farmworkers from Thailand (n=248), who were primarily exposed to organophosphate (OP) and pyrethroid pesticides. We measured maternal urinary levels of six non-specific OP metabolites expressed as three summary measures (dimethylalkylphosphates (DMAP), diethylalkylphosphates (DEAP), and dialkylphosphates (DAP) and three pyrethroid metabolites (3-phenoxybenzoic acid (3-PBA), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA, trans-DCCA) during early, middle, and late pregnancy, and adjusted for urine dilution using creatinine. RNA-sequencing was used to profile the placental transcriptome from which 21 co-expression network modules were identified by Weighted Gene Co-expression Network Analysis. Quantile g-computation analysis identified a positive mixture exposure effect on the E2f Target Module (β=0.013 per SD, p=0.012) and a negative mixture exposure effect (β=-0.016 per SD, p=0.008) on the Myogenesis Module. The pesticide metabolites driving the associations differed for each module on each module varied, highlighting differential susceptibilities within the placental transcriptome to various pesticides. The Myogenesis Module exhibited a consistently significant negative association in both the second trimester (β=-0.013 per SD, p=0.015) and the third trimester (β=-0.012 per SD, p=0.028). When stratifying by infant sex, the mixture exhibited a significant negative effect (β=-0.018 per SD, P=0.016) on the Myogenesis Module only in females. Other modules, such as epithelial-mesenchymal transition, though not demonstrating an overall mixture effect, did demonstrate differential impacts of the mixture by sex. These findings underscore the importance of considering the prenatal environment more holistically, understanding the placenta's susceptibility to contaminants, and incorporating sex-specific analyses to understand differential impacts.

Distinct Impacts of Prenatal and Postnatal Phthalate Exposure on Behavioral and Emotional Development in Children Aged 1.5 to 3 Years.

Development is a continuous process, but few studies have assessed the simultaneous impact of prenatal and postnatal phthalate exposure on children's behavioral and emotional development. A total of 491 mother-child pairs from the general population in southern Taiwan were studied from 2021 to 2022. Urinary concentrations of bisphenol A (BPA) and phthalate metabolites-mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and mono-2-ethylhexyl phthalate (MEHP)-were measured in pregnant mothers during the second trimester and in their corresponding children aged 1.5 to 3 years. Behavioral symptoms in children were evaluated using the Child Behavior Checklist (CBCL). Odds ratios (ORs) represent a 1-unit increase in log10-transformed creatinine-corrected maternal urine concentrations. Prenatal maternal urinary MnBP levels were associated with total problems (OR = 19.32, 95% CI: 1.80-43.13, p = 0.04), anxiety (OR = 33.58, 95% CI: 2.16-521.18, p = 0.01), and sleep problems (OR = 41.34, 95% CI: 1.04-1632.84, p = 0.04) in children. Additionally, urinary MnBP levels in children correlated with total problems (OR = 7.06, 95% CI: 1.01-49.05, p = 0.04) and internalizing problems (OR = 11.04, 95% CI: 1.27-95.72, p = 0.01). These findings suggest that prenatal and postnatal exposure to dibutyl phthalate (DBP), metabolized as MnBP, distinctly affects children's behavioral development.

Associating prenatal antibiotics exposure with attention deficit hyperactivity disorder symptoms in preschool children: The role of maternal vitamin D

BackgroundThe associations between prenatal antibiotics exposure and attention-deficit/hyperactivity disorder (ADHD) in preschoolers, and the role of maternal vitamin D in these associations, remain to be explored. ObjectivesTo evaluate the relationships between multiple maternal urinary antibiotics levels and preschoolers’ ADHD symptoms, and to identify the potential modifying effects of maternal vitamin D. MethodsBased on a prospective birth cohort, the present study included 2033 motherchild pairs. Maternal urine and serum samples were collected during all three trimesters to measure the urinary concentrations of 43 antibiotics (including two metabolites) and the serum vitamin D levels. The ADHD symptoms of preschoolers were assessed using the Diagnostic and Statistical Manual–oriented ADHD problems scale in the Achenbach Child Behavior Checklist. Multiple informant models in the form of logistic regression were conducted to investigate the associations between prenatal antibiotics exposure and preschooler ADHD symptoms, and these associations were stratified by child sex and maternal vitamin D status. ResultsCompared with the lowest tertile concentrations, maternal exposure to the middle tertile concentrations of doxycycline and human antibiotics/preferred as human antibiotics (HAs/PHAs), and the highest tertile concentrations of doxycycline during the first trimester were associated with an increased risk of ADHD symptoms in children. An increased risk of ADHD symptoms was observed in girls exposed to the highest tertile levels of sulfamethazine during the second trimester. Furthermore, pregnant women with vitamin D deficiency have a greater risk of ADHD symptoms in their offspring after exposure to doxycycline in the first trimester. ConclusionsMaternal exposure to doxycycline and HAs/PHAs during the first trimester increases the risk of ADHD symptoms in preschoolers. Mid-pregnancy sulfamethazine exposure increases the risk of ADHD symptoms in girls. Maternal vitamin D deficiency during pregnancy may exacerbate the adverse effects of doxycycline exposure on ADHD symptoms.

