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Obesity Reviews : An Official Journal... Jan 2022In recent decades, the incidence of type 2 diabetes (T2D) has increased dramatically in children and adolescents, posing a real public health problem. Beyond unhealthy... (Meta-Analysis)
Meta-Analysis
In recent decades, the incidence of type 2 diabetes (T2D) has increased dramatically in children and adolescents, posing a real public health problem. Beyond unhealthy diets and sedentary lifestyles, growing evidence suggests that some perinatal factors, such as low birth weight (LBW), are associated with higher risk of T2D in adulthood. In this regard, it remains unclear whether the increased risk is already present in childhood and adolescence. We conducted a systematic review and meta-analysis to clarify the association of LBW or being small for gestational age (SGA) with insulin resistance in childhood and adolescence. The systematic review resulted in 28 individual studies, and those with the same outcome were included within two random-effects meta-analyses. Compared with children or adolescents born with adequate size for gestational age, those SGA had 2.33-fold higher risk of T2D (95% confidence interval [CI]: 1.05-5.17). Furthermore, LBW and being SGA were associated with 0.20 higher mean homeostasis model assessment of insulin resistance (HOMA-IR) values (95% CI: 0.02-0.38). Given the high prevalence of preterm babies, from a population perspective, these results may be of great importance as they point to the existence of a potentially vulnerable subgroup of children and adolescents that could benefit from screening tests and early preventive strategies.
Topics: Adolescent; Adult; Birth Weight; Child; Diabetes Mellitus, Type 2; Female; Gestational Age; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Pediatric Obesity; Pregnancy; Premature Birth
PubMed: 34786817
DOI: 10.1111/obr.13380 -
BMC Pregnancy and Childbirth Apr 2023Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment.
METHODS
We conducted an updated systematic review (using PubMed and Cochrane Review) on low (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations and associations with a range of maternal and infant health outcomes. We examined associations by timing of Hb assessment (preconception; first, second, and third trimesters, as well as at any time point in pregnancy), varying cutoffs used for defining low and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted meta-analyses to obtain odds ratios (OR) and 95% confidence intervals.
RESULTS
The updated systematic review included 148 studies. Low maternal Hb at any time point in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22-1.35)), very low birthweight, VLBW (2.15 (1.47-3.13)), preterm birth, PTB (1.35 (1.29-1.42)), small-for-gestational age, SGA (1.11 (1.02-1.19)), stillbirth 1.43 (1.24-1.65)), perinatal mortality (1.75 (1.28-2.39)), neonatal mortality (1.25 (1.16-1.34), postpartum hemorrhage (1.69 (1.45-1.97)), transfusion (3.68 (2.58-5.26)), pre-eclampsia (1.57 (1.23-2.01)), and prenatal depression (1.44 (1.24-1.68)). For maternal mortality, the OR was higher for Hb < 90 (4.83 (2.17-10.74)) than for Hb < 100 (2.87 (1.08-7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16-1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09-1.25)), stillbirth (1.32 (1.09-1.60)), maternal mortality (2.01 (1.12-3.61)), gestational diabetes (1.71 (1.19-2.46)), and pre-eclampsia (1.34 (1.16-1.56)). Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent. Lower Hb cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia.
CONCLUSION
Both low and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is needed to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.
Topics: Pregnancy; Female; Child; Infant, Newborn; Humans; Pregnancy Outcome; Stillbirth; Premature Birth; Anemia, Iron-Deficiency; Pre-Eclampsia; Infant Health; Anemia; Hemoglobins
PubMed: 37076797
DOI: 10.1186/s12884-023-05489-6 -
Risk factors associated with childhood stunting in Indonesia: A systematic review and meta-analysis.Asia Pacific Journal of Clinical... 2023In Indonesia, stunting is one of the most public health concerns. This study aims to systematically review and meta-analyze childhood stunting risk factors in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
In Indonesia, stunting is one of the most public health concerns. This study aims to systematically review and meta-analyze childhood stunting risk factors in the country.
METHODS AND STUDY DESIGN
We did a systematic review and meta-analysis of observational (cross-sectional and longitudi-nal) studies on stunting risk factors published between 2010 and 2021 based on available publications in online databases of PubMed, ProQuest, EBSCO, and google scholar. The quality of the publications was evaluated using the Newcastle-Ottawa Quality Assessment Scale and organized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Publication bias was examined using Egger's and Begg's tests.
