Antisecretory factor in the perinatal period

Preterm birth is the major cause of neonatal morbidity and mortality. Human milk, especially mothers’ own milk, has many health benefits for infants, especially infants born preterm. The causes of preterm birth are not yet fully understood. Inflammation is suggested to be involved in the pathogenesis of preterm birth, in inflammatory complications in preterm infants as well as in complications during lactation. Antisecretory factor (AF) is a protein involved in regulation of secretory and inflammatory processes and has not previously been studied related to the perinatal period.

The aim of this thesis was to describe AF in the perinatal period related to preterm birth, human milk, inflammation, and infant outcome. The included studies are sub-studies in three longitudinal cohort studies, with an exploratory approach related to antisecretory factor. Methods used to determine levels of antisecretory factor were immunohistochemistry in paper I, enzyme-linked immunosorbent assay (ELISA) in paper II, and Sandwich ELISA in paper III and IV. The results demonstrated lower levels of AF and a higher degree of inflammation in placenta after preterm birth (paper I), an association between higher levels of AF in maternal plasma and higher levels in mothers’ own milk (paper II), higher levels of AF in colostrum versus mature milk in mothers own milk after term and preterm birth (paper III), preserved AF after Holder pasteurization (paper III), and that higher levels of AF in mothers own milk was associated with less adverse outcome and inflammation in preterm infants (paper IV).

In conclusion, this thesis is the most comprehensive description of antisecretory factor in the perinatal period to date. The results demonstrate a basic pattern of AF showing that AF levels in maternal plasma are reflected in maternal breastmilk, and that AF levels in breastmilk decreases with time after birth. Furthermore, Holder pasteurization of donor milk can be safely performed without concern that it may destroy AF. Additionally, the findings indicate that after preterm birth, lower levels of AF in both placenta and breastmilk are associated with more inflammation, and that higher levels of AF in mother’s own breastmilk may be protective for the infant and reduce the risk for inflammatory complications, such as sepsis, in the neonatal period. The significance of these novel findings implicates that AF may be involved in the complex pathophysiology related to inflammatory complications in the perinatal period and can serve as a base for further studies on mechanisms and interventions. Since effective prevention and treatments are lacking, AF may present as a possible modifiable factor to improve health in the perinatal period.

List of scientific papers

I. Low levels of anti-secretory factor in placenta are associated with preterm birth and inflammation. Gustafsson AM, Fransson E, Dubicke A, Hjelmstedt AK, Ekman-Ordeberg G, Silfverdal S-A, Lange S, Jennische E, Bohlin K. Acta Obstet Gynecol Scand. 2018.
https://doi.org/10.1111/aogs.13282

II. The Antisecretory Factor in Plasma and Breast Milk in Breastfeeding Mothers-A Prospective Cohort Study in Sweden. Gustafsson A, Granström E, Stecksén-Blicks C, West CE, Silfverdal SA. Nutrients. 2018 Sep 4;10(9):1227.
https://doi.org/10.3390/nu10091227

III. Changes in Antisecretory Factor in Human Milk During the Postpartum and Length of Gestation. Gustafsson A, Johansson E, Henckel E, Lange S, Bohlin K. J Hum Lact. 2021 Jun 1:8903344211021306.
https://doi.org/10.1177/08903344211021306

IV. Antisecretory factor in mothers own milk following preterm birth – association to neonatal inflammation and outcome. Gustafsson A, Johansson E, Henckel E, Olin A, Rodriguez L, Brodin P, Lange S, Bohlin K. [Manuscript]