Correlation of offspring thyroid function and maternal iodine status in iodine deficient-coastal area

Thyroid hormone is vital for children's growth and metabolism, relying on sufficient iodine levels for synthesis. Maternal intake determines iodine supply to fetuses and children under two years old. This study aimed to correlate offspring thyroid function with maternal iodine status in coastal areas. A cohort study was conducted, involving pregnant coastal residents. Maternal urinary iodine levels were measured via the ammonium persulfate method, while offspring thyroid stimulating hormones (TSHs) and free thyroxine hormone (fT4) levels were assessed using electro-chemiluminescence immunoassay (ECLIA). Iodine intake was determined through a semiquantitative food frequency questionnaire (FFQ). The correlation between offspring thyroid function and maternal iodine status was analyzed using Pearson’s correlation test. Differences in TSHs and fT4 levels among iodine status groups were examined using the One way-ANOVA test. Maternal iodine status was insufficient with a median urinary iodine of 125 μg/L, resulting in a 60.8% prevalence of iodine insufficiency. Iodine intake (62.20±43.45 μg/day) fell short of recommended levels (RDA). Offspring TSH was 2.29±1.07 μIU/mL, fT4 was 1.26±0.14 ng/dL. TSH and fT4 concentrations showed no significant inter-group differences (p=0.852, p=0.075). Offspring thyroid function did not correlate with maternal iodine status (TSHs: p=0.314; fT4: p=0.258). Offspring thyroid function did not correlate to maternal iodine status in a population of iodine-insufficient and mercury-contaminated coastal areas.

Association between gestational arsenic exposure and infant physical development: a prospective cohort study

BackgroundArsenic pollution is widespread worldwide. The association between gestational arsenic exposure and adverse birth outcomes has been demonstrated in previous studies; however, few investigations have examined whether gestational arsenic exposure has adverse effects on infant growth and development after birth.ObjectiveOur study was designed to evaluate particular associations between gestational arsenic exposure during pregnancy and newborn birth size and to investigate whether these associations continue to affect infants after birth.MethodsAn ongoing prospective cohort study of 1100 pregnant women was conducted at the Wuxi Maternity and Child Health Care Hospital. The total urinary arsenic concentrations in the 2nd and 3rd trimester were determined using atomic fluorescence spectrometry. The relationships between urinary arsenic concentration and foetal growth parameters (birth weight, head circumference, length, and ponderal index), SGA (Small for gestational age), and physical growth of infants within one year after birth were analysed.ResultsUrinary arsenic concentration in the 3rd trimester was associated with an increased incidence of SGA [adjusted model: OR = 2.860 (95% CI: 1.168, 7.020), P = 0.021)]. Arsenic exposure in late pregnancy had an adverse effect on the physical development of infants before the age of 1 year, and there was an interaction effect with the sex of infants. The weight and length of boys at 6 and 12 months negatively correlated with maternal urinary arsenic levels during late pregnancy.ConclusionsIn addition to affecting foetal growth, exposure to arsenic in the 3rd trimester also negatively affected the growth of offspring within the first year of life.

Titanium Dioxide Nanoparticles Induce Maternal Preeclampsia-like Syndrome and Adverse Birth Outcomes via Disrupting Placental Function in SD Rats.

