Obstetrics and Gynecology Commons^™

Maternal, Perinatal, Neonatal, And Postpartum Outcomes Following Severe Acute Respiratory Syndrome - Coronavirus-2 Infection In Pregnancy: A World Health Organization Multi-Country Prospective Cohort Study, Edna Kara, Sami Gottlieb, Nathalie Broutet, Anna Thorson, Marie Delnord, Ibukun-Oluwa Abejirinde, Ronaldo Silva, Marleen Temmerman, Rodney Adam, Ingrid Gichere

Pathology, East Africa

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised global concerns regarding its impact on pregnant women and their infants, particularly across evolving variants. This study aimed to determine if infection during pregnancy increased the risk of adverse maternal, perinatal, neonatal, or postpartum outcomes during pre-Omicron and Omicron periods.

Methods We conducted a prospective cohort study in 10 primarily low- and middle-income countries, comprising public and private maternity hospitals in rural and urban areas. Maternal age and comorbidity adjusted mixed-effects models with country-specific random intercepts were used to estimate relative risks (RRs) comparing participants with and without infection …

Just Opt For Caesarean Section And Pick The Birthdate': A Qualitative Study Exploring Women's Delivery Preferences After Caesarean Section In Urban Tanzania, Daudi Gidion, Columba Mbekenga, Miriam Mgonja, Marleen Temmerman, Muzdalfat Abeid

Obstetrics and Gynaecology, East Africa

Objectives To explore perspectives, preferences and decision-making regarding mode of delivery after a previous caesarean section among women in urban Tanzania.

Design A descriptive qualitative study using semi-structured in-depth interviews. Data were analysed using thematic analysis.

Setting A private tertiary hospital in Dar es Salaam, Tanzania.

Participants 11 women with one previous caesarean section who delivered at the study site were interviewed on the third day after delivery. Participants were purposively sampled to include both modes of delivery: five women underwent repeat caesarean section and six attempted a trial of labour after caesarean (TOLAC).

Results Thematic analysis identified four key …

Precise-Dyad: A Prospective Cohort Study Linking Maternal And Infant Health Trajectories In Sub-Saharan Africa, Marie-Laure Volvert, Robin Owino, Angela Koech, Onesmus Wanje, Isaac Mwaniki, Joseph Mutunga, Emily Mwadime, Geoffrey Omuse, Moses Mukhanya, Marvin Ochieng, Grace Mwashigadi, Agnes Mutua, Marleen Temmerman, Melissa Gladstone, Amina Abubakar, Helen Nabwera

Centre of Excellence in Women and Child Health

Purpose The PREgnancy Care Integrating Translational Science, Everywhere (PRECISE)-DYAD Study is a prospective observational cohort designed to investigate health outcomes among mother-child pairs (dyads) over the first 3 years of life in two contexts from sub-Saharan Africa. The primary objective of the study was to explore the effects of selected placenta-related complications, such as pregnancy hypertension, fetal growth restriction and preterm birth, on (1) Child health and development, and (2) Women’s health and well-being, including outcomes after stillbirth.

Participants The PRECISE-DYAD Study enrolled women (and their children) originally recruited into the PRECISE pregnancy cohort study in The Gambia and Kenya …

Why Pronatalism Fails The Planetary Health Test, Celine Delacroix, Marleen Temmerman, Nandita Bajaj, Ann Moore, Phoebe Barnard, William Ripple, William Rees, Michael Gerrard, Diana Coole, Robert Engelman

Centre of Excellence in Women and Child Health

No abstract provided.

Performance Of Road-Traffic-Based Exposure Proxies Against Personal Pm2.5 Measurements In Three Sub-Saharan African Countries, Handsome Nyoni, Terence Mushore, Laura Munthali, Sibusisiwe Makhanya, Laurine Chikoko, Stanley Luchters, Matthew Chersich, Fortunate Machingura, Liberty Makacha, Benjamin Barratt

