Third trimester POMC disregulation predicts use of anesthesia at vaginal delivery

In a prospective study, third trimester plasma levels of BE and ACTH were determined in 58 women who delivered vaginally. Peptide regulation was compared between subjects who used conduction anesthesia at delivery and subjects who did not. Third trimester levels of maternal BE and ACTH were significantly related; however, the relationship was significant only in subjects who did not receive conduction anesthesia (n = 24) at delivery. The normal co-release pattern between BE and ACTH in subjects receiving conduction anesthesia (n = 34) during birth was uncoupled. The use of conduction analgesia during vaginal delivery was significantly related to a disregulation index created to quantify the BE-ACTH release pattern. Uncoupled ACTH and BE patterns may result from modified control of pro-opiomelanocortin (POMC) expression during pregnancy or unique proteolytic processing of POMC, and may alter pain tolerance during delivery.

predicts use of anesthesia ar vaginal delivery.PEPTIDES 16(2) 187-190, 1995.-In a prospective study, third trimester plasma levels of BE and ACTH were determined in 58 women who delivered vaginally.Peptide regulation was compared between subjects who used conduction anesthesia at delivery and subjects who did not.Third trimester levels of maternal BE and ACTH were significantly related; however, the relationship was significant only in subjects who did not receive conduction anesthesia (n = 24) at delivery.The normal corelease pattern between BE and ACTH in subjects receiving conduction anesthesia (n = 34) during birth was uncoupled.The use of conduction analgesia during vaginal delivery was significantly related to a disregulation index created to quantify the BE-ACTH release pattern.Uncoupled ACTH and BE patterns may result from modified control of proopiomelanocortin (POMC) expression during pregnancy or unique proteolytic processing of POMC, and may alter pain tolerance during delivery.reduce the pain associated with child birth (7,16,29).The significance of elevated levels of coreleased peptides BE and adrenocorticotrophic hormone (ACTH) in maternal plasma and in amniotic fluid between conception and the third trimester of pregnancy is unknown (3,10,11,14,22,32).It is possible that patterns of peptide release during the third trimester prepare the mother for the pain and stress of delivery.The purpose of the present investigation was to determine whether third trimester opiate levels or disruption of coreleased proopiomelanocortin (POMC) products, BE and ACTH, predicted the use of conduction anesthesia during vaginal delivery.
(purple top) vacutainers and placed on ice immediately.All samples were centrifuged at 2000 X g (10 min) within 15 mitt (average was less than 10 mitt) and the plasma was decanted into polypropylene tubes containing 500 KIU/ml aprotinin (Sigma Chemical Company, St. Louis, MO).The samples were stored at -70°C until assayed.

Subjects
Fifty-eight subjects (from an initial sample of 76) who delivered vaginally constituted the study sample.All subjects giving consent were English-speaking adults with a singleton intrauterine pregnancy.Subjects were not excluded based on obstetric risk.Subjects were approached consecutively for participation during the late second trimester of their pregnancy.Informed consent was obtained according to the procedures of the University of California.
Samples were assayed in duplicate (200 ~1 per assay tube).[?]Anti-BE (rabbit) solution (100 ~1) was added to each tube and vortexed.The reaction was initiated by adding one anti-BE (rabbit)-coated polystyrene bead to the assay tube followed by a stationary incubation at room temperature for 20 + 4 h.The beads were then washed twice with phosphate-buffered saline and aspirated to dryness.The labeled antibody complex bound to the solid phase was measured using a Micromedic Isoflex Gamma Counter.The Allegro Beta-Endorphin Immunoassay system has a minimum detectable dose (MDD) of 10 pg/ml (95% confidence limit) with a coefficient of variance (CV) of 4.1% (intra-assay) and 9.0% (interassay) at the highest concentrations expected in the present study.Blood samples (20 ml/draw) were withdrawn at 27-29 weeks of gestation by antecubital venipuncture into siliconized EDTA agnostics).The antiserum employed has < 0.001% cross-reactivity with BE and ACTH fragments.Samples were assayed in duplicate (200 ~1 per assay tube).ACTH ['251]antibody solution (100 ~1) was added to the samples, vortexed, and incubated at room temperature for 20 2 2 h after the addition of an avidincoated bead.The solid matrix was washed with buffered surfactant in phosphate-buffered saline to remove unbound components, and the bound radiolabeled antibody complex was quantified using a Micromedic Isoflex Gamma Counter.The ACTH assay has a MDD of 1.0 pg/ml (95% confidence) with CV of 3.0% (intra-assay) at 35 pg/ml and 7.8% (inter-assay) at 36 pg/ml.
Data reduction for the RIA assays were done by a computer assisted four-parameter logistics program by DeLean, Munson, and Rodbard (9).

