Health care seeking for maternal and newborn illnesses in low- and middle-income countries: a systematic review of observational and qualitative studies [version 1; peer review: 2 approved]

First published: 19 Feb 2019Background: In low- and middle-income countries, a large number of maternal and newborn deaths occur due to delays in health care seeking. These delays occur at three levels i.e. delay in making decision to seek care, delay in access to care, and delay in receiving care. Factors that cause delays are therefore need to be understand to prevent and avoid these delays to improve health and survival of mothers and babies.    Methods: A systematic review of observational and qualitative studies to identify factors and barriers associated with delays in health care seeking. Results: A total of 159 observational and qualitative studies met the inclusion criteria. The review of observational and qualitative studies identified social, cultural and health services factors that contribute to delays in health care seeking, and influence decisions to seek care. Timely recognition of danger signs, availability of finances to arrange for transport and affordability of health care cost, and accessibility to a health facility were some of these factors. Conclusions: Effective dealing of factors that contribute to delays in health care seeking would lead to significant improvements in mortality, morbidity and care seeking outcomes, particularly in countries that share a major brunt of maternal and newborn morbidity and mortality. Registration: PROSPERO CRD42012003236.Zohra S. Lassi, Philippa Middleton, Zulfiqar A. Bhutta, Caroline Crowthe

The impact of interpersonal racism on oral health related quality of life among Indigenous South Australians: a cross-sectional study

Background: Interpersonal racism has had a profound impact on Indigenous populations globally, manifesting as negative experiences and discrimination at an individual, institutional and systemic level. Interpersonal racism has been shown to negatively influence a range of health outcomes but has received limited attention in the context of oral health. The aim of this paper was to examine the effects of experiences of interpersonal racism on oral healthrelated quality of life (OHRQoL) among Indigenous South Australians. Methods: Data were sourced from a large convenience sample of Indigenous South Australian adults between February 2018 and January 2019. Questionnaires were used to collect data on sociodemographic characteristics, cultural values, utilization of dental services, and other related factors. OHRQoL was captured using the Oral Health Impact Profile (OHIP-14) questionnaire. We defined the dependent variable ’poor OHRQoL’ as the presence of one or more OHIP-14 items rated as ‘very often’ or ‘fairly often’. Experiences of racism were recorded using the Measure of Indigenous Racism Experiences instrument. Interpersonal racism was classified into two categories (‘no racism’ vs ‘any racism in ≥ 1 setting’) and three categories (’no racism’, ’low racism’ (experienced in 1–3 settings), and ’high racism’ (experienced in 4–9 settings)). Logistic regression was used to examine associations between interpersonal racism, covariates and OHRQoL, adjusting for potential confounding related to socioeconomic factors and access to dental services. Results: Data were available from 885 participants (88.7% of the total cohort). Overall, 52.1% reported experiencing any interpersonal racism in the previous 12 months, approximately one-third (31.6%) were classified as experiencing low racism, and one-fifth (20.5%) experienced high racism. Poor OHRQoL was reported by half the participants (50.2%). Relative to no experiences of racism in the previous 12 months, those who experienced any racism (≥ 1 setting) were significantly more likely to report poor OHRQoL (Odds Ratio (OR): 1.43; 95% Confidence Interval (CI): 1.08–1.92), after adjusting for age, education level, possession of an income-tested health care card, car ownership, self-reported oral health status, timing of and reason for last dental visit, not going to a dentist because of cost, and having no family support. This was particularly seen among females, where, relative to males, the odds of having poor OHRQoL among females experiencing racism were 1.74 times higher (95% CI: 1.07–2.81). Conclusion: Our findings indicate that the experience of interpersonal racism has a negative impact on OHRQoL among Indigenous Australians. The association persisted after adjusting for potential confounding factors. Identifying this link adds weight to the importance of addressing OHRQoL among South Australian’s Indigenous population by implementing culturally-sensitive strategies to address interpersonal racism.Anna Ali, Alice R. Rumbold, Kostas Kapellas, Zohra S. Lassi, Joanne Hedges and Lisa Jamieso

Born too soon: care before and between pregnancy to prevent preterm births: from evidence to action

This article is part of the supplement: Born too soonProviding care to adolescent girls and women before and between pregnancies improves their own health and wellbeing, as well as pregnancy and newborn outcomes, and can also reduce the rates of preterm birth. This paper has reviewed the evidence based interventions and services for preventing preterm births; reported the findings from research priority exercise; and prescribed actions for taking this call further. Certain factors in the preconception period have been shown to increase the risk for prematurity and, therefore, preconception care services for all women of reproductive age should address these risk factors through preventing adolescent pregnancy, preventing unintended pregnancies, promoting optimal birth spacing, optimizing pre-pregnancy weight and nutritional status (including a folic acid containing multivitamin supplement, and ensuring that all adolescent girls have received complete vaccination. Preconception care must also address risk factors that may be applicable to only some women. These include screening for and management of chronic diseases, especially diabetes; sexually-transmitted infections; tobacco and smoke exposure; mental health disorders, notably depression; and intimate partner violence. The approach to research in preconception care to prevent preterm births should include a cycle of development and delivery research that evaluates how best to scale up coverage of existing, evidence-based interventions, epidemiologic research that assesses the impact of implementing these interventions, and discovery science that better elucidates the complex causal pathway of preterm birth and helps to develop new screening and intervention tools. In addition to research, policy and financial investment is crucial to increasing opportunities to implement preconception care, and rates of prematurity should be included as a tracking indicator in global and national maternal child health assessments.Sohni V Dean, Elizabeth Mary Mason, Christopher P Howson, Zohra S Lassi, Ayesha M Imam, and Zulfiqar A Bhutt

