Sleep disorders and associated factors among medical students in the Middle East and North Africa: a systematic review and meta-analysis.

Sleep disturbances like poor and insufficient sleep are common among medical students in the Middle East and North Africa (MENA) countries; however, the extent of medically defined sleep disorders (SDs) remains unclear. This meta-analysis determines SD prevalence and identifies associated factors among medical students in the MENA. PubMed, Web of Science, Google Scholar, and reference lists of included studies were searched (latest search: June 2022). Meta-analyses included 22 studies and were performed using random-effect models. Included studies used self-reported screening tools for assessing SDs and then estimated the proportion of participants at high risk of developing a SD. Central disorders of hypersomnolence were the most prevalent SD [prevalencepooled range: 30.9% (Jordan) to 62.5% (Saudi Arabia)], followed by insomnia disorders [prevalencepooled range: 30.4% (Jordan) to 59.1% (Morocco)], circadian rhythm sleep-wake disorders [prevalencepooled range: 13.5% (Jordan) to 22.4% (Saudi Arabia)], sleep-related breathing disorders [prevalencepooled range: 12.2% (Jordan) to 22.5% (Pakistan)], sleep-related movement disorders [prevalencepooled range: 5.9% (Egypt) to 30.6% (Saudi Arabia)], and parasomnias [prevalencepooled range: 5.6% (Jordan) to 17.4% (Saudi Arabia)]. Female sex, studying in the latter academic years, having anxiety, excessive internet use, and poor academic performance were significantly associated with SDs. SDs are prevalent among MENA medical students. Implementing student-centered interventions targeting high risk groups in medical schools should be considered to improve students' health and wellbeing.

The FORCIS database: A global census of planktonic Foraminifera from ocean waters.

Planktonic Foraminifera are unique paleo-environmental indicators through their excellent fossil record in ocean sediments. Their distribution and diversity are affected by different environmental factors including anthropogenically forced ocean and climate change. Until now, historical changes in their distribution have not been fully assessed at the global scale. Here we present the FORCIS (Foraminifera Response to Climatic Stress) database on foraminiferal species diversity and distribution in the global ocean from 1910 until 2018 including published and unpublished data. The FORCIS database includes data collected using plankton tows, continuous plankton recorder, sediment traps and plankton pump, and contains ~22,000, ~157,000, ~9,000, ~400 subsamples, respectively (one single plankton aliquot collected within a depth range, time interval, size fraction range, at a single location) from each category. Our database provides a perspective of the distribution patterns of planktonic Foraminifera in the global ocean on large spatial (regional to basin scale, and at the vertical scale), and temporal (seasonal to interdecadal) scales over the past century.

Pregnancy exposure registries for drugs and vaccines in low-income and middle-income countries: scoping review protocol.

INTRODUCTION: Data regarding the safety of drugs and vaccines in pregnant women are typically unavailable before licensure. Pregnancy exposure registries (PERs) are an important source of postmarketing safety information. PERs in low-income and middle-income countries (LMICs) are uncommon but can provide valuable safety data regarding their distinct contexts and will become more relevant as the introduction and use of new drugs and vaccines in pregnancy increase worldwide. Strategies to support PERs in LMICs must be based on a better understanding of their current status. We developed a scoping review protocol to assess the landscape of PERs that operate in LMICs and characterise their strengths and challenges. METHODS AND ANALYSIS: This scoping review protocol follows the Joanna Briggs Institute manual for scoping reviews. The search strategy will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Checklist. We will search PubMed, Embase, CINAHL and WHO's Global Index Medicus, as well as the reference lists of retrieved full-text records, for articles published between 2000 and 2022 that describe PERs or other resources that systematically record exposures to medical products during pregnancy and maternal and infant outcomes in LMICs. Title and abstracts will be screened by two authors and data extracted using a standardised form. We will undertake a grey literature search using Google Scholar and targeted websites. We will distribute an online survey to selected experts and conduct semistructured interviews with key informants. Identified PERs will be summarised in tables and analysed. ETHICS AND DISSEMINATION: Ethical approval is not required for this activity, as it was determined not to involve human subjects research. Findings will be submitted to an open access peer-reviewed journal and may be presented at conferences, with underlying data and other materials made publicly available.

