Physiologic proteinuria in labor and postpartum: The results of the postpartum proteinuria trial (PoPPy).

The urine protein to creatinine ratio (PC) is a sensitive and specific means of diagnosing preeclampsia in the antepartum period, but the 0.3 g protein per gram of creatinine threshold may be non-specific postpartum due to physiologic proteinuria after delivery. The objective of this study was to examine the reliability of PC in labor and postpartum and to determine if PC is affected by mode of delivery. This is the first study of its kind to examine physiologic proteinuria by catheterized PC in individual patients before and after delivery. This single-center prospective cohort study included two groups: term uncomplicated nulliparous patients in labor with epidural analgesia and patients for scheduled repeat cesarean deliveries. Patients with hypertension, antepartum proteinuria, renal disease, gross hematuria, or evidence of infection were excluded. Catheterized pre- and post-delivery urine PC were compared using paired t-tests. 27 and 40 patients were included in the vaginal and cesarean delivery groups, respectively. 52% of the vaginal delivery and 58% of the cesarean delivery groups were positive for proteinuria at the 0.3 g protein per g creatinine threshold. Pre- and post-delivery specimens were significantly different in the vaginal (mean difference 0.28, p = 0.05) and cesarean (mean difference 0.25, p < 0.01) delivery groups. The conclusions reached included the finding that PC measurements are unreliable in the immediate postpartum period regardless of mode of delivery, and utilizing the 0.3 threshold to diagnose preeclampsia in close proximity to delivery would contribute to increased false positive tests.

Maternal urinary metabolites of Di-(2-Ethylhexyl) phthalate in relation to the timing of labor in a US multicenter pregnancy cohort study.

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in consumer and medical products that can cross the placenta, disrupt steroid hormone synthesis, and activate peroxisome proliferator-activated receptor gamma. The authors examined DEHP exposure in relation to the timing of labor in a pregnancy cohort study of 283 women recruited in 4 US states (California, Iowa, Minnesota, and Missouri) between 2000 and 2004. The authors estimated associations between concentrations of DEHP metabolites and gestational age at delivery using linear regression models and associations between DEHP metabolites and clinical outcomes using logistic regression models. After covariate adjustment, women at the 75th percentile of DEHP metabolite concentrations had a 2-day-longer mean length of gestation than women at the 25th percentile (95% confidence interval: 1.4, 3.3). Log-unit increases in mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate concentrations were associated with increased odds of cesarean section delivery (30% and 50% increased odds, respectively), increased odds of delivering at 41 weeks or later (100% and 120% increased odds), and reduced odds of preterm delivery (50% and 60% decreased odds). These data suggest that DEHP may interfere with signaling related to the timing of parturition.

Labor as a bacteriuric event--assessment and risk factors.

OBJECTIVE: Little is known regarding the prevalence of early postpartum bacteriuria. We sought to evaluate the incidence of bacteriuria following labor and to identify risk factors predisposing to this condition. METHODS: Three hundred and fifty parturients were recruited, 301 were included in the analysis. Women receiving antibiotic drugs during delivery were excluded. Urine cultures were obtained from the study group before delivery and prior to discharge. Data regarding management of labor was collected prospectively. RESULTS: Positive urine cultures were present on admission in 5.4% of women, whereas 12.9% had a positive urine culture at discharge (p < 0.003). Bacteriuria was acquired during labor in 12.7% of patients who had negative cultures on admission. Escalating number of digital vaginal examinations (p = 0.04), recurrent bladder catheterization (p = 0.05), duration of epidural anesthesia (p = 0.002), and vacuum delivery (p = 0.02) correlated significantly with an increased risk for acquiring bacteriuria. CONCLUSION: Labor is a bacteriuric event. Iatrogenic interventions can predispose parturients with sterile urine cultures to postpartum bacteriuria.

Urinary cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate changes in spontaneous and induced onset active labor.

