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Dual roles of amniotic fluid nitric oxide and prostaglandin E2 in preterm labor with intra-amniotic infection.

We hypothesized that induction of nitric oxide synthase and cyclo-oxygenase-2 by bacterial products in intra-amniotic infection could increase the production of proinflammatory nitric oxide and prostaglandin E2 (PGE2) and cause preterm labor. Thus, we sought to determine amniotic fluid levels of nitric oxide metabolites (NOx) and PGE2 in preterm labor patients with and without intra-amniotic infection. Amniotic fluid from 13 preterm labor patients with intra-amniotic infection and 24 without intra-amniotic infection were studied. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture. Amniotic fluid was tested for NOx, PGE2, glucose, leukocyte counts, Gram stains, creatinine, pH, and specific gravity. NOx was determined using Griess reagent after reduction of nitrate to nitrite with aspergillus nitrate reductase. PGE2 was measured by an enzyme-linked immunoassay. Both amniotic fluid NOx and PGE2 were normalized by amniotic fluid creatinine. We found that amniotic fluid concentrations of NOx and PGE2 were significantly higher in preterm labor patients with intra-amniotic infection compared to those without intraamniotic infection (NOx: median 1.8 micromol/mg creatinine, range 0.7 to 6.8 vs. 1.3 micromol/mg creatinine, range 0.9 to 2.1, p=0.03; PGE2: median 33.5 ng/mg creatinine, range 0.0 to 1048.6 vs. 0.0 ng/mg creatinine, range 0.0 to 33.6, p=0.004). In addition, amniotic fluid NOx and PGE2 were positively correlated (r=0.343, p=0.0398). We conclude that there may be an interaction between the nitric oxide and prostaglandin pathways in intraamniotic infection. Increased production of amniotic fluid pro-inflammatory nitric oxide and PGE2 may play an important role in the pathogenesis of preterm labor in patients with intra-amniotic infection.

Adolescent↗

Pulsatile administration enhances the effect and reduces the dose of oxytocin required for induction of labor.

Pulsatile administration of oxytocin was compared with continuous infusion of oxytocin for induction of labor in pregnant rats. The dosages consisted of intravenous injections of 0, 2.5, and 5 mU oxytocin every 10 minutes and intravenous infusion of 1 mU/minute of oxytocin in 0.9% sodium chloride. These doses are within the range of endogenously secreted pulses. All treatments began on day 22 at 2 p.m. and continued for 8 hours. Pulsatile administration resulted in a marked reduction in the dose of oxytocin required to induce labor. Using 5 mU pulses, birth was induced with 18.4%, and using 2.5 mU pulses, with 24% of the dose needed using continuous infusion. Parturition was advanced by 12 hours on the average by oxytocin treatment, but no significant differences were observed between the various oxytocin dosage regimens in this regard or in regard to gestation length, induction-delivery interval, duration of delivery, or the proportion of living or dead pups. Significantly more uterine activity was induced with each mU of oxytocin using pulsatile administration than using continuous infusion. There was no evidence for down-regulation of oxytocin receptors during a continuous infusion of oxytocin. We postulate that the greater efficacy of oxytocin pulses to induce uterine activity and delivery in comparison to continuous infusions is due to a more effective stimulation of prostaglandin F2 alpha release from the decidua. The amount of oxytocin needed for induction of labor with 2.5 mU pulses was similar to the decrease in neurohypophyseal oxytocin content during the first stage of spontaneous labor, and uterine activity elicited was also similar to that observed during spontaneous labor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxytocin receptor blockade: a new principle in the treatment of preterm labor?

