Medically Assisted Reproduction and the Risk of Adverse Perinatal Outcomes

Over 5 million children have been born through in vitro fertilization (IVF) across the world. IVF is only one of the many methods of assisted reproduction, which can be used to achieve pregnancy in the context of infertility or subfertility. Since the birth of the first IVF child, Louise Brown, in 1978, a number of researchers have started to study the various impacts of the conception through these methods, on both mothers and children. A growing body of evidence suggests that conception through medically assisted reproduction (MAR) is not without risk. Given that MAR is relatively new and that our look back period is short, there is limited evidence on the risks associated to these procedures, both for the mother and the child. In this chapter, we aim to explore the association between MARs and adverse perinatal outcomes specifically. We will first provide you with an overview of the prevalence and trends of use of these methods around the world, and then delve into the associations between MARs and the risk of perinatal outcomes, namely prematurity, being born with low birth weight and/or small for gestational age, and lastly the impact of MARs on cognitive functions including cerebral palsy, behavioral problems, and autism, which are identified later in the child’s life

Validation of the nausea and vomiting of pregnancy specific health related quality of life questionnaire

<p>Abstract</p> <p>Background</p> <p>The only existing NVP-specific quality of life (QOL) questionnaire is the "Health-Related Quality of Life for Nausea and Vomiting during Pregnancy" (NVPQOL). However, the reliability and validity of the NVPQOL have never been established. In order to justify its usage, the internal consistency and criterion validity of the NVPQOL questionnaire must be ascertained.</p> <p>Methods</p> <p>A prospective observational study including pregnant women attending CHU Sainte-Justine or René-Laennec clinics for their prenatal care was conducted from 2004 to 2006. Women were eligible if they were ≥ 18 years of age and ≤ 16 weeks of gestation at the time of their first prenatal visit. During this initial visit, women who reported NVP were also asked to complete the NVPQOL and the SF-12. Cronbach's alpha coefficients were calculated as the measures of the internal consistency of the NVPQOL. With respect to the criterion validity, linear regression models were built to measure the association between the NVPQOL and the SF-12 scores.</p> <p>Results</p> <p>Of the 367 women included in the study, 288 (78.5%) reported NVP in the first trimester of pregnancy. Among these women, the Cronbach's alpha coefficients were high for the complete NVPQOL questionnaire (α = 0.98), and for the four distinct domains [physical symptoms and aggravating factors (α = 0.90); fatigue (α = 0.94); emotions (α = 0.86); limitations (α = 0.97)]. NVP-specific QOL as measured by the NVPQOL was significantly associated with physical and mental QOL as measured by the SF-12.</p> <p>Conclusion</p> <p>Our data suggest that the NVPQOL is a reliable and valid index to measure NVP-specific QOL in the first trimester of pregnancy.</p

Relationship between Adherence Level to Statins, Clinical Issues and Health-Care Costs in Real-Life Clinical Setting

AbstractObjectiveStatins have been shown to reduce the risk of major cardiovascular disease. We recognize that there is a major gap between the use of statins in actual practice and treatment guidelines for dyslipidemia. Low adherence to statins may have a significant impact on clinical issues and health-care costs. The objective is to evaluate the impact of low adherence to statins on clinical issues and direct health-care costs.MethodsA cohort of 55,134 patients newly treated with statins was reconstructed from the Régie de l'Assurance Maladie du Québec and Med-Echo databases. Subjects included were aged between 45 and 85, initially free of cardiovascular disease, newly treated with statins between 1999 and 2002, and followed-up for a minimum of 3 years. Adherence to statins was measured in terms of the proportion of days' supply of medication dispensed over a defined period, and categorized as ≥80% or <80%. The adjusted odds ratio (OR) of cardiovascular events between the two adherence groups was estimated using a polytomous logistic analysis. The mean costs of direct health-care services were evaluated. A two-part model was applied for hospitalization costs.ResultsThe mean high adherence level to statins was around to 96% during follow-up; and this value was at 42% for the low adherence level. The patients with low adherence to statins were more likely to have coronary artery disease (OR 1.07; 95% confidence interval [CI], 1.01–1.13), cerebrovascular disease (OR 1.13; 95% CI 1.03–1.25), and chronic heart failure within 3-year period of follow-up (OR 1.13; 95% CI 1.01–1.26). Low adherence to statins was also associated with an increased risk of hospitalization by 4% (OR 1.04; 95% CI 1.01–1.09). Among patients who were hospitalized, low adherence to statins was significantly associated with increase of hospitalization costs by approximately $1060/patient for a 3-year period.ConclusionLow adherence to statins was correlated with a higher risk of cardiovascular disease, hospitalization rate, and hospitalization costs. An increased level of adherence to statins agents should provide a better health status for individuals and a net economic gain

Quality Assessment of Clinical Practice Guidelines for the Prescription of Antidepressant Drugs During Pregnancy