Centre of Excellence in Women and Child Health

Particulate Matter (PM2.5) exposure contributes to the global disease burden, yet its monitoring remains sparse and uneven, with limited ground sensor infrastructure. Road-traffic proxy indicators can provide indirect estimates of PM2.5 where measurements are limited but require context-specific validation. We evaluated three PM2.5 road-traffic-related proxies: (i) population-Weighted Road Network Density (wRND), (ii) Euclidean (straight line) distance from highways (EH), and (iii) Euclidean distance from main roads (EM). We validated these proxies using high-resolution outdoor filtered PM2.5 personal exposure measurements collected over 1 year from 343 postpartum participants in The Gambia, Kenya, and Mozambique. Proxy-PM2.5 associations were assessed using Spearman correlation, …

Paracrine Signals From Hiv-1-Infected Immune Cells Reprogram Cervical Cancer Pathways, Charles Olwal, Ujjwal Rathore, Sara Makanani, Prashant Kaushal, Immy Ashley, Manisha Ummadi, Vincent Appiah, Alexandra Lindsey Zune, Sophie Blanc, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

No abstract provided.

Family Planning Exemplar Country Selection Methodology: Time Lag And Trends Analysis, Zahid Memon, Abeer Mian, Ira Martopullo, Narjis Hussain, Zeba Sathar, Ali Mohammad Mir, Michael Mbizvo, Marleen Temmerman, Jen Drake, Zulfiqar Bhutta

Centre of Excellence in Women and Child Health

Introduction While many countries achieved notable gains in contraceptive use levels after the 1994 International Conference on Population and Development which redefined family planning (FP) as a human right, there was a long period of 15 years when contraceptive use levels did not receive due attention. It was only later that its subsequent inclusion in the Sustainable Development Goals and the 2012 London Summit on FP renewed global commitment and a focus towards FP. This paper aims to select countries that identify as ‘exemplar’ low-middle-income countries that have achieved exceptional progress in FP. Examining these outliers can uncover actionable drivers …

Incidence And Risk Factors For Stillbirth In Kenya, Mozambique And The Gambia: The Precise Cohort Study, Grace Mwashigadi, Joseph Akuze, Angela Koech, Hawanatu Jah, Anna Roca, Geoffrey Omuse, Moses Mukhanya, Marleen Temmerman, Amina Abubakar, Patricia Okiro

Centre of Excellence in Women and Child Health

Background

Methods

Terminal Digit Preference And Threshold Avoidance In Digital Blood Pressure Measurements During Pregnancy: Secondary Analysis Of Data From The Clip And Precise Cohorts, Peter Dadelszen, Akshdeep Sandhu, Jeffrey Bone, Rahat Qureshi, Olukayode Dada, Ashalata Mallapur, Marleen Temmerman, Marie-Laure Volvert, Joseph Waiswa, Moses Mukhanya, Angela Koech

Centre of Excellence in Women and Child Health

Background:Screening for, detecting, and managing pregnancy hypertension is a core function of antenatal care. To reduce both training requirements and the risks of measurement error in blood pressure (BP) values, automated and semiautomated BP devices have been validated in pregnant women with normal BP and pregnant women with hypertension and introduced for serial antenatal measurement of BP.

Objectives:The study aimed to (1) determine whether or not repeated BP measurements reduced the presence of terminal digit preference and (2) discern whether or not there was evidence of threshold avoidance in the Community-Level Interventions for Preeclampsia (CLIP) trials compared with …

Fetal Vascular Malperfusion And Other Placental Lesions In Relation To Maternal Sars-Cov-2 Exposure: A Case–Control Study, Irene Mwandoto, Marleen Temmerman, Ingrid Gichere, Patricia Okiro

Pathology, East Africa

Background:

The morphologic characteristics of placentas associated with coronavirus disease-19 (COVID-19) have been described but with varying findings. Studies conducted at the onset of the pandemic reported frequency of Fetal Vascular Malperfusion (FVM), an umbrella term that describes occlusive vasculopathies that affect fetal circulation and their associated sequelae. Morphologic manifestations include thrombosis, avascular villi and vascular stromal karyorrhexis. Associated outcomes include fetal growth restriction, thromboembolic events such as neonatal stroke and fetal demise. Placental lesions associated with a severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection present a unique picture in histology, especially in the attempt to decipher the …

