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Pediatrics International : Official... 2024Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of administering sildenafil early on to prevent BPD remains uncertain. The aim of this study was to investigate the efficacy and safety of prophylactically administered sildenafil during the early life stages of preterm infants to prevent mortality and BPD.
METHODS
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Ichushi were searched. Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated the certainty of evidence (CoE) following the Grading of Recommendations Assessment and Development and Evaluation approach. The random-effects model was used for a meta-analysis of RCTs.
RESULTS
This review included three RCTs (162 infants). There were no significant differences between the prophylactic sildenafil and placebo groups in mortality (risk ratio [RR]: 1.32; 95% confidence interval [CI]: 0.16-10.75; very low CoE), BPD (RR: 1.20; 95% CI: 0.79-1.83; very low CoE), and all other outcome assessed (all with very low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials.
CONCLUSIONS
The prophylactic use of sildenafil in individuals at risk of BPD did not indicate any advantageous effects in terms of mortality, BPD, and other outcomes, or increased side effects.
Topics: Humans; Sildenafil Citrate; Bronchopulmonary Dysplasia; Infant, Newborn; Phosphodiesterase 5 Inhibitors; Treatment Outcome; Randomized Controlled Trials as Topic; Infant, Extremely Premature; Vasodilator Agents
PubMed: 38863262
DOI: 10.1111/ped.15749 -
PloS One 2024Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid, particularly glycine conjugate, may compromise blood flow and cause functional hypoxia-ischemia.
AIMS
This meta-analysis aims to assess the association between ICP and key pregnancy outcomes including emergency caesarian sections (C-sections), preeclampsia, hemorrhage, preterm birth, small for gestational age, admission rate to neonatal intensive care union (NICU), gestational age, and stillbirth.
MATERIALS AND METHODS
Literature search across five databases (PubMed, Embase, Web of Science) was done to detect relevant studies published up until June 2023. Meta-analysis of the identified studies was done using a random-effects model, and the results presented as Odds ratio (OR).
RESULTS
A literature search identified 662 studies. Of them, 21 met the inclusion criteria. There was a significant association between ICP and odds of C-section (OR: 1.42, p <0.001), preeclampsia (OR: 2.64, p <0.001), NICU admission (OR: 2.1, p <0.001), and pre-term birth (OR: 2.64, p <0.001). ICP was not associated with postpartum hemmorhage (OR: 1.31, p = 0.13), small for gestational age (OR: 0.87, p = 0.07), stillbirth (OR: 1.49, p = 0.29).
CONCLUSIONS
Our results confirm the adverse effects of ICP on co-existing pregnancy complications, obstetric and neonatal outcomes. ICP in associated with severe complications including increased rates of preeclampsia, emergency C-sections, preterm births, l gestational periods and higher rates of NICU admissions. These results may assist healthcare professionals in formulating comprehensive care guidelines for expectant mothers and newborns.
Topics: Humans; Pregnancy; Cholestasis, Intrahepatic; Female; Pregnancy Complications; Infant, Newborn; Pregnancy Outcome; Premature Birth; Stillbirth; Pre-Eclampsia; Cesarean Section; Gestational Age; Infant, Small for Gestational Age
PubMed: 38833446
DOI: 10.1371/journal.pone.0304604 -
Nutrition & Diabetes May 2024Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes.
BACKGROUND
Vitamin D deficiency has been linked with several adverse maternal and fetal outcomes.
OBJECTIVE
To summarize systematic reviews and meta-analyses evaluating the effects of vitamin D deficiency and of vitamin D supplementation in pregnancy on maternal and offspring health-related outcomes.
METHODS
Prior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD42022368003). We conducted searches in PubMed, Embase, and Cochrane Library for systematic reviews and meta-analyses on vitamin D in pregnancy, from database inception to October 2, 2023. All outcomes related to vitamin D in pregnancy obtained from the systematic reviews and meta-analyses were extracted.
DATA EXTRACTION
Two reviewers independently chose studies and collected information on health outcomes. The quality of the included articles' methodology was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2).
