Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes by Race/Ethnicity in a Large Integrated Health Care System.

OBJECTIVE: Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. STUDY DESIGN: A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. RESULTS: During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. CONCLUSION: The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. KEY POINTS: · Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2.. · The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders.. · White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection..

Rising Trends of Childhood Attention-Deficit/Hyperactivity Disorder in a Large Integrated Healthcare Delivery System in Southern California, 2010-2021.

OBJECTIVE: To evaluate trends of attention-deficit/hyperactivity disorder (ADHD) diagnosis rates among children aged 5-17 years over the past decade (2010-2021) and to investigate whether there have been differences in temporal changes based on race and ethnicity, sex, or income. STUDY DESIGN: Childhood ADHD diagnosis was ascertained from electronic health records using International Classification of Diseases ninth revision (314.xx) and International Classification of Diseases tenth revision (F90.x) codes. Data were stratified by child's sex, race and ethnicity, and household income, and rates of ADHD were estimated before and after adjustment for potential confounders. RESULTS: The overall ADHD diagnosis rates increased from 3.5% in 2010 to 4.0% in 2021. ADHD diagnosis was most prevalent among White children (6.1%), then Black (4.6%), Other/multiple (3.7%), Hispanic (3.1%), and Asian/Pacific Islander (PI) (1.7%). ADHD was also highly prevalent among boys (73.3%) or family income≥$70,000 (50.0%). ADHD diagnosis increased among Black (4.2% to 5.1%), Hispanic (2.8% to 3.6%), and Asian/PI children (1.5% to 2.0%) but remained stable for White (6.2% to 6.1%) and Other/multiple race/ethnic children (3.7% to 3.7%). Increases in the prevalence among girls were also observed. CONCLUSION: The prevalence of ADHD in children has risen with the largest increases observed for Black, Hispanic, and Asian/PI children. Rates among less affluent families and girls have also been increasing, narrowing the gaps in diagnosis rates previously observed. These increases may reflect improvements in screening and provision of care among demographics where ADHD has been historically underdiagnosed.

Placental abruption: Incidence and risk of recurrence in subsequent pregnancies.

AIM: To estimate the incidence of abruption in first births and recurrence in the subsequent birth in patients of a large US-based integrated health care system. METHODS: Retrospective population-based cohort study of patients with first two consecutive singleton births using data from the Kaiser-Permanente South California health care system who delivered over a period of 30 years (1991-2021), using longitudinally linked electronic health records. ICD-9/ICD-10 codes "641.20" and "O45.x" identified placental abruption. We calculated the incidence and rates of abruption in first and second pregnancies. We used logistic regression to estimate the adjusted odds ratios (aOR) for abruption in second pregnancies in patients with and without abruptions in their first pregnancies. RESULTS: Of the 126 264 patients with first two consecutive singleton births over the period, 805 had abruptions in their first births, and 861 in their second births. Rates of abruption in first and second births were 0.63% and 0.68%, respectively. Twenty-seven patients had abruptions in both first and second births. Rates of abruption in the second birth among individuals with and without previous placental abruption were 3.35% and 0.66%, respectively, giving an approximately five-fold increased odds of abruption in a second pregnancy in individuals who had abruption in their first birth when compared with those who did not have placental abruption in their first birth (aOR: 4.95, 95% confidence interval: 3.35-7.31, p < 0.00001). Interpregnancy interval had no statistically significant association with recurrence. CONCLUSION: Abruption in a first birth is associated with an approximately five-fold increased odds of abruption in a second birth.

Cholesterol deficiency as a mechanism for autism: A valproic acid model.

