Maternal Hypothalamic-Pituitary-Adrenal Disregulation during the Third Trimester Influences Human Fetal Responses

Abstract

Maternal peptides from the hypothalamic-pituitary-adrenal (HPA) axis rise during human pregnancy. The effects of circulating maternal adrenocorticotropin (ACTH) and β-endorphin (BE) on human fetal behavior was determined in 135 women during their 32nd week of gestation. Fetal behavior was measured by assessing heart rate habituation to a series of repeated vibroacoustic stimuli. Individual differences in habituation were determined by computing the number of consecutive responses above the standard deviation during a control period. There was no significant relation between levels of ACTH, BE and the rate of fetal heart rate habituation. However, an index of HPA disregulation (uncoupling of ACTH and BE) was related significantly to fetal behavior. Fetal exposure to high levels of maternal BE relative to ACTH was associated with significantly lower rates of habituation. Results indicate that maternal stress and stress-related peptides influence fetal response patterns. It is possible that this influence persists over the life span.

Exposure to Prenatal Psychobiological Stress Exerts Programming Influences on the Mother and Her Fetus

“…With measures of FHR we discovered that fetuses of women with elevated pCRH during the third trimester were less responsive to the presence of a novel stimulus [41]. In a subsequent study, we reported that FHR habituation was delayed when fetuses were exposed to over-expression of maternal endogenous opiates [42]. To evaluate programming influences on the fetus, we assessed the consequences of gestational stress during the early second trimester on fetal behavior in the early third trimester.…”

Timing of fetal exposure to stress hormones: Effects on newborn physical and neuromuscular maturation

“…One of the major placental stress signals in pregnant primates is the peptide corticotropin-releasing hormone (CRH). This peptide plays a key role in the maturation of the fetal hypothalamic-pituitary-adrenal-axis (HPA-axis) and other systems, and coordinates events that underlie both fetal growth and maturation and the time of onset of parturition (Hobel, Dunkel-Schetter, Roesch, Castro, & Arora, 1999;Sandman et al, 2006;Sandman et al, 2003;Sandman et al, 1999b;Wadhwa et al, 2004;Wadhwa, Porto, Garite, Chicz-DeMet, & Sandman, 1998).…”

“…The enzyme 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2) has been isolated in the human placenta and likely accounts for the relatively low transfer of maternal cortisol to the fetus by converting cortisol to its inactive form cortisone (Benediktsson et al, 1997;Bernal, Flint, Anderson, & Turnbull, 1980). 11β-HSD-2 shows steady increases throughout gestation until the last few weeks of gestation when decreases in 11β-HSD-2 are observed (Lopez Bernal, Anderson, & Turnbull, 1982;Murphy & Clifton, 2003;Sandman et al, 2003;Schoof et al, 2001;Shams et al, 1998). Although, 11β-HSD-2 provides protection for the fetus from maternal cortisol, it does not provide complete protection; thus, some maternal cortisol continues to reach the fetus.…”

Psychobiological Stress and Preterm Birth

“…The association between maternal plasma concentrations of CRH and preterm labor/delivery has been examined in many published studies (Markovic et al, 2007). During pregnancy, maternal stress threatens the fetal nervous system (Coe et al, 2003;Insel et al, 1990;Poland et al, 1999;Sanchez et al, 1993;Sandman et al, 2003;Sandman et al, 1999a;Sandman et al, 1999b;Weinstock, 1996) and shortens the length of gestation (Campbell et al, 1987;McLean et al, 1995;Wadhwa et al, 2004;Wadhwa et al, 1998;Wadhwa et al, 1993;Warren et al, 1992;Wolfe et al, 1988). The general findings are that plasma CRH concentrations of women in preterm labor are significantly higher than those of gestationalage matched controls and the rate of change of CRH over gestation is accelerated in women destined to deliver early.…”

“…We discovered that fetuses of women with elevated pCRH during the third trimester were less responsive to the presence of a novel stimulus (Sandman et al, 1999b). In a subsequent study we reported that fetal heart rate habituation was delayed when fetuses were exposed to over-expression of maternal endogenous BE (Sandman et al, 2003). To evaluate programming influences on the fetus, we assessed the consequences of gestational stress during the early second trimester on fetal behavior in the early third trimester.…”