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global burden of 87 risk factors in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk�outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk�outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk�outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95 uncertainty interval UI 9·51�12·1) deaths (19·2% 16·9�21·3 of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12�9·31) deaths (15·4% 14·6�16·2 of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253�350) DALYs (11·6% 10·3�13·1 of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0�9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10�24 years, alcohol use for those aged 25�49 years, and high systolic blood pressure for those aged 50�74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Community-based antibiotic delivery for possible serious bacterial infections in neonates in low-and middle-income countries

Background: The recommended management for neonates with a possible serious bacterial infection (PSBI) is hospitalisation and treatment with intravenous antibiotics, such as ampicillin plus gentamicin. However, hospitalisation is often not feasible for neonates in low- and middle-income countries (LMICs). Therefore, alternative options for the management of neonatal PSBI in LMICs needs to be evaluated. Objectives: To assess the effects of community-based antibiotics for neonatal PSBI in LMICs on neonatal mortality and to assess whether the effects of community-based antibiotics for neonatal PSBI differ according to the antibiotic regimen administered. Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 3), MEDLINE via PubMed (1966 to 16 April 2018), Embase (1980 to 16 April 2018), and CINAHL (1982 to 16 April 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Selection Criteria: We included randomised, quasi-randomised and cluster-randomised trials. For the first comparison, we included trials that compared antibiotics which were initiated and completed in the community to the standard hospital referral for neonatal PSBI in LMICs. For the second comparison, we included trials that compared simplified antibiotic regimens which relied more on oral antibiotics than intravenous antibiotics to the standard regimen of seven to 10 days of injectable penicillin/ampicillin with an injectable aminoglycoside delivered in the community to treat neonatal PSBI. Data Collection and Analysis: We extracted data using the standard methods of the Cochrane Neonatal Group. The primary outcomes were all-cause neonatal mortality and sepsis-specific neonatal mortality. We used the GRADE approach to assess the quality of evidence. Main Results: For the first comparison, five studies met the inclusion criteria. Community-based antibiotic delivery for neonatal PSBI reduced neonatal mortality when compared to hospital referral only (typical risk ratio (RR) 0.82, 95% confidence interval (CI) 0.68 to 0.99; 5 studies, n = 125,134; low-quality evidence). There was, however, a high level of statistical heterogeneity (I² = 87%) likely, due to the heterogenous nature of the study settings as well as the fact that four of the studies provided various co-interventions in conjunction with community-based antibiotics. Community-based antibiotic delivery for neonatal PSBI showed a possible effect on reducing sepsis-specific neonatal mortality (typical RR 0.78, 95% CI 0.60 to 1.00; 2 studies, n = 40,233; low-quality evidence).For the second comparison, five studies met the inclusion criteria. Using a simplified antibiotic approach resulted in similar rates of neonatal mortality when compared to the standard regimen of seven days of injectable procaine benzylpenicillin and injectable procaine benzylpenicillin and injectable gentamicin delivered in community-settings for neonatal PSBI (typical RR 0.81, 95% CI 0.44 to 1.50; 3 studies, n = 3476; moderate-quality evidence). In subgroup analysis, the simplified antibiotic regimen of seven days of oral amoxicillin and injectable gentamicin showed no difference in neonatal mortality (typical RR 0.84, 95% CI 0.47 to 1.51; 3 studies, n = 2001; moderate-quality evidence). Two days of injectable benzylpenicillin and injectable gentamicin followed by five days of oral amoxicillin showed no difference in neonatal mortality (typical RR 0.88, 95% CI 0.29 to 2.65; 3 studies, n = 2036; low-quality evidence). Two days of injectable gentamicin and oral amoxicillin followed by five days of oral amoxicillin showed no difference in neonatal mortality (RR 0.67, 95% CI 0.24 to 1.85; 1 study, n = 893; moderate-quality evidence). For fast breathing alone, seven days of oral amoxicillin resulted in no difference in neonatal mortality (RR 0.99, 95% CI 0.20 to 4.91; 1 study, n = 1406; low-quality evidence). None of the studies in the second comparison reported the effect of a simplified antibiotic regimen on sepsis-specific neonatal mortality. Authors’ Conclusions: Low-quality data demonstrated that community-based antibiotics reduced neonatal mortality when compared to the standard hospital referral for neonatal PSBI in resource-limited settings. The use of co-interventions, however, prevent disentanglement of the contribution from community-based antibiotics. Moderate-quality evidence showed that simplified, community-based treatment of PSBI using regimens which rely on the combination of oral and injectable antibiotics did not result in increased neonatal mortality when compared to the standard treatment of using only injectable antibiotics. Overall, the evidence suggests that simplified, community-based antibiotics may be efficacious to treat neonatal PSBI when hospitalisation is not feasible. However, implementation research is recommended to study the effectiveness and scale-up of simplified, community-based antibiotics in resource-limited settings.Jessica Duby, Zohra S Lassi, Zulfiqar A Bhutt

