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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2023

Contraceptive Sabotage and Contraceptive Use at the Time of Pregnancy: An Analysis of People with a Recent Live Birth in the United States

Contraceptive sabotage and other forms of intimate partner violence (IPV) can interfere with contraceptive use. We used 2012 to 2015 Pregnancy Risk Assessment Monitoring System data from 8,981 people residing in five states who reported that when they became pregnant, they were not trying to get pregnant. We assessed the relationships between ever experiencing contraceptive sabotage and physical IPV 12 months before pregnancy (both by the current partner) and contraceptive use at the time of pregnancy using multivariable logistic regression. We also assessed the joint associations between physical IPV 12 months before pregnancy and ever experienced contraceptive sabotage with contraceptive use at the time of pregnancy. Few people ever experienced contraceptive sabotage (1.8%; 95% confidence interval [CI]: 1.4, 2.3) or physical IPV 12 months before pregnancy (2.8%; 95% CI: 2.3, 3.3). In models adjusted for age, race/ethnicity, marital status, education, and state of residence, ever experiencing contraceptive sabotage was associated with contraceptive use at the time of pregnancy (adjusted odds ratio [aOR]: 1.73; 95% CI: 1.06, 2.82), but not with physical IPV 12 months before pregnancy (aOR: 0.69; 95% CI: 0.46, 1.02). When examining the joint association, compared to not ever experiencing contraceptive sabotage or physical IPV 12 months before pregnancy, ever experiencing contraceptive sabotage was significantly related to contraceptive use at the time of pregnancy (aOR: 1.72; 95% CI: 1.00, 2.95). However, it was not associated with experiencing physical IPV 12 months before pregnancy (aOR: 0.68; 95% CI: 0.45, 1.04) or with experiencing both contraceptive sabotage and physical IPV 12 months before pregnancy (aOR: 1.21; 95% CI: 0.42, 3.50), compared to not ever experiencing contraceptive sabotage or physical IPV 12 months before pregnancy. Our study highlights that current partner contraceptive sabotage may motivate those not trying to get pregnant to use contraception; however, all people in our sample still experienced a pregnancy.

Huber-Krum, Sarah↗
DOE OSTI2018

Ambient air pollution and pregnancy outcomes: A comprehensive review and identification of environmental public health challenges

There is a growing number of studies on the association between ambient air pollution and adverse pregnancy outcomes, but their results have been inconsistent. Consequently, a comprehensive review of this research area is needed. There was a wide variability in studied pregnancy outcomes, observed gestational windows of exposure, observed ambient air pollutants, applied exposure assessment methods and statistical analysis methods Gestational duration, preterm birth, (low) birth weight, and small for gestational age/intrauterine growth restriction were most commonly investigated pregnancy outcomes. Gestational windows of exposure typically included were whole pregnancy period, 1st, 2nd, 3rd trimester, first and last gestational months. Preterm birth was the outcome most extensively studied across various gestational windows, especially at the beginning and at the end of pregnancy. Particulate matter, nitrogen dioxide, ozone, and carbon monoxide were the most commonly used markers of ambient air pollution. Continuous monitoring data were frequently combined with spatially more precisely modelled estimates of exposure. Exposure to particulate matter and ozone over the entire pregnancy was significantly associated with higher risk for preterm birth: the pooled effect estimates were 1.09 (1.03–1.16) per 10 μg/m{sup 3} increase in particulate matter with an aerodynamic diameter of 10 µm or less (PM{sub 10}){sub ,}1.24 (1.08–1.41) per 10 μg/m{sup 3} increase in particulate matter with an aerodynamic diameter of 2.5 µm or less (PM{sub 2.5}), and 1.03 (1.01–1.04) per 10 ppb increase in ozone. For pregnancy outcomes other than PTB, ranges of observed effect estimates were reported due to smaller number of studies included in each gestational window of exposure. Further research is needed to link the routine pregnancy outcome data with spatially and temporally resolved ambient air pollution data, while adjusting for commonly defined confounders. Methods for assessing exposure to mixtures of pollutants, indoor air pollution exposure, and various other environmental exposures, need to be developed.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Pregnancy outcome and ultraviolet radiation; A systematic review