BACKGROUND: The aim of this prospective, randomized study was to investigate the changes in urinary cyclic guanosine 3',5'-monophosphate (cGMP) and cyclic adenosine 3',5'-monophosphate (cAMP) between the latent and the active phases of spontaneous and prostaglandin E(1) (PGE(1))-induced labor. METHODS: Seventy singleton pregnant women at 36-41(+) weeks' gestation without signs of fetal distress were enrolled. The first group consisted of 35 pregnant women in whom labor was induced by PGE(1) applied intravaginally. The second group consisted of 35 women who had spontaneous active labor. Clinical data of the two groups were assessed as labor progressed. RESULTS: After the onset of active labor, urinary cGMP/creatinine (U cGMP/Cr) decreased in both groups with the percentage decline of 35.2 and 9.7, respectively, but this difference was only significant in the PGE(1)-induced group (P=0.033). After the onset of active labor, urinary cAMP/creatinine (U cAMP/Cr) decreased in both groups with the percentage decline of 36.5 and 15.6, respectively, but this difference was only significant in the PGE(1)-induced group (P=0.001). The duration of the latent phase was significantly shortened in the PGE(1)-induced group compared with the spontaneous labor group (P<0.05). CONCLUSIONS: Decreased U cGMP/Cr and U cAMP/Cr may be a transition from the latent to the active phase in PGE(1)-induced labor. Our results suggest that U cGMP/Cr and U cAMP/Cr can serve as easily obtained secondary messenger markers of myometrial contractility and cervical ripening at the onset of active labor. The NO-cGMP system and the G-protein alpha-cAMP system in the human uterus may concomitantly contribute to uterine quiescence during pregnancy and show downregulation in U cGMP/Cr and U cAMP/Cr at the initiation of active labor.

Urinary nitric oxide metabolite changes in spontaneous and induced onset active labor.

BACKGROUND: The aim of this prospective, randomized study was to investigate the changes in urinary nitric oxide (NO) metabolite between the latent and the active phases of spontaneous and either prostaglandin E(1) (PGE(1)) or prostaglandin E(2) (PGE(2))-induced labors. METHODS: Eighty-eight singleton pregnant women at 36-41(+) weeks' gestation without signs of fetal distress were enrolled. The first group consisted of 29 pregnant women in whom labor was induced by PGE(1) applied intravaginally. The second group consisted of 29 pregnant women with labor induced by PGE(2) applied intracervically. The third group consisted of 30 women, who had spontaneous active labor. Clinical data of the three groups were assessed as labor progressed. RESULTS: Urinary nitric oxide/creatinine (U NO/Cr) decreased significantly after the onset of active labor in all three groups (p < 0.005), with the percentage decline of 42.2%, 28.6% and 10.1%, respectively. The magnitude of the difference in decline in U NO/Cr after active labor between the PGE(1)-induced and the spontaneous labor group was significantly reduced (p = 0.0047) after adjustment for potential confounders using the generalized estimating equations test (GEE). The duration of the latent phase was significantly shortened in the PGE(1)-induced group as compared with the spontaneous labor group (p < 0.01). CONCLUSIONS: Decreased U NO/Cr may facilitate transition from the latent to the active phase either in spontaneous or induced labors. Our results indicate that U NO/Cr can serve as an easily obtained marker for use in controlling myometrial contractility and cervical ripening at the onset of active labor. The nitric oxide system is present in the human uterus and may contribute to uterine quiescence during pregnancy and show down-regulation in U NO/Cr at the initiation of active labor.

Soluble tumor necrosis factor receptor in serum and urine throughout normal pregnancy and at delivery.

PROBLEM: To determine the concentration of the two soluble tumor necrosis factor receptors (sTNFR), sp55 and sp75, in healthy pregnant women. METHOD: Serum and urine samples were longitudinally collected from a group of pregnant women (N = 53) five times throughout pregnancy. Maternal and umbilical sera were obtained from some of the deliveries (N = 31). The samples were analysed using ELISA based on two monoclonal antibodies (IV4E and 3H5) against the soluble tumor necrosis factor receptors (sp55 and sp75). RESULTS: Serum concentration of sp55 and sp75 were increased in pregnant women compared to that of nonpregnant controls. Concentration of both sTNFRs increased towards term. Labor was associated with further increase of sp55. Concentrations of sp55 and sp75 in umbilical serum were significantly higher than those of maternal serum. Significant correlations were observed between maternal and umbilical sTNFR concentrations. CONCLUSIONS: The current study suggests that pregnancy is associated with an activation of mechanisms regulating the biological activities of TNF.

Enhanced urinary albumin excretion after 35 weeks of gestation and during labour in normal pregnancy.