The concentration of myometrial and decidual oxytocin receptors increases dramatically in normal women in late pregnancy, causing enhanced uterine sensitivity to physiologic levels of oxytocin. Similar increase in myometrial oxytocin receptors has been found in women in preterm labor, indicating a role for oxytocin also in idiopathic preterm labor. A newly synthesized oxytocin analogue, 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin, has been found to be a competitive inhibitor of oxytocin. The present study was conducted to test its efficacy in suppressing uterine contractions during preterm labor in women. Twelve patients with established, uncomplicated preterm labor between 27 and 33 weeks of gestational age were given intravenous infusions of the analogue for 1.5 to 13 hours during continuous external cardiotocographic monitoring. In nine patients inhibition of uterine contractions was achieved and further progression in cervical scores was arrested. In three patients, all at 27 weeks of gestational age, no significant tocolytic effect was observed during a 1.5-hour infusion of the analogue and the patients were then given ritodrine intravenously. No side effects were observed in any of the patients. These preliminary findings support the concept that an increased concentration of uterine oxytocin receptors is an important etiologic factor in uncomplicated preterm labor and therefore oxytocin receptor blockade may be a therapeutic alternative for this condition.

Adult↗

Infection and premature labor.

The possibility that infection can cause premature labor is appealing. If true, antibiotics treat the cause, in contrast to tocolytic agents, which treat symptoms. There is strong evidence that infection is a factor in premature labor. Historical data from the preantibiotic era in patients with pyelonephritis and pneumonia support this. Vaginal bacterial colonization studies and amniotic fluid studies indicate that a portion of women with preterm labor have an identifiable microbiologic profile. Preliminary reports on antibiotic intervention in asymptomatic women and women in premature labor are encouraging. This may be the dawn of a new era in the diagnosis and treatment of preterm labor.

Bacterial Infections↗

Plasma and erythrocyte profiles of nonesterified polyunsaturated fatty acids during normal pregnancy and labor.

This study was undertaken to determine the plasma and erythrocyte profiles of metabolically important nonesterified polyunsaturated fatty acids (PUFA), that is, free fatty acids, in each trimester of pregnancy and in labor. Blood was drawn from patients in the first, second, and third trimester and in labor. Nonesterified polyunsaturated fatty acids were extracted from erythrocytes with chloroform and methanol. The PUFAs from erythrocytes and plasma were then measured in their methylester form using high performance liquid chromatography (HPLC). Plasma levels of all PUFAs were similar in each trimester of pregnancy but levels of linoleic and linolenic acids were higher in laboring patients. Plasma levels of linoleic and arachidonic acid in the n-6 pathway (range 40 to 162 mg/L plasma) were higher than linolenic, eicosapentaenoic, and docosahexaenoic acids measured in the n-3 pathway (range 2.1 to 12.8 mg/L plasma). PUFA levels in erythrocytes were generally higher in the second trimester (range 2.6 to 79.7 mg/100-microL spun erythrocytes). In these erythrocytes, docosahexaenoic acid in the n-3 pathway and linoleic and arachidonic acids in the n-6 pathways were present in the highest amounts. Polyunsaturated fatty acids appear to be absorbed and mobilized in increasing amounts in plasma and erythrocytes with advancing gestational age and labor. This activity appears to be most pronounced in the second trimester. Further investigations into PUFA metabolism and the mechanisms which govern it could lead to a better understanding of the role of these important substances in normal and abnormal pregnancies as well as in the initiation of labor.

Cross-Sectional Studies↗

Temporal changes in rates and reasons for medical induction of term labor, 1980-1996.

OBJECTIVE: This study was undertaken to assess temporal changes in rates and reasons for medical induction of term labor. STUDY DESIGN: A retrospective medical record review was conducted on a population-based cohort of 1293 women with term deliveries. RESULTS: The rate of medical labor induction increased from 12.9% in 1980 to 25.8% in 1995. Stated indications also changed, with a 2-fold increase in induction for postdate gestation, a 23-fold increase in induction for macrosomia, a 15-fold increase in elective induction, and a 22-fold decline in induction for premature rupture of membranes. The average gestational age at delivery of postdate pregnancies declined from 41.9 weeks in 1980 to 41.0 weeks in 1995. By 1995, the average maternal length of stay and the percentage of cesarean deliveries were higher among women with induced labor at term than among those with spontaneous labor at term. CONCLUSION: Induction of term labor has almost doubled in prevalence during the past 15 years. The most common indications are elective induction and postdate pregnancy, often applied to gestations of 40 to 41 weeks' duration.