Effect of the COVID-19 pandemic on the proportion of physically active children and adults worldwide: A systematic review and meta-analysis.

Introduction: Safety measures implemented to address the COVID-19 pandemic have had a profound impact on the mobility of people worldwide We synthesized the global evidence on physical activity (PA) participation before and during the pandemic. Methods: We conducted a systematic review, searching PubMed, Embase, WHO Global literature on coronavirus disease (between January 2020 and April 2022), and reference lists. Meta-analysis and meta-regression were conducted to quantitatively synthesize the data. Results and discussion: Sixty-three primary studies were included. In children, the global pooled prevalence of PA was 46.4% before the pandemic, 40.6% during the pandemic before movement restriction (MR), and 19.5% during MR. A statistically significant decrease in prevalence was observed between the period before the pandemic and the period during which MR was implemented (p < 0.001). In adults, the global pooled prevalence (both sexes) decreased between the periods before the pandemic (64.7%) and during MR (57.0%). During the period of COVID-19 MR, children had significantly lower odds to meet the WHO PA recommendation than adults (19.5%, 95%CI: 15.8-23.8% vs. 57.0%, 95%CI: 43.3-62.5%; OR = 0.21; p ≤ 0.001). Patient populations were less active than the general population, and their PA levels decreased during the pandemic. Mental and physical health benefits of PA have been well-demonstrated. Prioritizing PA in health campaigns and strategies is critical to address health issues exacerbated during this pandemic. Protocol registration: doi: 10.17605/OSF.IO/GVABX.

The Impact of COVID-19 School Closure on Child and Adolescent Health: A Rapid Systematic Review.

School closures during pandemics raise important concerns for children and adolescents. Our aim is synthesizing available data on the impact of school closure during the coronavirus disease 2019 (COVID-19) pandemic on child and adolescent health globally. We conducted a rapid systematic review by searching PubMed, Embase, and Google Scholar for any study published between January and September 2020. We included a total of ten primary studies. COVID-19-related school closure was associated with a significant decline in the number of hospital admissions and pediatric emergency department visits. However, a number of children and adolescents lost access to school-based healthcare services, special services for children with disabilities, and nutrition programs. A greater risk of widening educational disparities due to lack of support and resources for remote learning were also reported among poorer families and children with disabilities. School closure also contributed to increased anxiety and loneliness in young people and child stress, sadness, frustration, indiscipline, and hyperactivity. The longer the duration of school closure and reduction of daily physical activity, the higher was the predicted increase of Body Mass Index and childhood obesity prevalence. There is a need to identify children and adolescents at higher risk of learning and mental health impairments and support them during school closures.

Perceived stress, stressors, and coping strategies among nursing students in the Middle East and North Africa: an overview of systematic reviews.

BACKGROUND: In nursing students, high stress levels can lead to burnout, anxiety, and depression. Our objective is to characterize the epidemiology of perceived stress, stressors, and coping strategies among nursing students in the Middle East and North Africa region. METHODS: We conducted an overview of systematic reviews. We systematically searched PubMed, Embase, PsycInfo, and grey literature sources between January 2008 and June 2020 with no language restrictions. We included any systematic review reporting measurable stress-related outcomes including stress prevalence, stressors, and stress coping strategies in nursing students residing in any of the 20 Middle East and North Africa countries. We also included additional primary studies identified through a hand search of the reference lists of relevant primary studies and systematic reviews. RESULTS: Seven systematic reviews and 42 primary studies with data from Bahrain, Egypt, Iraq, Jordan, Oman, Pakistan, Palestine, Saudi Arabia, and Sudan were identified. Most studies included nursing students undergoing clinical training. The prevalence range of low, moderate, and high perceived stress among nursing students was 0.8-65%, 5.9-84.5%, and 6.7-99.2%, respectively. Differences related to gender, training period, or the type of tool used to measure stress remain unclear given the wide variability in the reported prevalence measures across all stress levels. Common clinical training stressors were assignments, workload, and patient care. Academic training-related stressors included lack of break/leisure time, low grades, exams, and course load. Nursing students utilized problem focused (dealing with the problem), emotion focused (regulating the emotion), and dysfunctional (venting the emotions) stress coping mechanisms to alleviate their stress. CONCLUSIONS: Available data does not allow the exploration of links between stress levels, stressors, and coping strategies. Limited country-specific prevalence data prevents comparability between countries. Reducing the number or intensity of stressors through curriculum revision and improving students' coping response could contribute to the reduction of stress levels among students. Mentorship, counseling, and an environment conducive to clinical training are essential to minimize perceived stress, enhance learning, and productivity, and prevent burnout among nursing students.

