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Multiple courses versus a single course of antenatal corticosteroids (ACS) have been associated with mild respiratory benefits but also adverse outcomes like smaller head circumference and birth weight. Long-term effects warrant study. We systematically reviewed long-term outcomes (≥1 year) in both preterm and term birth after exposure to preterm multiple courses (including a rescue dose or course) versus a single course. We searched seven databases from January 2000 to October 2021. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies with births occurring in/after the year 2000, given advances in perinatal care. Two reviewers assessed titles/abstracts, articles, quality, and outcomes including psychological disorders, neurodevelopment, and anthropometry. Six follow-up studies of three RCTs and two cohort studies (over 2,860 children total) met inclusion criteria. Among children born preterm, randomization to multiple courses versus a single course of ACS was not associated with adjusted beneficial or adverse neurodevelopmental/psychological or other outcomes, but data are scant after a rescue dose (120 and 139 children, respectively, low certainty) and nonexistent after a rescue course. For children born at term (i.e., 27% of the multiple courses of ACS 5-year follow-up study of 1,728 preterm/term born children), preterm randomization to multiple courses (at least one additional course) versus a single course was significantly associated with elevated odds of neurosensory impairment (adjusted odds ratio = 3.70, 95% confidence interval: 1.57–8.75; 212 and 247 children, respectively, moderate certainty). In this systematic review of long-term outcomes after multiple courses versus a single course of ACS, there were no significant benefits or risks regarding neurodevelopment in children born preterm but little data after one rescue dose and none after a rescue course. However, multiple courses (i.e., at least one additional course) should be considered cautiously: after term birth, there are no long-term benefits but neurosensory harms. Key Points We systematically reviewed the long-term impact of multiple versus a single course of ACS. Long-term follow-up data were scant after a rescue dose and absent after one rescue course of ACS. In children born preterm, multiple courses of ACS were not associated with long-term benefits/harms. In children born at term, multiple courses of ACS were associated with neurosensory impairment. Preterm administration of multiple courses of ACS should be considered cautiously. [ABSTRACT FROM AUTHOR]

Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn's disease (CD). This systematic review of randomised controlled trials (RCT) and cohort studies analyses the impact of EEN/PEN v. CS on intestinal microbiota, mucosal healing as well as other clinically important outcomes, including clinical remission, relapse, adherence, adverse events and health-related quality of life (HRQL) in paediatric CD. Three RCT (n 76) and sixteen cohort studies (n 1104) compared EEN v. CS. With limited available data (one RCT), the effect on intestinal microbiome indicated a trend towards EEN regarding Shannon diversity. Based on two RCT, EEN achieved higher mucosal healing than CS (risk ratio (RR) 2·36, 95 % CI (1·22, 4·57), low certainty). Compared with CS, patients on EEN were less likely to experience adverse events based on two RCT (RR 0·32, 95 % CI (0·13, 0·80), low certainty). For HRQL, there was a trend in favour of CS based on data from two published abstracts of cohort studies. Based on thirteen cohort studies, EEN achieved higher clinical remission than CS (RR 1·18, 95 % CI (1·02, 1·38), very low certainty). Studies also reported no important differences in relapse and adherence. Compared with CS, EEN may improve mucosal healing with fewer adverse events based on RCT data. While limited data indicate the need for further trials, this is the first systematic review to comprehensively summarise the data on intestinal microbiome, mucosal healing and HRQOL when comparing enteral nutrition and CS in paediatric CD. [ABSTRACT FROM AUTHOR]

Background: Evidence has shown significant benefits of aspirin for preventing pre‐eclampsia. Objectives: The objective of this study was to systematically review recommendations from clinical practice guidelines and other recommendation documents on aspirin for the prevention of pre‐eclampsia. Search strategy: Ten databases were searched for statements from December 1, 2013, to January 1, 2022. Selection criteria: Without language restrictions, the most recent version of documents was considered. Data collection and analysis: Two authors independently extracted recommendations. Guideline quality was assessed using a modified AGREE‐II instrument and the AGREE‐REX tool. Main results: Out of 48 statements on the prevention of pre‐eclampsia, 46 had recommendations on use of aspirin. Of them, 39 were supported by evidence from systematic reviews or randomized controlled trials. Three statements reported aspirin's significant reductions in preterm pre‐eclampsia and one in perinatal death. Concerning quality, 41% of statements were rated as high quality in all domains of the AGREE‐II tool, 15% were rated high quality in all domains of the AGREE‐REX tool, and 11% were rated high quality in all domains on both tools. Conclusions: While 96% of statements advocated for use of aspirin, only 9% reported a significant reduction in preterm pre‐eclampsia or perinatal death. Based on the AGREE tools, future statements could use methodological improvement. Synopsis: Most statements advocated for use of aspirin for the prevention of pre‐eclampsia but only 9% reported compelling evidence. Methodological improvement is important for future statements. [ABSTRACT FROM AUTHOR]

CONTEXT: Deferred cord clamping (DCC) saves lives. It reduces extremely preterm infants' mortality by 30%, yet a minority of eligible infants receive it. This may in part be due to lack of awareness or confidence in evidence, or conflicting or vague guidelines. OBJECTIVE: To systematically review clinical practice guidelines and other statements on DCC and cord milking. DATA SOURCES: Ten academic and guideline databases were searched. STUDY SELECTION: Clinical practice guidelines and other statements (position statements and consensus statements) providing at least 1 recommendation on DCC or umbilical cord milking among preterm or term infants were included. DATA EXTRACTION: Data from included statements were extracted by 2 independent reviewers, and discrepancies were resolved through consensus. Guideline quality was appraised with modified Appraisal of Guidelines for Research and Evaluation II and Appraisal of Guidelines for Research and Evaluation Recommendation Excellence tools. RESULTS: Forty-four statements from 35 organizations were included. All endorsed DCC for uncompromised preterm infants, and 11 cautiously stated that cord milking may be considered when DCC is infeasible. Only half (49%) of the recommendations on the optimal duration of DCC were supported by high-quality evidence. Only 8% of statements cited a mortality benefit of DCC for preterm infants. LIMITATIONS: Because systematic reviews of guidelines are relatively novel, there are few tools to inform study execution; however, we used the Appraisal of Guidelines for Research and Evaluation II and the Appraisal of Guidelines for Research and Evaluation Recommendation Excellence to assess quality and were methodologically informed by previous systematic reviews of guidelines. CONCLUSIONS: Statements worldwide clearly encouraged DCC. Their implementability would benefit from noting the preterm mortality benefit of DCC and more granularity. [ABSTRACT FROM AUTHOR]

Objective: Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes., Study Design: We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible., Results: Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome ( p  = 0.86), nor for any of the secondary outcomes ( p  > 0.05)., Conclusion: Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention., Key Points: · We explored the impact of infant sex on perinatal outcomes after multiple versus a single course of ACS.. · Infant sex was not a significant effect modifier of ACS exposure and perinatal outcomes.. · Animal literature indicates that sex-specific differences after ACS exposure may emerge over time.. · Further investigation of long-term sex-specific outcomes is warranted.., Competing Interests: None declared., (Thieme. All rights reserved.)