RESULTS
We identified 16 eligible systematic reviews and meta-analyses, which included 250,569 women. Our results demonstrated that vitamin D deficiency in pregnancy is associated with increased risk of preterm birth, small-for gestational age/low birth weight infants, recurrent miscarriage, bacterial vaginosis and gestational diabetes mellitus. Vitamin D supplementation in pregnancy increases birth weight, and reduces the risk of maternal pre-eclampsia, miscarriage, and vitamin D deficiency, fetal or neonatal mortality, as well as attention-deficit hyperactivity disorder, and autism spectrum disorder in childhood. In women with gestational diabetes mellitus, vitamin D supplementation in pregnancy can reduce the risk of maternal hyperbilirubinemia, polyhydramnios, macrosomia, fetal distress, and neonatal hospitalization.
CONCLUSION
Due to the association with adverse maternal and offspring health outcomes, we recommend the vitamin D status in pregnancy should be monitored, particularly in women at high risk of vitamin D deficiency. It is suggested that pregnant women take a dose of >400 IU/day of vitamin D supplementation during pregnancy to prevent certain adverse outcomes.
Topics: Humans; Pregnancy; Female; Vitamin D Deficiency; Vitamin D; Pregnancy Complications; Dietary Supplements; Pregnancy Outcome; Systematic Reviews as Topic; Meta-Analysis as Topic; Infant, Newborn; Premature Birth
PubMed: 38816412
DOI: 10.1038/s41387-024-00296-0 -
Archives of Gynecology and Obstetrics Jul 2024The prevalence of benzodiazepines and related drugs (BZRDs) use during pregnancy increased sharply in recent years. Thus, there are concerns regarding the pregnancy... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The prevalence of benzodiazepines and related drugs (BZRDs) use during pregnancy increased sharply in recent years. Thus, there are concerns regarding the pregnancy outcomes following exposure to BZRDs.
METHODS
Two electronic databases were thoroughly searched to identify related clinical studies published from inception until June 2023. English-language cohort studies with high-quality comparing antenatal BZRDs exposure to an unexposed group on any delivery outcome were included.
RESULTS
Ten cohort studies that estimated adverse neonatal outcomes associated with exposure to BZRDs during pregnancy were included. Exposure to BZRDs during pregnancy was associated with an increased risk of congenital malformation [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.05-1.13, p < 0.001], heart malformation (OR 1.13, 95% CI 1.04-1.22, p = 0.003), preterm birth (OR 1.45, 95% CI 1.23-1.7, p < 0.001), SGA (OR 1.18, 95% CI 1.08-1.29, P < 0.001), LBW (OR 1.42, 95% CI 1.25-1.6, p = 0.001) or low Apgar score (OR 1.42, 95% CI 1.08-1.87, p = 0.011),compared with no exposure. Further analyses limited to the first trimester exposure yielded consistent results.
CONCLUSIONS
Exposure to BZRDs during pregnancy may be associated with several adverse neonatal outcomes. However, we could not rule out the potential indication confounding factor, further studies with high-quality that control for important confounders are still needed to verify our findings.
Topics: Humans; Pregnancy; Female; Benzodiazepines; Pregnancy Outcome; Infant, Newborn; Premature Birth; Abnormalities, Drug-Induced; Cohort Studies; Pregnancy Complications
PubMed: 38806942
DOI: 10.1007/s00404-024-07557-4 -
Balkan Medical Journal May 2024Premature rupture of membranes (PROM) is defined as the leakage of amniotic fluid before the onset of labor and delivery contractions. Some studies found that women who...
BACKGROUND
Premature rupture of membranes (PROM) is defined as the leakage of amniotic fluid before the onset of labor and delivery contractions. Some studies found that women who experienced PROM had significantly lower vitamin C blood levels than those who did not, while others found no significant differences. Previous systematic reviews and meta-analyses on the efficacy of vitamin C in the prevention of PROM had conflicting results.
