Interpretation
The observed progressive increase in cortisol levels during pregnancy is
consistent with previous evidence of increased maternal mean cortisol
level from about gestational week 25 - 28 as assessed by monthly
measurement of cortisol in saliva 32. Our present data
indicate a slightly earlier increase of cortisol concentrations during
pregnancy compared to previous studies as we found increased cortisol
levels as early as gestational weeks 18- 21 16. This
echoes the benefit of using HCC which reflects the average cortisol
concentrations over extended periods of time. The previously established
transient increase in cortisol levels associated with labour and the
subsequent decrease during the subsequent four days33-34 was not evident in our results. This was
expected, as each measurement covers one month which makes short-lived
fluctuations difficult to measure using hair extracts, and the hair
sample taken during labour also included one week before until three
weeks after childbirth. Hence, the elevation of cortisol associated with
labour was probably outweighed by the downswing in cortisol in the first
three postpartum weeks, in agreement with prior findings33, 35. In our study, the cortisol levels at the first
three months postpartum remained slightly higher than in the second
trimester, consistent with earlier reports of prolonged cortisol
elevation for two to three postpartum months 36-38.
This is in accordance with the reported suppressed dexamethasone test up
to six weeks postpartum and blunted ACTH response to CRH up to 12 weeks
postpartum 39 suggesting a slow restoration of the HPA
system functions. It seems possible that ACTH has a role in the observed
slow normalisation of cortisol level postpartum.
The present finding of higher cortisol levels among primiparous women in
line with prior reports may reflect these women’s worries, anxiety and
stress about the upcoming labour 21-22, 40-42. It is
notable that the tendency for slowly escalating cortisol levels observed
between weeks 14 and 25 is broken thereafter in multiparae, and the
cortisol level becomes lower in the third month before childbirth, and
then increases again following the same pattern as for primiparae but
remaining lower. The explanation for this could be a more rapid
inhibition of the mothers´ hypothalamic secretion of CRH by the placenta
CRH secondary to adaptive processes during the longstanding inhibition
during previous pregnancies. The influence of parity on the cortisol
level vanished directly after the childbirth and remained that way,
consistent with previous observations on salivary cortisol levels22.
The postpartum cortisol levels, were not related to those in the former
part of the second trimester but rather to those from about GW 18 until
childbirth, a period when the placenta CRH is becoming more dominant in
the regulation of the rising cortisol level 32. This
suggests that the HPA-axis has not fully normalised in the first three
postpartum months but is still under the influence of pregnancy-related
HPA alterations.
Taken together, the results suggest that the HPA axis may respond
differently to the placenta production of cortisol in multiparae. One
explanation could be that the negative feedback system is more prepared
and suppresses the cortisol production of the adrenal cortex quicker and
more effectively secondary to the initiation of cortisol placenta
production. Such a theory would not only explain the lower concentration
of cortisol in multiparae but also the lack of association between
cortisol levels in GW 14 -17 and the levels found in the periods when
placenta production has started. Similarly, in primiparae, the
concentrations are dominated for longer by the woman’s own secretion,
thereby explaining the closely related monthly cortisol levels of the
second trimester and the lack of relation to the levels found in the
third trimester.
Conclusion
Monthly measurements of HCC appear to closely mirror the activity of the
HPA-axis during pregnancy. Increasing cortisol concentrations were found
during pregnancy, with a decrease three months prior to childbirth in
multiparae. The results suggest a quicker suppression of the
hypothalamic CRH production by placenta CRH in multiparous women.