The escalating utilization of titanium dioxide nanoparticles (TiO2 NPs) in everyday products has sparked concerns regarding their potential hazards to pregnant females and their offspring. To address these concerns and shed light on their undetermined adverse effects and mechanisms, we established a pregnant rat model to investigate the impacts of TiO2 NPs on both maternal and offspring health and to explore the underlying mechanisms of those impacts. Pregnant rats were orally administered TiO2 NPs at a dose of 5 mg/kg body weight per day from GD5 to GD18 during pregnancy. Maternal body weight, organ weight, and birth outcomes were monitored and recorded. Maternal pathological changes were examined by HE staining and TEM observation. Maternal blood pressure was assessed using a non-invasive blood analyzer, and the urinary protein level was determined using spot urine samples. Our findings revealed that TiO2 NPs triggered various pathological alterations in maternal liver, kidney, and spleen, and induced maternal preeclampsia-like syndrome, as well as leading to growth restriction in the offspring. Further examination unveiled that TiO2 NPs hindered trophoblastic cell invasion into the endometrium via the promotion of autophagy. Consistent hypertension and proteinuria resulted from the destroyed the kidney GBM. In total, an exposure to TiO2 NPs during pregnancy might increase the risk of human preeclampsia through increased maternal arterial pressure and urinary albumin levels, as well as causing fetal growth restriction in the offspring.

Urinary sFlt-1 and PlGF as preeclampsia predictors: sFlt-1/creatinine ratio improves the prediction value

ObjectivesTo evaluate the correlation between maternal serum and urinary soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels and to assess their potential value in preeclampsia and fetal growth restriction. Study DesignThis case-control longitudinal prospective study was performed in 49 singleton pregnant women, divided into two clinical groups, low risk pregnancy (n = 23) and pregnancy complicated by preeclampsia (n = 26). Maternal serum and urinary sFlt-1 and PlGF levels were quantified by electrochemiluminescence. Every patient underwent an ultrasound for fetal biometry. Doppler assessment was done when estimated fetal weight was under the 10th centile. ROC curves were used to evaluate the predictive capability of serum and urinary angiogenic biomarkers and their ratios on preeclampsia. Linear regression was used to compare the values of serum and urinary sFlt-1 and PlGF and their ratios. ResultsUrine biomarkers were positively associated with their serum values, being the best associated urinary PlGF (R2 = 0.73), which also showed the highest predictive capability of preeclampsia of urine biomarkers (AUC 0.866). The predictive capability of urinary sFlt-1 was much lower (AUC 0.640), but increased when adjusting by serum creatinine, a more precise parameter (AUC 0.863). ConclusionsUrinary PlGF could be a lesser invasive alternative to circulating biomarkers to monitor pregnancies complicated with preeclampsia that need repeated controls of their pregnancy complication. Urinary sFlt-1 values need adjustment by serum creatinine to be reliable.

Maternal Exposure to Endocrine-Disrupting Chemicals: Analysis of Their Impact on Infant Gut Microbiota Composition.

Endocrine disruptors (EDCs) are chemicals that interfere with the endocrine system. EDC exposure may contribute to the development of obesity, type 2 diabetes, and cardiovascular diseases by impacting the composition of an infant's gut microbiota during the first 1000 days of life. To explore the relationship between maternal urinary levels of Bisphenol-A and phthalates (UHPLC-MS/MS), and the composition of the infant gut microbiota (16S rDNA) at age 12 months (T3) and, retrospectively, at birth (T0), 1 month (T1), and 6 months (T2), stool samples from 20 infants breastfed at least once a day were analyzed. Metataxonomic bacteria relative abundances were correlated with EDC values. Based on median Bisphenol-A levels, infants were assigned to the over-exposed group (O, n = 8) and the low-exposed group (B, n = 12). The B-group exhibited higher gut colonization of the Ruminococcus torques group genus and the O-group showed higher abundances of Erysipelatoclostridium and Bifidobacterium breve. Additionally, infants were stratified as high-risk (HR, n = 12) or low-risk (LR, n = 8) exposure to phthalates, based on the presence of at least three phthalates with concentrations exceeding the cohort median values; no differences were observed in gut microbiota composition. A retrospective analysis of gut microbiota (T0-T2) revealed a disparity in β-diversity between the O-group and the B-group. Considering T0-T3, the Linear Discriminant Effect Size indicated differences in certain microbes between the O-group vs. the B-group and the HR-group vs. the LR-group. Our findings support the potential role of microbial communities as biomarkers for high EDC exposure levels. Nevertheless, further investigations are required to deeply investigate this issue.

Prenatal phthalate exposure and fetal penile length and width.

Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. 57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

Urinary Nephrin Levels Among Pregnant Women With Preeclampsia in Lagos, Southwest Nigeria: An Analytical Cross-Sectional Study.