AIMS
We aimed to conduct a systematic review and meta-analysis to determine if there was a significant difference in vitamin C blood levels in women who had PROM versus the control group who did not and to determine if vitamin C supplements could help prevent it.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
We registered our protocol with PROSPERO (CRD42022371644). We searched PubMed/MEDLINE, Web of Science, and Scopus through February 15, 2024. Additionally, backward and forward citation searches were conducted. Studies were selected based on predetermined inclusion and exclusion criteria. Meta-Essentials: Workbooks for Meta-Analysis (Version 1.5) was used for analysis.
RESULTS
Twenty-five studies (26 reports) met all eligibility criteria, with 18 studies (18 reports) assessing vitamin C levels and seven studies (eight reports) evaluating efficacy. Women with PROM, whether preterm or term, had significantly lower vitamin C levels [Hedges' g, -1.48; 95% confidence interval (CI): -2.82, -0.14; = 0.020; = 94.08%) and specifically preterm PROM after removing the outlying study [Hedges' g, -1.29; 95% CI: -1.85, -0.73; < 0.001; = 87.35%). Vitamin C supplementation significantly reduced the risk of preterm or term PROM [risk ratio (RR), 0.57; 95% CI: 0.39, 0.81; < 0.001; = 12.17%), particularly for preterm PROM (RR, 0.67; 95% CI: 0.45, 0.99; p = 0.001; = 0.00%). There were no significant differences in vitamin C levels between women with term PROM and controls, and there were no differences in the risk of developing term PROM between women taking vitamin C supplements and controls. Results were not robust in all sensitivity analyses.
CONCLUSION
Women with PROM, particularly those who developed it preterm, appear to have significantly lower vitamin C levels, and vitamin C supplementation appears to be effective in reducing the risk of PROM, particularly preterm PROM. More high-quality studies with low risk of bias, more homogenous, and larger samples are needed to confirm these findings.
PubMed: 38775321
DOI: 10.4274/balkanmedj.galenos.2024.2024-2-79 -
Journal of Midwifery & Women's Health 2024Intrahepatic cholestasis of pregnancy (ICP) is a problem with an increasing incidence and negative maternal, fetal, and neonatal consequences. This problem is becoming... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Intrahepatic cholestasis of pregnancy (ICP) is a problem with an increasing incidence and negative maternal, fetal, and neonatal consequences. This problem is becoming increasingly important. This systematic review and meta-analysis aimed to determine the incidence of ICP and its adverse maternal, fetal, and neonatal adverse outcomes based on primary research studies.
METHODS
This systematic review and meta-analysis used Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and was conducted between June and September 2023 using the following keywords: obstetric cholestasis OR intrahepatic cholestasis AND pregnancy OR pregnant OR prenatal OR antenatal OR perinatal OR maternal OR fetal OR neonatal. Quality assessment of the studies was performed using the Critical Appraisal Checklists developed by the JBI Institute. Data were synthesized using meta-analysis methods.
RESULTS
The analysis included 10 studies published between 2013 and 2023. The meta-analysis showed that the incidence of ICP was 1.7% (odds ratio [OR], 0.021; 95% CI, 0.012-0.027), whereas maternal, fetal, and neonatal adverse outcomes included cesarean birth (OR, 2.938; 95% CI, 1.467-5.881), preterm birth or preterm prelabor rupture of membranes (OR, 4.241; 95% CI, 1.996-9.009), hypertensive disorders of pregnancy (OR, 3.715; 95% CI, 1.545-8.929), maternal infection (OR, 3.301; 95% CI, 2.917-3.737), neonatal intensive care unit admission (OR, 2.715; 95% CI, 1.458-5.056), birth weight less than or equal to 2500 g (OR, 2.518; 95% CI, 1.296-4.892), and small for gestational age (OR, 1.915; 95% CI, 1.424-2.573).
DISCUSSION
This systematic review and meta-analysis revealed that ICP has a high incidence and several maternal, fetal, and neonatal adverse outcomes. Therefore, midwives and other health professionals must be aware of these outcomes and provide appropriate care to pregnant individuals with ICP.
