Associations between Prepartum and Postpartum Maternal Symptoms of Depression, Anxiety and Stress Related to COVID-19 Pandemic and Childhood Sensory Avoidance: Results from Conception Study.

BACKGROUND: Prepartum and postpartum maternal symptoms of stress, anxiety and depression are likely to influence the child's sensory processing through hormonal alterations and an influence on mother-child interactions. OBJECTIVE: We investigated the associations between maternal prepartum and postpartum symptoms of depression, anxiety and stress related to the COVID-19 pandemic and childhood sensory avoidance at 18 months. METHODS: Longitudinal data from 409 participants followed during the COVID-19 pandemic were used. They completed questionnaires during pregnancy and up to 18 months after delivery. Maternal distress symptoms were assessed prenatally and at 18 months postnatally using the Edinburgh Postnatal Depression Scale, the Generalized Anxiety Disorders 7-item Scale and a 10-point scale assessing the level of stress felt related to the COVID-19 pandemic. Child sensory avoidance was assessed at 18 months postpartum using the Infant/Toddler Sensory Profile-Second Edition. Pearson correlations and multiple regressions measured the associations between maternal distress symptoms and child sensory avoidance. RESULTS: Prepartum and 18-month postpartum maternal depression and anxiety were significantly correlated with childhood sensory avoidance (p < 0.05). Together, these variables explained 7.18% (F = 2.12, p < 0.05) of the variance of childhood sensory avoidance. CONCLUSIONS: These results support the contributory effect of prepartum and postpartum maternal distress on childhood sensory development.

Maternal Mental Health in Pregnancy and Its Impact on Children's Cognitive Development at 18 Months, during the COVID-19 Pandemic (CONCEPTION Study).

BACKGROUND: The COVID-19 pandemic has significantly affected the mental health of pregnant persons. OBJECTIVE: We aimed to evaluate the impact of maternal mental health and antidepressant use on children's cognitive development. METHODS: We followed a cohort of children born during the COVID-19 pandemic. Maternal mental health was self-reported during pregnancy (Edinburgh Postnatal Depression Scale, General Anxiety Disorder-7, stress levels, and antidepressant use). The child's cognitive development was measured using the third edition of the Ages & Stages Questionnaires® (ASQ-3) at 18 months. Multivariate multinomial logistic regression models were built to assess the association between in utero exposure to maternal mental health and ASQ-3 domains: communication, gross motor, fine motor, problem-solving, and personal-social. RESULTS: Overall, 472 children were included in our analyses. After adjusting for potential confounders, a need for further assessment in communication (adjusted odds ratio (aOR) 12.2, 95% confidence interval (CI) (1.60;92.4)), and for improvement in gross motricity (aOR 6.33, 95%CI (2.06;19.4)) were associated with in utero anxiety. The need for improvement in fine motricity (aOR 4.11, 95%CI (1.00; 16.90)) was associated with antidepressant exposure. In utero depression was associated with a decrease in the need for improvement in problem solving (aOR 0.48, 95%CI (0.24; 0.98)). CONCLUSIONS: During the COVID-19 pandemic, maternal mental health appears to be associated with some aspects of children's cognitive development.

The impact of prenatal maternal mental health during the COVID-19 pandemic on birth outcomes: two nested case-control studies within the CONCEPTION cohort.