Background: Season and vitamin D are indirect and direct correlates of ultraviolet (UV) radiation and are associated with pregnancy outcomes. Further to producing vitamin D, UV has positive effects on cardiovascular and immune health that may support a role for UV directly benefitting pregnancy. Objectives: To investigate the effects of UV exposure on pregnancy; specifically fetal growth, preterm birth and hypertensive complications. Methods: We conducted a systematic review of Medline, EMBASE, DoPHER, Global Health, ProQuest Public Health, AustHealth Informit, SCOPUS and Google Scholar to identify 537 citations, 8 of which are included in this review. This review was registered on PROSPERO and a. narrative synthesis is presented following PRISMA guidance. Results: All studies were observational and assessed at high risk of bias. Higher first trimester UV was associated with and improved fetal growth and increased hypertension in pregnancy. Interpretation is limited by study design and quality. Meta-analysis was precluded by the variety of outcomes and methods. Discussion: The low number of studies and risk of bias limit the validity of any conclusions. Environmental health methodological issues are discussed with consideration given to design and analytical improvements to further address this reproductive environmental health question. Conclusions: The evidence for UV having benefits for pregnancy hypertension and fetal growth is limited by the methodological approaches utilized. Future epidemiological efforts should focus on improving the methods of modeling and linking widely available environmental data to reproductive health outcomes. - Highlights: • Biologically plausible pathways support an association between ultraviolet radiation (UV) and pregnancy outcomes. • This study is the first systematic review of prevailing literature on the relationship between UV and singleton pregnancy outcomes. • It focuses on both substantive findings and the methodologies that were used. • Only seven studies met the search criteria and these were methodologically heterogeneous demonstrating a paucity of evidence. • Given the plausibility of the UV pathway, more studies examining this hypothesis are needed.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Toxics (Pb, Cd) and trace elements (Zn, Cu, Mn) in women during pregnancy and at delivery, South Benin, 2014–2015

Highlights: • Lack of data on maternal exposure to toxic and trace elements in Africa. • Longitudinal blood measurements of Pb, Cd, Zn, Cu and Mn during pregnancy in Benin. • Evidence of maternal exposure to Pb and Cd. • Identification of potential sources for Pb exposure during pregnancy. During pregnancy, fetal development can be hindered by maternal exposure to toxic elements and abnormal concentrations of trace elements. Few data are available in African countries. Our goal was to assess the body burden of lead (Pb), cadmium (Cd), manganese (Mn), zinc (Zn) and copper (Cu) in pregnant women in Benin. The study was carried out in Sô-Ava district, from November 2015 to April 2016. Sixty women were recruited from the RECIPAL pre-conceptional cohort study. In all women, blood samples were collected during the first trimester of pregnancy. Thirty-two women had additional maternal and cord blood samples collected at delivery. Blood samples were analyzed by inductively coupled plasma mass spectrometry. At delivery, Cd median (IQR) concentration in maternal blood was 0.34 µg/L (0.24–0.46) in this non-smoking population. Pb median (IQR) concentration in maternal blood at delivery was 37.4 µg/L (30.5–52.0), with 31.3% of blood Pb levels above the 50 μg/L threshold. These pregnant women lived in semi-rural lakeside villages. Potential sources of Pb exposure identified during pregnancy were having water supply by drill pump and activities such as smoking fish by the woman and fishing by the household head. At delivery, Zn, Cu, and Mn median (IQR) concentrations in maternal blood were, respectively, 5415 μg/L (4894–5822), 1609 μg/L (1295–1771) and 16.0 μg/L (12.5–20.8). Pb, Cd, Mn and Cu blood concentrations were significantly higher at delivery than during the first trimester of pregnancy. Pb, Cd, Zn and Cu concentrations were significantly lower in cord blood than in maternal blood, contrary to Mn concentration, which was significantly higher in cord blood than in maternal blood at delivery. This exploratory study is the first one performed in Benin, and warns us about exposition of women from Sô-Ava district to Pb and Cd during pregnancy.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Application of physiologically based pharmacokinetic modeling for sertraline dosing recommendations in pregnancy

Pregnancy is a period of significant change that impacts physiological and metabolic status leading to alterations in the disposition of drugs. Uncertainty in drug dosing in pregnancy can lead to suboptimal therapy, which can contribute to disease exacerbation. A few studies show there are increased dosing requirements for antidepressants in late pregnancy; however, the quantitative data to guide dose adjustments are sparse. We aimed to develop a physiologically based pharmacokinetic (PBPK) model that allows gestational-age dependent prediction of sertraline dosing in pregnancy. A minimal physiological model with defined gut, liver, plasma, and lumped placental-fetal compartments was constructed using the ordinary differential equation solver package, ‘mrgsolve’, in R. We extracted data from the literature to parameterize the model, including sertraline physicochemical properties, in vitro metabolism studies, disposition in nonpregnant women, and physiological changes during pregnancy. The model predicted the pharmacokinetic parameters from a clinical study with eight subjects for the second trimester and six subjects for the third trimester. Based on the model, gestational-dependent changes in physiology and metabolism account for increased clearance of sertraline (up to 143% at 40 weeks gestational age), potentially leading to under-dosing of pregnant women when nonpregnancy doses are used. The PBPK model was converted to a prototype web-based interactive dosing tool to demonstrate how the output of a PBPK model may translate into optimal sertraline dosing in pregnancy. Quantitative prediction of drug exposure using PBPK modeling in pregnancy will support clinically appropriate dosing and increase the therapeutic benefit for pregnant women.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Machine learning approaches to predict gestational age in normal and complicated pregnancies via urinary metabolomics analysis

