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The effect of the COVID-19 pandemic on maternal mental health has been described in Canada and China but no study has compared the two countries using the same standardized and validated instruments. In this study, we aimed to evaluate and compare the impact of COVID-19 public health policies on maternal mental health between Canada and China, as we hypothesize that geographical factors and different COVID-19 policies are likely to influence maternal mental health. Pregnant persons >18 years old were recruited in Canada and China using a web-based strategy. All participants recruited between 26 June 2020 and 16 February 2021 were analyzed. Self-reported data included sociodemographic variables, COVID-19 experience and maternal mental health assessments (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7) scale, stress and satisfaction with life). Analyses were stratified by recruitment cohort, namely: Canada 1 (26 June 2020–10 October 2020), Canada 2 and China (11 October 2020–16 February 2021). Overall, 2423 participants were recruited, with 1804 participants within Canada 1, 135 within Canada 2 and 484 in China. The mean EDPS scores were 8.1 (SD, 5.1) in Canada 1, 8.1 (SD, 5.2) in Canada 2 and 7.7 (SD, 4.9) in China (p-value Canada 2/China: p = 0.005). The mean GAD-7 scores were 2.6 (SD, 2.9) in China, 4.3 (SD, 3.8) in Canada 1 (p < 0.001) and 5.8 (SD, 5.2) in Canada 2 (p < 0.001). When adjusting for stress and anxiety, being part of the Chinese cohort significantly increased the chances of having maternal depression by over threefold (adjusted OR 3.20, 95%CI 1.77–5.78). Canadian and Chinese participants reported depressive scores nearly double those of other crises and non-pandemic periods. Lockdowns and reopening periods have an important impact on levels of depression and anxiety among pregnant persons.

Attention deficit with hyperactivity disorder (ADHD) medications in pregnancy would be associated with ADHD in children, however, estimates can be confounded by genetic predispositions and environmental factors related to the mother-child pair. We aim to quantify the risk of ADHD in children associated with ADHD medication exposures during pregnancy. A prospective cohort study and sibling analysis conducted within The Quebec Pregnancy/Child Cohort (QPC). All full-term singleton live births covered by the provincial prescription drug insurance in Quebec from 1998 to 2015 were included. ADHD medication exposure during pregnancy was defined according to trimester of use and class-specific medication. ADHD in children was defined as having at least one diagnosis or one prescription filled for an ADHD medication. Cox proportional hazards regression models were used to calculate crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) in the overall cohort, the sub-cohort and the sibling analysis. Of 166,047 full-term singleton live births included, 25,454 (15.3%) had ADHD. In the overall cohort, maternal exposure to ADHD medication during pregnancy was associated with ADHD in children (aHR= 1.96, 95% CI 1.22-3.15). In the ADHD pregnant women sub-cohort (aHR= 1.56; 95% CI 0.93-2.62) and the sibling control analysis (aHR= 1.14; 95% CI 0.62-1.98), ADHD medications during pregnancy was not associated with an increased risk of ADHD in children. Our findings suggest that in utero exposure to ADHD medications was not associated with an increased risk of ADHD in children. This suggests that the association is due to genetic and/or family environmental factors.

Introduction: We aimed to measure the impact of the COVID-19 pandemic on maternal mental health, stratifying on pregnancy status, trimester of gestation, and pandemic period/wave.Methods: Pregnant persons and persons who delivered in Canada during the pandemic, >18 years, were recruited, and data were collected using a web-based strategy. The current analysis includes data on persons enrolled between 06/2020-08/2021. Maternal sociodemographic indicators, mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7), stress) were self-reported. Maternal mental health in pregnant women (stratified by trimester, and pandemic period/wave at recruitment) was compared with mental health of women who had delivered; determinants of severe depression were identified with multivariate logistic regression models.Results: 2,574 persons were pregnant and 626 had already delivered at recruitment. Participants who had delivered had significantly higher mean depressive symptom scores compared to those pregnant at recruitment (9.1 (SD, 5.7) vs. 8.4 (SD, 5.3), p=0.009). Among those who were pregnant at recruitment, depressive symptoms were significantly higher in women recruited in their third trimester, and those recruited during the 2nd wave of the pandemic. Maternal anxiety (aOR 1.51; 95%CI 1.44-1.59) and stress (aOR 1.35; 95%CI 1.24-1.48) were the most significant predictors of severe maternal depression (EDPS˃13) in pregnancy. Conclusion: The COVID-19 pandemic had a significant impact on maternal depression during pregnancy and in the post-partum period. Given that gestational depression/anxiety/stress have been associated with preterm birth and childhood cognitive problems, it is essential to continue following women/children, and develop strategies to reduce COVID-19’s longer-term impact.

