Human fetal serum cortisol levels related to gestational age: Evidence of a midgestational fall and a steep late gestational rise, independent of sex or mode of delivery

doi:10.1016/0002-9378(82)90579-8

American Journal of Obstetrics and Gynecology

Volume 144, Issue 3, 1 October 1982, Pages 276-282

https://doi.org/10.1016/0002-9378(82)90579-8 Get rights and content

Abstract

Levels of cortisol were determined in umbilical cord serum in the presence and absence of labor at various gestational ages. In the absence of labor, serum cortisol fell (P < 0.025) from 8.4 ng/ml at 15 to 17 weeks to 4 ng/ml at 17½ to 20 weeks, a change which coincides with a rapid drop in relative adrenal weight. By 35 to 36 weeks, the mean levels had risen to 20 ng/ml and there was a further increase between 37½ and 40 weeks (P < 0.01) to a mean level of 45.1 ng/ml. Data obtained at vaginal delivery after the spontaneous onset of labor over the period of 26 to 40 weeks were more variable but showed a similar pattern, with levels about twice those in absence of labor. No differences could be attributed to sex or to the anesthetic used. Thus, there appears to be a rise in the fetal level of cortisol with gestational age in late pregnancy, whether or not labor takes place. This rise is steepest immediately before the normal time of onset of labor and cannot be attributed to the stress associated with labor.

References (18)

B.E.P. Murphy
Cortisol and cortisone levels in the cord blood at delivery of premature infants with and without the respiratory distress syndrome
Am. J. Obstet. Gynecol
(1974)
S. Sybulski et al.
Relationship between cortisol levels in umbilical cord plasma and development of the respiratory distress syndrome in premature newborn infants
Am. J. Obstet. Gynecol
(1976)
S. Sybulski et al.
Cortisol levels in umbilical cord plasma in relation to labor and delivery
Am. J. Obstet. Gynecol
(1976)
P.L. Ballard et al.
Fetal sex and prenatal betamethasone therapy
J. Pediatr
(1980)
M.K.H. Leong et al.
Cortisol levels in maternal venous and umbilical cord arterial and venous serum at vaginal delivery
Am. J. Obstet. Gynecol
(1976)
Murphy, B. E. P.: Umbilical cord serum cortisol levels—A review of the literature. Submitted for...
B.E.P. Murphy
Non-chromatographic radiotransinassay for cortisol: Application to human adult serum, umbilical cord serum, and amniotic fluid
J. Clin. Endocrinol. Metab
(1975)
M. Baden et al.
A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome
Pediatrics
(1972)
E.L. Potter et al.

There are more references available in the full text version of this article.

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Pregnancy results in several modifications in adrenal cortex hormone physiology, but the adrenal medulla synthesis of catecholamines remains mostly unchanged. Placenta produces several hormones, such as progesterone, estrogens, androgens, human chorionic gonadotropin (hCG), corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH); it also serves as a barrier to protect the fetus against high maternal levels of cortisol, androgens, and catecholamines. The increased estrogens during pregnancy promote cortisol-binding globulin synthesis by the liver, which contributes to the increase in total cortisol. Placental CRH and ACTH can also contribute to increasing maternal cortisol by stimulating pituitary ACTH secretion and maternal adrenal steroidogenesis, respectively. Thus, maternal total plasma cortisol increases progressively by 1.5- to 2-fold and free cortisol by 1.3- to 3-fold during pregnancy. Pregnancy is associated with an upregulation of all components of the renin-angiotensin-aldosterone system partly to counteract the effects of progesterone, which acts as a mineralocorticoid antagonist. Total testosterone, free testosterone, and sex hormone-binding glycogen increase during pregnancy, but dehydroepiandrosterone sulfate, a substrate for placental estrogen synthesis, decreases by 50% during pregnancy.
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Previous studies have suggested that phthalates might disrupt fetal steroidogenesis. However, the evidence of the effects of prenatal phthalate exposure across pregnancy on fetal glucocorticoids was insufficient.
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We have shown that prenatal phthalate exposure during early and late trimester disrupted the infant steroidogenesis and these associations might be modified by infant sex. To the best of our knowledge, this is the first study to evaluate phthalate exposure at three trimesters during pregnancy in relation to infant glucocorticoids.
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Pregnancy is one of the defining characteristics of placental mammals. Key in the growth and development of the fetus during pregnancy are the dynamics of glucocorticoids (GCs) and their binding protein,corticosteroid-binding globulin (CBG), which determines how much of the GCs are free and biologically active. Out of more than 5000 species of placental mammals in 19 different orders, our understanding of the dynamics of maternal GCs and CBG during pregnancy is largely limited to the detailed study of 3 groups – sheep, laboratory rodents, and humans. The assumption is often made that what we see in these few species applies to the rest. To examine this generality, we compared patterns of maternal GCs over pregnancy from all placental mammals where data is available: in the blood of 13 species from 5 different orders and in metabolites in excreta in an additional 20 species from 9 orders. We found that maternal free GCs increase by late pregnancy in most taxa. This increase is achieved by either an increase in total GC secretion or a decrease in CBG. A major exception is found in the even-toed ungulates (sheep, cows, etc.) where maternal GCs and CBG remain stable, but where the fetal adrenals mature in late pregnancy and produce the majority of their own GCs. We conclude that patterns of change in maternal GCs and CBG during pregnancy are species-specific but are alternative means to the same end: increased fetal exposure to GCs in late pregnancy, which is essential for development.

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^∗: Career Investigator, Medical Research Council of Canada.

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Human fetal serum cortisol levels related to gestational age: Evidence of a midgestational fall and a steep late gestational rise, independent of sex or mode of delivery

Abstract

Am. J. Obstet. Gynecol

Am. J. Obstet. Gynecol

Am. J. Obstet. Gynecol

J. Pediatr

Cortisol levels in maternal venous and umbilical cord arterial and venous serum at vaginal delivery

Am. J. Obstet. Gynecol

Non-chromatographic radiotransinassay for cortisol: Application to human adult serum, umbilical cord serum, and amniotic fluid

J. Clin. Endocrinol. Metab

A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome

Pediatrics