The elucidation of dynamic metabolomic changes during gestation is particularly important for the development of methods to evaluate pregnancy status or achieve earlier detection of pregnancy-related complications. Some studies have constructed models to evaluate pregnancy status and predict gestational age using omics data from blood biospecimens; however, less invasive methods are desired. Here we propose a model to predict gestational age, using urinary metabolite information. In our prospective cohort study, we collected 2741 urine samples from 187 healthy pregnant women, 23 patients with hypertensive disorders of pregnancy, and 14 patients with spontaneous preterm birth. Using gas chromatography-tandem mass spectrometry, we identified 184 urinary metabolites that showed dynamic systematic changes in healthy pregnant women according to gestational age. A model to predict gestational age during normal pregnancy progression was constructed; the correlation coefficient between actual and predicted weeks of gestation was 0.86. The predicted gestational ages of cases with hypertensive disorders of pregnancy exhibited significant progression, compared with actual gestational ages. This is the first study to predict gestational age in normal and complicated pregnancies by using urinary metabolite information. Minimally invasive urinary metabolomics might facilitate changes in the prediction of gestational age in various clinical settings.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

The safety of pranlukast and montelukast during the first trimester of pregnancy: A prospective, two‐centered cohort study in Japan

Abstract For leukotriene receptor antagonists (LTRAs), especially pranlukast, safety data during pregnancy is limited. Therefore, we conducted a prospective, two‐centered cohort study using data from teratogen information services in Japan to clarify the effects of LTRA exposure during pregnancy on maternal and fetal outcomes. Pregnant women who being counseled on drug use during pregnancy at two facilities were enrolled. The primary outcome of this study was major congenital anomalies. The incidence of major congenital anomalies in women exposed to montelukast or pranlukast during the first trimester of pregnancy was compared with that of controls. Logistic regression analysis was performed to analyze the effects of maternal LTRA use during the first trimester of pregnancy on major congenital anomalies. The outcomes of 231 pregnant women exposed to LTRAs (montelukast n = 122; pranlukast n = 106; both n = 3) and 212 live births were compared with those of controls. The rate of major congenital anomalies in the LTRA group was 1.9%. Multivariable logistic regression analysis revealed that LTRA exposure was not a risk factor for major congenital anomalies (adjusted odds ratio, 0.78; 95% confidence interval, 0.23–2.05; p = 0.653). In addition, no significant difference was detected in stillbirth, spontaneous abortion, preterm birth, and low birth weight between the two groups. The present study revealed that montelukast and pranlukast were not associated with the risk of major congenital anomalies. Our findings suggest that LTRAs could be safely employed for asthma therapy during pregnancy.

Hatakeyama, Shiro↗
DOE OSTI2015

Preconception and early pregnancy air pollution exposures and risk of gestational diabetes mellitus

Background: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk. Methods: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5 μm (PM{sub 2.5}) and PM{sub 2.5} constituents, PM ≤ 10 μm (PM{sub 10}), nitrogen oxides (NO{sub x}), carbon monoxide, sulfur dioxide (SO{sub 2}) and ozone (O{sub 3}) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1–24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity. Results: Preconception maternal exposure to NO{sub X} (RR=1.09, 95% CI: 1.04, 1.13) and SO{sub 2} (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O{sub 3} was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy. Conclusion: Maternal exposures to NO{sub x} and SO{sub 2} preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O{sub 3} appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation. - Highlights: • Air pollution may be related to gestational diabetes (GDM). • No prior studies have examined preconception exposure. • Maternal exposure to NO{sub x} and SO{sub 2} before conception increased subsequent GDM risk. • NO{sub x} and SO{sub 2} exposure in the first seven weeks of pregnancy also increased GDM risk. • Early exposure to O{sub 3} reduced GDM risk but risk increased after 15 weeks gestation.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2012

Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage prepubertally. ► E2 appears as an endocrine disruptor that might contribute to childhood obesity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection

Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Utility of Physiologically Based Pharmacokinetic Modeling to Investigate the Impact of Physiological Changes of Pregnancy and Cancer on Oncology Drug Pharmacokinetics

The treatment of cancer during pregnancy remains challenging with knowledge gaps in drug dosage, safety, and efficacy due to the under-representation of this population in clinical trials. Our aim was to investigate physiological changes reported in both pregnancy and cancer populations into a PBPK modeling framework that allows for a more accurate estimation of PK changes in pregnant patients with cancer. Methods: Paclitaxel and docetaxel were selected to validate a population model using clinical data from pregnant patients with cancer. The validated population model was subsequently used to predict the PK of acalabrutinib in pregnant patients with cancer. Results: The Simcyp pregnancy population model reasonably predicted the PK of docetaxel in pregnant patients with cancer, while a modified model that included a 2.5-fold increase in CYP2C8 abundance, consistent with the increased expression during pregnancy, was needed to reasonably predict the PK of paclitaxel in pregnant patients with cancer. Changes in protein binding levels of patients with cancer had a minimal impact on the predicted clearance of paclitaxel and docetaxel. PBPK modeling predicted approximately 60% lower AUC and Cmax for acalabrutinib in pregnant versus non-pregnant patients with cancer. Conclusions: Our results suggest that PBPK modeling is a promising approach to investigate the effects of pregnancy and cancer on the PK of oncology drugs and potentially inform dosing for pregnant patients with cancer. Further evaluation and refinement of the population model are needed for pregnant patients with cancer with additional compounds and clinical PK data.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Feasibility of Vascular Parameter Estimation for Assessing Hypertensive Pregnancy Disorders

Abstract Hypertensive pregnancy disorders (HPDs), such as pre-eclampsia, are leading sources of both maternal and fetal morbidity in pregnancy. Noninvasive imaging, such as ultrasound (US) and magnetic resonance imaging (MRI), is an important tool for predicting and monitoring these high risk pregnancies. While imaging can measure hemodynamic parameters, such as uterine artery pulsatility and resistivity indices (PI and RI), the interpretation of such metrics for disease assessment relies on ad hoc standards, which provide limited insight to the physical mechanisms underlying the emergence of hypertensive pregnancy disorders. To provide meaningful interpretation of measured hemodynamic data in patients, advances in computational fluid dynamics can be brought to bear. In this work, we develop a patient-specific computational framework that combines Bayesian inference with a reduced-order fluid dynamics model to infer parameters, such as vascular resistance, compliance, and vessel cross-sectional area, known to be related to the development of hypertension. The proposed framework enables the prediction of hemodynamic quantities of interest, such as pressure and velocity, directly from sparse and noisy MRI measurements. We illustrate the effectiveness of this approach in two systemic arterial network geometries: an aorta with branching carotid artery and a maternal pelvic arterial network. For both cases, the model can reconstruct the provided measurements and infer parameters of interest. In the case of the maternal pelvic arteries, the model can make a distinction between the pregnancies destined to develop hypertension and those that remain normotensive, expressed through the value range of the predicted absolute pressure.

Biophysics↗
NASA NTRS2000

Physiology of a microgravity environment selected contribution: effects of spaceflight during pregnancy on labor and birth at 1 G

The events of parturition (labor, delivery, maternal care, placentophagia, and onset of nursing) were analyzed in female Norway rats (Rattus norvegicus) flown on either 11- or 9-day-long spaceflights beginning at the approximate midpoint of their pregnancies. Each space shuttle flight landed on the 20th day of the rats' pregnancies, just 48-72 h before parturition. After spaceflight, dams were continuously monitored and recorded by time-lapse videography throughout the completion of parturition and onset of nursing (days 22 and 23). Analyses of parturition revealed that, compared with ground controls, flight dams displayed twice the number of lordosis contractions, the predominant labor contraction type in rats. The number of vertical contractions (those that immediately precede expulsion of a pup from the womb), the duration of labor, fetal wastage, number of neonates born, neonatal birth weights, placentophagia, and maternal care during parturition, including the onset of nursing, were comparable in flight and ground control dams. Our findings indicate that, with the exception of labor contractions, mammalian pregnancy and parturition remain qualitatively and quantitatively intact after spaceflight during pregnancy.