Background Recent studies show a rapid growth among pregnant women using high potency opioids for common pain management during their pregnancy. No study has examined the duration of treatment among strong opioid users and weak opioid users during pregnancy. We aimed to investigate the prevalence of prescribed opioid use during pregnancy, in Quebec; and to compare the duration of opioid treatment between strong opioid users and weak opioid users. Methods Using the Quebec Pregnancy Cohort (1998–2015), we included all pregnancies covered by the Quebec Public Prescription Drug Insurance Program. Opioid exposure was defined as filled at least one prescription for any opioid during pregnancy or before pregnancy but with a duration that overlapped the beginning of pregnancy. Prevalence of opioids use was calculated for all pregnancies, according to pregnancy outcome, trimester of exposure, and individual opioids. The duration of opioid use during pregnancy was analyzed according to 8 categories based on cumulative duration ( Results Of 442,079 eligible pregnancies, 20,921 (4.7%) were exposed to opioids. Among pregnancies ending with deliveries (n = 249,234), 5.4% were exposed to opioids; the prevalence increased by 40.3% from 3.9% in 1998 to 5.5% in 2015, more specifically a significant increase in the second and third trimesters of pregnancy. Weak opioid, codeine was the most commonly dispensed opioid (70% of all dispensed opioids), followed by strong opioid, hydromorphone (11%), morphine (10%), and oxycodone (5%). The prevalence of codeine use decreased by 47% from 4.3% in 2005 to 2.3% in 2015, accompanied by an increased use of strong opioid, morphine (0.029 to 1.41%), hydromorphone (0.115 to 1.08%) and oxycodone (0.022 to 0.44%), from 1998 to 2015. The average durations of opioid exposure were significantly longer among pregnancies exposed to strong opioid as compared to weak opioid regardless of the cumulative duration or duration of action (P Conclusions Given the differences in the safety profile between strong opioids and the major weak opioid codeine, the increased use of strong opioids during pregnancy with longer treatment duration raises public health concerns.

Objectives The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics. Study Design and Setting Using the Quebec Pregnancy Cohort (1998–2015), first-trimester doxylamine–pyridoxine, metoclopramide, and ondansetron exposures were assessed for their association with MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting for potential confounders (aOR). Results Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine–pyridoxine, 958 to metoclopramide, and 31 to ondansetron. Doxylamine–pyridoxine and metoclopramide use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence interval [CI]: 1.03–1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03–1.57; 105 exposed cases), respectively. Doxylamine–pyridoxine exposure was associated with increased risks of spina bifida (aOR 1.87, 95% CI: 1.11–3.14; 23 exposed cases), nervous system (aOR 1.25, 95% CI: 1.06–1.47; 225 exposed cases), and musculoskeletal system defects (aOR 1.08, 95% CI: 1.02–1.14; 1,735 exposed cases). Metoclopramide exposure was associated with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14–4.48; 10 exposed cases). No statistically significant association was found between ondansetron exposure and the risk of overall MCM. Conclusion First-trimester doxylamine–pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.

Background Medications already available to treat other conditions are presently being studied in clinical trials as potential treatments for COVID-19. Given that pregnant women are excluded from these trials, we aimed to investigate their safety when used during pregnancy within a unique population source. Methods Using the population-based Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn (1998–2015). Taking potential confounders into account including indications for use, the risk of prematurity, low birth weight (LBW), small for gestational age (SGA), and major congenital malformation (MCM) associated with COVID-19 repurposed drug use during pregnancy were quantified using generalized estimation equations. Results Of the 231,075 eligible pregnancies, 107 were exposed to dexamethasone (0.05%), 31 to interferons (0.01%), 1,398 to heparins (0.60%), 24 to angiotensin-receptor blockers (ARB) (0.01%), 182 to chloroquine (0.08%), 103 to hydroxychloroquine (0.05%), 6,206 to azithromycin (2.70%), 230 to oseltamivir (0.10%), and 114 to HIV medications (0.05%). Adjusting for potential confounders, we observed an increased risk of prematurity related to dexamethasone (aOR 1.92, 95%CI 1.11–3.33; 15 exposed cases), anti-thrombotics (aOR 1.58, 95%CI 1.31–1.91; 177 exposed cases), and HIV medications (aOR 2.04, 95%CI 1.01–4.11; 20 exposed cases) use. An increased risk for LBW associated with anti-thrombotics (aOR 1.72, 95%CI 1.41–2.11; 152 exposed cases), and HIV medications (aOR 2.48, 95%CI 1.25–4.90; 21 exposed cases) use were also found. Gestational exposure to anti-thrombotics (aOR 1.20, 95%CI 1.00–1.44; 176 exposed cases), and HIV medications (aOR 2.61, 95%CI 1.51–4.51; 30 exposed cases) were associated with SGA. First-trimester dexamethasone (aOR 1.66, 95%CI 1.02–2.69; 20 exposed cases) and azithromycin (aOR 1.10, 95%CI 1.02–1.19; 747 exposed cases) exposures were associated with MCM. Conclusions Many available medications considered as treatments for COVID-19 are associated with adverse pregnancy outcomes. Caution is warranted when considering these medications during the gestational period.