Dysregulated cholesterol metabolism represents an increasingly recognized feature of autism spectrum disorder (ASD). Children with fetal valproate syndrome caused by prenatal exposure to valproic acid (VPA), an anti-epileptic and mood-stabilizing drug, have a higher incidence of developing ASD. However, the role of VPA in cholesterol homeostasis in neurons and microglial cells remains unclear. Therefore, we examined the effect of VPA exposure on regulation of cholesterol homeostasis in the human microglial clone 3 (HMC3) cell line and the human neuroblastoma cell line SH-SY5Y. HMC3 and SH-SY5Y cells were each incubated in increasing concentrations of VPA, followed by quantification of mRNA and protein expression of cholesterol transporters and cholesterol metabolizing enzymes. Cholesterol efflux was evaluated using colorimetric assays. We found that VPA treatment in HMC3 cells significantly reduced ABCA1 mRNA, but increased ABCG1 and CD36 mRNA levels in a dose-dependent manner. However, ABCA1 and ABCG1 protein levels were reduced by VPA in HMC3. Furthermore, similar experiments in SH-SY5Y cells showed increased mRNA levels for ABCA1, ABCG1, CD36, and 27-hydroxylase with VPA treatment. VPA exposure significantly reduced protein levels of ABCA1 in a dose-dependent manner, but increased the ABCG1 protein level at the highest dose in SH-SY5Y cells. In addition, VPA treatment significantly increased cholesterol efflux in SH-SY5Y, but had no impact on efflux in HMC3. VPA differentially controls the expression of ABCA1 and ABCG1, but regulation at the transcriptional and translational levels are not consistent and changes in the expression of these genes do not correlate with cholesterol efflux in vitro.

Toxic External Exposure Leading to Ocular Surface Injury.

The surface of the eye is directly exposed to the external environment, protected only by a thin tear film, and may therefore be damaged by contact with ambient particulate matter, liquids, aerosols, or vapors. In the workplace or home, the eye is subject to accidental or incidental exposure to cleaning products and pesticides. Organic matter may enter the eye and cause infection. Ocular surface damage can trigger a range of symptoms such as itch, discharge, hyperemia, photophobia, blurred vision, and foreign body sensation. Toxin exposure can be assessed clinically in multiple ways, including via measurement of tear production, slit-lamp examination, corneal staining, and conjunctival staining. At the cellular level, environmental toxins can cause oxidative damage, apoptosis of corneal and conjunctival cells, cell senescence, and impaired motility. Outcomes range from transient and reversible with complete healing to severe and sight-compromising structural changes. Classically, evaluation of tolerance and safety was carried out using live animal testing; however, new in vitro and computer-based, in silico modes are superseding the gold standard Draize test. This review examines how environmental features such as pollutants, temperature, and seasonality affect the ocular surface. Chemical burns to the eye are considered, and approaches to protect the ocular surface are detailed.

The Effect of Neonatal Sepsis on Risk of Autism Diagnosis.

OBJECTIVE: The study aimed to examine the association between neonatal sepsis and autism risk among children and whether the risk varied with the timing of exposure, child's sex, and race/ethnicity. STUDY DESIGN: We conducted a retrospective cohort study using electronic health records (EHR) extracted from Kaiser Permanente Southern California Health Care System. Mother-child dyads were constructed by linking records of children born to member mothers and continuing to receive care through the system during the follow-up period with those of their biological mothers (n = 469,789). Clinical health records were used to define neonatal sepsis. Diagnosis of autism was made by medical specialists. Potential confounders included maternal sociodemographic factors, obstetrical history, child's age, sex, race/ethnicity, and maternal and child medical history. Incident rates and adjusted hazard ratios (aHR) were used to estimate the associations. RESULTS: Compared with children without the diagnosis of autism, children with the condition were more likely to be from Asian/Pacific Islander descent and male sex. Exposed children showed higher rates of autism as compared with unexposed children (3.43 vs. 1.73 per 1,000 person-years, aHR: 1.67-95% confidence interval [CI]: 1.39-2.00). Both preterm (aHR: 1.47; 95% CI: 1.09-1.98) and term (aHR: 1.63; 95% CI: 1.29-2.06) births were associated with increased risk for autism. Although the magnitude of the HRs and incidence ratios for neonatal sepsis to increase autism risk varied between race ethnicities, neonatal sepsis was associated with significantly increased likelihood of autism diagnosis for all race-ethic groups except for Asian/Pacific Islanders. Although neonatal sepsis was associated with significantly increased autism risk for both boys and girls, incident rates and HR point estimates suggested that the effect may be stronger in girls. CONCLUSION: Neonatal sepsis is associated with increased risk of autism diagnosis in preterm- and term-born children. The association was significant for both girls and boys and all race ethnicities except for Asian-Pacific Islanders. KEY POINTS: · Neonatal sepsis is associated with increased risk of autism diagnosis.. · The association was significant in preterm- and term-born children.. · The association was significant for all race/ethnicities except for Asian-Pacific Islanders..