OBJECTIVE: Assess the association between prenatal mental health during the COVID-19 pandemic and preterm birth (PTB; delivery < 37 weeks gestation) and low birth weight (LBW; < 2500 g). METHODS: Pregnant individuals, > 18 years, were recruited in Canada and provided data through a web-based questionnaire. We analyzed data on persons recruited between 06/2020 and 08/2021 who completed questionnaires while pregnant and 2 months post-partum. Data on maternal sociodemographics, comorbidities, medication use, mental health (Edinburgh Postnatal Depression Scale, General Anxiety Disorder-7, stress), pandemic hardship (CONCEPTION-Assessment of Stress from COVID-19), and on gestational age at delivery and birth weight were self-reported. Crude and adjusted odds ratios (aOR) with 95% confidence interval (95%CI) were calculated to quantify the association between PTB/LBW and maternal mental health. RESULTS: A total of 1265 and 1233 participants were included in the analyses of PTB and LBW, respectively. No associations were observed between PTB and prenatal mental health (depression [aOR 1.01, 95%CI 0.91-1.11], anxiety [aOR 1.04, 95%CI 0.93-1.17], stress [aOR 0.88, 95%CI 0.71-1.10], or hardship [aOR 1.00, 95%CI 0.96-1.04]) after adjusting for potential confounders. The risk of PTB was increased with non-white ethnicity/race (aOR 3.85, 95%CI 1.35-11.00), consistent with the literature. Similar findings were observed for LBW (depression [aOR 1.03, 95%CI 0.96-1.13], anxiety [aOR 1.05, 95%CI 0.95-1.17], COVID stress [aOR 0.92, 95%CI 0.77-1.09], or overall hardship [aOR 0.97, 95%CI 0.94-1.01]). CONCLUSION: No association was found between prenatal mental health nor hardship during the COVID-19 pandemic and the risk of PTB or LBW. However, it is imperative to continue the follow-up of mothers and their offspring to detect long-term health problems early.

RéSUMé: OBJECTIF: Évaluer l'association entre la santé mentale prénatale pendant la pandémie de COVID-19 et les naissances prématurées (accouchement < 37 semaines de gestation) et les faibles poids à la naissance (< 2 500 g). MéTHODES: Des personnes enceintes de plus de 18 ans ont été recrutées au Canada et ont fourni des données prénatales via un questionnaire en ligne. Nous avons analysé les données des personnes recrutées entre 06/2020 et 08/2021, ayant rempli deux questionnaires dont un pendant la grossesse et un 2 mois post-partum. Les données sur les caractéristiques sociodémographiques maternelles, les comorbidités, l'utilisation de médicaments, la santé mentale (Échelle de dépression postnatale d'Édimbourg [EPDS], trouble anxieux généralisé-7 [GAD-7], stress), les difficultés liées à la pandémie (CONCEPTION­Évaluation du stress lié à la COVID-19) ainsi que l'âge gestationnel à l'accouchement et le poids à la naissance ont été auto-déclarées. Les rapports de cotes bruts et ajustés (aRC) avec un intervalle de confiance à 95% (IC 95%) ont été calculés pour quantifier l'association entre la prématurité/petit poids à la naissance et la santé mentale maternelle. RéSULTATS: Un total de 1 265 et 1 233 participants ont été inclus dans les analyses de NP et de FPN, respectivement. Aucune association n'a été observée entre la prématurité et la santé mentale prénatale (dépression [aRC 1,01, IC 95% 0,91­1,11], anxiété [aOR 1,04, IC 95% 0,93­1,17], stress [aRC 0,88, IC 95% 0,71­1,10], ni difficultés liées à la COVID-19 [aOR 1,00, IC 95% 0,96­1,04]) après ajustement pour les facteurs de confusion potentiels. Le risque de prématurité était plus élevé chez les personnes d'ethnie/race non blanche (aRC 3,85, IC 95% 1,35­11,00), en accord avec la littérature. Des résultats similaires ont été observés pour le faible poids à la naissance (dépression [aRC 1,03, IC 95% 0,96­1,13], anxiété [aRC 1,05, IC 95% 0,95­1,17], stress lié à la COVID [aRC 0,92, IC 95% 0,77­1,09], ou difficultés en lien avec la COVID-19 [aRC 0,97, IC 95% 0,94­1,01]). CONCLUSION: Aucune association n'a été trouvée entre la santé mentale prénatale ni les difficultés pendant la pandémie de COVID-19 et le risque de prématurité ou de petit poids à la naissance. Cependant, il est impératif de poursuivre le suivi des mères et de leurs enfants pour détecter précocement d'éventuels problèmes de santé à long terme.