Antidepressant use during the gestational period remains a controversial issue. The objective of this study was to appraise the quality of the available clinical practice guidelines (CPGs) that includes recommendations for antidepressant use during pregnancy. We systematically searched for documents published between January 2000 and September 2010 in MEDLINE / TRIP database and on clearinghouses and main scientific societies websites. Four appraisers evaluated each guideline using the Appraisal of Guidelines for Research and Evaluation tool (AGREE II). Intra-class correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated as an overall indicator of agreement. Twelve CPGs were included from a total of 539 references. Only two guidelines were specifically addressed to pregnant women. The overall agreement among reviewers was high (ICC: 0.94, 95% CI: 0.86-0.98). The mean scores and standard deviation (SD) for each of the AGREE II domains were: scope and purpose: 84.4% (12); stakeholder involvement: 67.4% (29.8); rigor of development: 68.6% (19.8); clarity and presentation: 83.4% (17.4); applicability: 44% (37.3); and editorial independence: 62.1% (30.4). After standardizing the scores of the 12 guidelines, 5 were considered as being “recommended”, 5 as “recommended with modifications, and 2 as “not recommended”. Among the five recommended guidelines, two were specifically conceived to the gestational period. CPGs containing recommendations for antidepressant use during pregnancy were of moderate to high quality. Future guidelines should take into account the observed drawbacks in some domains, and specifically focus a more in depth approach of depression during pregnanc

Identification of Novel CYP2D7-2D6 Hybrids: Non-Functional and Functional Variants

Polymorphic expression of CYP2D6 contributes to the wide range of activity observed for this clinically important drug metabolizing enzyme. In this report we describe novel CYP2D7/2D6 hybrid genes encoding non-functional and functional CYP2D6 protein and a CYP2D7 variant that mimics a CYP2D7/2D6 hybrid gene. Five-kilobyte-long PCR products encompassing the novel genes were entirely sequenced. A quantitative assay probing in different gene regions was employed to determine CYP2D6 and 2D7 copy number variations and the relative position of the hybrid genes within the locus was assessed by long-range PCR. In addition to the previously known CYP2D6*13 and *66 hybrids, we describe three novel non-functional CYP2D7-2D6 hybrids with gene switching in exon 2 (CYP2D6*79), intron 2 (CYP2D6*80), and intron 5 (CYP2D6*67). A CYP2D7-specific T-ins in exon 1 causes a detrimental frame shift. One subject revealed a CYP2D7 conversion in the 5′-flanking region of a CYP2D6*35 allele, was otherwise unaffected (designated CYP2D6*35B). Finally, three DNAs revealed a CYP2D7 gene with a CYP2D6-like region downstream of exon 9 (designated CYP2D7[REP6]). Quantitative copy number determination, sequence analyses, and long-range PCR mapping were in agreement and excluded the presence of additional gene units. Undetected hybrid genes may cause over-estimation of CYP2D6 activity (CYP2D6*1/*1 vs *1/hybrid, etc), but may also cause results that may interfere with the genotype determination. Detection of hybrid events, “single” and tandem, will contribute to more accurate phenotype prediction from genotype data

Reporting rates of opioid-related adverse events since 1965 in Canada : a descriptive retrospective study

Background : Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level. Objective : The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965. Methods : Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed. Results : Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1–5.2), and many fluctuations were observed: 1965–1974: +22.3% (95% CI 12.0–33.6); 1974–2000: − 4.1% (95% CI − 5.3 to − 2.9); 2000–2008: +30.3% (95% CI 22.6–38.4); 2008–2014: +4.1% (95% CI − 1.5 to 10.1); 2014–2017: −26.0% (95% CI − 44.7 to − 0.9); and, finally, 2017–2019: +35.4% (95% CI 3.8–76.7). Conclusion : Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap

3D Cohort Study : The Integrated Research Network in Perinatology of Quebec and Eastern Ontario

Background: The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps about the links between various adverse exposures during pregnancy with birth outcomes and later health outcomes in children. Methods: Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec and followed along with their children through to 2 years of age. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, mental health and life style, medical history, psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a biological specimen bank. Results: Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study (37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal blood and urine samples as well as vaginal secretions were collected for ≥98% of participants, cord blood for 81% of livebirths, and placental tissue for 89% of livebirths. Conclusions: The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical, life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of birth and early childhood neurodevelopmental outcomes

Epidemiology of nausea and vomiting of pregnancy: prevalence, severity, determinants, and the importance of race/ethnicity