This study reports on the urinary albumin to creatinine ratio during normal pregnancy, with special emphasis on the pre-delivery and labour periods. Albumin was determined in single voided urine specimens obtained from healthy non-pregnant women (n = 16) and healthy pregnant women (n = 203; Groups A and B, 133 females examined during clinic visits and presentation at obstetric department; Group C, 70 females examined during labour) by radioimmunoassay (RIA). The mean ratio (+/- SD) for albumin/creatinine (A/Cr) in non-pregnant women was 1.46 +/- 0.32 mg mmol-1 Cr. Thus, 2.10 mg mmol-1 Cr (mean+2 SD) was considered to be the upper limit of normo-albuminuria. During pregnancy, 73% of the women (97 out of 133, Groups A and B) excreted less than or equal to 2.10 mg mmol-1 Cr. During the first 35 weeks of gestation, 30 of 34 pregnant women (88%) excreted less than or equal to 2.10 mg mmol-1 Cr, the mean being 0.93 +/- 0.64 mg mmol-1 Cr (median 1.0 mg mmol-1). During 36-42 weeks of gestation, the median A/Cr was 1.93 mg mmol-1 Cr (range 0.43-12.16) and 32 of 99 (32%) had values greater than 2.10 mg mmol-1 Cr, an increase of more than two-fold (p less than 0.031) compared with the first 35 weeks. During labour, 61% of non-haematuric urines (33 of 54, Group C) were greater than 2.10 mg mmol-1 Cr, being 125% greater (p less than 0.006) than that observed during pregnancy. Thus in normal pregnancy, A/Cr is increased during the late period of pregnancy and during labour.

Paired analysis of thromboxane and prostacyclin metabolites in urine from healthy mothers and their children.

Eicosanoids have been implicated in the adaptation of the fetal to the neonatal circulation, but biochemical support for an activation of their synthesis in relation to birth has not been presented. We addressed this by assessing in pairs the excretion of two metabolites of thromboxane A2, 11-dehydro-TxB2 (dTx) and 2,3-dinor-TxB2 (Tx-M), and one metabolite of prostacyclin, 2,3-dinor-6-keto-PGF1 a (PGI-M), in the first voided urine from 13 healthy term neonates and in the immediate pre-delivery urine from their respective mothers. The excretion of dTx was higher (p less than 0.01) in the neonates than in their mothers (7430 and 1330 pg/mg creatinine, respectively), and so was the excretion of Tx-M (3730 and 900 pg/mg creatinine, respectively, p less than 0.001). Also the excretion of PGI-M was higher (p less than 0.05) in the neonates than in their mothers (2550 vs. 1510 pg/mg creatinine). Amniotic fluid contained detectable levels of both Tx-M and PGI-M. These data indicate that activation of platelets takes place in the neonate after separation of the fetal and maternal vascular circuits. The possible physiological implication of such activation requires further studies.

Melatonin in infants and mothers at delivery and in infants during the first week of life.

To evaluate the possible effect of the extreme and permanent changes in the hormonal milieu and in the lighting conditions at birth on the pineal hormone, melatonin (MT), we measured maternal vein and umbilical artery concentrations of MT in 19 parturients, post-partum urinary concentrations of MT in 14 mothers and their infants, and daytime (0800-2000 h) and night-time (2000-0800 h) urinary concentrations of MT and 6-sulphatoxymelatonin in 22 infants during the first 8 days of life. The mean MT concentrations in maternal venous blood and umbilical arterial blood did not differ significantly from each other and there was a positive correlation between them. The same was true for postpartum urinary MT of the mothers and their infants. There was no diurnal rhythm of MT during the first week of life. MT excretion in neonates was 2-5 pmol/12 h (only 1-5% in comparison with adults) and that of 6-sulphatoxymelatonin 150-300 pmol/12 h. In reverse phase high pressure liquid chromatography (HPLC) studies, 84-100% of total MT immunoreactivity was eluted at the same position as synthetic MT, and a small amount of hydrophobic MT-like immunoreactive material was also detected in five of the 10 urine extracts studied. This material (perhaps a novel neonatal metabolite of MT) may be indicative of immaturity of neonatal metabolism of MT although 6-hydroxylation is also functional in neonates. Although infant MT immediately after delivery at least partly reflects maternal MT secretion, our results show that the pineal gland is capable of producing MT at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostacyclin versus thromboxane metabolite excretion: changes in pregnancy and labor.

Urinary TXB2 and 6-keto-PGF1 alpha were measured by high pressure liquid chromatography combined with radioimmunoassay, in order to determine whether or not urinary excretion of 6-keto-PGF1 alpha and TXB2 followed a same pattern in pregnancy and labor. The excretion of 6-keto-PGF1 alpha was higher than that of TXB2 in both non-pregnant and pregnant women, but the ratio between them increased in pregnancy. The urinary excretion of both 6-keto-PGF1 alpha and TXB2 excretion was significantly increased (p less than 0.001) in pregnancy. Labor was associated with a much wider inter-individual variation in the excretion of 6-keto-PGF1 alpha and TXB2 than observed in pregnancy and in non-pregnant women. Also, the ratio between the two compounds varied more in labor than in pregnancy. The data indicate that the urinary levels of these two compounds do not follow a single well-determined pattern in pregnancy and labor.