Barriers and Facilitators Associated with Physical Activity in the Middle East and North Africa Region: A Systematic Overview.

Increasing physical inactivity levels in the Middle East and North Africa (MENA) region is a public health concern. We aimed to synthesize barriers and facilitators to physical activity and make appropriate recommendations to address physical inactivity. We conducted an overview of systematic reviews on physical activity barriers and facilitators in 20 MENA countries by systematically searching MEDLINE/PubMed and Google Scholar for systematic reviews published between 2008 and 2020. Our overview included four systematic reviews and 119 primary studies with data from 17 MENA countries. Lack of suitable sports facilities, time, social support and motivation, gender and cultural norms, harsh weather, and hot climate were the most commonly reported barriers to physical activity. Socio-demographic factors negatively associated with physical activity participation include advanced age, being female, less educated, and being married. Motivation to gain health benefits, losing/maintaining weight, being male, dietary habits, recreation, and increased Body Mass Index are positively associated with increased levels of physical activity. Interventions promoting physical activity in MENA should target schoolchildren, women and girls, working parents, and the elderly. Country-specific sociocultural and environmental factors influencing physical activity should be considered in the design of interventions. Current and future policies and national interventions must be consistently evaluated for effectiveness and desired outcomes.

Perinatal Mental Illness in the Middle East and North Africa Region-A Systematic Overview.

Aims: Perinatal mental illness (PMI) is associated with a high risk of maternal and infant morbidity. Recently, several systematic reviews and primary studies have explored the prevalence and risk factors of PMI in the Middle East and North Africa (MENA) region. To our knowledge, there has been no critical analysis of the existing systematic reviews (SRs) on this topic in the MENA region. Our systematic overview primarily aimed to synthesize evidence from the published SRs on PMI in the MENA countries focusing on a) the prevalence of PMI and b) the risk factors associated with PMI. Methods: We conducted a systematic overview of the epidemiology of PMI in the Middle East and North Africa region by searching the PubMed, Embase, and PsycInfo databases for relevant publications between January 2008 and July 2019. In addition to searching the reference lists of the identified SRs for other relevant SRs and additional primary studies of relevance (those which primarily discussed the prevalence of PMI and/or risk and protective factors), between August and October 2019, we also searched Google Scholar for relevant studies. Results: After applying our inclusion and exclusion criteria, 15 systematic reviews (SRs) and 79 primary studies were included in our overview. Studies utilizing validated diagnostic tools report a PMI prevalence range from 5.6% in Morocco to 28% in Pakistan. On the other hand, studies utilizing screening tools to detect PMI report a prevalence range of 9.2% in Sudan to 85.6% in the United Arab Emirates. Wide variations were observed in studies reporting PMI risk factors. We regrouped the risk factors applying an evidence-based categorization scheme. Our study indicates that risk factors in the relational, psychological, and sociodemographic categories are the most studied in the region. Conversely, lifestyle-related risk factors were less studied. Conclusions: Our systematic overview identifies perinatal mental illness as an important public health issue in the region. Standardizing approaches for estimating, preventing, screening, and treating perinatal mental illness would be a step in the right direction for the region.

Physical activity and sedentary behaviour in the Middle East and North Africa: An overview of systematic reviews and meta-analysis.

To support the global strategy to reduce risk factors for obesity, we synthesized the evidence on physical activity (PA) and sedentary behaviour in the Middle East and North Africa (MENA) region. Our systematic overview included seven systematic reviews reporting 229 primary studies. The meta-analysis included 125 prevalence measures from 20 MENA countries. After 2000, 50.8% of adults (ranging from 13.2% in Sudan to 94.9% in Jordan) and 25.6% of youth (ranging from 8.3% in Egypt to 51.0% in Lebanon) were sufficiently active. Limited data on PA behaviours is available for MENA countries, with the exception of Gulf Cooperation Council countries. The meta-regression identified gender and geographical coverage among youth, and the PA measurement as predictors of PA prevalence for both adults and youth. Our analysis suggests a significant PA prevalence increase among adults over the last two decades. The inconsistency in sedentary behaviour measurement is related to the absence of standardized guidelines for its quantification and interpretation. The global epidemic of insufficient PA is prevalent in MENA. Lower PA participation among youth and specifically females should be addressed by focused lifestyle interventions. The recognition of sedentary behaviour as a public health issue in the region remains unclear. Additional data on PA behaviours is needed from low- and middle-income countries in the region.