Adult↗

Misoprostol induction of labor among women with a history of cesarean delivery.

OBJECTIVE: Several reports have appeared of uterine rupture among women with a history of cesarean delivery who received misoprostol for induction of labor. A recent review suggested a uterine rupture rate of almost 6%, but the experience at our institution did not seem to reflect this high complication rate. This study was undertaken to compare complications of labor induction with misoprostol between women with a history of cesarean delivery and women without uterine scarring. STUDY DESIGN: A computerized database was used to select women with a viable fetus who underwent induction of labor with misoprostol during the period from January 1996 through December 1998. Patients were given 50 microg misoprostol every 4 hours. Women with a history of cesarean delivery were retrospectively compared with those without uterine scarring. RESULTS: A total of 425 women were given misoprostol for induction of labor: 48 had a history of cesarean delivery and 377 did not. Women with a history of cesarean delivery were more likely to be delivered abdominally (56% vs 28%; P <.04). Among women with a history of cesarean delivery, women who had a history of vaginal birth after cesarean were more likely to be delivered vaginally (92% vs 42%; P =.003). There was no difference in the overall rate of complications (2% with scarring vs 3% without scarring). There were no uterine ruptures. However, the previous cesarean group was more likely than the unscarred group to have blood loss >500 mL (38% vs 22%; P <.03). Although the incidences of fetal distress were similar, neonates born to women in the previous cesarean group were more likely to have an Apgar score <7 at 5 minutes (13% vs 5%; P <.04). CONCLUSION: Misoprostol induction of labor in women with a history of cesarean resulted in a higher rate of cesarean delivery than was seen among women without uterine scarring but was not associated with a higher incidence of complications. There were no uterine ruptures in either group.

Cesarean Section↗

Abnormal fetal heart rate tracing patterns during the first stage of labor: effect on perinatal outcome.

OBJECTIVE: The purpose of this study was to evaluate perinatal outcomes of infants who had pathologic fetal heart rate tracings during the first stage of labor, in comparison with pregnancies with normal tracings. STUDY DESIGN: The perinatal outcomes of 301 infants born at 37 to 42 weeks of gestation with pathologic fetal heart rate patterns during the first stage of labor were compared with 300 infants with normal fetal heart rate tracing patterns. The data were collected prospectively. Tracings were interpreted with the use of the National Institute of Child Health and Human Development fetal heart rate monitor guidelines. RESULTS: Hydramnios (odds ratio, 7.68; 95% CI, 1.75%-33.63%), oligohydramnios (odds ratio, 2.74; 95% CI, 1.01%-7.39%), and the presence of meconium-stained amniotic fluid (odds ratio, 1.91; 95% CI, 1.03%-3.3%) were independent factors that were associated with pathologic fetal heart rate monitoring during the first stage of labor in a multivariable analysis. The occurrences of umbilical arterial pH of <7.20, a 1-minute Apgar score of <7, a base deficit of 12 mmol/L or higher, and operative deliveries were significantly higher in the study group as compared with subjects with normal fetal heart rate monitoring. Late decelerations and severe variable decelerations (<70 bpm) during the first stage of labor were independent risk factors (odds ratio, 17.5; 95% CI, 1.61%-185.7% and odds ratio, 3.9; 95% CI, 1.36%-11.7%, respectively) that were associated with fetal acidosis (determined by both pH of <7.2 and a base deficit of 12 mmol/L or higher) in a multiple logistic model, controlled for hydramnios, oligohydramnios, meconium-stained amniotic fluid, augmentation by oxytocin, nulliparity, duration of first stage of labor, and birth weight. CONCLUSION: The operative delivery rate was higher among patients with abnormal first-stage fetal heart rate patterns. Late decelerations and severe variable decelerations were significant factors associated with fetal acidosis.