Medically assisted reproduction and the risk of being born small and very small for gestational age: Assessing prematurity status as an effect modifier.

Over the last decade, the use of medically assisted reproduction (MAR) has steadily increased but controversy remains with regards to its risks. We aimed to quantify the risk of being born small for gestational age (SGA) and very SGA (VSGA) associated with MARs overall and by type, namely ovarian stimulators (OS) and assisted reproductive technology (ART). We conducted a cohort study within the Quebec Pregnancy Cohort. Pregnancies coinciding with Quebec's MAR reimbursement PROGRAM period (2010-2014) with a singleton liveborn were considered. MAR was first defined dichotomously, using spontaneous conception as the reference, and categorized into three subgroups: OS alone (categorized as clomiphene and non-clomiphene OS), ART, OS/ART combined. SGA was defined as being born with a birth weight below the 10th percentile based on sex and gestational age (GA), estimated using populational curves in Canada, while VSGA was defined as being born with a birth weight below the 3rd percentile. We then estimated odds ratios (OR) for the association between MAR and SGA as well as VSGA using generalized estimated equation (GEE) models, adjusted for potential confounders (aOR). Two independent models were conducted considering MAR exposure overall, and MAR subgroup categories, using spontaneous conceptions as the reference. The impact of prematurity status (less than 37 weeks gestation) as an effect modifier in these associations was assessed by evaluating them among term and preterm pregnancies separately. A total of 57,631 pregnancies met inclusion criteria and were considered. During the study period, 2,062 women were exposed to MARs: 420 to OS alone, 557 to ART, and 1,085 to OS/ART combined. While no association was observed between MAR and SGA nor VSGA in the study population, MAR was associated with an increased risk for SGA (aOR 1.69, 95% CI 1.08-2.66; 25 exposed cases) among preterm pregnancies; no increased risk of SGA was observed in term pregnancies. MARs are known to increase the risk of preterm birth and our results further confirm that they also increase the risk of SGA among preterm pregnancies.

The Impact of COVID-19 on Maternal Mental Health during Pregnancy: A Comparison between Canada and China within the CONCEPTION Cohort.

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.

The Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO): Comparisons between Quebec, Manitoba, Saskatchewan, and Alberta.

BACKGROUND: Given that pregnant women taking medications are excluded from clinical trials, real-world evidence is essential. We aimed to build a Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO) and compare frequency of prematurity, low-birth-weight (LBW), major malformations, multiplicity, and gestational medication use across four provinces. METHODS: CAMCCO is a collaborative research infrastructure that uses real-world data from large provincial health care databases in Canada; developed with standardized methods to similarly construct population-based pregnancy/child cohorts with longitudinal follow-up by linking administrative/hospital/birth databases. CAMCCO also includes a common repository to i) share algorithms and case definitions based on diagnostic and procedural codes for research/training purpose, and ii) download aggregate data relevant to primary care providers, researchers, and decision makers. For this study, data from Quebec (1998-2015), Manitoba (1995-2019), Saskatchewan (1996-2020), and Alberta (2005-2018) are compared (Chi-square tests, p-values), and trends are calculated using Cochran-Armitage trend tests. RESULTS: Almost two-thirds (61%) of women took medications during pregnancy, mostly antibiotics (26%), asthma drugs (8%), and antidepressants (4%). Differences in the prevalence of prematurity (5.9-6.8%), LBW (4.0-5.2%), and multiplicity (1.0-2.5%) were statistically significant between provinces (p<0.001). Frequency of major malformations increased over time in Quebec (7-11%; p<0.001), Saskatchewan (5-11%; p<0.001), and Alberta (from 7-8%; p<0.001), and decreased in Manitoba (5-3%; p<0.001). Cardiovascular and musculoskeletal malformations were the most prevalent. INTERPRETATION: Medications are often used among Canadian pregnancies but adverse pregnancy outcomes vary across provinces. Digitized health data may help researchers and care providers understand the risk-benefit ratios related to gestational medication use, as well as province-specific trends.