Pregnant women may take nonsteroidal antiinflammatory drugs (NSAIDs), selective cyclooxygenase (COX)-2 inhibitors, or biological agents to relieve symptoms or manage disease flares in late pregnancy. We aimed to quantify the risk of prematurity associated with late pregnancy exposure to nonselective NSAIDs, selective COX-2 inhibitors, and biological agents. Using data from Quebec Pregnancy Cohort, we performed a population-based cohort study. We included all women who were covered by the Quebec Drug Plan and had a singleton live birth between January 1, 1998 and December 31, 2009. Late pregnancy exposure was defined as having filled at least 1 prescription for nonselective NSAIDs, selective COX-2 inhibitors, or biological agents in the 3 months before delivery. Prematurity was defined as

ObjectivesLeflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. We quantified the risk of major congenital malformation (MCM), prematurity, low birth weight (LBW) and spontaneous abortion associated with leflunomide exposure during pregnancy in humans.MethodsFrom a cohort of 289 688 pregnancies in Montreal, Quebec, Canada, from 1998 to 2015, first-trimester leflunomide exposure and other antirheumatic drug exposures were studied for their association with MCM and spontaneous abortions. Also second or third-trimester leflunomide exposures were examined for associations with prematurity and LBW. Logistic regression model-based generalised estimating equations were used.Results51 pregnancies were exposed to leflunomide during the first trimester, and 21 during the second/third trimesters. Adjusting for potential confounders, use of leflunomide during the first trimester of pregnancy was not associated with the risk of MCM (adjusted OR (aOR) 0.97, 95% CI 0.81 to 1.16; 5 exposed cases). No association was found between second/third-trimester exposure to leflunomide and the risk of prematurity (aOR 4.03, 95% CI 0.91 to 17.85; 7 exposed cases) nor LBW (aOR 1.06, 95%CI 0.90 to 1.25; 8 exposed cases). Pregnancy exposure to leflunomide was also not associated with the risk of spontaneous abortion (aOR 1.09, 95% CI 0.90 to 1.32; 11 exposed cases).ConclusionsMaternal exposure to leflunomide during pregnancy was not associated with statistically significant increased risk of MCMs, prematurity, LBW or spontaneous abortions. However, given that relatively few women were exposed to leflunomide during pregnancy in this cohort, caution remains warranted.

Background Administrative databases are increasingly used to measure drug exposure in perinatal pharmacoepidemiology. We aimed to estimate the concordance between records of prescriptions filled in pharmacies and self-reported drug use during pregnancy. Methods Data on self-reported medication use were collected at each trimester of pregnancy among a sub-sample from the Organization of Teratology Information Specialists Antidepressants in Pregnancy Cohort. Women were eligible if they were Quebec resident and provided their pharmacist's contact information. Maternal self-reports were compared with prescriptions filled in pharmacies, which are transferred to pharmaceutical services files of Quebec provincial health plan database (Regie de l'asssurance maladie du Quebec). Positive and negative predictive values (PPV and NPV) for medications taken chronically (antidepressants, thyroid hormones), acutely (antibiotics), and as needed (antiemetics, asthma medications) were calculated. Results Among the 93 participants (mean age = 30.2 ± 3.8 years), 41.9% (n = 39) took at least one antidepressant during pregnancy according to self-reports, and 39.8% (n = 37) according to pharmacy records. Other commonly used drugs were antiemetics (self-reported 22.6%, pharmacy record 24.7%), antibiotics (20.4%, 16.1%), asthma medications (15.1%, 15.1%), and thyroid hormones (10.8%, 8.6%). PPVs and NPVs were: (1) chronic medication: antidepressants PPV = 100% (95% confidence interval [CI], 100–100%), NPV = 96% (95% CI, 92–100%); thyroid hormones PPV = 100% (95% CI, 100–100%), NPV = 98% (95% CI, 95–100%); (2) Acute medication: antibiotics PPV = 87% (95% CI, 70–100%), NPV = 92% (95% CI, 86–98%); (3) as needed medications: antiemetics: PPV = 78% (95% CI, 62–95%), NPV = 96% (95% CI, 91–100%); asthma: PPV = 33% (95% CI, 3–64%), NPV = 99% (95% CI, 97–100%). Conclusion The high PPV and NPV validate the use of filled prescription data in large databases as a measure of medication exposure. Birth Defects Research 109:423–431, 2017. © 2017 Wiley Periodicals, Inc.