Prevalence And Determinants Of Fully Vaccinated Status For Covid-19 Among Pregnant Women In Brazil, Ghana, Kenya, And Pakistan, Vaishnavi Mathur, Jessica Schue, Berhaun Fesshaye, Prachi Singh, Emily Miller, Caroline Badzi, Emefa Modey, Marleen Temmerman, Ferdinand Okwaro, Renato Souza

Centre of Excellence in Women and Child Health

Maternal immunization provides essential maternal and fetal protection for several infectious diseases. The variability in vaccination guidelines for pregnant women across countries and through the course of the COVID-19 pandemic influenced the perception of both the general public and broader health care systems towards COVID-19 vaccination in pregnancy and moreover shaped the accessibility and decision-making trajectory of pregnant women to become fully vaccinated. As part of a larger multi-country, mixed-methods study, the purpose of this cross-sectional analysis is to assess what factors are associated with pregnant women being fully vaccinated for COVID-19 in Brazil, Ghana, Kenya, and Pakistan. In each …

Impaired Fetal Brain Growth And Neurodevelopmental Deficits At 2 Years: Deep Phenotyping Of Maternal–Fetal Pathophysiology, José Villar, Maria Carvalho, Robert Gunier, Rose Mcgready, Yolotzin Valdespino, Kim Lagerborg, Fernando Barros, Agustin Conde-Agudelo, Shane Norris, R. Ochieng

Obstetrics and Gynaecology, East Africa

Background Impaired fetal cranial growth trajectories, diverging before 20 weeks' gestation, are associated with growth, vision, and neurodevelopment deficits at age 2 years. We aimed to understand the maternal–fetal pathophysiological processes underlying childhood developmental deficiencies.

Methods: Between 2012 and 2019, the INTERBIO-21st Fetal Study enrolled 3598 pregnant women who initiated antenatal care before 14 weeks' gestation. We prospectively measured fetal cranial and linear growth and brain volume, and we monitored the infants' health, growth, and development from birth to age 2 years to identify growth and development phenotypes. We grouped the observed cranial growth into five distinct phenotypes: median growth …

Feasibility And Safety Of Intrapartum Foetal Pulse Oximetry Using A Disposable Scalp Probe: A Cross-Sectional Study, Felix Oindi, Mukaindo Mwaniki, Sikolia Wanyonyi, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background Assessment of foetal wellbeing during labour is critical for reducing adverse perinatal outcomes. While pulse oximetry is widely used in adult and paediatric medicine, its application in intrapartum foetal monitoring remains limited. This study aimed to evaluate the feasibility and safety of a foetal pulse oximeter device (OxiReed™, formerly First Touch™) for obtaining intrapartum foetal oxygen saturation (SpO₂) measurements.

Methods A cross-sectional study was conducted at a tertiary referral hospital involving 110 women in the first or second stage of labour. Eligible participants had singleton pregnancies at ≥ 34 weeks’ gestation, vertex presentation, and ruptured membranes. A disposable foetal …

Co-Designing An Adolescent Perinatal Mental Health Intervention In Kenya And Mozambique: The Inspire Project, Tatiana Salisbury, Fernando Chissale, Margrette Hanselmann, Evaline Langat, Sarah Kinja, Violet Naanyu, Mark Nyalumbe, Mellan Lilumbi, Lucy Nyaga, Marleen Temmerman

Centre of Excellence in Women and Child Health

Background Interventions to support adolescent perinatal mental health are limited and largely developed for delivery in high-income countries. This study aimed to co-design an intervention to improve mental health outcomes among pregnant and post-partum adolescent girls in Mozambique and Kenya.

Methods 159 adolescent girls (aged 15–19 years) and young women (aged 20–24 years) with experience of a pregnancy during adolescence, their partners and family members, service providers and community influencers were recruited in Kilifi County, Kenya and Moatize District, Mozambique. Those who consented took part in individual interviews, focus group discussions, observations, and workshops to identify key priorities for supporting …

Beyond Parallel Programmes: A Roadmap For Operational Integration Of Family Planning And Nutrition In Low- And Middle-Income Countries, Marleen Temmerman, Samuel Ojong

Centre of Excellence in Women and Child Health

No abstract provided.