Is in-utero exposure to cannabis associated with the risk of attention deficit with or without hyperactivity disorder? A cohort study within the Quebec Pregnancy Cohort.

IMPORTANCE AND OBJECTIVE: Prenatal cannabis effect on attention deficit with or without hyperactivity disorder (ADHD) remains to be determined. Our aim is to quantify the impact of in-utero exposure to cannabis on the risk of ADHD. DESIGN: Cohort study. SETTING: Questionnaires were mailed to women sampled from the Quebec Pregnancy Cohort (QPC). Data from questionnaires were then linked with their QPC (built with administrative health databases, hospital patient charts and birth certificate databases). PARTICIPANTS: Respondents who gave birth to a singleton live born between January 1998 and December 2003 and were continuously enrolled in the Régie de l'assurance maladie du Québec (RAMQ) medication insurance plan for at least 12 months before the first day of gestation and during pregnancy. EXPOSURE: In-utero cannabis exposure was based on mothers' answers to the question on cannabis use during pregnancy (yes/no) and categorised as occasionally, regularly exposed and unexposed if they chose one of these categories. OUTCOMES: ADHD was defined by a diagnosis of ADHD through the RAMQ medical services or MedEcho databases or a prescription filled for ADHD medication through RAMQ pharmaceutical services between birth and the end of the follow-up period. Follow-up started at the birth and ended at the index date (first diagnosis or prescription filled for ADHD), child death (censoring), end of public coverage for medications (censoring) or the end of study period, which was December 2015 (censoring), whichever event came first. RESULTS: A total of 2408 children met the inclusion criteria. Of these children, 86 (3.6%) were exposed to cannabis in-utero and 241 (10.0%) had an ADHD diagnosis or medication filled. After adjustments for potential confounders, no significant association was found between in-utero cannabis exposure (occasional (1.22 (95% CI 0.63 to 2.19)) or regular (1.22 (95% CI 0.42 to 2.79))) and the risk of ADHD in children. CONCLUSIONS: In-utero exposure to cannabis seemed to not be associated with the risk ADHD in children.

The COVID-19 Pandemic Impacted Maternal Mental Health Differently Depending on Pregnancy Status and Trimester of Gestation.

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 the mental health of women who had delivered; determinants of severe depression were identified with multivariate logistic regression models. Results: 2574 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). 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 has 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.

SARS-CoV-2 vaccine uptake and reasons for hesitancy among Canadian pregnant people: a prospective cohort study.

BACKGROUND: Several vaccines against SARS-CoV-2 have been developed and approved at an unparalleled speed. Given that SARS-CoV-2 vaccines are recommended to pregnant people, our aim was to quantify vaccination uptake, and describe vaccination hesitancy and behavioural attitudes surrounding SARS-CoV-2 vaccination in pregnancy in Canada. METHODS: The CONCEPTION study is an ongoing international study started in June 2020, evaluating the impact of the COVID-19 pandemic on the health of pregnant people and their children. For this study, pregnant people recruited from Apr. 20, 2021, to Feb. 8, 2022, and residing in Canada were invited to complete a Web-based survey. In addition to all CONCEPTION variables, data on vaccine uptake as well as personal knowledge of COVID-19 severity in pregnancy and of SARS-CoV-2 vaccine safety and efficacy were collected. Marginal risk differences and adjusted odds ratios (ORs) were calculated to assess determinants of SARS-CoV-2 vaccination during pregnancy. RESULTS: From Apr. 20, 2021, to Feb. 8, 2022, 603 pregnant people were recruited and gave consent, of which 83.7% (n = 505) were vaccinated and 16.3% (n = 98) were not vaccinated against SARS-CoV-2. Uptake of the influenza vaccine in 2020/21 was a significant predictor of being vaccinated against SARS-CoV-2 or intention to be vaccinated (marginal risk difference 3.2%, 95% confidence interval [CI] 3.0% to 3.3%, adjusted OR 4.43, 95% CI 2.32 to 9.25), and being employed (marginal risk difference 11.2%, 95% CI 10.6% to 11.9%, adjusted OR 2.17, 95% CI 1.03 to 4.35) increased the likelihood of being vaccinated against SARS-CoV-2. Self-assessed knowledge of COVID-19 severity and vaccine efficacy was not associated with vaccine uptake. INTERPRETATION: Among the Canadian pregnant people who responded to this study, vaccine uptake against SARS-CoV-2 was high. However, our results underscore the importance of improving knowledge transfer about the efficacy of SARS-CoV-2 vaccines in pregnancy to guide vaccination efforts.