Aim The use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN). Limited data are available on the risk of PPHN associated with serotonin norepinephrine reuptake inhibitors (SNRIs). We aimed to quantify both associations. Methods Using data from the Quebec Pregnancy Cohort between 1998 and 2009, we included women covered by the provincial drug plan who had a singleton live birth. Exposure categories were SSRI, SNRI and other antidepressant use; non-users were considered as the reference category. Generalized estimating equation models were used to obtain risk estimates and 95% confidence intervals (CIs). Confounding by indication was minimized by adjusting for history of maternal depression/anxiety before pregnancy. Results Overall, 143 281 pregnancies were included; PPHN was identified in 0.2% of newborns. Adjusting for maternal depression, and other potential confounders, SSRI use during the second half of pregnancy was associated with an increased risk of PPHN [adjusted odds ratio (aOR) 4.29, 95% CI 1.34, 13.77] compared with non-use of antidepressants; SNRI use during the same time window was not statistically associated with the risk of PPHN (aOR 0.59, 95% CI 0.06, 5.62). Use of SSRIs and SNRIs before the 20th week of gestation was not associated with the risk of PPHN. Conclusions Use of SSRIs in the second half of pregnancy was associated with the risk of PPHN. Given our results on SNRIs and the lack of statistical power for these analyses, it is unclear whether SNRI use during pregnancy also increases the risk of PPHN.

Expanded graphite/sulfur (EG/S) composites were prepared by microwave irradiation of mixtures of sulfur and expanded graphite with S/EG ratios from 4:1 to 12:1. Sulfur was sublimed and entered the EG pores when the mixtures were heated and was condensed to form particles within the pores during cooling. The pores of the EG acted as microcontainers to host the sulfur, and the material, with its interconnected and conductive pore walls, acted as a current collector for the cathode of the Li-S battery. The size of sulfur particles in the EG pores could be controlled by the S/EG mass ratio. When the ratio is 10:1, relatively uniform size sulfur particles could be obtained. Both the S/EG ratio and the sulfur particle size have an important effect on the capacity increase of the Li-S battery. Using a composite with a S/EG ratio of 10:1 as the cathode gives the highest capacity of 1 020 mAhg −1 at a rate of 0.1 C.

Women tend to discontinue their antidepressants during pregnancy. This study compared the risk of depressive symptoms in the second-half of pregnancy in women who discontinue or continue with or without dosage modification their antidepressant during gestation. Women were eligible if they called MothertoBaby during 2006-2010 and within 14 completed weeks of pregnancy. A total of 367 pregnant women were included. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure depression during the first and second half of pregnancy. Presence of depressive symptoms was defined as EPDS ≥13. Among participants, 149 did not use antidepressants, 38 used antidepressants at the beginning of pregnancy but discontinued before the end of second-trimester, and 180 used antidepressants continuously throughout pregnancy. Among continued users, 46 modified antidepressant dosage before the end of the second trimester, and 134 did not modify dosage. The majority of antidepressant users (150/218, 68.8%) had mild to moderate depression. Thirteen percent (13%) of women who continued antidepressant use throughout pregnancy without dosage modification remained depressed. Adjusting for potential confounders including maternal depression/anxiety before pregnancy, and compared to non-users, discontinued users were 5.95 times (95%CI: 1.54-23.02), and continued users without dosage modification 4.59 times (95%CI: 1.44-14.64) more at risk of depression in the second-half of pregnancy. Those with dosage modifications were at a similar risk of depression during pregnancy than non-users (adjusted odds ratio 0.58, 95%CI: 0.06-5.52). In conclusion, in a cohort of mild to moderate depressive pregnant women, discontinuing or continuing antidepressant use without dosage modification during pregnancy were associated with an increased risk of depression during the remaining gestational period.

The aim of the present study was to examine the function of unc-51 like autophagy activating kinase 2 (Ulk2) in non-small cell lung cancer (NSCLC). Western blotting was used to analyze the protein expression of Ulk2 in seven pairs of cancerous and adjacent non-cancerous NSCLC specimens. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to determine the mRNA expression of Ulk2 in 20 pairs of tumor and adjacent normal tissues. Two NSCLC cell lines, A549 and H460, were transfected with an Ulk2 overexpression plasmid or empty vector; cell proliferation and chemosensitivity were measured using an MTT assay, and flow cytometry and western blotting were used to evaluate apoptosis. A nude mouse tumorigenesis experiment was used to assess tumor volume in vivo, using A549 cells stably overexpressing Ulk2 and control cells. The protein expression levels of Ulk2 were significantly lower in 6/7 (85.7%) cases of NSCLC compared with in non-cancerous tissues, as determined by western blotting (P