Hyperemesis Gravidarum: Risk of Recurrence in Subsequent Pregnancies.

This study aimed to examine whether the recurrence risk of hyperemesis gravidarum (HG) is modified by the timing of diagnosis, the severity of illness, and interpregnancy interval. The Kaiser Permanente Southern California 1998-2020 longitudinally linked medical records were used to examine the recurrence risk of HG in the first two (n = 93,444) and first three (n = 17,492) successive pregnancies. The timing of diagnosis- and the severity of illness-specific recurrence risks were examined by estimating the adjusted relative risks (aRR). The risks of HG in the second pregnancy among patients with and without previous HG were 23.8% and 3.4%, respectively (aRR: 8.20; 95% confidence interval [CI]: 7.52, 8.94). The recurrence risk persisted regardless of the trimester at diagnosis and the gestational age of delivery in the first pregnancy. The recurrence risk was greater for patients with metabolic disturbances requiring in-hospital treatment (30.0%) than those managed on an outpatient basis (18.6%) in the first pregnancy (aRR: 10.84 95% CI: 9.66, 12.16). Although Asian/Pacific Islander (RR = 12.9) and White (RR = 8.9) patients had higher HG recurrence risk regardless of the gestational age at delivery in the first pregnancy, all patients had significant recurrence risk only if their first pregnancy was delivered after 32 weeks of gestation. African American patients had the highest recurrence rate (34.4%). HG recurrence risk was unaffected by interpregnancy interval and correlated with the number of previous pregnancies complicated by HG. There is an increased recurrence risk of HG in subsequent pregnancies that is influenced by race/ethnicity and gestational age at delivery. The number of pregnancies complicated by HG synergistically adds to the recurrence risk.

The role of massive demographic databases in intractable illnesses: Denomics for dementia.

Despite intensive research, effective treatments for many common and devastating diseases are lacking. For example, huge efforts and billions of dollars have been invested in Alzheimer's disease (AD), which affects over 50 million people worldwide. However, there is still no effective drug that can slow or cure AD. This relates, in part, to the absence of an animal model or cellular system that incorporates all the relevant features of the disease. Therefore, large scale studies on human populations and tissues will be key to better understanding dementia and developing methods to prevent or treat it. This is especially difficult because the dementia phenotype can result from many different processes and is likely to be affected by multiple personal and environmental variables. We hypothesize that analyzing massive volumes of demographic data that are currently available and combining this with genomic, proteomic, and metabolomic profiles of AD patients and their families, new insights into pathophysiology and treatment of AD may arise. While this requires much coordination and cooperation among large institutions, the potential for advancement would be life-changing for millions of people. In many ways this represents the next step in the information revolution started by the Human Genome Project.

Postpartum Migraine Headache Coding in Electronic Health Records of a Large Integrated Health Care System: Validation Study.