Non-NASA Center↗
DOE OSTI2015

Transjugular Intrahepatic Portosystemic Shunt Placement During Pregnancy: A Case Series of Five Patients

Background and AimsComplications of portal hypertension, such as variceal hemorrhage and ascites, are associated with significant increases in both mortality and complications during pregnancy. Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure for treating portal hypertension, but the safety of TIPS during pregnancy is largely unknown. In this series, we review five patients who underwent TIPS placement while pregnant and describe their clinical outcomes.MethodsFive pregnant patients with cirrhosis and portal hypertension underwent elective TIPS for complications of portal hypertension (four for secondary prevention of variceal bleeding and one for refractory ascites). Outcomes measured were recurrent bleeding episodes or need for further paracenteses during pregnancy, estimated radiation dose to the fetus and gestational age at delivery. All patients were followed after delivery to evaluate technical and clinical success of the procedure.ResultsAll five patients survived pregnancy and went on to deliver successfully. When TIPS was performed for secondary prevention of variceal bleeding (n = 4), no patients demonstrated variceal bleeding after TIPS placement. When TIPS was performed for refractory ascites (n = 1), no further paracenteses were required. All patients delivered successfully, albeit prematurely. Average radiation dose estimated to the fetus was 16.3 mGy.ConclusionsThis series suggests that TIPS can be performed in selective pregnant patients with portal hypertension, with little added risk to the mother or fetus.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5–1660 μg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D{sub 3}, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25 μg/L (range 1.9–145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D{sub 3} (−6.1 nmol/L [95%CI −9.5; −2.6] for a 25 μg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D{sub 3}. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30 nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25 μg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water. - Highlights: • Elevated drinking water lithium (Li) concentrations are increasingly reported. • We studied a Li-exposed population-based mother-child cohort in northern Argentina. • Li exposure during pregnancy affected maternal calcium homeostasis. • Blood Li was consistently inversely associated with maternal plasma vitamin D{sub 3}. • Associations were independent of season of sampling and lifestyle.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2012

Impact of Different Treatment Approaches on Pregnancy Outcomes in 99 Women Treated for Hodgkin Lymphoma

Purpose: The aim of this study was to evaluate the pregnancy outcomes in women with Hodgkin lymphoma (HL) diagnosis, treated between 1972 and 1999 at Department of Radiotherapy and Hematology of University 'Sapienza' of Roma. Methods and Materials: We retrospectively studied 99 female patients that conceived after treatment for HL. Fifty-nine (59%) were treated with chemotherapy and radiotherapy, 32 (32%) with radiotherapy alone as supradiaphragmatic or as infradiaphragmatic and 8 (8%) patients with chemotherapy alone. Results: Ninety-nine patients reported 145 pregnancies. We observed 132 deliveries (2 of them twin births) after a median of 55 months (range, 14-278 months) from the end of therapy. Twelve women (12%) experienced 13 miscarriages after a median of 50 months (range, 13-120) from the end of therapy. We recorded 9/132 (7%) premature births and 3/134 babies (2%) were underweight at the time of birth. We recorded 2 cases of congenital malformations. No statistical differences were recorded when adverse pregnancy outcomes were analyzed with respect to chemotherapy alone, radiotherapy alone, or combined therapy. Conclusions: No significant associations between pregnancy outcomes and therapeutic approaches were found. In particular, the infradiaphragmatic radiotherapy showed no statistical association with miscarriages, premature birth, and low birth weight at term when compared with other therapeutic approaches.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Pregnancy is accompanied by larger high density lipoprotein particles and compositionally distinct subspecies

Pregnancy is accompanied by significant physiological changes, which can impact the health and development of the fetus and mother. Pregnancy-induced changes in plasma lipoproteins are well documented, with modest to no impact observed on the generic measure of high density lipoprotein (HDL) cholesterol. However, the impact of pregnancy on the concentration and composition of HDL subspecies has not been examined in depth. In this prospective study, we collected plasma from 24 nonpregnant and 19 pregnant women in their second trimester. Using nuclear magnetic resonance (NMR), we quantified 11 different lipoprotein subspecies from plasma by size, including three in the HDL class. We observed an increase in the number of larger HDL particles in pregnant women, which were confirmed by tracking phospholipids across lipoproteins using high-resolution gel-filtration chromatography. Using liquid chromatography-mass spectrometry (LC-MS), we identified 87 lipid-associated proteins across size-speciated fractions. We report drastic shifts in multiple protein clusters across different HDL size fractions in pregnant females compared with nonpregnant controls that have major implications on HDL function. These findings significantly elevate our understanding of how changes in lipoprotein metabolism during pregnancy could impact the health of both the fetus and the mother.

59 BASIC BIOLOGICAL SCIENCES↗