Aims The aim of this study was to perform an up-to-date meta-analysis on the risk of cardiac malformations associated with gestational exposure to paroxetine, taking into account indication, study design and reference category. Method A systematic review of studies published between 1966 and November 2015 was conducted using embase and MEDLINE. Studies reporting major malformations with first trimester exposure to paroxetine were included. Potentially relevant articles were assessed and relevant data extracted to calculate risk estimates. Outcomes included any major malformations and major cardiac malformations. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models. Results Twenty-three studies were included. Compared with non-exposure to paroxetine, first trimester use of paroxetine was associated with an increased risk of any major congenital malformations combined (pooled OR 1.23, 95% CI 1.10, 1.38; n = 15 studies), major cardiac malformations (pooled OR 1.28, 95% CI 1.11, 1.47; n = 18 studies), specifically bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n = 4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n = 4 studies). Although the estimates varied depending on the comparator group, study design and malformation detection period, a trend towards increased risk was observed. Conclusions Paroxetine use during the first trimester of pregnancy is associated with an increased risk of any major congenital malformations and cardiac malformations. The increase in risk is not dependent on the study method or population.

Purpose Macrolides have been linked to the occurrence of congenital heart defects, but findings are inconsistent. We therefore aimed to estimate the risk of major congenital malformations (MCMs) after fetal exposure to macrolides, focusing on cardiac malformations. Methods From the Quebec Pregnancy Cohort (1998–2008), women exposed to a macrolide or penicillin in the first trimester and unexposed women were studied. There were 135 859 pregnancies included; 914 were exposed to azithromycin, 734 to erythromycin, 686 to clarithromycin, and 9106 to penicillin during the first trimester. Cases of MCMs were identified within the first year of life. Results After adjusting for potential confounders, azithromycin (RR = 1.19, 95%CI: 0.98, 1.44; 120 exposed cases), erythromycin (RR = 0.96, 95%CI: 0.74, 1.24; 66 exposed cases) and clarithromycin use (RR = 1.12, 95%CI: 0.99, 1.42; 79 exposed cases) during the first trimester of pregnancy were not statistically significantly associated with the risk of MCMs; no associations were observed for cardiac malformations. Conclusions First trimester exposure to any of the macrolides was not associated with an increased risk of overall MCMs or cardiac malformations specifically. Copyright © 2015 John Wiley & Sons, Ltd.

Aim Gestational diabetes mellitus is a common complication of pregnancy. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for fetal neurodevelopment. Docosahexaenoic acid (DHA) is the predominant n–3 LCPUFA in the brain and retina. Circulating absolute concentrations of total n–3 and n–6 LCPUFAs rise during normal pregnancy. It remains unclear whether gestational diabetes may affect the normal rise in circulating concentrations of LCPUFAs in the third trimester of pregnancy – a period of rapid fetal neurodevelopment. This study aimed to address this question. Methods In a prospective singleton pregnancy cohort, fatty acids in fasting plasma total lipids were measured at 24–28 and 32–35 weeks of gestation in women with (n = 24) and without gestational diabetes mellitus (n = 116). Fatty acid desaturase activity indices were estimated by relevant product-to-precursor fatty acid ratios. Dietary nutrient intakes were estimated by a food frequency questionnaire. Results Plasma absolute concentrations of total n–6 LCPUFAs rose significantly between 24–28 and 32–35 weeks of gestation in women with or without gestational diabetes, whereas total n–3 LCPUFAs and DHA concentrations rose significantly only in women without gestational diabetes (all P < 0.01). Delta–5 desaturase indices (20:4n–6/20:3n–6) were similar, but delta–6 desaturase indices (18:3n–6/18:2n–6) were significantly lower in women with gestational diabetes at 32–35 weeks of gestation. Dietary intakes of all fatty acids were comparable. Conclusion The normal rise in circulating absolute concentrations of DHA and total n–3 LCPUFAs in the third trimester of pregnancy may be compromised in gestational diabetes, probably due to impaired synthesis or mobilization rather than dietary intake difference.

Made available in DSpace on 2018-12-11T17:17:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01 Myeloperoxidase (MPO) is released from activated neutrophils. The inflammation in preeclampsia was found to be associated with endothelial dysfunction. We hypothesized that cardiac and circulating MPO levels are elevated in hypertensive pregnancy. Systolic and diastolic blood pressure and heart rate were measured on pregnancy days 14, 16, 18 and 20 in normal pregnant and hypertensive pregnant rats. Left and right ventricle weights, the number of viable fetuses, litter size, fetal and placenta weights were recorded on gestational day 21. Circulating and cardiac MPO activities, soluble fms-like tyrosine kinase-1 (sFlt-1) and vascular endothelial growth factor (VEGF) and nitric oxide (NO) were detected. The results showed increases in cardiac (left, but not right ventricle) and circulating MPO activities, and concomitantly lower number of viable fetuses, litter size, and fetal and placenta weights, and decreases in NO in hypertensive pregnant rats. Also, the increases in circulating sFlt-1 and VEGF were found in hypertensive pregnant group. In conclusion, maternal and fetal detrimental changes along with increases in circulating sFlt-1 and VEGF in hypertensive pregnancy may be associated with increases in cardiac and circulating MPO activities, confirming the causative role of inflammatory response in preeclampsia. Department of Thoracic and Cardiovascular Surgery Zhongnan Hospital Wuhan University Department of Gastroenterology Renmin Hospital of Wuhan University Department of Pharmacology Biosciences Institute of Botucatu Sao Paulo State University (UNESP) Department of Pharmacology Biosciences Institute of Botucatu Sao Paulo State University (UNESP)