RESULTS
A total of 17 studies from the literature search satisfied the inclusion criteria, with 642,596 subjects. The pooled stunting prevalence was 30.9% (95% CI 25.0%-36.8%). Children born with low birth weight (POR 2.39, 2.07-2.76), female (POR 1.05, 1.03-1.08), and did not get the deworming program (1.10, 1.07-1.12) are the primary child characteristics that contributed to stunting. Meanwhile, maternal age ≥ 30 years (POR 2.33, 2.23-2.44), preterm birth (POR 2.12, 2.15-2.19), and antenatal care <4 times (POR 1.25, 1.11-1.41) were among mother characteristics consistently associated with stunting. The primary household and community risk factors for stunting were food insecurity (POR 2.00, 1.37-2.92), unimproved drinking water (POR 1.42, 1.26-1.60), rural residence (POR 1.31, 1.20-1.42), and unimproved sanitation (POR 1.27, 1.12-1.44).
CONCLUSIONS
A diverse range of risk factors associated with childhood stunting in In-donesia demonstrates the need to emphasize nutrition programs by scaling up to more on these determinants.
Topics: Child; Infant, Newborn; Pregnancy; Humans; Female; Adult; Indonesia; Cross-Sectional Studies; Premature Birth; Growth Disorders; Mothers
PubMed: 37382316
DOI: 10.6133/apjcn.202306_32(2).0001 -
Pediatric Research Jan 2020Neonatal intensive care practices have resulted in marked improvements in the survival of premature infants; however, they remain at significant risk for adverse...
BACKGROUND
Neonatal intensive care practices have resulted in marked improvements in the survival of premature infants; however, they remain at significant risk for adverse neurodevelopmental outcomes. The impact of current nutritional practices on brain development following early extra-uterine exposure in premature infants is not well known.
METHODS
We performed a systematic review to investigate nutritional effects on postnatal brain development in healthy term and prematurely born infants utilizing advanced magnetic resonance imaging tools.
RESULTS
Systematic screen yielded 595 studies for appraisal. Of these, 22 total studies were selected for inclusion in the review, with findings summarized in a qualitative, descriptive fashion.
CONCLUSION
Fat and energy intake are associated with improved brain volume and development in premature infants. While breast milk intake and long-chain polyunsaturated fatty acid supplementation has been proven beneficial in term infants, the impact in preterm infants is less well understood.
Topics: Age Factors; Bottle Feeding; Brain; Breast Feeding; Child Development; Gestational Age; Humans; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Magnetic Resonance Imaging; Neurogenesis; Nutritional Status; Premature Birth
PubMed: 31349359
DOI: 10.1038/s41390-019-0508-3 -
BMJ (Clinical Research Ed.) Sep 2020To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and meta-analysis.
DATA SOURCES
Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 6 October 2020, along with preprint servers, social media, and reference lists.
STUDY SELECTION
Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.
DATA EXTRACTION
At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.
RESULTS
192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19.
CONCLUSION
Pregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020178076.
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Female; Global Health; Humans; Infant, Newborn; Intensive Care, Neonatal; Pandemics; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Prognosis; Risk Factors; SARS-CoV-2
PubMed: 32873575
DOI: 10.1136/bmj.m3320 -
BMJ (Clinical Research Ed.) Aug 2023To systematically review the proportions of infants with early exposure to antenatal corticosteroids but born at term or late preterm, and short term and long term... (Meta-Analysis)
Meta-Analysis
The proportions of term or late preterm births after exposure to early antenatal corticosteroids, and outcomes: systematic review and meta-analysis of 1.6 million infants.
OBJECTIVE
To systematically review the proportions of infants with early exposure to antenatal corticosteroids but born at term or late preterm, and short term and long term outcomes.
DESIGN
Systematic review and meta-analyses.
DATA SOURCES
Eight databases searched from 1 January 2000 to 1 February 2023, reflecting recent perinatal care, and references of screened articles.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials and population based cohort studies with data on infants with early exposure to antenatal corticosteroids (<34 weeks) but born at term (≥37 weeks), late preterm (34-36 weeks), or term/late preterm combined.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened titles, abstracts, and full text articles and assessed risk of bias (Cochrane risk of bias tool for randomised controlled trials and Newcastle-Ottawa scale for population based studies). Reviewers extracted data on populations, exposure to antenatal corticosteroids, and outcomes. The authors analysed randomised and cohort data separately, using random effects meta-analyses.
