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BMJ (Clinical Research Ed.) Apr 2016To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of pre-eclampsia.
DESIGN
Systematic review and meta-analysis of cohort studies.
DATA SOURCES
PubMed and Embase databases, 2000-15.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Cohort studies with ≥ 1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤ 16 weeks' gestation.
DATA EXTRACTION
Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors.
RESULTS
There were 25,356,688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.
CONCLUSIONS
There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at "high risk" of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.
Topics: Aspirin; Body Mass Index; Chronic Disease; Cohort Studies; Early Diagnosis; Female; Humans; Hypertension, Pregnancy-Induced; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy in Diabetics; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Risk Factors
PubMed: 27094586
DOI: 10.1136/bmj.i1753 -
International Journal of Environmental... Aug 2022Pregestational type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and gestational diabetes mellitus (GDM) are associated with increased rates of adverse maternal and... (Review)
Review
Pregestational type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and gestational diabetes mellitus (GDM) are associated with increased rates of adverse maternal and neonatal outcomes. Adverse outcomes are more common in women with pregestational diabetes compared to GDM; although, conflicting results have been reported. This systematic review aims to summarise and synthesise studies that have compared adverse pregnancy outcomes in pregnancies complicated by pregestational diabetes and GDM. Three databases, Pubmed, EBSCOhost and Scopus were searched to identify studies that compared adverse outcomes in pregnancies complicated by pregestational T1DM and T2DM, and GDM. A total of 20 studies met the inclusion criteria and are included in this systematic review. Thirteen pregnancy outcomes including caesarean section, preterm birth, congenital anomalies, pre-eclampsia, neonatal hypoglycaemia, macrosomia, neonatal intensive care unit admission, stillbirth, Apgar score, large for gestational age, induction of labour, respiratory distress syndrome and miscarriages were compared. Findings from this review confirm that pregestational diabetes is associated with more frequent pregnancy complications than GDM. Taken together, this review highlights the risks posed by all types of maternal diabetes and the need to improve care and educate women on the importance of maintaining optimal glycaemic control to mitigate these risks.
Topics: Cesarean Section; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Infant, Newborn; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 36078559
DOI: 10.3390/ijerph191710846 -
Scientific Reports Aug 2021Understanding changes in oral flora during pregnancy, its association to maternal health, and its implications to birth outcomes is essential. We searched PubMed,... (Meta-Analysis)
Meta-Analysis
Understanding changes in oral flora during pregnancy, its association to maternal health, and its implications to birth outcomes is essential. We searched PubMed, Embase, Web of Science, and Cochrane Library in May 2020 (updated search in April and June 2021), and conducted a systematic review and meta-analyses to assess the followings: (1) oral microflora changes throughout pregnancy, (2) association between oral microorganisms during pregnancy and maternal oral/systemic conditions, and (3) implications of oral microorganisms during pregnancy on birth outcomes. From 3983 records, 78 studies were included for qualitative assessment, and 13 studies were included in meta-analysis. The oral microflora remains relatively stable during pregnancy; however, pregnancy was associated with distinct composition/abundance of oral microorganisms when compared to postpartum/non-pregnant status. Oral microflora during pregnancy appears to be influenced by oral and systemic conditions (e.g. gestational diabetes mellitus, pre-eclampsia, etc.). Prenatal dental care reduced the carriage of oral pathogens (e.g. Streptococcus mutans). The Porphyromonas gingivalis in subgingival plaque was more abundant in women with preterm birth. Given the results from meta-analyses were inconclusive since limited studies reported outcomes on the same measuring scale, more future studies are needed to elucidate the association between pregnancy oral microbiota and maternal oral/systemic health and birth outcomes.
Topics: Female; Humans; Microbiota; Mouth; Periodontal Diseases; Pregnancy; Pregnancy Outcome; Premature Birth; Publication Bias; Risk
PubMed: 34413437
DOI: 10.1038/s41598-021-96495-1 -
BMJ (Clinical Research Ed.) Sep 2016To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified.
DESIGN
Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials.
DATA SOURCES
Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.
APPRAISAL AND DATA EXTRACTION
Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools.
RESULTS
25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses.
CONCLUSIONS
This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42013004608.
Topics: Birth Weight; Diabetes, Gestational; Dystocia; Evidence-Based Medicine; Female; Fetal Macrosomia; Glucose Tolerance Test; Humans; Hyperglycemia; Infant, Newborn; Pregnancy; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 27624087
DOI: 10.1136/bmj.i4694 -
The Cochrane Database of Systematic... Oct 2019Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia.