To quantify the risk of major congenital malformations (MCMs) associated with gestational combination antiretroviral use.Population-based prospective cohort study.Using the Quebec Pregnancy Cohort from 1998 to 2015, we included women who were covered by the Quebec Drug Plan and had a singleton livebirth. All antiretroviral use alone or in combination were considered. MCMs overall and organ-specific malformations in the first year of life were identified.In total, 214 240 pregnancies met inclusion criteria; 0.09% (n = 198) occurred while on antiretroviral combinations during the first trimester; 169 HIV-positive women without antiretroviral treatment were included. Compared with the general population in this cohort, the prevalence of MCMs was significantly higher in unexposed HIV-positive women (14.8 vs. 8.6%, P = 0.004) but not in antiretroviral-exposed HIV-positive women (10.3%, P = 0.41). Adjusting for potential confounders, including maternal HIV status, antiretroviral use during the first trimester was not associated with the risk of MCMs (adjusted odds ratio 0.59, 95% confidence interval 0.33-1.06). However, antiretroviral combination use during the first trimester was associated with an increased risk of defects of the small intestine (adjusted odds ratio 10.32, 95% confidence interval 2.85-37.38, P = 0.0004).Antiretroviral therapy during the first trimester was not associated with the risk of overall MCMs but may be associated with an increased risk of defects of the small intestine. However, HIV-positive pregnant women who are not treated with antiretrovirals during pregnancy seem to have a higher risk of malformations; this is not seen among those who are treated, which could indicate that the underlying condition puts women at risk and not the treatment.

To explore the hypothesis that female fetus is associated with greater maternal insulin resistance during pregnancy.In a singleton pregnancy cohort study (n = 299), we compared maternal insulin resistance according to fetal sex, based on plasma biomarkers from a 50-g 1-h oral glucose tolerance test at 24-28 weeks gestation. The primary outcome was plasma glucose-to-insulin ratio. Other outcomes included plasma proinsulin-to-insulin ratio, and insulin, proinsulin, leptin, adiponectin and insulin-like growth factor I and II concentrations.After adjusting for maternal race, age, parity, education, pre-pregnancy BMI, smoking and alcohol use, history of gestational diabetes, and gestational age at blood sampling, plasma insulin concentrations were significantly higher (mean ± sd: 66.4 ± 50.5 vs. 51.0 ± 46.1 mU/l; adjusted P = 0.001), and glucose-to-insulin ratios significantly lower (2.60 ± 2.03 vs. 3.77 ± 4.98 mg/dl/mU/l; adjusted P = 0.002) in women bearing a female vs those bearing a male fetus, despite similar glucose levels (116.4 ± 27.2 vs. 117.0 ± 31.9 mg/dl; adjusted P = 0.92).There were no significant differences in proinsulin-to-insulin ratios, or leptin, adiponectin, insulin-like growth factor I and insulin-like growth factor II concentrations by fetal sex.Female fetus may be associated with greater maternal insulin resistance during pregnancy.

Importance Benzodiazepine use in early pregnancy is associated with spontaneous abortion (SA). However, to date, the association between specific benzodiazepine agent exposure and the risk of SA has not been examined. Objective To quantify the risk of SA associated with gestational benzodiazepine incident use by drug class, duration of action, and specific benzodiazepine agent. Design, Setting, and Participants This nested case-control study within the Quebec Pregnancy Cohort, Montreal, Quebec, Canada, includes all pregnancies covered by the Quebec Prescription Drug Insurance Plan from January 1, 1998, through December 31, 2015. Each case was randomly matched with up to 5 controls. Statistical analysis was performed from January 1, 1998, through December 31, 2015. Exposures Benzodiazepine exposure was defined as 1 or more filled prescriptions between the first day of the last menstrual period and the index date (the calendar date of the SA diagnosis). Benzodiazepine exposure was categorized by overall use, long- or short-acting benzodiazepine, and specific benzodiazepine agents. Main Outcomes and Measures Spontaneous abortion defined as a pregnancy loss between the beginning of the sixth week of gestation and the 19th completed week of gestation. Conditional logistic regression models were used to calculate odds ratios (OR) and 95% CIs. Results Of the 442 066 pregnancies included in the Quebec Pregnancy Cohort, 27 149 (6.1%) ended with SA, with a mean (SD) maternal age of 24.2 (6.5) years. Among pregnancies ending with SA, 375 (1.4%) were among women exposed to benzodiazepines in early pregnancy compared with 788 (0.6%) of the 134 305 matched control pregnancies (crude OR, 2.39; 95% CI, 2.10-2.73). Adjusting for potential confounders, including maternal mood and anxiety disorders before pregnancy, and compared with nonuse, benzodiazepine exposure in early pregnancy was associated with an increased risk of SA (adjusted OR, 1.85; 95% CI, 1.61-2.12). The risk was similar among pregnancies exposed to short-acting (284 exposed cases; adjusted OR, 1.81; 95% CI, 1.55-2.12) and long-acting (98 exposed cases; adjusted OR, 1.73; 95% CI, 1.31-2.28) benzodiazepines during early pregnancy. All benzodiazepine agents were independently associated with an increased risk of SA (range of adjusted ORs, 1.13-3.43). Conclusions and Relevance An increased risk of SA was observed among early pregnancies with incident exposure to short- and long-acting benzodiazepines and all specific benzodiazepine agents during early pregnancy. Insomnia, anxiety, and mood disorders are prevalent during pregnancy; clinicians should carefully evaluate the risk-benefit ratio of prescribing benzodiazepines in early pregnancy since alternative nonpharmacologic treatments exist.