MAIN OUTCOME MEASURES
The primary outcome was the proportion of infants with early exposure to antenatal corticosteroids but born at term. Secondary outcomes included the proportions of infants born late preterm or term/late preterm combined after early exposure to antenatal corticosteroids and short term and long term outcomes versus non-exposure for the three gestational time points (term, late preterm, term/late preterm combined).
RESULTS
Of 14 799 records, the reviewers screened 8815 non-duplicate titles and abstracts and assessed 713 full text articles. Seven randomised controlled trials and 10 population based cohort studies (1.6 million infants total) were included. In randomised controlled trials and population based data, ∼40% of infants with early exposure to antenatal corticosteroids were born at term (low or very low certainty). Among children born at term, early exposure to antenatal corticosteroids versus no exposure was associated with increased risks of admission to neonatal intensive care (adjusted odds ratio 1.49, 95% confidence interval 1.19 to 1.86, one study, 5330 infants, very low certainty; unadjusted relative risk 1.69, 95% confidence interval 1.51 to 1.89, three studies, 1 176 022 infants, I=58%, τ=0.01, low certainty), intubation (unadjusted relative risk 2.59, 1.39 to 4.81, absolute effect 7 more per 1000, 95% confidence interval from 2 more to 16 more, one study, 8076 infants, very low certainty, one study, 8076 infants, very low certainty), reduced head circumference (adjusted mean difference -0.21, 95% confidence interval -0.29 to -0.13, one study, 183 325 infants, low certainty), and any long term neurodevelopmental or behavioural disorder in population based studies (eg, any neurodevelopmental or behavioural disorder in children born at term, adjusted hazard ratio 1.47, 95% confidence interval 1.36 to 1.60, one study, 641 487 children, low certainty).
CONCLUSIONS
About 40% of infants exposed to early antenatal corticosteroids were born at term, with associated adverse short term and long term outcomes (low or very low certainty), highlighting the need for caution when considering antenatal corticosteroids.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022360079.
Topics: Child; Infant, Newborn; Infant; Humans; Female; Pregnancy; Premature Birth; Infant, Premature; Adrenal Cortex Hormones; Glucocorticoids; Parturition
PubMed: 37532269
DOI: 10.1136/bmj-2023-076035 -
Sexually Transmitted Infections Aug 2020Genital chlamydia infection in women is often asymptomatic, but may result in adverse outcomes before and during pregnancy. The purpose of this study was to examine the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Genital chlamydia infection in women is often asymptomatic, but may result in adverse outcomes before and during pregnancy. The purpose of this study was to examine the strength of the relationships between chlamydia infection and different reproductive health outcomes and to assess the certainty of the evidence.
METHODS
This review was registered and followed the Cochrane guidelines. We searched three databases to quantitatively examine adverse outcomes associated with chlamydia infection. We included pregnancy and fertility-related outcomes. We performed meta-analyses on different study designs for various adverse outcomes using unadjusted and adjusted analyses.
RESULTS
We identified 4730 unique citations and included 107 studies reporting 12 pregnancy and fertility-related outcomes. Sixty-eight studies were conducted in high-income countries, 37 studies were conducted in low-income or middle-income countries, and 2 studies were conducted in both high-income and low-income countries. Chlamydia infection was positively associated with almost all of the 12 included pregnancy and fertility-related adverse outcomes in unadjusted analyses, including stillbirth (OR=5.05, 95% CI 2.95 to 8.65 for case-control studies and risk ratio=1.28, 95% CI 1.09 to 1.51 for cohort studies) and spontaneous abortion (OR=1.30, 95% CI 1.14 to 1.49 for case-control studies and risk ratio=1.47, 95% CI 1.16 to 1.85 for cohort studies). However, there were biases in the design and conduct of individual studies, affecting the certainty of the overall body of evidence. The risk of adverse outcomes associated with chlamydia is higher in low-income and middle-income countries compared with high-income countries.
CONCLUSION
Chlamydia is associated with an increased risk of several pregnancy and fertility-related adverse outcomes in unadjusted analyses, especially in low-income and middle-income countries. Further research on how to prevent the sequelae of chlamydia in pregnant women is needed.