Women's Participation in Household Decision Making and Justification of Wife Beating: A Secondary Data Analysis from Pakistan’s Demographic and Health Survey

Introduction: Globally, women's empowerment is one of the important factors impacting the development of the nation. However, several women in developing countries, including Pakistan, experience a high level of gender discrimination and inequity. In this study, data from the Demographic and Health Survey (DHS) were used to measure empowerment and its predictors among women in Pakistan. Methods: Pakistan's 2017-2018 DHS dataset was used to measure women's empowerment using two indicators, i.e., participation in decision making and views on wife beating among 4216 married women. The determinants of empowerment, such as age, place of residence, regions, wealth index, education, partner's education, partner's occupation, number of children, consanguinity, the age difference between husband and wife, house and land ownership, and house inheritance, are reported as prevalence ratios (PRs) with a 95% confidence intervals (CI). Multivariate regression models were used to produce covariate-adjusted PRs and 95% CIs. Results: More than half of all women were empowered (52.5%). Upon multivariate analysis, we identified that women from the province of Punjab (adjusted PR (aPR), 1.44; 95% CI, 1.20-1.73), Sindh (aPR, 1.62; 95% CI, 1.35-1.96), and KPK (aPR, 1.09; 95% CI, 0.91-1.31) compared to those living in Baluchistan; from the richest quantile (aPR, 1.65; 95% CI, 1.37-1.99), followed by the richer quantile (aPR, 1.54; 95% CI, 1.28-1.84), the middle quantile (aPR, 1.52; 95% CI, 1.28-1.81), and the poorer quantile (aPR, 1.24; 95% CI, 1.04-1.47) compared to women who were from the poorest quantile; who were highly educated (aPR, 1.45; 95% CI, 1.25-1.67), followed by those who had a secondary education (aPR, 1.32; 95% CI, 1.16-1.50) and a primary education (aPR, 1.17; 95% CI, 1.02-1.35) compared to women who were not educated; and had exposure to mass media (aPR, 1.20; 95% CI, 1.06-1.36) compared to those who had no exposure were more empowered. Conclusion: To conclude, women's empowerment in Pakistan is affected by various socioeconomic factors, as well as exposure to mass media. Targeted strategies are needed to improve access to education, employment, and poverty alleviation among women, particularly those living in rural areas. Various mass media advertisements should be practiced, targeting community norms and supporting women's empowerment.Zohra S. Lassi, Anna Ali and Salima Mehera

Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis

Published online by Cambridge University Press: 06 January 2020Gestational diabetes mellitus (GDM) is a pregnancy complication that affects one in seven pregnancies. Emerging evidence demonstrates that children born of pregnancies complicated by GDM may be at increased risk of cardiovascular disease (CVD) in adulthood. Therefore, the aim of this study was to determine cardiovascular risk factors in offspring exposed to GDM in utero. PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Information was extracted on established CVD risk factors including blood pressure, lipids, blood glucose, fasting insulin, body mass index (BMI), and endothelial/microvascular function. The review protocol is registered in PROSPERO (CRD42018094983). Prospective and retrospective studies comparing offspring exposed to GDM compared to controls (non-GDM pregnancies) were considered. We included studies that defined GDM based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) definition, or prior definitions. The PRISMA guidelines were followed in conducting this systematic review. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Study selection, data extraction, and quality assessment were done by two independent reviewers. The data were pooled using a random-effects model. Of 59 eligible studies, 24 were included in the meta-analysis. Offspring exposed to GDM had higher systolic blood pressure (mean difference (MD): 1.75 mmHg, 95% CI 0.57-2.94; eight studies, 7264 participants), BMI z-score (MD 0.11, 95% CI 0.02-0.20; nine studies, 8759 participants), and glucose (standard MD 0.43, 95% CI 0.08-0.77; 11 studies, 6423 participants) than control participants. In conclusion, offspring exposed to GDM have elevated systolic blood pressure, BMI, and glucose. Those exposed to GDM in utero may benefit from early childhood blood pressure measurements.Maleesa M. Pathirana, Zohra S. Lassi, Claire T. Roberts and Prabha H. Andraweer

Author response to: Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis

Letter to the EditorThis commentary is an author response to Yu and colleagues regarding the manuscript entitled ‘Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis’. We address their concern regarding minor errors in our manuscript, our search strategy and assessment of heterogeneity.Maleesa M. Pathirana, Zohra S. Lassi, Claire T. Roberts, and Prabha H. Andraweer