In this paper, we designed a new type of high precision 1 μA constant current source after deeply studying the high precision precise dc constant current source. Compared with the traditional constant current source, in this paper we adopted complex amplifier added with floating power supply outside to design high precision dc constant current source which is for China's space use , its output current is 1 μA, resolution is 0.1 nA, accuracy is 0.5. This high precise dc constant current source is mainly used for new model rocket engine performance testing in aerospace, but also can be widely applied in different fields in need of precision measurement.

Importance: Polymorphic expression of drug metabolizing enzymes affects the metabolism of antidepressants, and thus can contribute to drug response and/or adverse events. Pregnancy itself can affect CYP2D6 activity with profound variations determined by CYP2D6 genotype. Objective: To investigate the association between CYP2D6 genotype and the risk of antidepressant discontinuation, dosage modification, and the occurrence of maternal CYP2D6, Antidepressants, Depression during pregnancy. Setting: Data from the Organization of Teratology Information Specialists (OTIS) Antidepressants in Pregnancy Cohort, 2006–2010, were used. Women were eligible if they were within 14 completed weeks of pregnancy at recruitment and exposed to an antidepressant or having any exposures considered non-teratogenic. Main Outcomes and Measures: Gestational antidepressant usage was self-reported and defined as continuous/discontinued use, and non-use; dosage modification was further documented. Maternal depression and anxiety were measured every trimester using the telephone interviewer-administered Edinburgh Postnatal Depression Scale and the Beck Anxiety Inventory, respectively. Saliva samples were collected and used for CYP2D6 genotype analyses. Logistic regression models were used to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals. Results: A total of 246 pregnant women were included in the study. The majority were normal metabolizers (NM, n = 204, 83%); 3.3% (n = 8) were ultrarapid metabolizers (UM), 5.7% (n = 14) poor metabolizers (PM), and 8.1% (n = 20) intermediate metabolizers (IM). Among study subjects, 139 women were treated with antidepressants at the beginning of pregnancy, and 21 antidepressant users (15%) discontinued therapy during pregnancy. Adjusting for depressive symptoms, and other potential confounders, the risk of discontinuing antidepressants during pregnancy was nearly four times higher in slow metabolizers (poor or intermediate metabolizers) compared to those with a faster metabolism rate (normal or ultrarapid metabolizers), aOR = 3.57 (95% CI: 1.15-11.11). Predicted CYP2D6 metabolizer status did not impact dosage modifications. Compared with slow metabolizers, significantly higher proportion of women in the fast metabolizer group had depressive symptom in the first trimester (19.81 vs. 5.88%, P = 0.049). Almost 21% of treated women remained depressed during pregnancy (14.4% NM-UM; 6.1% PM-IM). Conclusions and Relevance: Prior knowledge of CYP2D6 genotype may help to identify pregnant women at greater risk of antidepressant discontinuation. Twenty percent of women exposed to antidepressants during pregnancy remained depressed, indicating an urgent need for personalized treatment of depression during pregnancy.

Objective Antidepressant use during gestation has been associated with risk of major congenital malformations but estimates can lack statistical power or be confounded by maternal depression. We aimed to determine the association between first-trimester exposure to antidepressants and the risk of major congenital malformations in a cohort of depressed/anxious women. Setting and participants Data were obtained from the Quebec Pregnancy Cohort (QPC). All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included. Outcome measures Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin–norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and other antidepressants) and types were individually compared with non-exposure during the first trimester (depressed untreated). Major congenital malformations overall and organ-specific malformations in the first year of life were identified. Results 18 487 pregnant women were included. When looking at the specific types of antidepressant used during the first trimester, only citalopram was increasing the risk of major congenital malformations (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases), although there was a trend towards increased risk for the most frequently used antidepressants. Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) increased the risk of certain organ-specific defects: paroxetine increased the risk of cardiac defects (aOR 1.45, 95% CI 1.12 to 1.88), and ventricular/atrial septal defects (aOR 1.39, 95% CI 1.00 to 1.93); citalopram increased the risk of musculoskeletal defects (aOR 1.92, 95% CI 1.40 to 2.62), and craniosynostosis (aOR 3.95, 95% CI 2.08 to 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95% CI 1.07 to 4.38). Conclusions Antidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression.