TRIAL REGISTRATION NUMBER
CRD42017056818.
Topics: Abortion, Spontaneous; Chlamydia Infections; Chlamydia trachomatis; Endometritis; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Infertility, Female; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnancy, Ectopic; Premature Birth; Puerperal Infection; Reproductive Tract Infections; Stillbirth
PubMed: 31836678
DOI: 10.1136/sextrans-2019-053999 -
JAMA Psychiatry Dec 2019Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these...
IMPORTANCE
Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified.
OBJECTIVE
To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes.
DATA SOURCES
PubMed, Scopus, and PsycINFO were searched from database inception to April 5, 2019.
EVIDENCE REVIEW
Only meta-analyses of observational studies with a cohort or case-control study design were eligible. Two independent reviewers recorded the data and assessed the methodological quality of the included meta-analyses. Evidence of association was ranked according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant.
RESULTS
Forty-five meta-analyses (17.9%) from 4471 studies identified and 252 full-text articles scrutinized were selected that described 120 associations, including data from 1012 individual effect size estimates. Seventy-four (61.7%) of the 120 associations were nominally statistically significant at P ≤ .05 using random-effects models. Fifty-two associations (43.4%) had large heterogeneity (I2 > 50%), whereas small-study effects were found for 17 associations (14.2%) and excess significance bias was found for 9 associations (7.5%). Convincing evidence emerged from both main and sensitivity analyses for the association between antidepressant use and risk of suicide attempt or completion among children and adolescents, autism spectrum disorders with antidepressant exposure before and during pregnancy, preterm birth, and low Apgar scores. None of these associations remained supported by convincing evidence after sensitivity analysis, which adjusted for confounding by indication.
CONCLUSIONS AND RELEVANCE
This study's findings suggest that most putative adverse health outcomes associated with antidepressant use may not be supported by convincing evidence, and confounding by indication may alter the few associations with convincing evidence. Antidepressant use appears to be safe for the treatment of psychiatric disorders, but more studies matching for underlying disease are needed to clarify the degree of confounding by indication and other biases. No absolute contraindication to antidepressants emerged from this umbrella review.
Topics: Adolescent; Antidepressive Agents; Apgar Score; Autism Spectrum Disorder; Child; Female; Humans; Mental Disorders; Meta-Analysis as Topic; Observational Studies as Topic; Pregnancy; Premature Birth; Prenatal Exposure Delayed Effects; Suicide, Attempted; Suicide, Completed
PubMed: 31577342
DOI: 10.1001/jamapsychiatry.2019.2859 -
JAMA Aug 2019Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent,... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.
OBJECTIVE
To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.
DATA SOURCES AND STUDY SELECTION
Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.
DATA EXTRACTION AND SYNTHESIS
The primary authors provided individual participant data that were analyzed using mixed-effects models.
MAIN OUTCOMES AND MEASURES
The primary outcome was preterm birth (<37 weeks' gestational age).
RESULTS
From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).
CONCLUSIONS AND RELEVANCE
Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Female; Gestational Age; Humans; Hypothyroidism; Infant, Newborn; Iodide Peroxidase; Pregnancy; Pregnancy Complications; Premature Birth; Thyroid Diseases; Thyroid Function Tests; Thyrotropin; Thyroxine
PubMed: 31429897
DOI: 10.1001/jama.2019.10931 -
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.The Cochrane Database of Systematic... Dec 2020Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Despite early evidence indicating a beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery, some uncertainty remains about their effectiveness particularly with regard to their use in lower-resource settings, different gestational ages and high-risk obstetric groups such as women with hypertension or multiple pregnancies. This updated review (which supersedes an earlier review Crowley 1996) was first published in 2006 and subsequently updated in 2017.
OBJECTIVES
To assess the effects of administering a course of corticosteroids to women prior to anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 September 2020), ClinicalTrials.gov, the databases that contribute to the WHO International Clinical Trials Registry Platform (ICTRP) (3 September 2020), and reference lists of the retrieved studies.
SELECTION CRITERIA
We considered all randomised controlled comparisons of antenatal corticosteroid administration with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following rupture of membranes or spontaneous labour), regardless of other co-morbidity, for inclusion in this review.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness based on predefined criteria developed by Cochrane Pregnancy and Childbirth, extracted data and checked them for accuracy, and assessed the certainty of the evidence using the GRADE approach. Primary outcomes included perinatal death, neonatal death, RDS, intraventricular haemorrhage (IVH), birthweight, developmental delay in childhood and maternal death.