<p>Abstract</p> <p>Background</p> <p>Studies that contributed to the epidemiology of nausea and vomiting of pregnancy have reported conflicting findings, and often failed to account for all possible co-variables necessary to evaluate the multidimensional associations. The objectives of this study were to: 1) Estimate the prevalence and the severity of nausea and vomiting of pregnancy during the 1^stand the 2^ndtrimester of pregnancy, and 2) Identify determinants of presence and severity of nausea and vomiting of pregnancy during the 1^stand 2^ndtrimesters separately, with a special emphasis on the impact of race/ethnicity.</p> <p>Methods</p> <p>A prospective study including pregnant women attending the Centre Hospitalier Universitaire (CHU) Sainte-Justine or René-Laennec clinics for their prenatal care was conducted from 2004 to 2006. Women were eligible if they were ≥ 18 years of age, and ≤ 16 weeks of gestation. Women were asked to fill out a 1^sttrimester self-administered questionnaire and were interviewed over the telephone during their 2^ndtrimester of pregnancy. Presence of nausea and vomiting of pregnancy was based on the reporting of pregnant women (yes/no); severity of symptoms was measured by the validated modified-PUQE index.</p> <p>Results</p> <p>Of the 367 women included in the study, 81.2% were Caucasians, 10.1% Blacks, 4.6% Hispanics, and 4.1% Asians. Multivariate analyses showed that race/ethnicity was significantly associated with a decreased likelihood of reporting nausea and vomiting of pregnancy (Asians vs. Caucasians OR: 0.13; 95%CI 0.02–0.73; and Blacks vs. Caucasians OR: 0.29; 95%CI 0.09–0.99).</p> <p>Conclusion</p> <p>Our study showed that race/ethnicity was associated with the reporting of nausea and vomiting of pregnancy in the 1^sttrimester of pregnancy.</p

Méta-analyse de l'efficacité de l'activité physique dans le traitement et la prévention de l'ostéoporose

Une méta-analyse de l'efficacité de l'activité physique dans le traitement et la prévention de l'ostéoporose a été effectuée sur 15 études publiées entre janvier 1966 et août 1992. Les études ont été repérées par Medline et en vérifiant les bibliographies des articles pertinents. Chaque publication devait évaluer un programme d'activité physique en mesurant la masse osseuse de femmes provenant d'un groupe expérimental et témoin. Trois individus ont recueilli les informations numériques nécessaires à la méta-analyse et évalué la rigueur scientifique de chaque publication. Une version adaptée de l'instrument de Chalmers, évaluant le protocole d'étude, les analyses statistiques, et la présentation des résultats a été utilisée pour déterminer les scores de qualité de chaque étude. Des grandeurs de l'effet ont été calculées selon Hedges et Olkin pour chaque variable et site mesurés dans les publications. La méthode de DerSimonian et Laird a permis de déterminer la mesure globale de l'effet lors du regroupement des études. Cent soixante-dix-neuf publications ont été générées par la recension des écrits. Parmi celles-ci, 115 étaient descriptives, 28 transversales, trois n'avaient pas de groupe témoin, une était sous forme de résumé, 12 visaient la prévention, trois le traitement, et 16 ont dues être rejetées. La raison principale des rejets était le manque d'informations nécessaires à la méta analyse. Une étude était considérée à caractère préventif lorsque des femmes en santé participaient au programme d'exercice. Par contre, lorsque des femmes souffrant d'ostéoporose étaient enrôlées dans le programme, l'étude adhérait au groupe traitement. Toutes les analyses ont été faites séparément pour les études de prévention et de traitement. La cote moyenne de qualité a été de 44% avec une étendue variant de 22 à 76%, les cotes les plus élevées provenant des études à devis aléatoire. La durée des programmes d'exercice était de 5 mois à 4 ans pour les études de prévention, et de 5 à 8 mois pour les études de traitement. Les sites et les variables les plus fréquemment étudiés à l'intérieur des études étaient la colonne lombaire et le radius, le contenu minéral des os et la densité minérale osseuse. Dans les 12 études visant la prévention, aucun effet significatif de l'activité physique n'a été observé sur la colonne lombaire. Toutefois, un effet de l'exercice a été détecté sur l'avant-bras (IC95% = [0,017; 0,277]) et sur le rapport contenu minéral et épaisseur de l'os au niveau du radius distal (lC95% = [0,0155;0,2193]). Aucun effet significatif n'a été observé dans les trois publications visant le traitement de l'ostéoporose. Même si plusieurs effets ont été non-significatifs, la puissance à détecter une différence de masse osseuse de 6%/an entre les groupes expérimental et témoin variaient de 88 à 97%. En ce qui concerne les caractéristiques des études, il n'y a eu aucun effet significatif de l'intensité des programmes (p=0,1169), de la durée de ceux-ci (p=0,3827), de l'observance (p=0,1450), de la taille de l'échantillon des études (p=0,4521), et du devis expérimental (p=0,1169) sur la masse osseuse. Par contre, une relation quadratique entre le score de qualité et la mesure de l'effet a été observée (p=0,0499). Selon les résultats obtenus par la présente méta-analyse, les programmes d'activité physique comprenant la marche, la course, l'aérobie, et le conditionnement physique, d'une durée médiane de 1 an, et d'intensité moyenne sont plus efficaces en prévention de l'ostéoporose, et d'avantage sur l'avant-bras. Cependant, en se basant sur les résultats publiés à ce jour dans la littérature, nous sommes dans l'impossibilité de recommander l'activité physique pour traiter ou prévenir l'ostéoporose au site lombaire