Administrative databases are increasingly used to measure drug exposure in perinatal pharmacoepidemiology. We aimed to estimate the concordance between records of prescriptions filled in pharmacies and self-reported drug use during pregnancy.Data on self-reported medication use were collected at each trimester of pregnancy among a sub-sample from the Organization of Teratology Information Specialists Antidepressants in Pregnancy Cohort. Women were eligible if they were Quebec resident and provided their pharmacist's contact information. Maternal self-reports were compared with prescriptions filled in pharmacies, which are transferred to pharmaceutical services files of Quebec provincial health plan database (Régie de l'asssurance maladie du Québec). Positive and negative predictive values (PPV and NPV) for medications taken chronically (antidepressants, thyroid hormones), acutely (antibiotics), and as needed (antiemetics, asthma medications) were calculated.Among the 93 participants (mean age = 30.2 ± 3.8 years), 41.9% (n = 39) took at least one antidepressant during pregnancy according to self-reports, and 39.8% (n = 37) according to pharmacy records. Other commonly used drugs were antiemetics (self-reported 22.6%, pharmacy record 24.7%), antibiotics (20.4%, 16.1%), asthma medications (15.1%, 15.1%), and thyroid hormones (10.8%, 8.6%). PPVs and NPVs were: (1) chronic medication: antidepressants PPV = 100% (95% confidence interval [CI], 100-100%), NPV = 96% (95% CI, 92-100%); thyroid hormones PPV = 100% (95% CI, 100-100%), NPV = 98% (95% CI, 95-100%); (2) Acute medication: antibiotics PPV = 87% (95% CI, 70-100%), NPV = 92% (95% CI, 86-98%); (3) as needed medications: antiemetics: PPV = 78% (95% CI, 62-95%), NPV = 96% (95% CI, 91-100%); asthma: PPV = 33% (95% CI, 3-64%), NPV = 99% (95% CI, 97-100%).The high PPV and NPV validate the use of filled prescription data in large databases as a measure of medication exposure. Birth Defects Research 109:423-431, 2017. © 2017 Wiley Periodicals, Inc.

In order to improve the durability of the wood fiber reinforced external wall board, silica fume, a kind of inorganic silica material was added in the board. The properties of the boards containing different amount of silica fume were studied. The durability was effectively characterized by determining the fracture work and bending strength after wetting-drying cycles test of the board. The results showed that the fracture work and bending strength of the board obviously increased when the proportion of silica fume and cement was 1:9~1:3.

Asbestos is used as reinforcing fiber in nearly all the current external wall board manufacturing process, but it has harmful effects on the human body. In this paper, composite-fiber reinforced external wall board without asbestos was successfully prepared using plant fibers as reinforcing material instead of asbestos by compression molding. Effect of the content of wood fiber, wood powder, quartz sand and water on the density and mechanical properties of the board were studied in this work. Besides, the optimized preparation method for composite-fiber reinforced external wall board without asbestos was achieved.

Based on the data of 600 years global above class 5 volcanic explosion index (VEI) and the comparison of the northern hemispheric ground temperature, the western pacific high, the northern Atlantic high and the sea surface temperature anomaly (SSTA) in the northern Atlantic westerly region, it is showed that: (1) The global strong volcano activities have obvious century timescale cycles about 88 and 100 years, accounting for about 21.65% of total variance for VEI, an about 33-year interdecadal timescale cycle, and an 11-year cycle associated with solar activity. (2) The western Pacific subtropical high in July has a 33-year period oscillation accordant to the volcanic activity, which is considered to be the response to the 33-year periodic volcanic activity. (3) In the North Atlantic, the volcanic activities inspire the summer North Atlantic sub-tropical high with 88-year cycle oscillation, winter (January) northern Atlantic westerly region SSTA with 100-year oscillation and summer (July) SSTA 88-year cycle oscillation. (4) Analysis shows that the 88-year periodic variation of northern hemispheric ground temperature is the response to the 88-year cycle of volcanic activity.

Aiming at Job Shop Scheduling Problem with Minimal Makespan, This paper is designed to use genetic algorithm to solve the problem of job shop scheduling, and also achieves the algorithm by using the C#. Application shows that the genetic algorithm to solve job shop scheduling problem is efficient and has good application value.