BACKGROUND: Migraine is a common neurological disorder characterized by repeated headaches of varying intensity. The prevalence and severity of migraine headaches disproportionally affects women, particularly during the postpartum period. Moreover, migraines during pregnancy have been associated with adverse maternal outcomes, including preeclampsia and postpartum stroke. However, due to the lack of a validated instrument for uniform case ascertainment on postpartum migraine headache, there is uncertainty in the reported prevalence in the literature. OBJECTIVE: The aim of this study was to evaluate the completeness and accuracy of reporting postpartum migraine headache coding in a large integrated health care system's electronic health records (EHRs) and to compare the coding quality before and after the implementation of the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes and pharmacy records in EHRs. METHODS: Medical records of 200 deliveries in all 15 Kaiser Permanente Southern California hospitals during 2 time periods, that is, January 1, 2012 through December 31, 2014 (International Classification of Diseases, 9th revision, Clinical Modification [ICD-9-CM] coding period) and January 1, 2017 through December 31, 2019 (ICD-10-CM coding period), were randomly selected from EHRs for chart review. Two trained research associates reviewed the EHRs for all 200 women for postpartum migraine headache cases documented within 1 year after delivery. Women were considered to have postpartum migraine headache if either a mention of migraine headache (yes for diagnosis) or a prescription for treatment of migraine headache (yes for pharmacy records) was noted in the electronic chart. Results from the chart abstraction served as the gold standard and were compared with corresponding diagnosis and pharmacy prescription utilization records for both ICD-9-CM and ICD-10-CM coding periods through comparisons of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), as well as the summary statistics of F-score and Youden J statistic (J). The kappa statistic (κ) for interrater reliability was calculated. RESULTS: The overall agreement between the identification of migraine headache using diagnosis codes and pharmacy records compared to the medical record review was strong. Diagnosis coding (F-score=87.8%; J=82.5%) did better than pharmacy records (F-score=72.7%; J=57.5%) when identifying cases, but combining both of these sources of data produced much greater accuracy in the identification of postpartum migraine cases (F-score=96.9%; J=99.7%) with sensitivity, specificity, PPV, and NPV of 100%, 99.7%, 93.9%, and 100%, respectively. Results were similar across the ICD-9-CM (F-score=98.7%, J=99.9%) and ICD-10-CM coding periods (F-score=94.9%; J=99.6%). The interrater reliability between the 2 research associates for postpartum migraine headache was 100%. CONCLUSIONS: Neither diagnostic codes nor pharmacy records alone are sufficient for identifying postpartum migraine cases reliably, but when used together, they are quite reliable. The completeness of the data remained similar after the implementation of the ICD-10-CM coding in the EHR system.

Adapting an organ-on-chip device to study the effect of fetal sex and maternal race/ethnicity on preterm birth related intraamniotic inflammation leading to fetal neuroinflammation.

PROBLEM: Fetal neuroinflammation has been linked to preterm birth-related intraamniotic infection and inflammation; However, the contribution of fetal sex and maternal race/ethnicity is unknown. To determine if fetal sex and maternal race/ethnicity influence neuroinflammation, an organ-on-chip (OOC) model were established under normal or pathologic conditions utilizing amniotic fluid. METHOD OF STUDY: OOC is composed of two-cell culture chambers connected by Type IV collagen-coated microchannels. Human fetal astroglia (SVGp12) and microglia (HMC3) were co-cultured at an 80:20 ratio in the inner chamber. The outer chamber contained amniotic fluid (AF) from male and female fetuses of White Hispanic (WH) and African-American (AA) pregnant women with or without lipopolysaccharide (LPS-100 ng/ml) and incubated for 48 h. Glial migration (brightfield microscopy), activation (Immunocytochemistry), and cytokine production (Luminex assays) were quantified and compared (N = 4 for each category of sex and race/ethnicity). RESULTS: In a pooled analysis, AF+LPS did not induce glial activation or inflammatory changes compared to AF alone. When stratified by sex, male AF+LPS promoted significant glial activation (high CD11b:p < 0.05; low Iba1:p < 0.01) compared to male AF without LPS; however, this was not associated with changes in pro-inflammatory cytokines. When stratified by race/ethnicity, AF+LPS induced glial activation in both groups, but a differential increase in pro-inflammatory cytokines was seen between WH and AA AF (WH-interleukin-1ß: p < 0.05; AA-interleukin-8: p < 0.01). CONCLUSION: This OOC model of fetal neuroinflammation has determined that race/ethnicity differences do exist for perinatal brain injury. The fetal sex of neonates was not a determining factor of susceptibility to intraamniotic inflammation leading to neuroinflammation.