Availability Of Cancer Screening Across Hiv Treatment Sites In The Iedea Consortium, Rachael Pellegrino, Bryan Shepherd, Sanjay Pujari, Valeria Fink, Gad Murenzi, Miriam Nakalembe, Sally Coburn, Eliane Rohner, Antoine Jaquet, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

Cancer remains a leading cause of morbidity and mortality in people with HIV, and the importance of cancer screening increasesas this population ages. In 2017, 2020, and 2023, cross-sectional surveys were conducted at HIV care sites across 5 continentswithin the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We described cancer screening avail-ability in 2023 and over time for cervical and anal cancer screening using generalized estimating equations with a logit linkfunction to account for site clustering, rurality, and country income. Of the 220 sites in the 2023 survey, 61% (134/220) reportedcervical cancer screening by cytology or human papillomavirus (HPV) …

Availability Of Cancer Screening Across Hiv Treatment Sites In The Iedea Consortium, Rachael Pellegrino, Bryan Shepherd, Sanjay Pujari, Valeria Fink, Gad Murenzi, Miriam Nakalembe, Sally Coburn, Eliane Rohner, Antoine Jaquet, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

Cancer remains a leading cause of morbidity and mortality in people with HIV, and the importance of cancer screening increasesas this population ages. In 2017, 2020, and 2023, cross-sectional surveys were conducted at HIV care sites across 5 continentswithin the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We described cancer screening avail-ability in 2023 and over time for cervical and anal cancer screening using generalized estimating equations with a logit linkfunction to account for site clustering, rurality, and country income. Of the 220 sites in the 2023 survey, 61% (134/220) reportedcervical cancer screening by cytology or human papillomavirus (HPV) …

Beyond Parallel Programmes: A Roadmap For Operational Integration Of Family Planning And Nutrition In Low- And Middle-Income Countries, Marleen Temmerman, Samuel Ojong

Centre of Excellence in Women and Child Health

No abstract provided.

Daily Outdoor Pm2.5 Exposure Characterization And Road Edge Effect During A 2022 - 2023 Monitoring Campaign In Gambia, Kenya And Mozambique, Terence Mushore, Handsome Nyoni, Laura Munthali, Sibusisiwe Makhanya, Laurine Chikoko, Anotida Chapunza, Stanley Luchters, Matthew Chersich, Marleen Temmerman, Angela Koech

Centre of Excellence in Women and Child Health

Air pollution is a major contributor to mortality and adverse health outcomes, particularly in pregnant women and children, with vehicular emissions as a key source. This study aimed to characterize long-term exposure to fine particulate matter (PM2.5), evaluate potential health risks, and quantify the contribution of road transport and proximity to roads in The Gambia, Kenya, and Mozambique. Multi-temporal personal exposure data were interpolated into continuous spatial surfaces and aggregated into daily averages, which were then compared with World Health Organization (WHO) guidelines to assess potential health impacts. Multi-distance buffers at 10 m intervals up to 1000m from major roads …

A Physician Survey On Research And Implementation Priorities For Caffeine Citrate Use In Newborn Care In Sub-Saharan Africa, Olufunke Bolaji, Osayame Ekhaguere, Franck Houndjahoue, Nicholas Embleton, Helen Nabwera

Centre of Excellence in Women and Child Health

Background:Evidence on caffeine citrate (CC) for apnoeaof prematurity (AOP) originate from high-income countries. This study aimed to develop consensus on research design for evidence in sub-Saharan Africa (SSA).

Methods:We surveyed physicians in newborn units across SSA to assess their opinions on CC research and their preferred study designs.

Participants rated four study designs:a) an observational before-and-after study; a randomized controlled trial (RCT) of b) caffeine versus placebo; c) caffeine versus aminophylline; d) a traditional or stepped wedge cluster trial.  They  assessed  each  design  using  a  Likert  scale  for  evidence, feasibility, and ethics considerations.

Results:Ninety-two   newborn   physicians …

Benefits, Challenges, And The Way Forward: Medical Specialists' Perception On Family Physician Integration In Healthcare System In Tanzania, Juvenalius Anselm, Roselyter Riang’A, Neelam Ismail, Davis Rubagumya, Jesca Munishi, Sumayyah Saudin, Lynn Moshi, Willbroad Kyejo, Nancy Matillya

Family Medicine, East Africa

Background Family medicine provides comprehensive care by integrating biomedical, behavioral, and social sciences. While established in some sub-Saharan countries, it remains new and unintegrated in Tanzania’s public health system. Its integration is vital for healthcare reform to enhance patient care and system quality.This study aimed to understand the perceptions of medical specialists regarding the integration of family physicians into the Tanzanian healthcare system.