Herpes simplex virus type 1 epidemiology in the Middle East and North Africa: systematic review, meta-analyses, and meta-regressions.

This study aimed at characterizing herpes simplex virus type 1 (HSV-1) epidemiology in the Middle East and North Africa (MENA). HSV-1 records were systematically reviewed. Findings were reported following the PRISMA guidelines. Random-effects meta-analyses were implemented to estimate pooled mean HSV-1 seroprevalence. Random-effects meta-regressions were conducted to identify predictors of higher seroprevalence. Thirty-nine overall seroprevalence measures yielding 85 stratified measures were identified and included in the analyses. Pooled mean seroprevalence was 65.2% (95% CI: 53.6-76.1%) in children, and 91.5% (95% CI: 89.4-93.5%) in adults. By age group, seroprevalence was lowest at 60.5% (95% CI: 48.1-72.3%) in <10 years old, followed by 85.6% (95% CI: 80.5-90.1%) in 10-19 years old, 90.7% (95% CI: 84.7-95.5%) in 20-29 years old, and 94.3% (95% CI: 89.5-97.9%) in ≥30 years old. Age was the strongest predictor of seroprevalence explaining 44.3% of the variation. Assay type, sex, population type, year of data collection, year of publication, sample size, and sampling method were not significantly associated with seroprevalence. The a priori considered factors explained 48.6% of the variation in seroprevalence. HSV-1 seroprevalence persists at high levels in MENA with most infections acquired in childhood. There is no evidence for declines in seroprevalence despite improving socio-economic conditions.

Ovarian Stimulation, Intrauterine Insemination, Multiple Pregnancy and Major Congenital Malformations: A Systematic Review and Meta- Analysis- The ART_Rev Study.

INTRODUCTION: Multiple pregnancies are a recognized adverse effect of assisted reproductive technologies; nevertheless, there is no consensus on the incremental risk associated with the ovarian stimulation (OS) used alone and intrauterine insemination (IUI). The relationship between OS and IUI and the risk of major congenital malformations (MCM) is unclear. OBJECTIVE: To summarise the literature and evaluate the risk of multiple pregnancy and MCM associated with OS used alone and IUI used with or without OS compared to natural conception (spontaneously conceived infants without any type of fertility treatments). METHODS: We carried out a systematic review to identify published papers between 1966 and 2014 in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. We included observational studies and randomized clinical trials related to the risk of multiple pregnancies and MCM conceived following OS alone or IUI compared to natural conception (spontaneously conceived infants without any fertility treatments). The quality of the included studies was evaluated using The Cochrane Collaboration's tool for assessing risk of bias for RCTs and the Newcastle-Ottawa Scale for observational studies. RESULTS: There were 63 studies included in this review. Our systematic review suggests that the use of any OS alone was associated with an increased risk of multiple pregnancy compared to natural conception (pooled RR 8.80, 95% CI 5.09- 15.20; p= 0.000; 9 studies). Similar increases in the risk of multiple pregnancies were observed following clomiphene citrate used without assisted reproductive technologies. Compared to natural conception, the use of IUI with or without OS was associated with an increased risk of multiple pregnancy (pooled RR 9.73, 95% CI 7.52 -12.60; p= 0.000; 6 studies). Compared to natural conception, the use of any OS alone was associated with an increased risk of any MCM (RR pooled 1.18, 95%CI 1.03-1.36; 11 studies), major musculoskeletal malformations (pooled RR 1.48, 95%CI 1.21-1.81; 7 studies), and malformations of the nervous system (pooled RR 1.73, 95%CI 1.15-2.61; 6 studies). Compared to natural conception, the use of IUI was associated with an increased risk of any MCM (pooled RR 1.23, 95%CI 1.10-1.37; 10 studies), major urogenital (pooled RR 1.52, 95%CI 1.04-2.22; 7 studies), and musculoskeletal malformations (pooled RR 1.54, 95%CI 1.20-1.98; 7 studies). The overall quality of the included studies was acceptable. CONCLUSIONS: The increased risk of multiple pregnancy and certain types of MCM associated with the use of less invasive fertility treatments, such as OS and IUI, found in this review, highlights the importance of the practice framing. Heterogeneity in OS protocols, the combination with other fertility agents, the limited number of studies and the methodological quality differences reduce our ability to draw conclusions on specific treatment. More observational studies, assessing the risk of multiple pregnancy or MCM, as a primary outcome, using standardized methodologies, in larger and better clinically defined populations are needed.

