Dissertation committee:
1) Κουτσιλιέρης Μιχαήλ, Καθηγητής, Ιατρική, ΕΚΠΑ
2) Στεφανίδης Κωνσταντίνος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
3) Μαυραγάνη Κλειώ, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
4) Αρμακόλας Αθανάσιος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
5) Φιλλίπου Αναστάσιος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
6) Σιμοπούλου Μαρία, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
7) Χατζηγεωργίου Αντώνιος, Επίκουρος Καθηγητής, Ιατρική, ΕΚΠΑ
Summary:
Introduction: The homeostatic balance of a living organism may be subject to
disturbance and deregulation. Any environmental factor resulting to this situation may
be defined as a stressor. From a teleological point of view, stress response is a
fundamental requirement for the survival of the human species. Labor is considered an
intense and stressful condition, both for the mother and for the fetus. At the terminal
stages of pregnancy, and as fetal development progresses, the intrauterine environment
is inadequate to fully support further fetal survival, hence the fetus experiences a severe
stressful stimuli. This stressful stimuli is one of the most crucial factors leading to labor
onset. Furthermore, as suggested from studies performed on both humans and animal
models, birth stress is strongly related to the long-term programming of the infant
Hypothalamus-Pituitary-Adrenal (HPA) axis. Several studies in the field provide data
regarding stress hormonal response during vaginal delivery (VD). Nevertheless,
nowadays, approximately one-third of births in the United States of America (USA) are
performed via cesarean section (CS) delivery. Despite the fact that CS is widely
employed as a delivery method, further investigation on the topic of the physiology vis
a vis the CS delivery is required, especially regarding the stress related hormonal
response during this practice.
Aim and Scope: The aim of this study is to provide a comprehensive analysis of the
stress related hormonal response during VD and elective CS, through the evaluation of
the levels of Cortisol, Interleukin 6 (IL-6), Growth Hormone (GH) and Insulin-like
Growth Factor 1 (IGF-1).
Materials and Methods: This prospective observational study was carried out between
May 1, 2016, and September 31, 2018 at the Department of Obstetrics and Gynecology,
“Ippokrateio” General Hospital-Health Center of Kos, Kos Island, Greece, in
collaboration with the Department of Physiology, Medical School, National and
Kapodistrian University of Athens, Greece. The sample size of this study (n=50) was
divided in two groups according to the type of delivery, namely the Vaginal Delivery
Group (VDG) (n=26) and the Caesarean Section Group (CSG) (n=24). The inclusion
criteria for recruitment in the study were the following: healthy women aged 20-43
years old, with hitherto uncomplicated singleton pregnancies and favorable obstetric
history who underwent spontaneous VD or elective caesarean section CS prior to labour
onset, at a gestational age ranging from 36-40 weeks. Previous CS and desire of the
parturient to avoid the prospect of pain related anxiety and distress that pregnant women
may associate with vaginal delivery were the only indications for what is described
herein as an elective scheduled CS. Maternal peripheral blood samples were collected
from all study participants. Women were subjected to blood sampling from the median
antebrachial vein at three different time-points. Time-Point 1 (TP1): samples collected
at the first stage of labor (cervical diameter <6 cm) for VDG or 30 minutes following
admission to the hospital for CSG. Time-Point 2 (TP2): samples collected 120 minutes
following placenta delivery. Time-Point 3 (TP3): samples collected 48 hours following
placenta delivery. Umbilical cord blood samples were collected following placenta
delivery from the umbilical cord vein. Blood serum concentrations of Cortisol,
Interleukin-6 (IL-6), Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1)
were determined by employing standard Enzyme-linked Immunosorbent Assay
(ELISA). The VDG and the CSG groups were statistically compared to each other with
respect to the levels of GH, IGF-1, Cortisol and IL-6 at TP1, TP2 and TP3, respectively.
Furthermore, statistical analysis was performed with regards to clinical data extracted
from medical records namely maternal age, gestational age, Body Mass Index (BMI),
parity, infants’ Apgar score (at 5 minutes), infants’ weight and infants’ sex. All data
analyses were performed using the ‘’R Programming Language for Statistical
Purposes’’.
Results: Maternal age and BMI, newborn’s weight and sex, along with Apgar score did
not differ with statistical significance between the two groups. A statistically significant
difference was observed between the studied groups regarding the gestational age at the
time of the delivery. Women in the VDG gave birth on average at 38.54 weeks of
gestation in comparison to those subjected to elective CS who gave birth at 37.46 weeks
of gestation. No statistically significant difference could be established between the two
groups regarding all the aforementioned hormones in the TP1, indicating a wellcontrolled population. Cortisol levels did not differ at TP3 between the VDG and the
CSG. The CSG presented with lower levels compared to the VDG (129.93±63.10 vs
299.58±74.00, P-value <0.001) at TP2. IL-6 levels were lower in the CSG at TP2
(20.15±7.25 vs 48.70±7.45, P-value <0.001) and higher at TP3 (21.85±6.35 vs
6.86±5.86, P-value <0.001) compared to the VDG. IGF-1 levels were higher at TP2 in
the CSG (230±80.63 vs 173.15±38.12, P-value =0.004) in comparison to VDG, but
were similar between the two groups at TP3 (101.38±80.63 vs 88.19±18.89, P-value
=0.94). No statistically significant difference established between the two groups in any
of the time-points regarding GH levels. Cortisol and IL-6 levels in the umbilical blood
did not present with a statistically significant difference between the two groups. IGF1 and GH levels in the umbilical blood were statistically significantly higher in the
CSG.
Discussion: The rationale of the present research was to examine, and attempt
respective associations between cortisol, IL-6, GH, and IGF-1 levels during either VD
or elective CS, in an effort to provide evidence regarding stress related hormonal
response during VD and elective CS. Data presented herein indicate that CS is a
significantly less stressful procedure for mothers in comparison to VD, and is further
associated with less intense inflammation with an albeit a longer inflammatory response
period. From the infants’ perspective, GH and IGF-1 appear to be increased in the
umbilical cord blood of CS born neonates. Nonetheless, whether this may be attributed
to mode of delivery remains unanswered. This study interestingly brings to literature
data extending to significant perinatal and pediatric interest. Data presented herein
along with previously published data strengthen the scenario that labor physiology
during CS differs vastly considering respective observations during VD. The clinical
end-point of the present study is that, until research reveals the holy grail of optimal
practice, clinicians are bound to abide by current guidelines avoiding CS overuse and
evaluating each case management in the era of personalized medicine, considering that
the physiological response during CS is significantly differentiated in comparison to
VD.
