Pregnancy Urine Research Articles

Gestational exposure to organophosphate ester flame retardants and risk of childhood obesity in the environmental influences on child health outcomes consortium

Introduction: Organophosphate esters (OPEs) are increasing in use as flame retardants and plasticizers and concerns have been raised given their endocrine-disrupting activities and possible obesogenic consequences. However, longitudinal studies on gestational OPE exposure and childhood obesity are scarce. This study examined whether OPE levels in maternal urine during pregnancy were associated with the risk of childhood obesity. Methods: OPEs were analyzed in pregnancy urine samples of 5,087 individuals from 14 studies contributing to the Environmental influences on Child Health Outcomes (ECHO) Cohort. BDCPP, DBUP/DIBP, and DPHP, detected in > 80 % of the samples, were modeled continuously and by tertiles; whereas BCPP, BBOEP, and BCETP, detected in 50–80 % of samples, were modeled categorically (not-detected, low, and high). Childhood obesity was defined by BMI z-score ≥ 95th percentile according to WHO (<2 years) and the CDC (≥2 years) metrics. Adjusted modified Poisson regression models assessed childhood obesity risk and the mixture effect was assessed using Bayesian kernel machine regression (BKMR). Results: BMI measurements were available for 3,827 children in infancy (0.5–1.9 years), 3,921 children in early childhood (2.0–4.9 years), and 2,541 children in mid-childhood (5.0–10.0 years). Obesity was present in 16–21 % of children across age groups. In mid-childhood DBUP/DIBP second and third versus first tertiles were associated with increased obesity risk (RR 1.14; 95 % CI: 1.02, 1.28; and RR 1.11; 95 % CI: 0.97, 1.27; respectively); whereas BDCPP second and third versus first tertiles reflected an inverse association with obesity risk (RR 0.85; 95 % CI: 0.80, 0.91 and RR 0.91; 95 % CI: 0.77, 1.07; respectively). No association with obesity risk was observed for DPHP, BCPP, BBOEP, and BCETP. Directions observed were consistent with those seen in BKMR models. Conclusions: This study identified mixed associations between gestational OPE exposure and childhood obesity. Further investigation across a comprehensive range of OPE exposures is warranted.

Prenatal exposure to environmental phenols and phthalates and altered patterns of DNA methylation in childhood

IntroductionEpigenetic marks are key biomarkers linking the prenatal environment to health and development. However, DNA methylation associations and persistence of marks for prenatal exposure to multiple Endocrine Disrupting Chemicals (EDCs) in human populations have not been examined in great detail. MethodsWe measured Bisphenol-A (BPA), triclosan, benzophenone-3 (BP3), methyl-paraben, propyl-paraben, and butyl-paraben, as well as 11 phthalate metabolites, in two pregnancy urine samples, at approximately 13 and 26 weeks of gestation in participants of the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study (N = 309). DNA methylation of cord blood at birth and child peripheral blood at ages 9 and 14 years was measured with 450K and EPIC arrays. Robust linear regression was used to identify differentially methylated probes (DMPs), and comb-p was used to identify differentially methylated regions (DMRs) in association with pregnancy-averaged EDC concentrations. Quantile g-computation was used to assess associations of the whole phenol/phthalate mixture with DMPs and DMRs. ResultsPrenatal BPA exposure was associated with 1 CpG among males and Parabens were associated with 10 CpGs among females at Bonferroni-level significance in cord blood. Other suggestive DMPs (unadjusted p-value < 1 × 10−6) and several DMRs associated with the individual phenols and whole mixture were also identified. A total of 10 CpG sites at least suggestively associated with BPA, Triclosan, BP3, Parabens, and the whole mixture in cord blood were found to persist into adolescence in peripheral blood. ConclusionsWe found sex-specific associations between prenatal phenol exposure and DNA methylation, particularly with BPA in males and Parabens in females. Additionally, we found several DMPs that maintained significant associations with prenatal EDC exposures at age 9 and age 14 years.

Predictors of upstream inflammation and oxidative stress pathways during early pregnancy