Topics: Humans; Pregnancy; Cholestasis, Intrahepatic; Female; Pregnancy Complications; Infant, Newborn; Incidence; Pregnancy Outcome; Premature Birth; Cesarean Section
PubMed: 38750666
DOI: 10.1111/jmwh.13640 -
BMC Pregnancy and Childbirth May 2024Given the increasing incidence of negative outcomes during pregnancy, our research team conducted a dose-response systematic review and meta-analysis to investigate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Given the increasing incidence of negative outcomes during pregnancy, our research team conducted a dose-response systematic review and meta-analysis to investigate the relationship between ultra-processed foods (UPFs) consumption and common adverse pregnancy outcomes including gestational diabetes mellitus (GDM), preeclampsia (PE), preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) infants. UPFs are described as formulations of food substances often modified by chemical processes and then assembled into ready-to-consume hyper-palatable food and drink products using flavors, colors, emulsifiers, and other cosmetic additives. Examples include savory snacks, reconstituted meat products, frozen meals that have already been made, and soft drinks.
METHODS
A comprehensive search was performed using the Scopus, PubMed, and Web of Science databases up to December 2023. We pooled relative risk (RR) and 95% confidence intervals (CI) using a random-effects model.
RESULTS
Our analysis (encompassing 54 studies with 552,686 individuals) revealed a significant association between UPFs intake and increased risks of GDM (RR = 1.19; 95% CI: 1.10, 1.27; I = 77.5%; p < 0.001; studies = 44; number of participants = 180,824), PE (RR = 1.28; 95% CI: 1.03, 1.59; I = 80.0%; p = 0.025; studies = 12; number of participants = 54,955), while no significant relationships were found for PTB, LBW and SGA infants. Importantly, a 100 g increment in UPFs intake was related to a 27% increase in GDM risk (RR = 1.27; 95% CI: 1.07, 1.51; I = 81.0%; p = 0.007; studies = 9; number of participants = 39,812). The non-linear dose-response analysis further indicated a positive, non-linear relationship between UPFs intake and GDM risk P = 0.034, P = 0.034), although no such relationship was observed for PE (P = 0.696, P = 0.812).
CONCLUSION
In summary, both prior to and during pregnancy, chronic and excessive intake of UPFs is associated with an increased risk of GDM and PE. However, further observational studies, particularly among diverse ethnic groups with precise UPFs consumption measurement tools, are imperative for a more comprehensive understanding.
Topics: Humans; Pregnancy; Female; Pregnancy Outcome; Diabetes, Gestational; Infant, Newborn; Fast Foods; Infant, Small for Gestational Age; Premature Birth; Pre-Eclampsia; Infant, Low Birth Weight; Pregnancy Complications; Food Handling; Food, Processed
PubMed: 38750456
DOI: 10.1186/s12884-024-06489-w -
The Cochrane Database of Systematic... May 2024Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version.
OBJECTIVES
To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies.
SELECTION CRITERIA
We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably reduced severe intraventricular haemorrhage (grade 3 or 4) (RR 0.76, 95% CI 0.60 to 0.98; 5 RCTs, 5885 infants; NNTB 92, 95% CI 55 to 1102; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported.
AUTHORS' CONCLUSIONS
The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age, and probably reduces severe intraventricular haemorrhage for infants. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Bias; Cerebral Palsy; Magnesium Sulfate; Neuroprotective Agents; Premature Birth; Randomized Controlled Trials as Topic; Tocolytic Agents
PubMed: 38726883
DOI: 10.1002/14651858.CD004661.pub4 -
Journal of Psychosomatic Obstetrics and... Dec 2024To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the impact of low-dose aspirin (LDA) on obstetrical outcomes through a meta-analysis of placebo-controlled randomized controlled trials (RCTs).