Ex vivo toxicity of E-cigarette constituents on human placental tissues.

Globally, ∼50 % of women smoke during pregnancy and the prevalence of vaping is increasing among women of reproductive age. However, the health effects of vaping during pregnancy are largely unknown. This study examined the effects of e-cig constituents alone and in combination (propylene glycol [PG], vegetable glycerin [VG], and nicotine) on human placental tissue viability (MTT assay) and immunoassayed levels of placenta-derived biomarkers, i.e., 8-isoprostane (8-IsoP), heme oxygenase-1 (HO-1), interleukin-6 (IL-6), ß-estradiol (E2), progesterone (P4), allopregnanolone (AP), and brain-derived neurotrophic factor (BDNF). Placental explant cultures were exposed ex vivo for 24 h to media-containing either nicotine (0-5000 nM), PG/VG (0-8 % v/v at 50/50 ratio), or a combination of both. No effects on tissue viability were observed at PG/VG concentrations < 8 % (v/v), while viability significantly reduced at PG/VG concentrations ≥ 10 % (v/v); biomarker studies employed only non-cytotoxic doses. Exposure to PG/VG decreased levels of 8-IsoP, IL-6, and E2, and treatment with 2 % or 8 % PG/VG significantly reduced HO-1 levels, compared to non-treated controls. Exposure to nicotine alone at 2,500 nM and 5,000 nM reduced MTT activity by 20 % (P = 0.04) and 70 % (P < 0.001), respectively, and significantly increased (P < 0.001) levels of HO-1 and BDNF, compared to controls. Treatment with nicotine alone and in combination with PG/VG reduced IL-6 and E2 levels. Interestingly, nicotine-induced toxicity was attenuated by PG/VG addition to nicotine-treated groups. These studies demonstrate that e-cig constituents negatively impact the human placenta and alters production of critical placental biomarkers, suggesting that vaping is an unsafe alternative for pregnant women or their unborn fetus.

Expression of CYP450 enzymes in human fetal membranes and its implications in xenobiotic metabolism during pregnancy.

BACKGROUND: Environmental exposure to toxicants is a major risk factor for spontaneous preterm birth (PTB, <37 weeks). Toxicants and drugs administered to patients are metabolized primarily by the cytochrome P450 (CYP450) system. Along with the adult and fetal liver, the placenta, a critical feto-maternal interface organ, expresses CYP450 enzymes that metabolize these xenobiotics. However, the contribution of the fetal membranes, another tissue of the feto-maternal interface, to the expression of CYP450 enzymes and the detoxification of xenobiotics remains unknown. AIMS: This study characterized CYP450 expression and determined the functional activity of CYP450 enzymes in fetal membranes. MAIN METHODS: RNA sequencing (RNA-Seq) of placental and fetal membrane tissues and cells was done. Differential expressions of CYP450 genes were compared and validated via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) between the two tissues. The functional activity of major CYP450 enzymes was determined using a fluorophore-based enzymatic assay in the presence and absence of their corresponding inhibitors. KEY FINDINGS: With the exception of genes that regulate cholesterol metabolism, the expression profile of CYP450 genes was similar between placental and fetal membranes tissues/cells. RT-qPCR analysis confirmed these findings with significant levels of mRNA for major CYP450 genes being detectable in amnion epithelial cells (AECs) and chorion trophoblasts cells (CTCs). Biochemical analyses revealed significant CYP450 enzymatic activities that were sensitive to specific inhibitors for both AECs and CTCs, suggesting that the genes were expressed as functional enzymes. SIGNIFICANCE: This is the first study to determine global expression of CYP450 enzymes in fetal membranes which may play a role in xenobiotic metabolism during pregnancy. Given that many women are exposed to environmental toxins or require medications during pregnancy, a better understanding of their role in metabolism is required to develop safer therapeutics and prevent adverse outcomes.

Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes in a Large Health Maintenance Organization.