BackgroundInflammation and oxidative stress are critical to pregnancy, but most human study has focused on downstream, non-causal indicators. Oxylipins are lipid mediators of inflammation and oxidative stress that act through many biological pathways. Our aim was to characterize predictors of circulating oxylipin concentrations based on maternal characteristics. MethodsOur study was conducted among 901 singleton pregnancies in the LIFECODES Fetal Growth Study, a nested case-cohort with recruitment from 2007 to 2018. We measured a targeted panel of oxylipins in early pregnancy plasma and urine samples from several biosynthetic pathways, defined by the polyunsaturated fatty acid (PUFA) precursor and enzyme group. We evaluated levels across predictors, including characteristics of participants’ pregnancy, socioeconomic determinants, and obstetric and medical history. ResultsCurrent pregnancy and sociodemographic characteristics were the most important predictors of circulating oxylipins concentrations. Plasma oxylipins were lower and urinary oxylipins higher for participants with a later gestational age at sampling (13–23 weeks), higher prepregnancy BMI (obesity class I, II, or III), Black or Hispanic race and ethnicity, and lower socioeconomic status (younger age, lower education, and uninsured). For example, compared to those with normal or underweight prepregnancy BMI, participants with class III prepregnancy obesity had 45–46% lower plasma epoxy-eicosatrienoic acids, the anti-inflammatory oxylipins produced from arachidonic acid (AA) by cytochrome P450, and had 81% higher urinary 15-series F2-isoprostanes, an indicator of oxidative stress produced from non-enzymatic AA oxidation. Similarly, in urine, Black participants had 92% higher prostaglandin E2 metabolite, a pro-inflammatory oxylipin, and 41% higher 5-series F2-isoprostane, an oxidative stress indicator. ConclusionsIn this large pregnancy study, we found that circulating levels of oxylipins were different for participants of lower socioeconomic status or of a systematically marginalized racial and ethnic groups. Given associations differed along biosynthetic pathways, results provide insight into etiologic links between maternal predictors and inflammation and oxidative stress.

Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy

BackgroundHuman chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. ObjectivesTo investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. MethodsWe utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. ResultsIn 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: −0.06 [−0.11 to −0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: −0.13 [−0.19 to −0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with −0.27 lower hCG (95% CI: −0.34 to −0.19). DiscussionHigher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.

#2550 THE ANTI-AGING FACTOR, α-KLOTHO EXPRESSION DURING HUMAN PREGNANCY AND ITS COMPLICATIONS: PREECLAMPSIA AND SMALL-FOR-GESTATIONAL-AGE NEONATE

Abstract Background and Aims Pre-eclampsia (PE) is defined as arterial hypertension associated with proteinuria and may cause dysfunction of vital organs as kidney, liver, brain and other organs. PE is consider as the leading cause of maternal and perinatal morbidity worldwide [1,2]. IUGR definition is abnormal fetal growth compared with growth potential of a specific infant. α-Klotho (αKL) protein has three isoforms: a single transmembrane (mKL) form, a shed soluble form, and a secreted soluble circulating protein (sKL). mKL is expressed in the kidney and placenta. Nowadays, αKL levels correlation to pregnancy or pregnancy's complications, such as preeclampsia (PE) or intra-uterine growth restriction (IUGR) is not clear. The research goals were to monitor αKL concentrations during pregnancy and to investigate its expression alterations in correlation to pregnancy complication [3,4,5]. Method The research included 49 participants, recruited at the Baruch Padeh Poriya medical center, Obstetric Department. The participants were divided into two groups: healthy and complicated pregnancy (PE, IUGR or both). Blood and urine samples were collected during pregnancy and post-delivery (PD). Placental samples were subjected to biochemical (WB) and Elisa), morphological (H&amp;E) histological (IHC) staining and genetic analysis (qPCR). αKL activity was assessed using specific assigned Elisa kit. Results sKL during pregnancy show constant concentration that was similar in both healthy and complicated pregnancy. Significant decrease was measured in PE in sKL concentration at PD compared to its level during pregnancy. αKL activity was dramatically reduced in complicated pregnancies compared with healthy pregnancy during and PD. Placental tissue section staining presents decrease in mKL level in the placenta of complicated pregnancy group compared with healthy group. Additionally, we found significant decline in the expression of mRNA of mKL in PE/IUGR placentas compared with healthy group. Conclusion 1. sKL level was similar in both healthy and complicated pregnancy, our results suggest low activity of sKL in complicated pregnancy compared with control. 2. Complicated pregnancy is manifested in decline in mKL, also with low activity of sKL compared with control, and gene expression between healthy and complicated pregnancy. 3. A dramatic and significant decline in NO molecules concentration in urine of complicated pregnancy compared with healthy pregnancy.

Paraben exposure and couple fecundity: a preconception cohort study.

