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Effective management of foetal anaemia in Rh(D) alloimmunised pregnant women with intrauterine transfusion: a Systematic Review
Prescott, B., Jackson, D. E.
Hematology, transfusion and cell therapy. 2023
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Editor's Choice
Abstract
BACKGROUND Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal anaemia in alloimmunised pregnant women. If left untreated hydrops can develop thereby reducing the chance of survival. Survival rates have improved but the procedure is not without complications. Procedure-related complications can be associated with early gestational age, hence delaying IUT could improve outcomes. This review aims to determine the effectiveness and safety of IUTs by examining survival and mortality rates, procedure-related complications with associated foetal mortality and the influence of hydrops. STUDY DESIGN AND METHOD A systematic review was conducted by searching keywords in four scientific databases from January 2000 to April 2022. A meta-analysis was performed with the OpenMeta-Analyst software using an arcsine transformed proportion with the binary random-effects model and maximum likelihood method. RESULTS Fifteen studies were identified as eligible and used in the meta-analysis. The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present. CONCLUSION The findings of this systematic review and meta-analysis provide evidence that IUT is a safe and effective treatment for foetal anaemia in the absence of hydrops when experienced personnel perform the procedure to minimise the risk of procedure-related complications.
PICO Summary
Population
Rh(D) alloimmunised pregnant women (15 studies).
Intervention
Systematic review and meta-analysis to determine the effectiveness and safety of intrauterine transfusions (IUTs).
Comparison
Outcome
The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present.
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Placental Transfusion Strategies in Preterm Infants in Low- and Middle-Income Countries: A Systematic Review and Network Meta-Analysis
Ramaswamy VV, Bandyopadhyay T, Abiramalatha T, Shaik NB, Pullattayil SAk, Jasani B, Hegde V, Trevisanuto D, Weiner GM
Neonatology. 2022;:1-16
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Abstract
INTRODUCTION Placental transfusion strategies in preterm newborns have not been evaluated in low- and middle-income countries (LMICs). The objective of this systematic review was to compare placental transfusion strategies in preterm newborns in LMICs, including delayed cord clamping (DCC) for various time intervals, DCC until cord pulsations stop, umbilical cord milking, and immediate cord clamping (ICC). METHODS Medline, Embase, CINAHL, and CENTRAL were searched from inception. Observational studies and randomized controlled trials (RCTs) were included. Two authors independently extracted data for Bayesian random-effects network meta-analysis (NMA) if more than 3 interventions reported an outcome or a pairwise meta-analysis was utilized. RESULTS Among newborns <34 weeks of gestation, NMA of 9 RCTs could not rule out benefit or harm for survival from DCC 30-60 s compared to ICC: relative risk (RR) (95% credible interval) 0.96 (0.78-1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120 s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01-1.22), very low certainty. We could not detect differences in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60 s and 120 s might improve the hematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty). CONCLUSIONS In LMICs, DCC for 60 s and 120 s might improve hematocrit level in preterm newborns, and DCC for 45 s may decrease the risk of receipt of inotropes in newborns <34 weeks, with no conclusive effect on survival.
PICO Summary
Population
Preterm newborns in low- and middle-income countries (9 studies).
Intervention
Delayed cord clamping (DCC) for various time intervals.
Comparison
DCC until cord pulsations stop. Umbilical cord milking. Immediate cord clamping (ICC).
Outcome
Network meta-analysis of 9 randomised controlled trials could not rule out benefit or harm for survival from DCC 30-60s compared to ICC: relative risk (RR), (95% credible interval) 0.96 (0.78 to 1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01 to 1.22), very low certainty. Differences were not detected in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60s and 120s might improve the haematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty).
3.
Non-Invasive Prenatal Fetal Blood Group Genotype and Its Application in the Management of Hemolytic Disease of Fetus and Newborn: Systematic Review and Meta-Analysis
Alshehri AA, Jackson DE
Transfusion medicine reviews. 2021
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Editor's Choice
Abstract
Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.
PICO Summary
Population
Women whose pregnancy was at risk of haemolytic disease of foetus and new born (HDFN), (19 studies).
Intervention
Systematic review and meta-analysis on non-invasive prenatal analysis (NIPT) in conjunction with quantitative maternal alloantibody analysis.
Comparison
Outcome
NIPT was estimated highly sensitive/specific for foetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons were optimum to increase accuracy. NIPT permitted cost-effectiveness and was associated with low emotional stress. Knowledge of parental ethnicity was important for correct NIPT result interpretations and quantitative screening. Cut-off titre ≥8-up-to-32 was relevant for anti-D alloantibodies, while, lower titre was for anti-K. Alloimmunisation was influenced by maternal RHD status, gravida status, and history of adverse obstetrics.