Apgar Score↗

Comparative efficacy and cost of the prostaglandin analogs dinoprostone and misoprostol as labor preinduction agents.

OBJECTIVE: The purpose of this study was to compare the relative efficacy and cost of three commercially available prostaglandin analogs, misoprostol (Cytotec), dinoprostone gel (Prepidil), and dinoprostone insert (Cervidil), as labor preinduction agents. STUDY DESIGN: One-hundred eleven women with an unfavorable cervix who underwent labor induction were assigned randomly to receive either misoprostol 50 microg every 6 hours for two doses, dinoprostone gel 0.5 mg every 6 hours for two doses, or dinoprostone insert 10 mg for one dose intravaginally. Twelve hours later, oxytocin induction was initiated per standardized protocol. Efficacy and cost of the labor preinduction/induction with the study treatments were compared. RESULTS: Mean Bishop score change (+/-SD) over the initial 12-hour interval was significantly greater in the misoprostol group (5.2 +/- 3.1) compared with the dinoprostone insert (3.2 +/- 2.3) or the dinoprostone gel groups (2.2 +/- 1.3, P <.0001). The proportion of women who reached complete dilation (68.4%, 50.0%, 51.4%, respectively; P =.14) and who were delivered (60.5%, 47.4%, 40.0%, respectively; P =.10) within 24 hours of the initiation of induction were not significantly different between the misoprostol, dinoprostone insert, and dinoprostone gel groups. Induction-to-delivery intervals, however, were significantly shorter among women who treated with misoprostol (24.0 +/- 10.8 hours) compared with either the dinoprostone gel (31.6 +/- 13.4 hours) or the dinoprostone insert (32.2 +/- 14.7 hours, P <.05). Overall mean cost per patient that was incurred by labor induction was significantly less for the misoprostol group ($1036.13) compared with the dinoprostone insert group ($1565.72) or the dinoprostone gel group ($1572.92, P <.0001). No significant differences were noted with respect to the mode of delivery or to the adverse maternal/neonatal outcome. CONCLUSION: Misoprostol is more cost-effective than the comparable commercial dinoprostone prostaglandin preparations as an adjuvant to labor induction in women with an unfavorable cervix.

Cervical Ripening↗

Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes.

OBJECTIVE: The purpose of this study was to determine whether abnormal placentation (defined as the failure of physiologic transformation of spiral arteries) is present in patients with preterm labor and intact membranes who delivered a preterm neonate. STUDY DESIGN: A cross-sectional study was conducted to examine the histopathologic findings in the placental bed and placenta of patients with preterm labor and intact membranes (n=27), preeclampsia (n=43), and healthy pregnant women at term (n=103). Immunohistochemistry studies with cytokeratin 7 and periodic acid-Schiff were used to detect trophoblast and fibrinoid, respectively, and diagnose the failure of physiologic transformation of the spiral arteries. RESULTS: The mean percentage of spiral arteries with failure of physiologic transformation in the myometrium was significantly higher in patients with preterm labor and preeclampsia than in normal pregnant women at term (P=.0004 and P<.0001, respectively). Similar findings were observed in the decidual segment of spiral arteries within the placental bed (P=.001 and P<.0001). In contrast, the mean percentage of the spiral arteries with failure of physiologic transformation in the decidua of the basal plate was not significantly different between patients with preterm labor and normal pregnant women (P=.17). CONCLUSION: Failure of physiologic transformation of the spiral arteries in the myometrial and decidual segments of the placental bed is frequent in patients with preterm labor and intact membranes.

Adult↗

Opposing actions of prostaglandins and oxytocin determine the onset of murine labor.