Is pre-conception exposure to parabens associated with fecundity in couples of childbearing age? Paraben exposure in female partners was associated with reduced couple fecundity and anti-Müllerian hormone (AMH) might be one of the possible mediators. The reproductive toxicity of parabens, a class of widely used preservatives, has been suggested but evidence regarding their effects on couple fecundity is scarce. In this couple-based prospective cohort study, a total of 884 pre-conception couples who participated in the Shanghai Birth Cohort between 2013 and 2015 were included. Concentrations of six parabens were measured in urine samples collected from couples. Malondialdehyde, C-reactive protein, and AMH were assessed in female partners. The outcomes included couple fecundability (time-to-pregnancy, TTP) and infertility (TTP > 12 menstrual cycles). Partner-specific and couple-based models were applied to estimate the associations. The joint effect of paraben mixture on couple fecundity was estimated by quantile-based g-computation (q-gcomp). Mediation analysis was used to assess the mediating roles of oxidative stress, inflammation and ovarian reserve. A total of 525 couples (59.4%) conceived spontaneously. In the partner-specific model, propyl paraben (PrP), butyl paraben (BuP), and heptyl paraben (HeP) in female partners were associated with reduced fecundability (fecundability odds ratio (95% CI): 0.96 (0.94-0.98) for PrP; 0.90 (0.87-0.94) for BuP; 0.42 (0.28-0.65) for HeP) and increased risk of infertility (rate ratio (95% CI): 1.06 (1.03-1.10) for PrP; 1.14 (1.08-1.21) for BuP; 1.89 (1.26-2.83) for HeP). Similar associations were observed in the couple-based model. AMH played a significant mediation role in the association (average causal mediation effect (95% CI): 0.001 (0.0001-0.003)). Paraben exposure in male partners was not associated with couple fecundity. The joint effect of paraben mixture on couple fecundity was non-significant. Self-reported pregnancy and single urine sample may lead to misclassification. The mediation analysis is limited in that levels of sex hormones were not measured. The inclusion of women with irregular menstrual cycles might affect the results. It is possible that the observed association was due to reverse causation. This is the first study to assess the effects of paraben exposure on couple fecundity in Asians. Given the widespread exposure to parabens in couples of childbearing age, the present findings may have important public health implications. This study was supported in part by the National Natural Science Foundation of China (41991314), the Shanghai Science and Technology Development Foundation (22YF1426700), the Science and Technology Commission of Shanghai Municipality (21410713500), and the Shanghai Municipal Health Commission (2020CXJQ01). All authors declare no conflict of interest. N/A.

Association between Prenatal Marijuana and Tobacco Smoke Exposures and Small for Gestational Age at Birth.

The aim of this study was to determine the association of prenatal marijuana exposure with and without tobacco smoke exposure and small for gestational age (SGA) at birth. We conducted a secondary analysis of the prospective Lifestyle and Early Achievement in Families (LEAF) cohort enrolled from 2010 to 2015. We included singleton nonanomalous liveborn pregnancies. We assessed marijuana use inclusive of any pregnancy urine specimen with a Δ9-THC-COOH concentration of more than 15 ng/mL by mass spectrometry, self-report on questionnaire, and/or electronic health record; and self-reported maternal tobacco use. Because of the high co-frequency of marijuana with tobacco exposure in pregnancy and the known association between tobacco and fetal growth restriction, we modeled the exposure as: both marijuana and tobacco (hereafter "co-use"), only marijuana, only tobacco, and neither (reference). Incidence of SGA in each group was compared with the neither group. The primary outcome was SGA less than 10th percentile, and secondarily less than 5th percentile, using parity-specific definitions per 2017 US natality reference data. Among 325 assessed mothers, 46% had neither exposure, 11% had only prenatal marijuana exposure, 20% only tobacco exposure, and 23% co-use exposure. A third (33%) of infants were SGA less than 10th percentile and 20% SGA less than 5th percentile. Marijuana exposure only was associated with an increased risk of SGA less than 10th percentile (43 vs. 26%; adjusted relative risk [aRR]: 1.66; 95% confidence interval [CI]: 1.02-2.69), and SGA less than5th percentile (30 vs. 13%; aRR: 2.26; 95% CI: 1.15-4.47). Tobacco was not associated with SGA less than 10th percentile, but was with SGA less than 5th percentile (26 vs. 13%; aRR: 2.01; 95% CI: 1.13, 3.56). Co-use was not associated with increased SGA risk in multivariate analysis, but was in sensitivity analysis when tobacco use was defined using a cotinine assay rather than self-report (SGA <10th percentile, aRR: 1.97; 95% CI: 1.24-3.15) and (SGA <5th percentile, aRR: 2.03; 95% CI: 1.09-3.78). Prenatal marijuana exposure in addition to tobacco may increase the risk of SGA. Given the rising prevalence of marijuana use in pregnancy, further research is warranted to understand how in utero marijuana exposure may impact fetal growth and birth weight with and without tobacco exposure. · Marijuana and tobacco are commonly used together in pregnancy.. · Prenatal marijuana and tobacco exposure may increase the risk of a small for gestational age infant.. · Further research is warranted to understand how in utero marijuana exposure impacts fetal growth..

Gestational Antibodies to C. pneumoniae, H. pylori and CMV in Women with Preeclampsia and in Matched Controls.