METHODS
A systematic search of the PubMed, Cochrane Library, Web of Science and Embase databases from inception to January 2024 was conducted to identify studies exploring the role of aspirin on pregnancy, reporting obstetrical-related outcomes, including preterm birth (PTB, gestational age <37 weeks), small for gestational age (SGA), low birth weight (LBW, birthweight < 2500g), perinatal death (PND), admission to the neonatal intensive care unit (NICU), 5-min Apgar score < 7 and placental abruption. Relative risks (RRs) were estimated for the combined outcomes. Subgroup analyses were performed by risk for preeclampsia (PE), LDA dosage (<100 mg vs. ≥100 mg) and timing of onset (≤20 weeks vs. >20 weeks).
RESULTS
Forty-seven studies involving 59,124 participants were included. Compared with placebo, LDA had a more significant effect on low-risk events such as SGA, PTB and LBW. Specifically, LDA significantly reduced the risk of SGA (RR = 0.91, 95% CI: 0.87-0.95), PTB (RR = 0.93, 95% CI: 0.89-0.97) and LBW (RR = 0.94, 95% CI: 0.89-0.99). For high-risk events, LDA significantly lowered the risk of NICU admission (RR = 0.93, 95% CI: 0.87-0.99). On the other hand, LDA can significantly increase the risk of placental abruption (RR = 1.72, 95% CI: 1.23-2.43). Subgroup analyses showed that LDA significantly reduced the risk of SGA (RR = 0.86, 95% CI: 0.77-0.97), PTB (RR = 0.93, 95% CI: 0.88-0.98) and PND (RR = 0.65, 95% CI: 0.48-0.88) in pregnant women at high risk of PE, whereas in healthy pregnant women LDA did not significantly improve obstetrical outcomes, but instead significantly increased the risk of placental abruption (RR = 5.56, 95% CI: 1.92-16.11). In pregnant women at high risk of PE, LDA administered at doses ≥100 mg significantly reduced the risk of SGA (RR = 0.77, 95% CI: 0.66-0.91) and PTB (RR = 0.56, 95% CI: 0.32-0.97), but did not have a statistically significant effect on reducing the risk of NICU, PND and LBW. LDA started at ≤20 weeks significantly reduced the risk of SGA (RR = 0.76, 95% CI: 0.65-0.89) and PTB (RR = 0.56, 95% CI: 0.32-0.97).
CONCLUSIONS
To sum up, LDA significantly improved neonatal outcomes in pregnant women at high risk of PE without elevating the risk of placental abruption. These findings support LDA's clinical application in pregnant women, although further research is needed to refine dosage and timing recommendations.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abruptio Placentae; Aspirin; Infant, Low Birth Weight; Infant, Small for Gestational Age; Pre-Eclampsia; Pregnancy Outcome; Premature Birth; Randomized Controlled Trials as Topic
PubMed: 38712869
DOI: 10.1080/0167482X.2024.2344079 -
The Cochrane Database of Systematic... May 2024Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in infants. Maternal RSV vaccination is a preventive strategy of great... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in infants. Maternal RSV vaccination is a preventive strategy of great interest, as it could have a substantial impact on infant RSV disease burden. In recent years, the clinical development of maternal RSV vaccines has advanced rapidly.