Sleep-disordered breathing in high-risk pregnancies is associated with elevated arterial stiffness and increased risk for preeclampsia.

BACKGROUND: Impaired vascular function is a central feature of pathologic processes preceding the onset of preeclampsia. Arterial stiffness, a composite indicator of vascular health and an important vascular biomarker, has been found to be increased throughout pregnancy in those who develop preeclampsia and at the time of preeclampsia diagnosis. Although sleep-disordered breathing in pregnancy has been associated with increased risk for preeclampsia, it is unknown if sleep-disordered breathing is associated with elevated arterial stiffness in pregnancy. OBJECTIVE: This prospective observational cohort study aimed to evaluate arterial stiffness in pregnant women, with and without sleep-disordered breathing and assess the interaction between arterial stiffness, sleep-disordered breathing, and preeclampsia risk. STUDY DESIGN: Women with high-risk singleton pregnancies were enrolled at 10 to 13 weeks' gestation and completed the Epworth Sleepiness Score, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaires at each trimester. Sleep-disordered breathing was defined as loud snoring or witnessed apneas (≥3 times per week). Central arterial stiffness (carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness), peripheral arterial stiffness (carotid-radial pulse wave velocity), wave reflection (augmentation index, time to wave reflection), and hemodynamics (central blood pressures, pulse pressure amplification) were assessed noninvasively using applanation tonometry at recruitment and every 4 weeks from recruitment until delivery. RESULTS: High-risk pregnant women (n=181) were included in the study. Women with sleep-disordered breathing (n=41; 23%) had increased carotid-femoral pulse wave velocity throughout gestation independent of blood pressure and body mass index (P=.042). Differences observed in other vascular measures were not maintained after adjustment for confounders. Excessive daytime sleepiness, defined by Epworth Sleepiness Score >10, was associated with increased carotid-femoral pulse wave velocity only in women with sleep-disordered breathing (Pinteraction=.001). Midgestation (first or second trimester) sleep-disordered breathing was associated with an odds ratio of 3.4 (0.9-12.9) for preeclampsia, which increased to 5.7 (1.1-26.0) in women with sleep-disordered breathing and hypersomnolence, whereas late (third-trimester) sleep-disordered breathing was associated with an odds ratio of 8.2 (1.5-39.5) for preeclampsia. CONCLUSION: High-risk pregnant women with midgestational sleep-disordered breathing had greater arterial stiffness throughout gestation than those without. Sleep-disordered breathing at any time during pregnancy was also associated with increased preeclampsia risk, and this effect was amplified by hypersomnolence.

Prevalence and duration of prescribed opioid use during pregnancy: a cohort study from the Quebec Pregnancy Cohort.

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 (< 90 days vs. ≥90 days), duration of action (short-acting vs. long-acting) and strength of the opioid (weak vs. strong). 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 < 0.05). 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.

A longitudinal analysis of arterial stiffness and wave reflection in preeclampsia: Identification of changepoints.