Some research has suggested a possible role for past infection in the development of preeclampsia. The objective of this study was to explore the role of Helicobacter pylori, cytomegalovirus, and Chlamydophila pneumoniae in the development of preeclampsia in a prospective pregnancy sample. We conducted a nested case-control study in The Archive for Child Health (ARCH), a pregnancy cohort of 867 unselected women enrolled at the first prenatal visit with archived blood and urine in pregnancy. We matched 21 cases of preeclampsia to 52 unaffected controls on maternal age (±4 years), race, parity, and gestational age at blood draw. Using conditional logistic regression, we examined theassociation between preeclampsia status and immunoglobulins G (IgG) tested by indirect ELISA to each of the three microorganisms, adjusting for potential confounders. No significant difference was found between cases and controls. The unadjusted odds ratio was 1.5 (95%CI: 0.2-9.1), 0.6 (95%CI: 0.2-1.9), and 1.9 (95%CI: 0.6-5.6) for H. pylori, cytomegalovirus and C. pneumoniae respectively. After controlling for confounders analysis found increased odds of H. pylori IgG (AOR: 1.9; 95% CI: 0.2-15.3) and C. pneumoniae IgG (AOR: 2.3; 95% CI: 0.6-9.2) for preeclampsia, albeit being not significant. Conversely, cytomegalovirus IgG had lower odds for preeclampsia (AOR: 0.4; 95% CI: 0.1-1.7). Past infection with H. pylori, and C. pneumoniae in early pregnancy showed a higher risk of preeclampsia, but the findings failed to achieve statistical significance. Cytomegalovirus was not associated with preeclampsia in these data. These preliminary findings encourage future research in populations with high prevalence of these infections.

Effect of Nitya virechana before intrauterine insemination

In modern medical science, diagnosis and treatment are based on a direct vision which is made by a number of diagnostic tests. When infertility evaluation failed to detect any cause of infertility, it is called “Unexplained Infertility.” Intra-uterine insemination (IUI) is a basic treatment option in such unexplained cases. In Ayurvedic classics, Ritu (~menstruation), Kshetra (~uterus), Ambu (~nutrition), and Beeja (~ovum and/or sperm) are described as essential factors for conception. Adequate physiological functioning of these factors is also necessary with the absence of causative factors to achieve conception. Along with that normal psychology is also described as an important aspect for conception. A 35-year-old female presented to Stree Roga Evum Prasuti Tantra OPD, on December 2019 with chief complaints of long-standing unexplained infertility. The patient was advised IUI along with Ayurvedic management. Vata is a principle Dosha in Vandhyatva (~infertility) and Mridu sanshodhana (~mild purification) described as a line of treatment to treat vitiated Vata dosha. Virechana is also maintained for “Agarbha” Stree (~infertile woman). Hence, the patient was treated with Nitya virechana (~daily therapeutic purgation) by Eranda sneha (~castor oil). Eranda sneha maintains Agni (~digestive power) and normalizes Vata dosha by Vata anulomana karma (~carminatives). It also affects the psychological status of the patient by Medhya (~intellect power) and Smritikara (~improving memory) properties. This concept was followed in this case to manage infertility. After the second cycle of IUI, urine pregnancy was achieved in April 2020, and delivered a healthy male baby in November 2020.

High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American maternal-child cohort

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014–2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 μg/g creatinine and 3.69 μg/g creatinine in early and late pregnancy, respectively. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.

Parental Preconception and Prenatal Environmental Exposures and Child Neurobehavioral Outcomes

BACKGROUND AND AIM: There are limited studies quantifying the effects of paternal and maternal preconception environmental exposures on children’s health. The Preconception Environmental exposure And Childhood health Effects (PEACE) Study includes children (age 6-13 years) who were born to couples in the Environment and Reproductive Health (EARTH) Study and aims to determine the extent to which maternal and paternal preconception phthalate exposures are associated with neurobehavioral outcomes. METHODS: The PEACE study began in 2019 and is ongoing. A total of 478 eligible children (includes multiples) were born to 451 mothers who participated in the EARTH study (2005-2017). Study staff collected multiple maternal and paternal preconception urine samples before pregnancy and prenatal maternal urine samples during each trimester of pregnancy. We quantified 10 urinary phthalate metabolites in these samples. Children’s behavior, executive function, and reciprocal social behaviors are being assessed via parent-report using the Behavior Assessment System for Children-3 (BASC-3), Behavior Rating Inventory of Executive Function (BRIEF), and Social Responsiveness Scale-2 (SRS-2), respectively. Trained staff collected additional information about diet, sleep, physical activity, product use, and COVID-19 stress. RESULTS:As of March 2021, we enrolled 95 mothers, 57 fathers, and 120 children in the PEACE Study who completed visits either in person or virtually. Of children who completed the study, 64 (53%) were boys and 97 (81%) were White. Mean BASC-3 total behavior problem scores were 48.7 (SD: 7.6). Ten percent of children had scores indicative of being at-risk for behavioral problems (T-score60). Average BRIEF and SRS-2 scores were 48.2 (SD: 9.5) and 46.9 (SD:6.1), respectively. CONCLUSIONS:The PEACE Study will provide new information about the potential impact of parental preconception environmental chemical exposures on children’s health. In addition, the PEACE study will be able to leverage the rich data repository that includes parental chemical, built environment, and dietary exposures. KEYWORDS: Children's environmental health, Neurodevelopmental outcomes, Phthalates, Male, Chemical exposures, Endocrine disrupting chemicals, Female

