Changes in perinatal management and outcomes of extremely preterm infants born below 26 weeks of gestation in a tertiary referral hospital in Sweden: Comparison between 2004-2007 and 2012-2016.

INTRODUCTION: Perinatal management of extremely preterm births in Sweden has changed toward active care from 22-23 gestational weeks during the last decades. However, considerable regional differences exist. This study evaluates how one of the largest perinatal university centers has adapted to a more active care between 2004-2007 and 2012-2016 and if this has influenced infant survival. MATERIAL AND METHODS: In this historical cohort study, women admitted with at least one live fetus and delivered at 22-25 gestational weeks (stillbirths included) at Karolinska University Hospital Solna during April 1, 2004-March 31, 2007, and January 1, 2012-December 31, 2016, were compared regarding rates of obstetric and neonatal interventions, and infant mortality and morbidity. Maternal, pregnancy and infant data from 2004-2007 were obtained from the Extreme Preterm Infants in Sweden Study while data from 2012-2016 were extracted from medical journals and quality registers. The same definitions of interventions and diagnoses were used for both study periods. RESULTS: A total of 106 women with 118 infants during 2004-2007 and 213 women with 240 infants during 2012-2016 were included. Increases between the study periods were seen regarding cesarean delivery (overall rate 14% [17/118] during 2004-2007 vs. 45% [109/240] during 2012-2016), attendance of a neonatologist at birth (62% [73/118] vs. 85% [205/240]) and surfactant treatment at birth in liveborn infants (60% [45/75] vs. 74% [157/211]). Antepartum stillbirth rate decreased (13% [15/118] vs. 5% [12/240]) and the proportion of live births increased (80% [94/118] vs. 88% [211/240]) while 1-year survival (64% [60/94] vs. 67% [142/211]) and 1-year survival without major neonatal morbidity (21% [20/94] vs. 21% [44/211]) among liveborn infants did not change between the study periods. At 22 gestational weeks, interventions rates were still low during 2012-2016, most obvious regarding antenatal steroid treatment (23%), attendance of a neonatologist (51%), and intubation at birth (24%). CONCLUSIONS: Both obstetric and neonatal interventions at births below 26 gestational weeks increased between 2004-2007 and 2012-2016 in this single center study; however, at 22 gestational weeks they were still at a low level during 2012-2016. Despite more infants being born alive, 1-year survival did not increase between the study periods.

Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero.

OBJECTIVE: In utero exposure of the fetus to Ro/La autoantibodies may lead to congenital heart block (CHB). In the mother, these autoantibodies are associated with activation of the type I interferon (IFN)-system. As maternal autoantibodies are transferred to the fetus during pregnancy, we investigated whether the type I IFN-system is activated also in newborns of anti-Ro/La positive mothers, and whether fetal IFN activation is affected by maternal immunomodulatory treatment. METHODS: Blood drawn at birth from anti-Ro/La positive mothers, their newborns and healthy control pairs was separated into plasma and peripheral blood mononuclear cells (PBMC). PBMC were analysed directly or cultured. mRNA expression was analysed by microarrays, cell surface markers by flow cytometry, and IFNα levels by immunoassays. RESULTS: We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/La positive women, but also in their newborns. CD14+ monocytes of both anti-Ro/La positive mothers and their neonates showed increased expression of Sialic acid-binding Ig-like lectin-1, indicating cellular activation. Notably, the IFN score of neonates born to mothers receiving immunomodulatory treatment was similar to that of controls, despite persistent IFN activation in the mothers. In both maternal and neonatal PBMC, IFNα production was induced when cells were cultured with anti-Ro/La positive plasma. CONCLUSIONS: Ro/La autoantibody-exposed neonates at risk of CHB have signs of an activated immune system with an IFN signature. This study further demonstrates that neonatal cells can produce IFNα when exposed to autoantibody-containing plasma, and that maternal immunomodulatory treatment may diminish the expression of IFN-regulated genes in the fetus.