Hypertensive disorders in pregnancy are one of the leading causes of maternal and perinatal morbidity and mortality worldwide. The clinical utility of urinary nephrin as a diagnostic biomarker of preeclampsia is currently of research interest. However, this is yet to gain significant traction within clinical settings. We evaluated the association between maternal urinary nephrin levels and the occurrence and severity of preeclampsia among pregnant women in Lagos, Nigeria. We conducted an analytical cross-sectional study involving pregnant women diagnosed with preeclampsia as well as their age- and gestational-age-matched normotensive counterparts. We tested the association between high maternal urinary nephrin levels and the occurrence of preeclampsia without and with severe features. P < 0.05 was reported as statistically significant. The study showed that for every unit increase in urinary nephrin levels, the odds of preeclampsia increased by about ninefold (adjusted Odds ratio = 8.9, 95% confidence interval: 2.8-29.2, P < 0.001). The levels of urinary nephrin increased steadily with increasing severity of the disease: 1.9 ± 0.8 ng/mL in preeclampsia without severe features, 2.7 ± 0.7 ng/mL in preeclampsia with at least one severe feature, and 3.3 ±1.1 ng/mL in eclampsia. There was an association between elevated levels of urinary nephrin and preeclampsia and its severe variant. However, there is a need for more robust studies with a longitudinal characterization of urinary nephrin levels to establish causal relationships with preeclampsia, explore other potential risk factors of preeclampsia, and define the clinical usefulness of urinary nephrin as a potentially reliable and accurate predictive marker of preeclampsia among women in low- and middle-income countries (LMIC) settings.

Sex-specific associations of maternal and childhood urinary arsenic levels with emotional problems among 6-year-age children: Evidence from a longitudinal cohort study in China

BackgroundArsenic exposure has been linked to neurobehavior development disorders among children in cross-sectional studies, but there is little information on the effects of prenatal and childhood arsenic exposure on childhood behavior problem, especially emotional problems. ObjectiveTo explore the relationship between prenatal and childhood arsenic exposure and behavior problems among six-year-old children. Methods389 mother-child pairs from a longitudinal birth cohort were enrolled in the study. The concentrations of arsenic in maternal and 6-year-old children’s urine were measured using inductively coupled plasma mass spectrometry (ICP-MS). Neurobehavioral development in 6-year-old children was assessed by Child Behavior Checklist (CBCL). Generalized linear regression models were used to relate arsenic exposure to the score of different domains in CBCL. ResultsThe median concentrations of maternal and 6-year-old children’s urinary arsenic were 22.22 and 33.86 μg/L, respectively. After adjusting for potential covariates, natural logarithm transformed concurrent urinary arsenic levels were significantly associated with scores of anxious and depressed problems in 6-year-old girls (β = 0.71, 95% CI: 0.12–1.31, p = 0.018). Furthermore, in terms of the trajectory of arsenic exposure, compared with the “consistently low” group, the “low to high” group (β = 2.73, 95% CI: −3.99 to 9.45, p = 0.425) had a greater effect on total score of CBCL than “high to low” group (β = −0.93, 95% CI: −7.22 to 5.36, p = 0.771) in girls, although insignificant. ConclusionsOur results suggested that concurrent arsenic exposure might have an adverse effect of emotional status in girls. Further studies are needed to verify the findings and explore the mechanisms of the sex-specific association.

Maternal environmental, occupational, and urinary metabolite levels of benzene compounds and their association with congenital heart diseases in offspring: a case‒control study in China

The conclusions about the association of maternal pregnancy environment, occupation, and benzene compounds with fetal CHD are not entirely consistent. Eight hundred seven CHD cases and 1008 controls were included in this study. All occupations were classified and coded against the Occupational Classification Dictionary of the People’s Republic of China (2015 version). Logistic regressions were used to explore the correlation among environmental factors, occupation types, and CHDs in offspring. We found that living near public facilities and having exposure to chemical reagents and hazardous substances were significant risk factors for CHDs in offspring. We found that offspring of mothers who worked in agriculture and similar work during pregnancy suffered from CHD. The risk of all CHDs in the offspring of pregnant women working in production manufacturing and related work was significantly higher than that in unemployed pregnant women, the risk was also observed in 4 subtypes of CHDs. We compared the concentrations of the five metabolite (MA, mHA, HA, PGA, and SPMA) levels of benzene compounds in the urine of mothers in case and control groups and found no significant differences. Our study suggests that maternal exposure during pregnancy and certain environmental and occupational conditions are risk factors for CHD in offspring, but did not support an association between concentrations of metabolites of benzene compounds in the urine of pregnant women and CHDs in their offspring.

