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Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

ABSTRACT: Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.3 or 1.0 ppm) at either gestational day (GD)10 or GD20, with longitudinal functional assessments and molecular endpoints conducted at term. Exposure at GD10 led to placental transcriptional changes at term that were consistent with markers in human preeclampsia, including reduced mmp10 and increased cd36, fzd1, and col1a1. O3 exposure, at both early and late gestation, induced a significant increase in maternal circulating soluble FMS-like tyrosine kinase-1 (sFlt-1), a known driver of preeclampsia. Otherwise, exposure to 0.3 ppm O3 at GD10 led to several late-stage cardiovascular outcomes in dams that were not evident in GD20-exposed dams, including elevated uterine artery resistance index and reduced cardiac output and stroke volume. GD10 O3 exposure proteomic profile in maternal hearts characterized by a reduction in proteins with essential roles in metabolism and mitochondrial function, whereas phosphoproteomic changes were consistent with pathways involved in cardiomyopathic responses. Thus, the developing placenta is an indirect target of inhaled O3 and systemic maternal cardiovascular abnormalities may be induced by O3 exposure at a specific window of gestation.

SUBMITTER: Garcia M

PROVIDER: S-EPMC8453811 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. OBJECTIVE:We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. STUDY DESIGN:Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days' and 22 weeks 6 days' gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. RESULTS:Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. CONCLUSION:In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies.

Project description:BackgroundStudies examining the effects of low-level gestational methylmercury exposure from fish consumption on infant neurobehavioral outcomes in the offspring are limited and inconclusive. Our objective was to examine the effects of low-level gestational exposure to methylmercury on neurobehavioral outcomes in early infancy.MethodsWe assessed neurobehavior of 344 infants at 5-weeks using the NICU Network Neurobehavioral Scale (NNNS). Gestational mercury exposure was measured as whole blood total mercury (WBTHg) in maternal and cord blood. We collected fish consumption information and estimated polyunsaturated fatty acid (PUFA) intake. We examined the association between gestational mercury exposure and NNNS scales using regression, adjusting for covariates.ResultsGeometric mean of maternal and cord WBTHg were 0.64 and 0.72 μg/L, respectively. Most mothers (84%) reported eating fish during pregnancy. Infants with higher prenatal mercury exposure showed increased asymmetric reflexes among girls (p=0.04 for maternal WBTHg and p=0.03 for cord WBTHg), less need for special handling during the assessment (p=0.03 for cord WBTHg) and a trend of better attention (p=0.054 for both maternal WBTHg and cord WBTHg). Similarly, infants born to mothers with higher fish consumption or estimated PUFA intake also had increased asymmetric reflexes and less need for special handling. In models simultaneously adjusted for WBTHg and fish consumption (or PUFA intake), the previously observed WBTHg effects were attenuated; and higher fish consumption (or PUFA intake) was significantly associated with less need for special handling.ConclusionsIn a cohort with low level mercury exposure and reporting low fish consumption, we found minimal evidence of mercury associated detrimental effects on neurobehavioral outcomes during early infancy. Higher prenatal mercury exposure was associated with more frequent asymmetric reflexes in girls. In contrast, infants with higher prenatal mercury exposure and those whose mothers consumed more fish had better attention and needed less special handling, which likely reflect the beneficial nutritional effects of fish consumption.

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Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

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