Effect of antenatal corticosteroid administration-to-birth interval on maternal and newborn outcomes: a systematic reviewResearch in context

Summary: Background: Antenatal corticosteroids (ACS) are highly effective at improving outcomes for preterm newborns. Evidence suggests the benefits of ACS may vary with the time interval between administration-to-birth. However, the optimal ACS administration-to-birth interval is not yet known. In this systematic review, we synthesised available evidence on the relationship between ACS administration-to-birth interval and maternal and newborn outcomes. Methods: This review was registered with PROSPERO (CRD42021253379). We searched Medline, Embase, CINAHL, Cochrane Library, Global Index Medicus on 11 Nov 2022 with no date or language restrictions. Randomised and non-randomised studies of pregnant women receiving ACS for preterm birth where maternal and newborn outcomes were reported for different administration-to-birth intervals were eligible. Eligibility screening, data extraction and risk of bias assessment were performed by two authors independently. Fetal and neonatal outcomes included perinatal and neonatal mortality, preterm birth-related morbidity outcomes and mean birthweight. Maternal outcomes included chorioamnionitis, maternal mortality, endometritis, and maternal intensive care unit admission. Findings: Ten trials (4592 women; 5018 neonates), 45 cohort studies (at least 22,992 women; 30,974 neonates) and two case–control studies (355 women; 360 neonates) met the eligibility criteria. Across studies, 37 different time interval combinations were identified. There was considerable heterogeneity in included administration-to-birth intervals and populations. The odds of neonatal mortality, respiratory distress syndrome and intraventricular haemorrhage were associated with the ACS administration-to-birth interval. However, the interval associated with the greatest improvements in newborn outcomes was not consistent across studies. No reliable data were available for maternal outcomes, though odds of chorioamnionitis might be associated with longer intervals. Intepretation: An optimal ACS administration-to-birth interval likely exists, however variations in study design limit identification of this interval from available evidence. Future research should consider advanced analysis techniques such as individual patient data meta-analysis to identify which ACS administration-to-birth intervals are most beneficial, and how these benefits can be optimised for women and newborns. Funding: This study was conducted with funding support from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research (SRH), a co-sponsored programme executed by the World Health Organization

Single sustained inflation followed by ventilation leads to rapid cardiorespiratory recovery but causes cerebral vascular leakage in asphyxiated near-term lambs

Background A sustained inflation (SI) rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF) and cerebral vascular integrity in asphyxiated near-term lambs. Methods Lambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6), a single 30 s SI (single SI; n = 6) or conventional ventilation (no SI; n = 6). Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage. Results CaBF increased more rapidly and to a greater extent during a single SI (p = 0.01), which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01). Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001) in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs. Conclusions Ventilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation

Elevated airway liquid volumes at birth: a potential cause of transient tachypnea of the newborn

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