PURPOSE: Preeclampsia (PrE) is a leading complication of pregnancy characterized by vascular dysfunction. Characterizing the longitudinal changes in vascular function prior to PrE onset is critical to the identification of optimal timepoints for vascular assessment and the development of effective early screening strategies. METHODS: In this prospective longitudinal study of women with singleton high-risk pregnancies, arterial stiffness and wave reflection parameters were assessed using applanation tonometry at 10-13 weeks' gestation and repeated every 4 weeks throughout pregnancy. Changepoints in carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation index (AIx), time to wave reflection (T1R), pulse pressure amplification (PPA), and subendocardial viability ratio (SEVR) were compared between women who did and did not subsequently develop PrE. RESULTS: A changepoint in cfPWV and crPWV was detected at 14-17 weeks' gestation. cfPWV then increased in women who went on to develop PrE but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22-25 weeks' gestation. Conversely, crPWV converged in the two groups from a baseline difference of 1.05 m/s (95% credible interval: 0.37, 1.72). Women who subsequently developed PrE demonstrated an increase in AIx at 18-21 weeks' gestation that was not seen in women who did not develop PrE until 30-33 weeks. No differences in T1R, PPA, or SEVR were observed between the groups. CONCLUSIONS: Altered vascular adaptations were detected using measures of arterial stiffness and wave reflection in the early second trimester of pregnant women who developed PrE compared to those who did not. These findings demonstrate the potential clinical utility of arterial stiffness and wave reflection parameters as an early screening tool for PrE, which can be used to inform clinical management of high-risk pregnancies.

Comparative safety and effectiveness of inhaled bronchodilators and corticosteroids for treating asthma-COPD overlap: a systematic review and meta-analysis.

OBJECTIVE: To determine the safety and effectiveness of current pharmacotherapies consisting of long-acting beta2-agonist (LABA) and/or inhaled corticosteroids (ICS) in patients with asthma-COPD overlap. DATA SOURCES: A systematic search was conducted using the PubMed, EMBASE, and Web of Science databases up to June 2018. STUDY SELECTIONS: Only studies comparing the safety and effectiveness of LABA and/or ICS in patients with asthma-COPD overlap were included. A meta-analysis was performed to calculate risk ratio (RR) and 95% confidence interval (CI) using Inverse Variance Random-effects model. RESULTS: From a total of 3382 articles retrieved, three randomized controlled trials (RCTs), six cohort studies (CS), one nested case control study fulfilled the inclusion criteria for three independent meta-analyses representing 181,603 participants. Three CS results show LABA was associated with decreased risk of myocardial infarction (combined RR: 0.80, 95% CI 0.74-0.87) versus non-LABA use; ICS/LABA was associated with a lower risk of death or hospitalization (combined RR: 0.82, 95% CI 0.75-0.90) compared to no use. Results from RCTs, no clear difference in lung function decline in FEV1 was found (combined mean difference: 0.08, 95% CI 0.15-0.32) in patients receiving ICS and/or LABA compared to placebo. However, due to lack of data, exacerbations, fractures and nontuberculous mycobacterial pulmonary disease outcomes were not meta-analyzed. CONCLUSIONS: Among patients with asthma-COPD overlap, LABA is associated with decreased risk of myocardial infarction; and the combination therapy of ICS/LABA appears to reduce the risk of death or hospitalization. More studies of quality data and larger number of patients are needed. REGISTRATION: PROSPERO (CRD42018090863).

Medically assisted reproduction and the risk of preterm birth: a case-control study using data from the Quebec Pregnancy Cohort.