Ovarian Stimulators, Intrauterine Insemination, and Assisted Reproductive Technologies Use and the Risk of Major Congenital Malformations-The AtRISK Study.

OBJECTIVE: To quantify the risk of major congenital malformations (MCMs) associated with the use of ovarian stimulators alone, intrauterine insemination (IUI), and assisted reproductive technologies (ARTs). METHODS: We conducted a case-control analysis using a birth cohort, built with the linkage of data obtained by a self-administered questionnaire, medical, pharmaceutic, and birth databases. Cases were pregnancies with at least one live birth with an MCM. Controls were pregnancies that did not result in major or minor congenital malformations. Multiple logistic regression models were used to calculate the odds ratios (ORs) and confidence intervals (CIs). RESULTS: Among the 5021 pregnancies identified, 825 were cases of MCM and 4196 were controls. Compared with spontaneous conception, the use of ART increased the risk of major urogenital malformations (adjusted OR, 3.11; 95% CI, 1.33-7.27). The use of IUI was associated with an increased risk of major musculoskeletal malformations (adjusted OR, 2.02; 95% CI, 1.10-3.71). Among the 471 women who used fertility treatments for conception, the use of ART was associated with an increased risk of any MCM (adjusted OR, 1.66; 95% CI, 1.00-2.79) and urogenital malformations (adjusted OR, 7.18; 95% CI, 1.59-32.53) when compared with ovarian stimulators used alone. CONCLUSIONS: The use of ART and IUI was associated with an increased risk of major musculoskeletal and urogenital malformations. ART was associated with a higher risk of MCM compared to ovarian stimulators used alone. Even the adjustment, a contribution of the underlying subfertility problems cannot completely ruled out given the differences in the severity of subfertility.

The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis.

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.

Antimalarial drugs for preventing malaria during pregnancy and the risk of low birth weight: a systematic review and meta-analysis of randomized and quasi-randomized trials.

BACKGROUND: It is known that antimalarial drugs reduce the risk of low birth weight (LBW) in pregnant patients. However, a previous Cochrane review did not evaluate whether the level of antimalarial drug resistance could modify the protective effect of antimalarial drugs in this regard. In addition, no systematic review exists comparing current recommendations for malaria prevention during pregnancy to alternative regimens in Africa. Therefore, we conducted a comprehensive systematic review and meta-analysis to assess the efficacy of antimalarial drugs for malaria prevention during pregnancy in reducing the risk of LBW. METHODS: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for articles published up to 21 November 2014, in English or French, and identified additional studies from reference lists. We included randomized and quasi-randomized studies reporting LBW as one of the outcomes. We extracted data and assessed the risk of bias in selected studies. All pooled analyses were based on a random effect model, and we used a funnel plot and trim and fill method to test and adjust for publication bias. RESULTS: A total of 25 studies met the inclusion criteria (37,981 subjects). Compared to no use, all combined antimalarial drugs were associated with a 27% (RR 0.73, 95% CI 0.56-0.97, ten studies) reduction in the risk of LBW. The level of antimalarial drug resistance modified the protective effect of the antimalarial drug used for prevention of LBW during pregnancy. Sulfadoxine-pyrimethamine was not associated with a reduction in the risk of LBW in regions where the prevalence of the dihydropteroate synthase 540E mutation exceeds 50% (RR 0.99, 95% CI 0.80-1.22, three studies). The risk of LBW was similar when sulfadoxine-pyrimethamine was compared to mefloquine (RR 1.05, 95% CI 0.86-1.29, two studies). CONCLUSION: Prophylactic antimalarial drugs and specifically sulfadoxine-pyrimethamine may no longer protect against the risk of LBW in areas of high-level resistance. In Africa, there are currently no suitable alternative drugs to replace sulfadoxine-pyrimethamine for malaria prevention during pregnancy.