Prenatal exposure to lipophilic endocrine-disrupting chemicals and liver injury in children using chemical mixture approaches

BACKGROUND AND AIM: Exposure to Endocrine Disrupting Chemicals (EDC) may increase liver injury, but few studies have examined these associations in children and most focused on a single chemical group. We evaluated the associations between a wide range of prenatal EDC exposures and child liver injury. METHODS: We studied 1108 healthy children from the Human Early-Life Exposome (HELIX) project, a collaborative network of six established longitudinal population-based birth cohort studies in Europe. Thirty lipophilic EDCs (including 3 organochlorine pesticides, 5 polychlorinated-biphenyl, 2 polybrominated-diphenyl-ethers [PBDEs], 5 high molecular weight phthalates (HMWP), 5 low molecular weight phthalates, 6 phenols and 4 organophosphate pesticides) were measured in maternal pregnancy blood or urine. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and cytokeratin 18 (CK18) were measured in child serum at follow-up between age 6-11 years. Liver injury was defined as having any liver enzyme (ALT, AST or GGT) above the 90th percentile. We used Bayesian generalized linear mixed regressions (Bglmr) to estimate associations of individual chemicals, Bayesian Weighted Quantile Sum (BWQS) and Bayesian Kernel Machine Regression (BKMR) to assess the overall association of each chemical group with liver injury and CK18, adjusting for confounders. RESULTS:BWQS results indicated that organochlorine pesticides and PBDEs were associated with increased odds of liver injury (OR[95%CI] by chemical mixture quartile increase=1.44[1.23, 1.72] and 1.59[1.37, 1.90], respectively); whereas HMWP were associated with decreased odds of liver injury (OR[95%CI]=0.71[0.59, 0.85]). A quartile increase of PBDEs was positively associated with CK18 (Estimate[95%CI]=5.33 Units/Liter [2.52,8.16]). Bglmr and BKMR showed associations in same direction as the BWQS results. There was evidence of effect heterogeneity by sex for organochlorine pesticides and HMWPs with liver injury status. CONCLUSIONS:Using multiple chemical mixture approaches we found that prenatal exposures to persistent pollutants, especially to organochlorine compounds, and PBDEs, may be associated with increased risk for liver injury in childhood. KEYWORDS: Chemical exposures, Endocrine disrupting chemicals, Mixtures analysis, Modeling, Environmental epidemiology

High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American Maternal-Child cohort

BACKGROUND AND AIM: Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. In this analysis, we measured urinary cotinine, a widely used biomarker of tobacco exposure, and conducted high-resolution metabolomics (HRM) to identify biological perturbations associated with prenatal tobacco smoke exposures and adverse birth outcomes. METHODS: We collected early and late pregnancy urine samples for cotinine measurement and serum samples for HRM profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014-2016). Using an untargeted HRM workflow, we investigated how the biological perturbations in maternal metabolome mediate the association between prenatal smoke exposures and adverse birth outcomes (preterm birth, early term birth vs. full term birth; gestational age at birth) using a meet-in-the-middle approach. RESULTS:The median maternal urinary cotinine level was 4.77 ug/g creatinine, with 29 subjects higher than 100 ug/g creatinine. In total, 16,481 and 13,043 metabolic features were extracted from serum samples using hilic and c18 columns, respectively. Thirteen metabolic pathways were found to be associated with cotinine level and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine exposure, preterm birth, and shorter gestational length, which include glutamate, serine, choline, and taurine; these metabolites are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. CONCLUSIONS:The metabolic perturbations associated with cotinine exposure were closely connected within a metabolic network related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings support the future development of targeted interventions to reduce adverse birth outcomes associated with tobacco smoke exposure, especially among African American who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes. KEYWORDS: Tobacco Smoke Exposures, Metabolomics, Birth Outcomes, Preterm Birth

#36: A Review of Maternal and Neonatal Characteristics and Outcomes in Pregnant Women with Serious Infectious Complications from Injection Drug Use