BACKGROUND: The use of fertility treatments has been growing over the past decade, but these treatments are not without risk. We aimed to quantify the risk of preterm birth associated with the use of ovarian stimulators (OS) and assisted reproductive technologies (ART) overall and by type of fertility treatment. METHODS: We conducted a case-control analysis of data from the Quebec Pregnancy Cohort. We included singleton pregnancies ending in a live birth during the time when Quebec operated a universal reimbursement program for assisted reproduction (2010-2015). Fertility treatments were defined dichotomously, and pregnancies resulting from spontaneous conception were used as the reference. We categorized fertility treatments into subgroups: ovarian stimulators alone, ART alone and OS and ART combined. Preterm birth was defined as birth before 37 weeks' gestation. We estimated odds ratios (ORs) for the association between type of assisted reproduction and preterm birth using generalized estimating equation models and adjusted ORs for potential confounders. RESULTS: A total of 57 624 pregnancies were included in the study. During the study period, 2055 pregnancies were conceived through the use of OS, ART or both: 419 involved OS alone, 150 involved ART alone and 1486 involved both OS and ART. When we adjusted for potential confounders, conception with OS, ART or both was associated with an increased risk of preterm birth (adjusted OR 1.46, 95% confidence interval [CI] 1.25-1.72, 182 exposed cases). All types of assisted reproduction were associated with an increased risk of preterm birth compared with pregnancies conceived spontaneously (OS alone: adjusted OR 1.47, 95% CI 1.04-2.07; ART alone: adjusted OR 1.76, 95% CI 1.01-3.06; OS and ART combined: adjusted OR 1.43, 95% CI 1.19-1.73). Use of OS or ART or both was associated with an increased risk of late, moderate and extremely preterm birth (extremely preterm birth: adjusted OR 2.39, 95% CI 1.30-4.39). INTERPRETATION: Compared with pregnancies conceived spontaneously, pregnancies conceived through the use of OS, ART or both were associated with a 46% increased risk of preterm birth. Physicians should advise patients of the increased risks of late, moderate and extremely preterm birth so that they can make informed choices.

New evidence for concern over the risk of birth defects from medications for nausea and vomitting of pregnancy.

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.

Associations between low- and high-dose oral fluconazole and pregnancy outcomes: 3 nested case-control studies.

BACKGROUND: While topical azoles are the first-line treatment for fungal infections, oral fluconazole is frequently used during pregnancy. We aimed to assess the effect of exposure to low and high doses of fluconazole during pregnancy on the occurrence of spontaneous abortions, major congenital malformations and stillbirths. METHODS: Within the Quebec Pregnancy Cohort (1998-2015), we identified women exposed to low- (≤ 150 mg) and high-dose (> 150 mg) fluconazole, and women who were not exposed. For each case of spontaneous abortion or stillbirth, up to 5 controls were randomly selected using an incidence density sampling method matched on gestational age at diagnosis of spontaneous abortion or stillbirth (index date) and the year of the last menstrual period. For cases of major congenital malformation, we considered all liveborn babies as controls. Generalized estimation equation models were used to analyze the 3 main outcomes separately. RESULTS: Within a cohort of 441 949 pregnancies, 320 868 pregnancies were included in the analyses of spontaneous abortions, 226 599 of major congenital malformations and 7832 of stillbirths. Most (69.5%) women exposed to fluconazole in pregnancy received the common single therapeutic dose of 150 mg (low dose); the remainder received a dose of > 150 mg (high dose). Use of oral fluconazole during early pregnancy was associated with an increased risk of spontaneous abortion compared with no exposure (adjusted odds ratio [OR] for 345 cases exposed to low-dose treatment 2.23, 95% confidence interval [CI] 1.96-2.54; adjusted OR for 249 cases exposed to high-dose treatment 3.20, 95% CI 2.73-3.75). Exposure to fluconazole during the first trimester did not increase the risk of overall major congenital malformations; however, exposure to a high dose during the first trimester was associated with an increased risk of cardiac septal closure anomalies (adjusted OR 1.81, 95% CI 1.04-3.14; 13 exposed cases) compared with no exposure. No association was found between exposure to fluconazole during pregnancy and the risk of stillbirth. INTERPRETATION: Any maternal exposure to fluconazole during pregnancy may increase risk of spontaneous abortion and doses higher than 150 mg during the first trimester may increase risk of cardiac septal closure anomalies.

Can We Rely on Pharmacy Claims Databases to Ascertain Maternal Use of Medications during Pregnancy?