Methods A descriptive qualitative study was conducted through in-depth interviews with ten medical specialists from Aga Khan Hospital and Muhimbili National Hospital in Dar es Salaam. Thematic analysis was employed in this study.

Results Integration of family …

Pregnancy Outcomes Among Women With And Without Hiv Infections Who Underwent Excisional Treatment For High-Grade Cervical Intraepithelial Neoplasia: A Retrospective Cohort Study In Low-Resource Settings, Poli Amubuomombe, Peter Itsura, Philiph Tonui, Elkanah Orang'o, Benjamin Odongo, Patrick Loehrer, Susan Cu-Uvin

Obstetrics and Gynaecology, East Africa

Objective The standard treatment for high-grade squamous intraepithelial lesions is excisional involving the uterine cervix, while surveillance is an acceptable approach for low-grade squamous intraepithelial lesions. There is controversy about excisional treatment on pregnancy outcomes. The objective of this study was to determine pregnancy outcomes in women living with and without HIV who underwent excisional treatment for high-grade cervical intraepithelial lesions.

Design This retrospective cohort study compared the pregnancy outcomes of women with and without HIV who were or were not treated for cervical intraepithelial lesions. A cohort of 488 women with and without HIV infection who did or did …

Prevalence And Risk Factors For Laparoscopic Managed Ectopic Pregnancies At A Tertiary Referral Hospital - A 10-Year Synopsis: A Cross Sectional Study, Steve Mutiso, Eric Mugambi

Obstetrics and Gynaecology, East Africa

Background Ectopic pregnancies (EP) are a common pregnancy associated complication. They are associated with significant morbidity, and rarely mortality, if not managed properly. EP have a myriad of predisposing factors that help identify patients at risk and facilitate early diagnosis and intervention. We set out to conduct an audit of EP managed surgically at our hospital for a 10-year period and discern the incidence, prevalence and risk factors of their occurrence.

Methods This study was designed as a Retrospective Clinical Audit based at the Aga Khan University Hospital (AKUH). Study population was all women admitted to AKUH with a diagnosis …

International Normative Charts For Twin Weight, Length, And Head Circumference At Birth, By Gestational Age And Sex: The Twin Neonatal Cross-Sectional Study Of The Intergrowth-21st Project, Francesca Giuliani, Sonia Deantoni, Enrico Bertino, Yasmin A. Jaffer, Manorama Purwar, Fernando C. Barros, Leila Cheikh Ismail, Wu Qingqing, Ilaria Stura, Maria Carvalho

Obstetrics and Gynaecology, East Africa

Assessing the size of twins at birth using charts developed for singletons may over diagnose small for gestational age in this sub-population. The study aimed to produce international, twin-specific, newborn size normative charts by gestational age and sex. This longitudinal observational study in eight geographically diverse settings prospectively collected data between May 2009 and August 2013 from healthy pregnant women and their newborn twins. The participants were enrolled as part of the INTERGROWTH-21st study, and recruited based on World Health Organization recommendations for evaluation of anthropometric measures. All the women met, in addition to the underlying population characteristics of low …

Normative Growth Trajectories Of Fetal Brain Regions Validated By Satisfactory Maturation Of Neurodevelopmental Domains At 2 Years Of Age, Madeleine Wyburd, Stephen Kennedy, Michelle Fernandes, Nicola Dinsdale, Linde Hesse, Robert Gunier, Leila Ismail, Eric Ohuma, Michael Gravett, Maria Carvalho

Obstetrics and Gynaecology, East Africa

We previously constructed a qualitative, 3D ultrasound derived atlas of the normative spatiotemporal dynamics of fetal brain maturation. Here, using the same healthy multi-national cohort, we applied deep learning methods to 4205 fetal brain scans from 18–27 weeks’ gestation, to produce an extensive, quantitative description of the growth of 16 fetal brain structures associated with satisfactory domain-specific neurodevelopmental scores at 2 years of age. The methodology, which is publicly available, takes less than 10 seconds per scan. We define 28 region-specific, functionally relevant, normative growth trajectories, a ratio between the relative volumes of the insular (rILV) and parietal (rPLV) lobes …