OBJECTIVE: This study aimed to examine whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy is associated with increased odds of perinatal complications and viral transmission to the infant. STUDY DESIGN: A retrospective cohort study of women who delivered at Kaiser Permanente Southern California hospitals (April 6, 2020-February 28, 2021) was performed using data extracted from electronic health records (EHRs). During this time polymerize chain reaction (PCR)-based tests for SARS-CoV-2 was universally offered to all pregnant women at labor and delivery admission, as well as earlier in the pregnancy, if they were displaying symptoms consistent with SARS-CoV-2 infection or a possible exposure to the virus. Adjusted odds ratio (aOR) was used to estimate the strength of associations between positive test results and adverse perinatal outcomes. RESULTS: Of 35,123 women with a singleton pregnancy, 2,203 (6%) tested positive for SARS-CoV-2 infection with 596 (27%) testing positive during the first or second trimester and 1,607 (73%) during the third trimester. Women testing positive were younger than those who tested negative (29.7 [5.4] vs. 31.1 [5.3] years; mean [standard deviation (SD)]; p < .001). The SARS-CoV-2 infection tended to increase the odds of an abnormal fetal heart rate pattern (aOR: 1.10; 95% confidence interval [CI]: 1.00, 1.21; p = 0.058), spontaneous preterm birth (aOR: 1.28; 95% CI: 1.03, 1.58; p = 0.024), congenital anomalies (aOR: 1.69; 95% CI: 1.15, 2.50; p = 0.008), and maternal intensive care unit admission at delivery (aOR: 7.44; 95% CI: 4.06, 13.62; p < 0.001) but not preeclampsia/eclampsia (aOR: 1.14; 95% CI: 0.98, 1.33; p = 0.080). Eighteen (0.8%) neonates of mothers who tested positive also had a positive SARS-CoV-2 test after 24 hours of birth, but all were asymptomatic during the neonatal period. CONCLUSION: These findings suggest that prenatal SARS-CoV-2 infection increases the odds of some adverse perinatal outcomes. The likelihood of vertical transmission from the mother to the fetus was low (0.3%), suggesting that pregnancy complications resulting from SARS-CoV-2 infection pose more risk to the baby than transplacental viral transmission. KEY POINTS: · SARS-CoV-2 infection is associated with increased odds of adverse perinatal outcomes.. · The odds of specific adverse outcomes were greater when a mother was infected earlier in pregnancy.. · The proportion of vertical transmission from mother to fetus was 0.3%.

The Effect of Abuse and Mistreatment on Healthcare Providers (TEAM): A Survey Assessing the Prevalence of Aggression From Patients and Their Families and Its Impact.

OBJECTIVE: Aggression from patients and families on health care providers (HCP) is common yet understudied. We measured its prevalence and impact on HCPs in inpatient and outpatient settings. METHODS: Four thousand six hundred seven HCPs employed by a community teaching hospital received an anonymous survey with results analyzed. RESULTS: Of 1609 HCPs (35%) completing the survey, 88% of inpatient staff reported experiencing different types of aggression compared to 82% in outpatient setting. Almost half did not report it to their supervisor. Younger staff were more likely to report abuse. Negative impacts on productivity and patient care were reported. A third of all responders' indicated negative effects on mental health. CONCLUSIONS: Despite negative impacts on staff wellbeing and productivity, patient/family aggression toward HCPs is highly prevalent and underreported. Our healthcare system needs measures to address staff security and wellness.

Effect of 2,6-xylidine (DMA) on secretion of biomarkers for inflammation and neurodevelopment by the placenta.

