Introduction
Caesarean section (CS) is a well-known and potentially life-saving
surgical procedure. The global rate of deliveries by CS has increased
from 12.1% in 2000 to 21.1% of deliveries in 2015 (1). It is estimated
that 9-19% of CSs can be justified by medical indications (2, 3), and
the World Health Organization currently recommends CS for up to 15% of
deliveries(4). Yet, national frequencies varies greatly and range from
0.6% in South Sudan (1) to 55-65% in Brazil (5).
Recently, increasing evidence has shown that birth delivery mode has an
impact on child health (6). CS is associated to early complications such
as birth asphyxia, respiratory disturbances (7), soft tissue injury (8),
and to neurological and psychological complications such as autism
spectrum disorders (9), ADHD (10), psychosis (11), anxiety, depression,
and sleep disturbances (12). Notable CS-associated late-term
complications for the child includes implications of the immune system:
systemic connective tissue disorders, juvenile arthritis (13),
inflammatory bowel disease, immune deficiencies, asthma (14, 15), sepsis
(16), type 1 diabetes (14), celiac disease (17), and autoimmune diseases
(12).
Compared to infants delivered vaginally, a delivery by CS is thought to
alter the short-term immune response in new-borns by variation of
bacterial colonization of the intestinal tract, due to lack of exposure
to the vaginal and anal microbiota during delivery (18, 19). Further,
the level of foetal stress during CS is lower compared to vaginal
delivery (VD), as both the initiation of birth and the contractions
during VD may trigger many biological effects (20). Pre-labour CS, i.e.
CS before the onset of labour, are more often associated with several of
the above mentioned complications compared with in-labour CS (7, 11, 13,
14, 17), suggesting that important endocrine, physiological and
biochemical processes in the infant are initiated by labour. Most
biomarker studies reported regarding CS versus VD have excluded cases
with in-labour CS, thus the studies cannot explain if the differences
found are due to the surgery or the lack of labour.
Infant males are known to be more fragile due to yet unknown biological
mechanisms (21); they are more often prematurely spontaneously aborted
(22), born premature or late, stillborn, have a higher infant mortality,
and are also more often delivered by CS (23).
Accordingly, we aimed to explore the delivery mode’s effects on the
immune system and brain per se of the infants, by measuring
inflammatory, stress, growth, and neurotrophic biomarkers in more than
7000 neonatal dried blood spot samples (DBSS). Further, we wanted to
elucidate potential gender- and gestational age-dependent differences of
the biomarker levels.