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 (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. 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.

Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, and mortality: A systematic review and meta-analyses.

BACKGROUND: Low circulating levels of adiponectin, an anti-inflammatory and vasculoprotective adipokine, are associated with obesity, type 2 diabetes, and atherosclerotic disease. Presence of unstable plaques in the carotid artery is a known etiological factor causing ischemic strokes. Herein, we systematically reviewed the association between circulating adiponectin and progression of carotid atherosclerotic disease, particularly evaluating the occurrence of (1) carotid atherosclerotic plaques, (2) ischemic stroke, and (3) mortality in subjects who suffered a previous ischemic stroke. METHODS: Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The effect size and 95% confidence intervals (CIs) of the individual studies were pooled using fixed-effect or random-effect models. The quality of the eligible studies was evaluated using the Newcastle-Ottawa quality assessment scale. Sensitivity, subgroup, and meta-regression analyses were performed to address the impact of various risk factors on the association between adiponectin and ischemic stroke risk. RESULTS: Twelve studies fulfilled the inclusion criteria for 3 independent meta-analyses. The association of increasing circulating adiponectin levels (5µg/mL-increment) with presence of carotid plaque was not conclusive (n=327; OR: 1.07; 95% CI: 0.85-1.35; 2 studies), whereas high adiponectin levels showed a significant 8% increase in risk of ischemic stroke (n=13,683; 7 studies), with a more sizable association observed among men compared to women. HDL was observed to have a marginal effect on the association between adiponectin and ischemic stroke, while other evaluated parameters were not found to be effect modifiers. A non-significant association of adiponectin with mortality was yielded (n=663; OR: 2.58; 95% CI: 0.69-9.62; 3 studies). Although no publication bias was evident, there was significant between-study heterogeneity in most analyses. CONCLUSION: It appears that the direction of the relationship between adiponectin and carotid atherosclerotic plaque presence is dependent on the duration, severity, and nature of the underlying disease, while increased adiponectin levels were associated with an increase in risk for ischemic stroke. Lastly, the results from the mortality meta-analysis remain inconclusive. Future properly designed studies are necessary to further elucidate the role of adiponectin on atherosclerotic plaque development, and its related outcomes.

Circulating Chemerin Is Associated With Carotid Plaque Instability, Whereas Resistin Is Related to Cerebrovascular Symptomatology.

OBJECTIVE: The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology. APPROACH AND RESULTS: Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985-0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (P=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004-1.594). CONCLUSIONS: Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.

Circulating adiponectin and carotid intima-media thickness: A systematic review and meta-analysis.

BACKGROUND: Adiponectin (APN) is an adipokine with insulin-sensitizing, anti-inflammatory, and vasculoprotective properties. Hypoadiponectinemia has been linked with disease states, such as obesity, type 2 diabetes, and cardiovascular disease. Carotid intima-media thickness (cIMT) is a strong and independent predictor of both coronary and cerebrovascular events, and has been used as a surrogate marker of subclinical atherosclerosis. The aim of this report is to systematically review the evidence on the relationship between APN and cIMT in a wide range of individuals. MATERIALS AND METHODS: Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The "sign test" and "vote count" methods were used to estimate the direction and significance of the relationship between APN and cIMT. The quality of the eligible studies was evaluated using an adapted version of the New Castle Ottawa quality assessment scale. RESULTS: Fifty-five articles fulfilled the inclusion criteria, comprised of only cross-sectional studies, including healthy subjects, general population, and individuals with metabolic, inflammatory, or other chronic diseases. Most associations between APN and cIMT followed a negative direction in the healthier and general populations, and also in cohorts with metabolic disorders and other chronic diseases, but not in those with inflammatory diseases (sign test). These associations were generally found to be weak or non-significant among all cohort groups studied (vote count). CONCLUSION: Our results are suggestive but not conclusive for an inverse association between APN levels and cIMT in diseased and non-diseased populations.