Prostaglandins (PGs) have been recently proven essential for parturition in mice. To dissect the contributions of the two cyclooxygenase (COX) isoforms to the synthesis of PGs during pregnancy, we have characterized the parturition phenotype of COX-1-deficient mice. We find that mice with targeted disruption of the COX-1 gene have delayed parturition resulting in neonatal death. Results of matings of COX-1-deficient females with COX-1 intact males, and blastocyst transfer of COX-1-deficient or -intact embryos into wild-type foster mothers, proved necessity and sufficiency of maternal COX-1 for the normal onset of labor. COX-1 expression is induced in gravid murine uterus and by in situ hybridization; this induction is localized to the decidua. Measurement of uterine PGs further confirmed that COX-1 accounted for the majority of PGF2alpha production. To evaluate the interaction of PGs with oxytocin during murine labor, we generated mice deficient in both oxytocin and COX-1. Surprisingly, the combined oxytocin and COX-1-deficient mice initiated labor at the normal time. COX-1-deficient mice demonstrated impaired luteolysis, as evidenced by elevated serum progesterone concentration and ovarian histology late in gestation, and delayed induction of uterine oxytocin receptors. In contrast, simultaneous oxytocin and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2alpha production. These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation.

Animals↗

The effect of treating bacterial vaginosis on preterm labor.

OBJECTIVE: Multiple studies suggest that bacterial vaginosis (BV) causes preterm labor; yet its routine treatment remains controversial. In order to help to elucidate this controversy, we performed a thorough review of studies with levels of evidence ranging from I to II-II. METHODS: We searched for all of the studies from the years 1994 to 2001 via Medline's database, including MD Consult and Ovid Mednet. RESULTS: Several trials discovered a decrease in the incidence of preterm labor when BV was treated, but most of those trials were performed on women with a history of preterm labor. However, the majority of trials reviewed advise against treatment of a general low-risk obstetric population, as there was no significant decrease in preterm labor. CONCLUSIONS: Therefore, based on the above studies and the current guidelines of the Centers for Disease Control and Prevention (CDC), treating pregnant women in high-risk populations who are diagnosed with BV provides the clinician with an opportunity to possibly prevent preterm labor in this population. In nulliparous women without a history of preterm birth, treatment is recommended if other risk factors are present (e.g. gonorrhea or chlamydia). However, in the general low-risk populations, routine screening is not indicated.

Adult↗

Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation?

OBJECTIVE: To determine whether broad-spectrum antibiotic administration to patients with preterm labor and intact membranes is associated with an improvement in neonatal and maternal outcomes, particularly in patients with microbial invasion of the amniotic cavity (MIAC) or endocervical inflammation (ECI). METHODS: A prospective clinical trial was conducted in which women in premature labor were alternately allocated to receive either antibiotics or placebo, and information about MIAC and ECI collected. Eighty-four pregnant women between 24 and 34 weeks of gestation with spontaneous preterm labor were enrolled. Exclusion criteria were cervical dilatation greater than 3 cm, clinical chorioamnionitis, abruption, rupture of membranes, vaginal bleeding, and several additional fetal and maternal conditions that may influence perinatal outcome. Amniocentesis was offered to all patients and the cervix and vagina were sampled for microbiological and cytological studies. Eligible patients were allocated to receive either clindamycin-gentamycin or placebo for 7 days. Corticosteroids and tocolysis with beta-adrenergic agents were used according to the standard management of our institution. MIAC was defined as the presence of a positive amniotic fluid culture obtained by trans-abdominal amniocentesis. ECI was diagnosed when a significant increase in the white blood cell count of the endocervical secretions was found. A composite neonatal morbidity/mortality outcome was created, including severe neonatal morbidity (respiratory distress syndrome, asphyxia, sepsis, pneumonia, intraventricular hemorrhage) and mortality. RESULTS: Thirty-nine women received antibiotics and 40 received placebo. The prevalence of ECI and MIAC in both groups was comparable (antibiotic group ECI 61.5% (24/39) and MIAC 20.5% (8/39); placebo group ECI 62.5% (25/40) and MIAC 20% (8/40); p > 0.05). Overall, there were no significant differences in maternal infections and composite neonatal outcomes between antibiotic and placebo groups. Women who received antibiotics had a lower rate of subsequent rupture of membranes compared to patients who received placebo (2.6% (1/39) vs. 25% (10/40), respectively; p = 0.007). A sub-analysis showed that among patients with ECI, antibiotic administration was associated with a lower rate of composite neonatal morbidity/mortality outcome compared to those who received placebo (4.2% (1/24) vs. 28% (7/25), respectively; p < 0.05). This association was also present in patients with ECI without MIAC (0% (0/16) vs. 27.8% (5/18); p < 0.05), but not in patients with ECI and MIAC (antibiotic group 12.5% (1/8) vs. placebo group 28.6% (2/7); p > 0.05). CONCLUSIONS: The combination of antibiotics used in this study did not improve maternal or perinatal outcome in patients with preterm labor and intact membranes. Further studies are required to determine if women with endocervicitis presenting with preterm labor and intact membranes may benefit from antibiotic administration.