Use of Conduction Anesthesia
Maternal medical and obstetric history, prenatal care (gestational age at first prenatal visit, total number of prenatal visits), antepartum risk, labor and delivery parameters, and birth outcome were obtained from medical charts (30).Maternal labor and delivery parameters included mode of delivery and the use of anesthesia during delivery.For the purpose of the present analysis, only subjects with vaginal delivery were included.Use of conduction anesthesia was recorded if the subject received epidural anesthetic (general anesthesia was used with one subject).(25.63 2 28.28 vs. 17 +-21X), this effect was not statistically significant, F(1, 56) = 1.61, p = 0.21).

Third
BE and ACTH are systemically coreleased from the adenohypophysis in healthy adults in response to pain, physical stress (17,26), and psychological stress (19,20,23).The precise mechanism responsible for the regulation of peptides in the third trimester of pregnancy is not known, but it most probably involves hypothalamic control of adenohypophyseal function (21).The placenta acquires endocrine properties (28); however, it probably does not contribute to the disregulation observed among women requiring conduction anesthesia at birth.For instance, although the placenta releases CRF into maternal blood, it is bound and biologically inactive as a source of pituitary stimulation of BE and ACTH (4.33).The placenta also releases BE (5,6), but it is N-acetylated (1,35) and may not be detected by our assay.Uncoupling of BE and ACTH may be related to differential proteolytic processing of PGMC.There is disagreement whether ACTH and BE are translated from the PGMC molecule by different (2) or identical (25) enzymes.The intriguing possibility (2) that ACTH and BE are cleaved by different enzymes provides a mechanism to explain the current findings.The pattern of disregulation observed in this study could result from either decreased activity of the enzyme mPC1 (less ACTH) or increased activity of the enzyme mPC2 (relatively more BE).Because enzyme activity is controlled by genetic and environmental factors (12) the differential regulation of PC1 and PC2 could account for the release patterns observed in this study.
Elevation of BE at birth may provide analgesic relief from the pain of vaginal delivery (7,16,29).Findings from this study suggest that disregulation or uncoupling of the relationship between BE and ACTH during the third trimester prospectively predicted maternal utilization of conduction anesthesia during vaginal delivery.Subjects with normal corelease patterns did not receive anesthesia during birth.It is conceivable that changes in the release pattern of ACTH and BE during the third trimester in some women may alter peptide receptor sensitivity.If opiate receptors are altered by these release patterns during the third trimester, It is possible that third trimester disregulation of BE-ACTH release results from activity of PC1 and PC2 enzymes triggered by environmental factors such as stress (12).Uncoupling of BE and ACTH in women who use conduction anesthesia at birth may be a marker of conditions such as anxiety and stress known to relate to increased pain at birth (24,34).Consequently, determining the pattern of BE and ACTH during the third trimester may provide important information about risk during birth and suggest strategies for the management, care, and pain relief of women at delivery.
at delivery may reflect the stress of birth and may possibly ACTH assay.Plasma levels of ACTH were measured by a commercially available radioimmunoassay (Nichols Institute Di-188 SANDMAN ET AL.

FIG. 2 .
FIG.2.Women who received conduction anesthesia at delivery had a significantly higher disregulation index during the third trimester than women delivering without anesthesia.

TABLE 1
DEMOGRAPHIC CHARACTERISTICS OF THE STUDY SAMPLEthe elevation of BE at term may not be effective in modulating the experience of pain of vaginal delivery, requiring the use of anesthesia in these women.