OBJECTIVES
To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review.
SELECTION CRITERIA
All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups.
AUTHORS' CONCLUSIONS
Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.
Topics: Aspirin; Female; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Maternal Mortality; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic
PubMed: 31684684
DOI: 10.1002/14651858.CD004659.pub3 -
A Systematic Review and Meta-Analysis of Outcomes of Pregnancy in CKD and CKD Outcomes in Pregnancy.Clinical Journal of the American... Nov 2015We undertook a systematic review and meta-analysis of published cohort studies and case-control studies to estimate (1) the risk of pregnancy complications among... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
We undertook a systematic review and meta-analysis of published cohort studies and case-control studies to estimate (1) the risk of pregnancy complications among patients with CKD versus those without CKD and (2) the risk of CKD progression among pregnant patients versus nonpregnant controls with CKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We searched electronic databases for studies published between 1946 and 2014, and we reviewed articles using validity criteria. Random-effects analytical methods were used.
RESULTS
Twenty-three studies (14 with data for adverse pregnancy outcomes and 9 for renal outcomes) with 506,340 pregnancies were included. Pregnancy with CKD had greater odds of preeclampsia (odds ratio [OR], 10.36; 95% confidence interval [95% CI], 6.28 to 17.09), premature delivery (OR, 5.72; 95% CI, 3.26 to 10.03), small for gestational age/low birth weight (OR, 4.85; 95% CI, 3.03 to 7.76), cesarean section (OR, 2.67; 95% CI, 2.01 to 3.54), and failure of pregnancy (OR, 1.80; 95% CI, 1.03 to 3.13). Subgroup analysis showed that odds of preeclampsia (P<0.01) and premature delivery (P<0.01) were higher in women with nondiabetic nephropathy compared with diabetic nephropathy, and the odds of preeclampsia (P=0.01) and premature delivery (P<0.01) were higher in women with macroproteinuria compared with microproteinuria. The median for follow-up time for renal events was 5 years (interquartile range, 5-14.7 years). There were no significant differences in the occurrence of renal events between CKD pregnant women and those without pregnancy (OR, 0.96; 95% CI, 0.69 to 1.35). Subgroup analysis showed that publication year, sample size, follow-up years, type of primary disease, CKD classification, level of serum creatinine at baseline, proteinuria, and level of systolic BP did not modify the renal outcomes.
CONCLUSIONS
The risks of adverse maternal and fetal outcomes in pregnancy are higher for women with CKD versus pregnant women without CKD. However, pregnancy was not a risk factor for progression of renal disease in women with CKD before pregnancy.
Topics: Case-Control Studies; Cohort Studies; Disease Progression; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Renal Insufficiency, Chronic
PubMed: 26487769
DOI: 10.2215/CJN.09250914 -
The Lancet. Diabetes & Endocrinology Apr 2022Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia.
METHODS
In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585.
FINDINGS
We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT concentrations were not associated with the outcomes measured.
INTERPRETATION
Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies.
FUNDING
Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.
Topics: Female; Humans; Hypertension, Pregnancy-Induced; Hyperthyroidism; Hypothyroidism; Male; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prospective Studies; Thyroid Diseases; Thyrotropin; Thyroxine
PubMed: 35255260
DOI: 10.1016/S2213-8587(22)00007-9 -
Nutrients Feb 2020Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during... (Meta-Analysis)
Meta-Analysis
Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.