Abstract Background Pregnant people who inject drugs (PWID) and their infants are unique populations that have emerged from the opioid epidemic. Numerous studies have evaluated vertical transmission of HIV, HCV, sequelae of neonatal abstinence syndrome, and maternal and fetal mortality in these mother-infant dyads; however there still remains a large knowledge gap regarding how serious infections in pregnant PWID affect more proximal outcomes such as fetal and maternal distress leading to preterm delivery, risk of neonatal sepsis, need for invasive diagnostic procedures to rule-out neonatal sepsis such as lumbar puncture, neonatal intensive care unit (NICU) admission, and potential consequences of prolonged intrauterine antibiotic exposure. Methods We identified pregnant PWID ≥18 years old with serious infectious complications (defined as (sepsis, endocarditis, osteomyelitis, epidural abscesses, septic arthritis/bursitis, thrombophlebitis, and skin and soft tissue infections requiring IV antibiotics) admitted between 2017–2018 to the University of Kentucky Medical Center and their neonates treated at Kentucky Children’s Hospital. Patients were identified using positive urine or serum pregnancy test results, IVDU-associated ICD9/10 codes, infectious disease, neonatology, and obstetrics notes. Results 261 women with infectious complications from IVDU were identified, 25 were pregnant and 16 dyads were able to be matched with identification of 14 viable neonates born at the University of Kentucky. Mean maternal age was 31 years and median 30 years. Mean gestational age (GA) at time of admission was 25 weeks with median 29 weeks. Sepsis was the most common complication reported 18 (72%) followed by endocarditis 11 (44%). Staphylococcus aureus was the most isolated organism (16) 64% with 12 (48%) of isolates identified as MRSA and MSSA comprising 4 (16%). 96% were screened for HCV, with 72% HCV antibody positive and 32% with detectable viral load. There was 1 reported maternal death, 1 spontaneous abortion and 2 intrauterine fetal demises (IUFD) in the 3rd trimester and no neonatal deaths. Average GA at time of delivery was 33 weeks with median 36 weeks. 6 (42%) were routine deliveries with 3 (22%) deliveries for emergent maternal indications and 5 emergent deliveries for fetal indications (36%). 12 neonates (86%) required NICU admission with average length of stay 17 days and median 10 days. 10 (71%) underwent limited sepsis screen with 9 (64%) receiving at least 48 hours of antibiotics and 3 (22%) receiving an extended course. However none of the blood cultures yielded any organisms. All passed their hearing screening and had no evidence of renal dysfunction or cytopenias. Conclusions Pregnant PWID dyads may be at increased risk for morbidity and mortality secondary to infectious complications of IVDU. The majority of neonates were delivered early for either fetal distress or maternal distress. 2 mothers suffered IUFD in the 3rd trimester and the majority of the neonates required NICU admission (86%) due to prematurity-related factors, concern for neonatal abstinence syndrome or concern for infectious complications. Over half received 48+ hours of antibiotics in the NICU however none of the neonatal blood cultures yielded an organism. Larger cohort studies are needed to better ascertain risk in these expanding populations.

Gestational Exposure to Organophosphate Pesticides and Longitudinally Assessed Behaviors Related to Attention-Deficit/Hyperactivity Disorder and Executive Function.

The brain’s prefrontal cortex directs higher-order cognitive and behavioral processes that are important for attention, working memory, and inhibitory control. We investigated whether gestational exposure to organophosphate (OP) pesticides was associated with these abilities in childhood and early adolescence. Between 1999 and 2000, we enrolled pregnant women in a birth cohort drawn from an agricultural region of California. We measured dialkyl phosphate (DAP) metabolites of OP pesticides in maternal pregnancy urine samples (13 and 26 weeks) and estimated associations with behaviors related to attention-deficit/hyperactivity disorder and executive function, assessed longitudinally; 351 families provided neurodevelopmental outcome data at any point when the child was aged 7–12 years. We assessed function across multiple dimensions (e.g., working memory, attention), methods (e.g., behavior reports, child assessment), and reporters (e.g., mothers, teachers, child self-reports). Higher gestational DAP concentrations were consistently associated with behaviors related to attention-deficit/hyperactivity disorder and executive function. For example, a 10-fold increase in gestational DAP concentration was associated with poorer longitudinally assessed Behavior Rating Inventory of Executive Function scores, as reported by mothers (β = 4.0 (95% confidence interval: 2.1, 5.8); a higher score indicates more problems), and Weschler Intelligence Scale for Children—Fourth Edition Working Memory scores (a 3.8-point reduction; β = −3.8 (95% confidence interval: −6.2, −1.3)). Reducing gestational exposure to OP pesticides through public health policy is an important goal.