Administration, Oral↗

ST analysis of the fetal electrocardiogram during labor: Nordic observational multicenter study.

OBJECTIVE: To assess the diagnostic power of cardiotocography (CTG) plus the ST interval of the electrocardiogram (ECG) clinical guidelines with combined fetal heart rate and ST waveform analysis of the fetal ECG recorded during labor, to identify an adverse labor outcome (neonatal neurological symptoms and/or metabolic acidosis). STUDY DESIGN: An observational, multicenter study was undertaken in 12 Nordic labor wards. A total of 573 women in labor were monitored using a prototype of the STAN S 21 recorder with fetal ECG data and computerized ST analysis. RESULTS: Fifteen cases of intrapartum fetal hypoxia identified from neurological neonatal symptoms and/or cord artery pH < 7.05 with base deficit in extracellular fluid > 12.0 mmol/l were recorded. All these cases were identified by CTG + ST clinical guidelines. Five developed neonatal symptoms and had ECG abnormalities during the first stage of labor and, of the remaining ten, eight showed ST changes during active pushing in the second stage. Another eight cases had acidemia only and normal neonatal outcome. Seven of these displayed CTG + ST abnormalities. The high sensitivity of CTG + ST to predict fetal acidosis was associated with a marked increase in positive predictive values compared with conventional CTG. CONCLUSION: The STAN clinical guidelines identify fetuses at risk of intrapartum asphyxia.

Acidosis↗

Induction of labor with vaginal prostaglandin E2.

OBJECTIVE: To determine the effects of labor induction with vaginal prostaglandin E2 (PGE2) on mode of delivery in post-term pregnancies and to identify possible predictors of successful vaginal delivery. METHODS: The study group consisted of 211 women with post-term pregnancy (gestational age more than a full 41 weeks) admitted for induction of labor with vaginal applications of PGE2. Findings were compared with women with spontaneous onset of labor (group 2, n = 510). Women with previous Cesarean section were excluded from both study and control groups. RESULTS: The rate of Cesarean section was significantly higher in the study group (19.4%) than in the control group (9%). A logistic regression model was used to control for maternal and gestational age, gravidity, parity, nulliparity rate, number of used PGE2 tablets, oligohydramnios and delivery weight as possible predictors of Cesarean section (R2 = 0.56, p < 0.001). On stepwise analysis, nulliparity (OR 45.2, 95% CI 2.93-695.5), number of PGE2 applications (OR 2.79, 95% CI 1.04-7.52) and maternal age (OR 1.23, 95% CI 1.01-1.50) were independently and significantly associated with increased risk of Cesarean section. PGE2 induction was a significant independent predictor of Cesarean section (OR 2.3, 95% CI 1.3-3.9). CONCLUSION: PGE2 induction of labor was successful in approximately 80% of patients with post-term pregnancy, with apparently no serious maternal or fetal complications. Risk factors intrinsic to the patient, and labor induction itself, were the reasons for excess Cesarean deliveries in women with prolonged pregnancies.

Administration, Intravaginal↗

The challenges of informed consent for rapid HIV testing in labor.