Maternal urinary vascular endothelial growth factor (VEGF) versus N.T. pro brain natriuretic peptide (NT-pro BNP) as novel biomarkers for placental accreta spectrum (PAS): A case-control study

This study planned to compare the predictive ability of maternal urinary vascular endothelial growth factor (VEGF) versus N-terminal pro B-type natriuretic peptide (NT-pro BNP) for prediction of placenta accreta spectrum (PAS). This was a prospective case-control study carried out in a tertiary university hospital. It included pregnant women between 37-39 weeks. The study included 50 pregnant women classified in two groups. Group (Ι, n=25) were pregnant women with PAS, and group (II, n=25) women with uncomplicated pregnancies, as controls. Urine samples were collected, and quantitative analyses of VEGF and NT-pro BNP were performed by ELISA. VEGF was assessed with a cut point of 215.6 pg/ml and NT-pro BNP with a cut point of 182.2 pg/ml to predict the condition of PAS. Both biomarkers were good predictors of PAS with the area under the ROC curve (AUC) equal to (0.871 and 0.904), respectively. However, maternal urinary VEGF levels could predict PAS better than NT-pro BNP (OR=9.967, 95%CI 2.032-48.879, p=0.005) versus (OR=8.066, 95% CI 1.520 - 42.811, p=0.014) in NT-pro BNP. In conclusion, third trimester urinary levels of both VEGF and NT-pro BNP appear to be s crucially good predictors for PAS. However, VEGF is superior to NT-pro BNP in predicting women with PAS. These biomarkers present promising candidates as they can help to detect patients at high probability of PAS. They can be assessed by non-invasive, simple, and low-cost procedures.

The relationship between urinary selenium levels and risk of gestational diabetes mellitus: A nested case-control study.

Selenium (Se) is an essential trace element for the human body. Serum Se and urinary Se are also biomarkers to assess Se exposure status. However, studies focusing on the association between urinary Se and the risk of gestational diabetes mellitus (GDM) are rare. To investigate the association between urinary Se and the risk of GDM. A nested case-control study based on a prospective birth cohort in Wuhan, China, which focuses on the effects of prenatal environmental factors exposure on pregnant women and children's health was conducted. Two hundred and twenty-six cases and 452 controls were included. Maternal urine samples were collected before GDM diagnosis, and the urinary Se levels were determined. We assessed the association of urinary Se with GDM by conditional logistic regression with maternal urinary Se level as a categorical variable, and estimated the association between Se and glucose levels by multiple linear regression. The potential modifier roles of maternal age and fetal sex have also been assessed. Lower urinary level of Se was significantly associated with a higher risk of GDM (OR = 2.35 for the tertile 1, 95% CI:1.36-4.06; adjusted OR = 1.79 for the tertile 2, 95%CI:1.09-2.95; p for trend = 0.01). Fetal sex had an interaction with Se in the association with GDM. The association was more pronounced among pregnant women with female fetuses than with male fetuses. Our study suggested a significant negative association between urinary Se and the risk of GDM, and this association may vary depending on the fetal sex.

Co-exposure to toxic metals and phthalates in pregnant women and their children’s mental health problems aged four years — Taiwan Maternal and Infant Cohort Study (TMICS)

BackgroundChildhood and adolescent mental health problems may increase the global burden of disease. Neurotoxic metals are associated with inflammation and cytotoxicity in the brain. In addition, prenatal phthalate ester (PAE) exposure is associated with cognitive function deficits. However, the effect of co-exposure to toxic metals, PAEs, and their association with child behavior is less well studied. Hence, we aimed to investigate prenatal co-exposure to the metals and PAEs and the consequent behavioral outcomes in early childhood. MethodsWe followed pregnant women and their newborns from the Taiwan Maternal and Infant Cohort Study between 2015 and 2017, with a focus on women from the central, southern, and eastern areas of Taiwan. We quantified maternal urinary concentrations of metals and metabolites of PAEs as surrogates of prenatal exposure. We recorded the Child Behavior Checklist scores according to caregiver reports at 4 years of age, and identified Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-oriented problems. ResultsUltimately, 408 children were included in the statistical analysis. Maternal urinary copper levels were significantly associated with depressive problems (odds ratio [OR] = 2.13) in children. Maternal urinary concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) were also significantly associated with depressive symptoms (odds ratio [OR] = 1.51 and 1.53, respectively). Further analysis considering prenatal co-exposure to metals and PAEs showed that co-exposure to these materials was significantly associated with autism spectrum problems (OR = 3.11). ConclusionsWe observed that prenatal single exposure or co-exposure to metals and PAEs may play a role in some DSM-5-oriented problems in children at 4 years of age. Reduction of exposure to toxic metals and PAEs in pregnancy is suggested to prevent increased mental health problems in children.