Cigarette smoke enhances placental inflammation and interferes with steroidogenesis. However, the chemicals in the smoke responsible for these biological activities are unclear. 2,6 xylidine (also called 2,6 Dimethylaniline, DMA) is a component of cigarette smoke that has carcinogenic properties but its effects on the placenta are unknown. Therefore, we hypothesized that DMA may interfere with placental steroidogenesis or enhance placental inflammation. Placental explant cultures were treated with 0-50,000 nM DMA and concentrations of progesterone (P4), estradiol (E2), testosterone (T), IL-1ß, TNF-α, IL-6, sgp130, HO-1, IL-10, 8-Isoprostane (8-IsoP), and BDNF in the conditioned medium were quantified. Since many environmental toxins enhance the proinflammatory host response to infection, we also performed experiments on placental cultures co-stimulated with 107 heat-killed E. coli. DMA alone significantly reduced P4 and T secretion but enhanced E2 secretion. The toxin also reduced placental secretion of IL-6, sgp130, and BDNF. For bacteria-stimulated cultures, DMA increased secretion of P4 and T, and proinflammatory cytokines (IL-1ß, TNF-α) but had mixed effects on anti-inflammatory markers, increasing some (sgp130, IL-10) and reducing others (HO-1). However, DMA enhanced 8-IsoP levels by bacteria-stimulated placental cultures, suggesting that it increases oxidative stress by the tissues. These studies suggest that DMA affects secretion of biomarkers by the placenta and may promote inflammation. Further studies are needed to determine if these observed changes occur in vivo and the extent to which DMA exposure increases the risk of adverse pregnancy outcomes associated with smoking in pregnancy.

Perinatal outcomes after bariatric surgery.

BACKGROUND: Bariatric surgery is a widely used treatment option for obesity that often provides long-term weight control and health benefits. Although a growing number of women are becoming pregnant after bariatric surgery, only a few population-based studies have assessed the impact thereof on perinatal outcomes. OBJECTIVE: This study aimed to examine the association between bariatric surgery and adverse perinatal outcomes in pregnant women and to examine whether the risk for adverse perinatal outcomes is modified by the postsurgery weight, gestational weight gain, type of bariatric surgery, timing of pregnancy after bariatric surgery, and maternal comorbidities. STUDY DESIGN: A retrospective cohort study was performed with the use of the Bariatric Surgery Registry and hospital inpatient and outpatient physician encounter records. The International Classification of Diseases, Ninth and Tenth Revision codes from hospitalizations during pregnancy and infant birth records were used to ascertain the outcomes of interest. Women eligible for BS who delivered at ≥20 weeks of gestation (n=20,213) at Kaiser Permanente Southern California hospitals (January 1, 2007 to December 31, 2018) were included in the study. Adjusted odds ratios were derived from logistic regression models with inverse probability of treatment weighting to adjust for confounding using propensity scores. RESULTS: Bariatric surgery was associated with a reduction in the risks for gestational diabetes (adjusted odds ratio, 0.60; 95% confidence interval, 0.53-0.69; P<.001), preeclampsia (adjusted odds ratio, 0.53; 95% confidence interval, 0.46-0.61; P<.001), chorioamnionitis (adjusted odds ratio, 0.45; 95% confidence interval, 0.32-0.63; P<.001), cesarean delivery (adjusted odds ratio, 0.65; 95% confidence interval, 0.59-0.72; P<.001), large for gestational age neonate (adjusted odds ratio, 0.23; 95% confidence interval, 0.19-0.29; P<.001), macrosomia (adjusted odds ratio, 0.24; 95% confidence interval, 0.19-0.30; P<.001), and neonatal intensive care unit admission (adjusted odds ratio, 0.70; 95% confidence interval, 0.61-0.81; P<.001). However, bariatric surgery was also associated with a significantly increased risk for small for gestational age neonates (adjusted odds ratio, 2.46; 95% confidence interval, 2.16-2.79; P<.001). The risk for the adverse outcomes is independent of the time interval between the surgery and subsequent pregnancy. CONCLUSION: These data suggest that there are many pregnancy outcome benefits for women with severe obesity who undergo bariatric surgery; however, women who have undergone bariatric surgery before pregnancy should be monitored closely to reduce the risk for small for gestational age neonates and postpartum hemorrhage.

Exposure to polybrominated diphenyl ether-47 increases the risk of post-partum depression.