Almost two billion people are deficient in key vitamins and minerals, mostly women and children in low- and middle-income countries (LMICs). Deficiencies worsen during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child, but could be mitigated by interventions like micronutrient supplementation. To our knowledge, this is the first systematic review that aimed to compile evidence from both efficacy and effectiveness trials, evaluating different supplementation interventions on maternal, birth, child health, and developmental outcomes. We evaluated randomized controlled trials and quasi-experimental studies published since 1995 in peer-reviewed and grey literature that assessed the effects of calcium, vitamin A, iron, vitamin D, and zinc supplementation compared to placebo/no treatment; iron-folic (IFA) supplementation compared to folic acid only; multiple micronutrient (MMN) supplementation compared to IFA; and lipid-based nutrient supplementation (LNS) compared to MMN supplementation. Seventy-two studies, which collectively involved 314 papers (451,723 women), were included. Meta-analyses showed improvement in several key birth outcomes, such as preterm birth, small-for-gestational age (SGA) and low birthweight with MMN supplementation, compared to IFA. MMN also improved child outcomes, including diarrhea incidence and retinol concentration, which are findings not previously reported. Across all comparisons, micronutrient supplementation had little to no effect on mortality (maternal, neonatal, perinatal, and infant) outcomes, which is consistent with other systematic reviews. IFA supplementation showed notable improvement in maternal anemia and the reduction in low birthweight, whereas LNS supplementation had no apparent effect on outcomes; further research that compares LNS and MMN supplementation could help understand differences with these commodities. For single micronutrient supplementation, improvements were noted in only a few outcomes, mainly pre-eclampsia/eclampsia (calcium), maternal anemia (iron), preterm births (vitamin D), and maternal serum zinc concentration (zinc). These findings highlight that micronutrient-specific supplementation should be tailored to specific groups or needs for maximum benefit. In addition, they further contribute to the ongoing discourse of choosing antenatal MMN over IFA as the standard of care in LMICs.
Topics: Anemia; Child; Child Development; Child, Preschool; Developing Countries; Dietary Supplements; Female; Humans; Income; Infant; Maternal Nutritional Physiological Phenomena; Micronutrients; Minerals; Poverty Areas; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic; Vitamins
PubMed: 32075071
DOI: 10.3390/nu12020491 -
International Journal of Gynaecology... Oct 2022To evaluate the risk levels for maternal and perinatal complications at > 40, > 45 and > 50 years old compared with younger controls. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the risk levels for maternal and perinatal complications at > 40, > 45 and > 50 years old compared with younger controls.
METHODS
Electronic databases were searched from their inception until March 2021. We included studies reporting pregnancy outcome in pregnant women aged 40, 45, and 50 years or older compared with controls at the time of delivery. Case reports and case series were excluded. The primary outcome was the incidence of stillbirth. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). Heterogeneity was measured using I (Higgins I ). Subgroup analyses in women older than 45 years and in those older than 50 years were performed.
RESULTS
Twenty-seven studies, including 31 090 631 women, were included in the meta-analysis. The overall quality of the included studies was moderate to high. Most of the included studies were retrospective cohort studies (21/27), four were population-based studies, and two were cross-sectional studies. Women aged ≥40 years had significantly higher risk of stillbirth (RR 2.16, 95% CI 1.86-2.51), perinatal mortality, intrauterine growth restriction, neonatal death, admission to neonatal intensive care unit, pre-eclampsia, preterm delivery, cesarean delivery, and maternal mortality compared with women younger than 40 years old (RR 3.18, 95% CI 1.68-5.98). The increased risks for maternal mortality were 42.76 and 11.60 for women older than 50 years and for those older than 45 years, respectively, whereas those for stillbirth were 3.72 and 2.32. The risk of stillbirth and cesarean delivery was significantly higher in women >45 years compared with those aged 40-45 years, and in those aged >50 years compared with those aged 45-50 years. The risk of maternal mortality was significantly higher in women aged >50 years compared with those aged 40-45 (RR 60.40, 95% CI 13.28-274.74).
CONCLUSION
The risk of stillbirth, cesarean delivery, and maternal mortality increases with advancing maternal age. The risk ratios for maternal mortality were 3.18, 11.60, and 42.76 in women older than 40, older than 45, and older than 50 years, respectively. These data should be used when women with advanced maternal age are counseled regarding their risk in pregnancy.
SYSTEMATIC REVIEW REGISTRATION
The review was registered with the PROSPERO International Prospective Register of Systematic Reviews (registration No.: CRD42020208788).
Topics: Adult; Female; Humans; Infant, Newborn; Maternal Age; Middle Aged; Perinatal Death; Pregnancy; Pregnancy Outcome; Premature Birth; Retrospective Studies; Stillbirth
PubMed: 35044694
DOI: 10.1002/ijgo.14100 -
Ultrasound in Obstetrics & Gynecology :... Jul 2019Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to...
OBJECTIVE
Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field.
METHODS
MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding.
RESULTS
From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90 centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation.
CONCLUSIONS
This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Biomarkers; Body Mass Index; Female; Humans; Mass Screening; Meta-Analysis as Topic; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Prospective Studies; Pulsatile Flow; Risk Factors; Sensitivity and Specificity; Ultrasonography; Uterine Artery
PubMed: 30267475
DOI: 10.1002/uog.20117