Maternal Urinary Fluoride levels during pregnancy and ADHD symptoms during childhood

Background and aim. There is little evidence linking fluoride in urinary levels and symptoms or diagnosis of ADHD. In the Basque Country, the fluoridation of drinking water is compulsory for municipalities &amp;#x3e;30,000 inhabitants. The objective is to analyze the relationships between fluoride levels in urine collected during pregnancy and ADHD symptomatology at 4, 8 and 11 y Methods. Data from 201 to 255 mother-child pairs from the Infancia y Medio Ambiente (INMA) birth cohort with maternal urinary F adjusted for creatinine (MUFcr) during pregnancy and child assessments of ADHD-like behaviors at age of 4, 8 and 11 years was available. ADHD symptoms were reported by ADHD-DSM-IV checklist at age 4, and Conners&amp;#x27; Rating Scales-Revised at age 8 and 11. Clinical approach was also carried out using the cut offs of each test. Multiple linear regression and zero inflated binomial regression were used when the outcomes were analyzed as continuous; for a clinical approach, logistic regression was used. Covariates, and biomarkers of neurotoxicants were available. Results: MUFcr levels in pregnancy varied according to the source of drinking water [(mean (95% CI)] being 0.85 (0.77, 0.93) in mothers drinking fluoridated water and 0.45 (0.40, 0.51) in those drinking non-fluoridated water (p&amp;#x3c;0.01). No association was found between MUFcr levels during pregnancy and inattention, hyperactivity or ADHD score of symptoms at 4, 8 or 11 years. E.g. at the age of 4, for each 1 mg F/g increase across the whole pregnancy, inattention, hyperactivity-impulsivity and ADHD scores did not change significantly: (β =0.16, CI 95%:-1.58, 1.90), (β =0.19, CI 95%: 1.56, 1.95) and (β = 0.35, CI 95%: -2.75, 3.46). Nor was any association observed when a clinical approximation of the problem was used. Conclusions: Higher levels of MUFcr in pregnant women were not associated with global measures of ADHD during childhood

Prenatal exposure to nickel and atopic dermatitis at age 3 years: a birth cohort study with cytokine profiles.

Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 μg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1β, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure. This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.

Prenatal phthalate exposure and placental telomere length

Telomere shortening is an established marker of cellular aging, and can be induced by stress and environmental exposure, promoting disease. Likewise placental telomere length (TL) has been shown to physiologically shorten throughout gestation with evidence of accelerated shortening in adverse pregnancy outcomes such as PPROM, IUGR, and preeclampsia. Our objective was to assess the association of maternal urinary levels of di(2-ethylhexyl) phthalate (DEHP) metabolites with placental TL.

Serum Netrin-1 and Urinary KIM-1 levels as potential biomarkers for the diagnosis of early preeclampsia

The aim of this study was to evaluate whether the Serum Netrin-1 and Urinary KIM-1 (Kidney Injury Molecule-1) levels are associated with the detection of preeclampsia. A total of 90 patients, including 36 normal pregnant women, 29 patients with nonsevere preeclampsia and 25 patients with severe preeclampsia, were included in this study. Maternal serum Netrin-1 and Urinary KIM-1 levels were measured by using an enzyme-linked immunosorbent assay (ELISA). The results showed that the Levels of Netrin-1 and KIM-1 were statistically higher in women with preeclampsia as compared with normal pregnant women. Furthermore, the Netrin-1 level in women with severe preeclampsia was significantly higher than nonsevere preeclamptic women. inconclusion the current study showed that Maternal serum level of Netrin-1 and Urinary level of KIM-1 can be used as early biomarkers for the detection of preeclampsia. IMPACT STATEMENT What is already known on this subject? Preeclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks' gestation. Netrin-1 was found to promote angiogenesis. Alteration of placental angiogenesis in early pregnancy is a well-known reason for placental dysfunction such as preeclampsia. Kidney injury with proteinuria is a characteristic feature of preeclampsia. Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. Due to these facts, we aimed to investigate the role of maternal serum Netrin-1 and Urine KIM-1 levels in preeclampsia presence and severity. What the results of this study add? A significant relationship between Netrin-1 and KIM-1 levels with preeclampsia. What the implications are of these findings for clinical practice and/or further research? Based on these findings, we concluded that increased levels of Netrin-1 and KIM-1 are associated with severe preeclampsia.