The Use Of A Standardized Checklist For Image Acquisition: An Obstetric Ultrasound Quality Improvement Study, Ingrid Gichere, Nidhi Leekha, Sikolia Wanyonyi

Obstetrics and Gynaecology, East Africa

Introduction A complete anatomical survey during the mid-trimester ultrasound is critical for detecting fetal anomalies. In sub-Saharan Africa, detection rates remain low, contributing to a significant disease burden. This study evaluated whether implementing a standardized electronic checklist, based on existing guidelines, would improve image acquisition.

Methods We carried out a pre- and post-intervention quasi-experimental quality improvement study. An electronic checklist replaced the previous ultrasound report template. A baseline review involved 385 mid-trimester scans conducted between November 2022 and December 2023. Following checklist implementation and targeted sonographer training, 238 scans were reassessed from July to December 2024. The image acquisition rate …

Qualitative Exploration Of Factors Associated With Covid-19 Vaccination Among Pregnant Women In Kenya, Violet Naanyu, Ferdinand Okwaro, Ingrid Gichere, Mandeep Sura, Prachi Singh, Berhaun Fesshaye, Marleen Temmerman

Centre of Excellence in Women and Child Health

The COVID-19 pandemic significantly disrupted societies worldwide, and COVID-19 vaccination has been identified as instrumental in the fight against the pandemic. While studies have examined uptake of COVID-19 vaccination, more research is needed to gain a better understanding of the factors influencing pregnant women’s decisions to get vaccinated. In this study, we used a cross-sectional descriptive qualitative study to explore the attitudes, beliefs, and behaviors related to COVID-19 vaccination during pregnancy in Kenya. A total of 50 in-depth interviews were conducted between October 2023 to March 2024 with a purposively drawn sample of 25 pregnant and 25 postpartum women during …

Sexual Dysfunction In Women With Endometriosis In A Low-Middle-Income Country, Edna Chacha, Charles Muteshi, Felix Oindi, Elsie Wandera

Obstetrics and Gynaecology, East Africa

Background Endometriosis affects up to 10% of reproductive-age women and significantly impairs quality of life including sexual function, intimate relationships, fertility, and psychological wellbeing. While its impact has been extensively studied in Western populations, there is limited Sub-Saharan African data exploring how the disease affects female sexual health and distress. This study aimed to assess sexual function and sexual distress among women with endometriosis at a tertiary hospital in Kenya.

Methods A cross-sectional study was conducted involving 108 women aged 18 to 49 with confirmed endometriosis from January to June 2022. The study used validated self-administered questionnaires: Female Sexual Function …

Surgical Interventions For Treating Vesicovaginal Fistula In Women, Yoshiyuki Okada, Tomomi Matsushita, Takeshi Hasegawa, Hisashi Noma, Erika Ota, Bob Achila, Yasukuni Yoshimura

Obstetrics and Gynaecology, East Africa

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

To assess the benefits and harms of surgical interventions for treating vesicovaginal fistula in women.

Age-Specific Distribution Of Cervical Precancer And Cancer Among Women Living With Hiv Across Seven Countries: A Systematic Review And An Individual Patient Data Meta-Analysis, Shona Dalal, Karin Sundström, Ronaldo Silva, Katayoun Taghavi, Helen Cejtin, Michael Chung, Sharon Greene, Smita Joshi, Helen Kelly, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

Background Women living with HIV have an elevated risk for cervical cancer, present earlier, and have more recurrent human papillomavirus (HPV) infections compared with women without HIV. To update WHO recommendations on screening and treatment to prevent cervical cancer, we aimed to identify whether women living with HIV should be screened for cervical cancer at a specific age, the optimal screening interval following a negative cervical screen, and the screening interval following treatment.

Methods We conducted a systematic literature review on cervical cancer and HIV by searching MEDLINE, Embase, CENTRAL, the Cochrane Library, and clinical trial registries covering Jan 1, …