MAIN RESULTS
We included 27 studies (11,272 randomised women and 11,925 neonates) from 20 countries. Ten trials (4422 randomised women) took place in lower- or middle-resource settings. We removed six trials from the analysis that were included in the previous version of the review; this review only includes trials that meet our pre-defined trustworthiness criteria. In 19 trials the women received a single course of steroids. In the remaining eight trials repeated courses may have been prescribed. Fifteen trials were judged to be at low risk of bias, two had a high risk of bias in two or more domains and we ten trials had a high risk of bias due to lack of blinding (placebo was not used in the control arm. Overall, the certainty of evidence was moderate to high, but it was downgraded for IVH due to indirectness; for developmental delay due to risk of bias and for maternal adverse outcomes (death, chorioamnionitis and endometritis) due to imprecision. Neonatal/child outcomes Antenatal corticosteroids reduce the risk of: - perinatal death (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.77 to 0.93; 9833 infants; 14 studies; high-certainty evidence; 2.3% fewer, 95% CI 1.1% to 3.6% fewer), - neonatal death (RR 0.78, 95% CI 0.70 to 0.87; 10,609 infants; 22 studies; high-certainty evidence; 2.6% fewer, 95% CI 1.5% to 3.6% fewer), - respiratory distress syndrome (RR 0.71, 95% CI 0.65 to 0.78; 11,183 infants; studies = 26; high-certainty evidence; 4.3% fewer, 95% CI 3.2% to 5.2% fewer). Antenatal corticosteroids probably reduce the risk of IVH (RR 0.58, 95% CI 0.45 to 0.75; 8475 infants; 12 studies; moderate-certainty evidence; 1.4% fewer, 95% CI 0.8% to1.8% fewer), and probably have little to no effect on birthweight (mean difference (MD) -14.02 g, 95% CI -33.79 to 5.76; 9551 infants; 19 studies; high-certainty evidence). Antenatal corticosteroids probably lead to a reduction in developmental delay in childhood (RR 0.51, 95% CI 0.27 to 0.97; 600 children; 3 studies; moderate-certainty evidence; 3.8% fewer, 95% CI 0.2% to 5.7% fewer). Maternal outcomes Antenatal corticosteroids probably result in little to no difference in maternal death (RR 1.19, 95% CI 0.36 to 3.89; 6244 women; 6 studies; moderate-certainty evidence; 0.0% fewer, 95% CI 0.1% fewer to 0.5% more), chorioamnionitis (RR 0.86, 95% CI 0.69 to 1.08; 8374 women; 15 studies; moderate-certainty evidence; 0.5% fewer, 95% CI 1.1% fewer to 0.3% more), and endometritis (RR 1.14, 95% CI 0.82 to 1.58; 6764 women; 10 studies; moderate-certainty; 0.3% more, 95% CI 0.3% fewer to 1.1% more) The wide 95% CIs in all of these outcomes include possible benefit and possible harm.
AUTHORS' CONCLUSIONS
Evidence from this updated review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. Treatment with antenatal corticosteroids reduces the risk of perinatal death, neonatal death and RDS and probably reduces the risk of IVH. This evidence is robust, regardless of resource setting (high, middle or low). Further research should focus on variations in the treatment regimen, effectiveness of the intervention in specific understudied subgroups such as multiple pregnancies and other high-risk obstetric groups, and the risks and benefits in the very early or very late preterm periods. Additionally, outcomes from existing trials with follow-up into childhood and adulthood are needed in order to investigate any longer-term effects of antenatal corticosteroids. We encourage authors of previous studies to provide further information which may answer any remaining questions about the use of antenatal corticosteroids without the need for further randomised controlled trials. Individual patient data meta-analyses from published trials are likely to provide answers for most of the remaining clinical uncertainties.
Topics: Adrenal Cortex Hormones; Betamethasone; Bias; Cerebral Intraventricular Hemorrhage; Developmental Disabilities; Dexamethasone; Female; Fetal Organ Maturity; Humans; Hydrocortisone; Infant, Newborn; Lung; Maternal Death; Perinatal Death; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 33368142
DOI: 10.1002/14651858.CD004454.pub4