INTRODUCTION: Post-partum depression (PPD) affects up to 19.1% of pregnancies and is associated with increased levels of proinflammatory cytokines, inflammation, and reductions in brain-derived neurotrophic factor (BDNF). Previous work by our team suggests that environmental toxins such as polybrominated diphenyl ethers (PBDEs) enhance placental inflammation and reduce BDNF production. Nearly, 100% of studied women in California have some level of exposure to these compounds due to extensive use of the flame retardants. High levels of exposure to PBDEs has been linked to increased risk of adverse pregnancy complications associated with placental inflammation such as preterm birth and gestational diabetes but their effects on risk of PPD is unclear. OBJECTIVE: To determine if PPD is associated with higher levels of PBDE-47, the most common PBDE congener in maternal plasma. METHODS: PBDE-47 was quantified in first trimester plasma samples collected from a cohort of 367 asymptomatic pregnant women that were routinely screened for depressive symptoms for 1 year post-partum. Data were analyzed using general linear models and multivariable logistic regression to determine if higher levels of PBDE-47 in the first trimester are associated with development of PPD. RESULTS: Women who developed PPD (n = 22) had significantly higher PBDE-47 levels in their plasma (p=.031) relative to those in which PPD was not diagnosed. Logistic regression analysis suggested that each two-fold increase in PBDE-47 concentrations increased the risk of PPD by 22% (OR = 1.22, 95% CI: 1.03, 1.47). Groups were similar regarding PTB rate, race-ethnicity, parity, child's sex, maternal pre-pregnancy obesity status, maternal age, family income, and study center. Results remained significant after adjustment for these possible confounding factors. CONCLUSIONS: These results suggest that PBDE-47 exposure in the first trimester is associated with increased risk of PPD.

Enhancement of placental inflammation by Dibutyl Phthalate.

Recent studies suggest that women with high exposures to dibutyl phthalate (DBP) are at increased risk for preterm birth, a condition associated with aberrant inflammation in the placenta often caused by subclinical infections. Placental inflammation is also a risk factor for neurodevelopmental disorders whose risk may also be enhanced by DBP. It is unclear, however, if DBP enhances placental inflammation. Therefore, we studied the effects of DBP on the production of biomarkers of placental inflammation and neurodevelopment under basal conditions and a setting of mild infection. Placental explant cultures established from women undergoing elective caesarean delivery were treated with DBP with and without co-stimulation by 107 CFU/mL heat-killed E. coli for 24 h at 37 °C. Conditioned medium was harvested and concentrations of IL-1ß, TNF-α, IL-10, HO-1 and BDNF, a biomarker for neurodevelopment, were quantified. DBP significantly enhanced IL-6 production in basal cultures but had no significant on the other biomarkers quantified. Both TNF-α and IL-1ß production was enhanced by DBP for cultures co-stimulated with E. coli. Although marginal enhancement of IL-6, and IL-10 were observed for bacteria co-treated cultures, results were either non-monotonic or only approached statistical significance. HO-1 production tended to be reduced at the highest concentration of DBP tested and BDNF production was reduced by DBP in a dose-dependent manner for bacteria-stimulated cultures. These results suggest that DBP enhances basal IL-6 production but has little or no effect on other biomarkers studied. However, DBP enhances IL-1ß and TNF-α production but reduces BDNF production by bacteria-stimulated cultures.

Short communication: Ex-vivo effects of fluoxetine on production of biomarkers for inflammation and neurodevelopment by the placenta.

Fluoxetine is commonly prescribed during pregnancy but developmental exposure to the drug, like infection, is associated with sex-specific behavioral changes in the offspring. We evaluated the effects of Fluoxetine on production of biomarkers for inflammation (pro/anti-inflammatory cytokines) and neurodevelopment (Brain-Derived Neurotrophic Factor, BDNF) in the presence and absence of infection in female and male placenta explant cultures. In addition to minor anti-inflammatory effects of the drug, Fluoxetine had significant sex- and infection-dependent effects on BDNF production. Further studies are needed to determine the extent to which these observed changes occur in vivo and their impact on pregnancy and neurodevelopmental outcomes.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth.

OBJECTIVES: Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. METHODS: Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. RESULTS: We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. CONCLUSIONS: These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.