MO653RISK FACTORS FOR DIABETIC NEPHROPATHY AMONG NEWLY DIAGNOSED TYPE 2 DIABETIC PATIENTS WITH NORMAL BLOOD PRESSURE

Abstract Background and Aims Diabetes mellitus (DM) is the leading cause of chronic kidney disease; principally resulting from the increasing prevalence of type 2 DM (T2DM). Patients with T2DM pass through pre-diabetic stages and at the time of diagnosis, up to half of the T2DM patients may have different macro- and micro-vascular complications, including diabetic nephropathy. Hypertension has adverse impacts on diabetic nephropathy. This study was designed to evaluate the risk factors for diabetic nephropathy among newly detected T2DM patients with normal blood pressure. Method This case-control study was done at out-patient department of a referral hospital in Dhaka, Bangladesh from January 2018 to June 2019. Newly detected (&amp;lt;3 months), adult (≥18 years), T2DM patients of either sex, who underwent test for urine albumin-to-creatinine ratio (UACR), at least twice (6 weeks apart), within a 6-month period, were included in this study. Patients with hypertension (newly diagnosed or known cases/on antihypertensive medications), known kidney disease, features of glomerulonephritis, systemic diseases including systemic lupus erythematosus and vasculitis, history of recent fever and exercise, urinary tract infection and pregnancy were excluded. Patients with UACR ≥30 mg/g in at least two (of three, if done) samples were cases and those with UACR &amp;lt;30 mg/g were controls. Results Total patients were 135, including 27 cases [moderately increased proteinuria (previously, microalbuminuria) (UACR 30 – 299 mg/g) = 25 and severely increased proteinuria (previously, overt proteinuria) (UACR ≥300 mg/g) = 2] and 108 controls. Mean age was 42.9 years and there was female (64.8%) predominance. Thirteen percent patients were smokers, 12% had dyslipidaemia, 51% had family history of DM and 44.9% had family history of diabetic nephropathy. Besides diabetic nephropathy, other chronic complications of DM were diabetic retinopathy (6.7%), diabetic peripheral neuropathy (0.7%) and coronary artery disease (1.5%). Regarding risk factors for diabetic nephropathy, family history of DM [odds ratio (OR) = 2.31, 95% confidence interval (CI) = 0.923 – 5.415, p = 0.003) and diabetic nephropathy (OR = 3.28, 95% CI = 1.523 – 9.297, p = 0.001), smoking (OR = 3.08, 95% CI = 1.066 – 0.934, p = 0.003), dyslipidaemia (OR = 2.11, 95% CI = 0.241 – 3.464, p = 0.004) and coexisting diabetic retinopathy (OR = 6.51, 95% CI = 1.46 – 11.79, p = 0.003) were significant. On multivariate logistic regression, family history of DM (OR = 2.13, 95% CI = 1.412 – 4.216, p = 0.003) and diabetic nephropathy (OR = 3.31, 95% CI = 2.145 – 5.249, p = 0.001), smoking (OR = 3.11, 95% CI = 2.234 – 4.123, p = 0.003), dyslipidaemia (OR = 2.14, 95% CI = 1.363 – 3.324, p = 0.005) and diabetic retinopathy (OR = 6.23, 95% CI = 4.197 – 9.464, p = 0.004) were significant. Conclusion Family history of DM and diabetic nephropathy, smoking, dyslipidaemia and concomitant diabetic retinopathy were significant risk factors for diabetic nephropathy among newly diagnosed T2DM patients with normal blood pressure.

Development and analysis of surface plasmon resonance based refractive index sensor for pregnancy testing

In the proposed work, a two-dimensional photonic crystal fiber (PCF) based on the surface plasmon resonance (SPR) refractive index sensor has been demonstrated and designed which is so much helpful to gain a better sensitivity response in urine observation. In order to detect the pregnancy, the simulation and analysis have been performed in both normal and pregnant urine with the effective refractive indices values of 1.335, 1.34, 1.342 and 1.343 within the range of working wavelength from 1.75 µm to 2 µm. From this testing sensor, the optical parameters of the dispersion relation, birefringence, coupling length, confinement loss, insertion loss, sensor length, crosstalk, sensitivity response, resonance wavelength, resolution, and sensitivity per line-width have been analyzed. Besides, Finite element method (FEM) is used for the numerical investigations. From this investigation, the highest value of sensitivity response, sensitivity per line-width, and the resolution of 68051.344 nm/RIU, 314 RIU−1, and 9.39 × 10−6 RIU are gained. It is noted that the proposed sensor offers significant sensing performances for the polarized modes. The main goal of this investigation is to develop the concepts of optoelectronics and laser bio-sensor in the field of biological detection systems. As a result, this structure of optical biosensor will be applicable through the modified optical fiber in biological changes.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial

BackgroundFire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis.MethodsNinety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd.DiscussionIt is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis.Trial registrationClinicaltrials.govNCT03953885. Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome

P1034EVALUATION OF RISK FACTORS FOR DIABETIC NEPHROPATHY AMONG NEWLY DIAGNOSED TYPE 2 DIABETIC SUBJECTS

Abstract Background and Aims Diabetes mellitus (DM) is the leading cause of chronic kidney disease in developed as well as in developing countries, principally resulting from the increasing prevalence of type 2 DM (T2DM). Patients with T2DM pass through pre-diabetic stages and half of the T2DM patients remain undiagnosed. During diagnosis, one-third to half of the T2DM patients may have different macro- and micro-vascular complications including diabetic nephropathy. This study was designed to evaluate risk factors for diabetic nephropathy among newly detected T2DM subjects. Method A case-control study was done at out-patient department of a tertiary care hospital in Dhaka, Bangladesh from October 2016 to June 2017. Newly detected (&amp;lt;3 months) adult (≥18 years) T2DM patients of either sex, who underwent test for urine albumin-to-creatinine ratio (UACR) at least twice, at least 6 weeks apart, within a 6-month period, were included in this study. Patients with diagnosed kidney diseases, features of glomerulonephritis, systemic diseases like systemic lupus erythematosus and vasculitis, history of recent fever and exercise, urinary tract infection and pregnancy were excluded. Patients with UACR ≥30 mg/g in at least two (of three, if done) samples were cases and those with UACR &amp;lt;30 mg/g were controls. Results Total patients were 100, including 35 cases [moderately increased proteinuria (previously, microalbuminuria) (UACR 30-299 mg/g) = 33 and severely increased proteinuria (previously, overt proteinuria) (UACR ≥300 mg/g) = 2] and 65 controls. Mean age was 46.6±12.3 years and there was female predominance (male:female ratio was 1:2). Twenty four percent patients were smokers, 50% were hypertensive and 46% had dyslipidaemia. Seventy five percent of the study participants had positive family history of DM and 39% had family history of diabetic nephropathy. Mean body mass index (BMI) was 26.3±2.9 kg/m2. Mean fasting blood glucose (mmol/L), 2-h post glucose value (mmol/L) and mean glycated haemoglobin (HbA1c) (%) were 9.2±2.9, 14.5±4.1 and 7.9±1.3 respectively. Eighty percent of the patients were asymptomatic regarding DM. Besides nephropathy, other chronic complications of DM were diabetic retinopathy (17%), neuropathy (11%), coronary artery disease (11%) and cerebrovascular disease (4%). Regarding risk factors for diabetic nephropathy, family history of DM (OR 1.62, p 0.0001) and diabetic nephropathy (OR 25.13, p 0.003), presence of hypertension (OR 4.93, p 0.001) and coexisting diabetic retinopathy (OR 14.18, p 0.046) were significant. On multivariate logistic regression, family history of DM (OR 1.77, p 0.001) and diabetic nephropathy (OR 24.31, p 0.001), higher BMI (&amp;gt;25 kg/m2) (OR 2.11, p 0.013), hypertension (OR 4.31, p 0.003) and diabetic retinopathy (OR 14.09, p 0.021) were significant. Conclusion One-third of the newly detected type 2 diabetic subjects had diabetic nephropathy in this study. Family history of DM and diabetic nephropathy, higher BMI, presence of hypertension and diabetic retinopathy were significant risk factors for diabetic nephropathy.

Prenatal and childhood arsenic exposure through drinking water and food and cognitive abilities at 10 years of age: A prospective cohort study

BackgroundOur studies of children in a rural Bangladeshi area, with varying concentrations of arsenic in well-water, indicated modest impact on child verbal cognitive function at 5 years of age. ObjectivesFollow-up of arsenic exposure and children’s cognitive abilities at school-age. MethodsIn a nested sub-cohort of the MINIMat supplementation trial, we assessed cognitive abilities at 10 years of age (n = 1523), using Wechsler Intelligence Scale for Children (WISC-IV). Arsenic in maternal urine and erythrocytes in early pregnancy, in child urine at 5 and 10 years, and in hair at 10 years, was measured using Inductively Coupled Plasma Mass Spectrometry. ResultsMedian urinary arsenic at 10 years was 58 µg/L (range 7.3–940 µg/L). Multivariable-adjusted regression analysis showed that, compared to the first urinary arsenic quintile at 10 years (<30 µg/L), the third and fourth quintiles (30–45 and 46–73 µg/L, respectively) had 6–7 points lower Full developmental raw scores (B: −7.23, 95% CI −11.3; −3.18, and B: −6.37, 95% CI −10.5; −2.22, respectively), corresponding to ~0.2 SD. Verbal comprehension and Perceptual reasoning seemed to be affected. Models with children’s hair arsenic concentrations showed similar results. Maternal urinary arsenic in early pregnancy, but not late pregnancy, showed inverse associations with Full developmental scores (quintiles 2–4: B: −4.52, 95% CI −8.61; −0.43, B: −5.91, 95% CI −10.0; −1.77, and B: −5.98, 95%CI −10.2; −1.77, respectively, compared to first quintile), as well as with Verbal comprehension, Perceptual reasoning, and Processing speed, especially in girls (p < 0.05 for interaction of sex with Full developmental scores and Perceptual reasoning). In models with all exposure time points included, both concurrent exposure at 10 years and early prenatal exposure remained associated with cognitive abilities. ConclusionsBoth early prenatal and childhood arsenic exposure, even at low levels (about 50 µg/L in urine), was inversely associated with cognitive abilities at school-age, although the estimates were modest.