Association between ovarian stimulators with or without intrauterine insemination, and assisted reproductive technologies on multiple births.

OBJECTIVE: We sought to quantify the risk of multiple births associated with the use of different modalities of medically assisted reproduction. STUDY DESIGN: We conducted a case-control study using a birth cohort from 2006 through 2009. This cohort was built with the linkage of data obtained by a self-administered questionnaire and medical, hospital, pharmaceutical, birth, and death databases in Quebec. Cases were pregnancies resulting in multiple live births (International Classification of Diseases, Ninth Revision/International Statistical Classification of Diseases, 10th Revision codes). Each case was matched, on maternal age and year of delivery, with 3 singleton pregnancies (controls) randomly selected among all Quebec singleton pregnancies. Data on the use of different fertility treatments were collected by a self-administered questionnaire. Multiple logistic regression models, adjusted for body mass index, number of previous live births, ethnicity, family income, place of residence, marital status, subfertility, reduction of embryos, diabetes, metformin treatment, folic acid supplementation, and lifestyle factors, were used to calculate the odds ratios (ORs) and confidence intervals (CIs). We evaluated the associations between each type of fertility treatment (ovarian stimulators used alone, intrauterine insemination [IUI] used with ovarian stimulation, and assisted reproductive technologies [ART]) and the risk of multiple births. RESULTS: A total of 1407 cases of multiple births and 3580 controls were analyzed. More than half of multiple births following medically assisted reproduction (53.6%) occurred among women having used ovarian stimulation with or without IUI. The use of ovarian stimulators alone and IUI with ovarian stimulation increase the risk of multiple births (adjusted OR, 4.5; 95% CI, 3.2-6.4; and adjusted OR, 9.32; 95% CI, 5.60-15.50, respectively) compared to spontaneous conception. The use of invasive ART was associated with a greatly increased risk of multiple births. Among only the 465 women who used medically assisted reproduction for conception, the use of IUI with ovarian stimulation was associated with an increased risk of multiple births (adjusted OR, 1.98; 95% CI, 1.12-3.49) when compared to ovarian stimulators used alone. Invasive ART were associated with an increased risk of multiple births (adjusted OR, 6.81; 95% CI, 3.72-12.49) when compared to ovarian stimulators used alone. CONCLUSION: Although the risk of multiple births associated with invasive ART can be decreased by elective implementing of single embryo transfer, special attention should be paid to the greatly increased risk associated with ovarian stimulation used alone or with IUI.

Epidemiology of major congenital malformations with specific focus on teratogens.

BACKGROUND: Major congenital malformations (MCMs) are a significant cause of infant morbidity and mortality and constitute an important societal and economic burden. METHODS: We conducted a literature review to synthesize current evidence on MCMs. Specific objectives were to: 1) summarize internationally reported prevalence of MCMs based on registries and surveillance systems; 2) describe the epidemiology of different MCM types including critical periods and causative factors; 3) to identify the role played by principal known teratogens on the increase in the risk of MCMs; and 4) determine challenges associated with the epidemiologic assessment of potential risk factors for MCMs as well as potential preventive measures. RESULTS: It is estimated that 7.9 million infants worldwide are born every year with a MCM, yet there is considerable variation in reported rates across countries. This may be attributable to varying definitions arising from heterogeneity among different classes with respect to critical periods for embryogenesis and organogenesis. There is also substantial etiologic heterogeneity among MCMs classes that potentially contribute to challenges in epidemiologic studies. Modifiable factors such as pharmacologic exposures have received considerable attention and a number of drugs have been shown to be teratogenic including folic acid antagonists, angiotensin converting enzyme inhibitors, antidepressants, anticonvulsants, coumarin derivatives and retinoids including isotretinoin. CONCLUSION: The majority of MCMs are due to unexplained causes. Other contributing factors include genetics, environmental factors, multifactorial inheritance, maternal-related conditions, and maternal drug or chemical exposure. However, there remains a need to better understand the epidemiology of MCMs when studying drug effect during gestation.