BACKGROUND: Although increasing attention has been focused on the adequacy of the informed consent process for participation in research studies, there has been little systematic evaluation of the process, particularly when consent is obtained in the labor and delivery setting. The Mother Infant Rapid Intervention at Delivery (MIRIAD) study is an ongoing multisite study initiated by the Centers for Disease Control and Prevention (CDC) designed to evaluate the feasibility of offering 24-hour counseling and voluntary rapid HIV testing and antriretroviral therapy when indicated to women with unknown HIV status who are in labor. METHODS: To address concerns about obtaining informed consent from women in labor, we have completed focus groups, conducted a pilot of the informed consent process among women in labor, developed flip-charts to enhance comprehension, and plan an ongoing evaluation of the informed consent process throughout the course of the MIRIAD study. RESULTS: In the pilot study, approximately 70% of women were able to state in their own words the purpose and benefits of the research study. Substantially fewer women (25%) were able to state one or more risks of the study. CONCLUSIONS: We hope that the MIRIAD study will make a valuable contribution by defining best approaches for informed consent and will provide guidance when it is necessary to obtain consent from laboring women for crucial interventions.

AIDS Serodiagnosis↗

Stress during labor and delivery and early lactation performance.

The amount of stress experienced by both the mother and fetus during labor and delivery varies considerably and is likely to be different in primiparous and multiparous women. In this study we explored relations between the birth experience and lactation performance of 40 women. Stress hormones were measured in serum or plasma during pregnancy, parturition (cord and maternal blood), and lactation. Milk samples were obtained and breast-feeding frequency was recorded each day during the first 2 wk postpartum. Four outcomes were used as markers of lactogenesis: the time when the subject first felt fullness in the breasts, 24-h milk volume on day 5 postpartum, milk lactose concentration on day 5, and the day of appearance of casein in the milk as determined by gel electrophoresis. There were significant intercorrelations among the outcome variables, except for milk lactose. Compared with multiparous women, primiparous mothers experienced a delay in breast fullness and lower milk volume on day 5. In multiple regression analyses excluding subjects who had cesarean deliveries (n = 5), markers of both fetal and maternal stress during labor and delivery (cord glucose concentration and maternal exhaustion score) were associated with delayed breast fullness and casein appearance; delayed casein appearance was also associated independently with a longer duration of labor. Milk volume on day 5 was lower in women with higher exhaustion scores, and, in multiparous women, those who breast-fed less frequently on day 2. The milk lactose concentration was inversely related to pregnancy weight gain. These results indicate that primiparity, long labor, stress to the mother and fetus during labor and delivery, and elevated cord glucose concentrations are risk factors for delayed lactogenesis.

Adult↗

Prostaglandin e and f receptor expression and myometrial sensitivity at labor onset in the sheep.

Prostaglandins (PGs) play a pivotal role in the initiation and progression of term and preterm labor. Uterine activity is stimulated primarily by PGE(2) and PGF(2alpha) acting on prostaglandin E (EP) and prostaglandin F (FP) receptors, respectively. Activation of FP receptors strongly stimulates the myometrium, whereas stimulation of EP receptors may lead to contraction or relaxation, depending on the EP subtype (EP1-4) expression. Thus, the relative expression of FP and EP1-4 may determine the responsiveness to PGE(2) and PGF(2alpha). The aims of this study were to characterize the expression of EP1-4 and FP in intrauterine tissues and placentome, together with myometrial responsiveness to PG, following the onset of dexamethasone-induced preterm and spontaneous term labor. Receptor mRNA expression was measured using quantitative real-time polymerase chain reaction using species-specific primers. There was no increase in myometrial contractile receptor expression at labor onset, nor was there a change in sensitivity to PGE(2) and PGF(2alpha). This suggests expression of these receptors reaches maximal levels by late gestation in sheep. Placental tissue showed a marked increase in EP2 and EP3 receptor expression, the functions of which are unknown at this time. Consistent with previous reports, these results suggest that PG synthesis is the main factor in the regulation of uterine contractility at labor. This is the first study to simultaneously report PG E and F receptor expression in the key gestational tissues of the sheep using species-specific primers at induced-preterm and spontaneous labor onset.

Animals↗