OBJECTIVES
To assess the efficacy and safety of maternal respiratory syncytial virus (RSV) vaccination for preventing RSV disease in infants.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register and two other trials registries on 21 October 2022. We updated the search on 27 July 2023, when we searched MEDLINE, Embase, CENTRAL, CINAHL, and two trials registries. Additionally, we searched the reference lists of retrieved studies and conference proceedings. There were no language restrictions on our searches.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing maternal RSV vaccination with placebo or no intervention in pregnant women of any age. The primary outcomes were hospitalisation with clinically confirmed or laboratory-confirmed RSV disease in infants. The secondary outcomes covered adverse pregnancy outcomes (intrauterine growth restriction, stillbirth, and maternal death) and adverse infant outcomes (preterm birth, congenital abnormalities, and infant death).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods and assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS
We included six RCTs (25 study reports) involving 17,991 pregnant women. The intervention was an RSV pre-F protein vaccine in four studies, and an RSV F protein nanoparticle vaccine in two studies. In all studies, the comparator was a placebo (saline, formulation buffer, or sterile water). We judged four studies at overall low risk of bias and two studies at overall high risk (mainly due to selection bias). All studies were funded by pharmaceutical companies. Maternal RSV vaccination compared with placebo reduces infant hospitalisation with laboratory-confirmed RSV disease (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.31 to 0.82; 4 RCTs, 12,216 infants; high-certainty evidence). Based on an absolute risk with placebo of 22 hospitalisations per 1000 infants, our results represent 11 fewer hospitalisations per 1000 infants from vaccinated pregnant women (15 fewer to 4 fewer). No studies reported infant hospitalisation with clinically confirmed RSV disease. Maternal RSV vaccination compared with placebo has little or no effect on the risk of congenital abnormalities (RR 0.96, 95% CI 0.88 to 1.04; 140 per 1000 with placebo, 5 fewer per 1000 with RSV vaccination (17 fewer to 6 more); 4 RCTs, 12,304 infants; high-certainty evidence). Maternal RSV vaccination likely has little or no effect on the risk of intrauterine growth restriction (RR 1.32, 95% CI 0.75 to 2.33; 3 per 1000 with placebo, 1 more per 1000 with RSV vaccination (1 fewer to 4 more); 4 RCTs, 12,545 pregnant women; moderate-certainty evidence). Maternal RSV vaccination may have little or no effect on the risk of stillbirth (RR 0.81, 95% CI 0.38 to 1.72; 3 per 1000 with placebo, no difference with RSV vaccination (2 fewer to 3 more); 5 RCTs, 12,652 pregnant women). There may be a safety signal warranting further investigation related to preterm birth. This outcome may be more likely with maternal RSV vaccination, although the 95% CI includes no effect, and the evidence is very uncertain (RR 1.16, 95% CI 0.99 to 1.36; 6 RCTs, 17,560 infants; very low-certainty evidence). Based on an absolute risk of 51 preterm births per 1000 infants from pregnant women who received placebo, there may be 8 more per 1000 infants from pregnant women with RSV vaccination (1 fewer to 18 more). There was one maternal death in the RSV vaccination group and none in the placebo group. Our meta-analysis suggests that RSV vaccination compared with placebo may have little or no effect on the risk of maternal death (RR 3.00, 95% CI 0.12 to 73.50; 3 RCTs, 7977 pregnant women; low-certainty evidence). The effect of maternal RSV vaccination on the risk of infant death is very uncertain (RR 0.81, 95% CI 0.36 to 1.81; 6 RCTs, 17,589 infants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
The findings of this review suggest that maternal RSV vaccination reduces laboratory-confirmed RSV hospitalisations in infants. There are no safety concerns about intrauterine growth restriction and congenital abnormalities. We must be careful in drawing conclusions about other safety outcomes owing to the low and very low certainty of the evidence. The evidence available to date suggests RSV vaccination may have little or no effect on stillbirth, maternal death, and infant death (although the evidence for infant death is very uncertain). However, there may be a safety signal warranting further investigation related to preterm birth. This is driven by data from one trial, which is not fully published yet. The evidence base would be much improved by more RCTs with substantial sample sizes and well-designed observational studies with long-term follow-up for assessment of safety outcomes. Future studies should aim to use standard outcome measures, collect data on concomitant vaccines, and stratify data by timing of vaccination, gestational age at birth, race, and geographical setting.
Topics: Humans; Pregnancy; Female; Respiratory Syncytial Virus Infections; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Vaccines; Infant; Infant, Newborn; Stillbirth; Premature Birth; Pregnancy Complications, Infectious; Hospitalization; Fetal Growth Retardation; Pregnancy Outcome; Vaccination; Congenital Abnormalities; Bias; Infant Death
PubMed: 38695784
DOI: 10.1002/14651858.CD015134.pub2