Changes in urinary 6-keto-prostaglandin F1 alpha excretion during pregnancy and labor.

Urinary excretion of 6-keto-PGF1 alpha was measured by high pressure liquid chromatography and radioimmunoassay at various stages of pregnancy and labor. In the first trimester of pregnancy, urinary 6-keto-PGF1 alpha concentrations were not different from those measured before pregnancy, but they showed a significant increase in the second trimester of pregnancy (p less than 0.001). The levels rose further in the third trimester, although this increase was not statistically significant when compared to levels obtained in the second trimester. There was no evidence for a significant change in 6-keto-PGF1 alpha excretion with the onset of labor. During well-established, progressive labor mean values of 6-keto-PGF1 alpha excretion were about twice as high as before the onset of labor, but the range of values during labor was so wide that there was no statistical difference with values obtained in the second half of pregnancy. It is concluded that the increase in the urinary excretion of 6-keto-PGF1 alpha occurs later in pregnancy than the increase in TXB2 excretion and that labor at term is not associated with marked changes in 6-keto-PGF1 alpha excretion.

Epidermal growth factor in urine of nonpregnant women and pregnant women throughout pregnancy and at delivery.

Human epidermal growth factor (EGF) concentrations were measured by a specific solid phase RIA in random urine samples collected throughout the menstrual cycle of normal menstruating women (n = 8), women with tubal sterilization (n = 6), women taking a low dose oral contraceptive (n = 5), and women throughout pregnancy (n = 52) and delivery (n = 35). There were no differences in EGF concentrations between the proliferative and secretory phases of the menstrual cycle (P greater than 0.05). Normal menstruating women had higher urinary EGF concentrations [mean +/- SE, 37.2 +/- 6.0 micrograms/g creatinine (4.23 +/- 0.68 ng/mumol)] than women with tubal sterilization [32.7 +/- 4.0 (3.71 +/- 0.45)] or women taking a low dose oral contraceptive [19.5 +/- 6.0 (2.21 +/- 0.68)], but the differences were not significant (P greater than 0.05). During pregnancy, urinary EGF concentrations increased linearly from 6-20 weeks gestation (r = 0.76; P less than 0.001), then declined toward term (r = -0.71; P less than 0.001). EGF concentrations in early pregnancy (less than 12 weeks) or at term did not differ significantly from those in normal menstruating women (P greater than 0.05). For women delivering normal, appropriate for gestational age (AGA) infants, there was no correlation between urinary EGF concentrations and fetal weight or sex (P greater than 0.05). Urinary EGF concentrations in women delivering normal AGA infants [52.7 +/- 2.5 (5.98 +/- 0.28); n = 16] did not differ significantly (P greater than 0.05) from those in women with class A/B diabetes [41.9 +/- 2.8 (4.76 +/- 0.31); n = 6] or women delivering twins [45.6 +/- 2.6 (5.18 +/- 0.29); n = 8] with a greater fetoplacental mass. However, women delivering an intrauterine growth-retarded fetus with decreased fetoplacental mass had lower urinary EGF concentrations (24.9 +/- 2.2 (2.83 +/- 0.25); n = 5] than women with normal AGA infants (P less than 0.01). The significance of the rise in the urinary EGF concentration late in the second trimester and lower urinary EGF concentrations in women delivering intrauterine growth-retarded infants is not known, but may reflect an important physiological role for EGF in fetal-maternal hormonal interaction and development.

Urinary free catecholamines--diagnostic application of an HPLC technique to the investigation of neural crest tumours.

Experience in the use of an in-house urinary free catecholamine assay for the investigation of possible neural crest tumours in a District General Hospital laboratory is described. Elevated excretion of catecholamines and vanillylmandelic acid was found in a number of cases including phaeochromocytoma and neuroblastoma. These as well as several other situations in which elevated catecholamine and vanillylmandelic acid values were found are discussed.

Increase in urinary thromboxane excretion during pregnancy and labor.

Urinary TXB2 excretion was measured during pregnancy and labor using high pressure liquid chromatography and radioimmunoassay. From the first trimester onwards TXB2 levels in urine of pregnant women (n = 60) were significantly (p less than 0.001) higher than in non-pregnant women (n = 12) and they increased, albeit not significantly, with advancing gestation. Labor was associated with a two-fold increase in urinary TXB2 excretion. Levels in established labor were significantly higher than at any other time in pregnancy (p less than 0.001), but the levels in incipient labor showed considerable overlap with these in late pregnancy. Thus urinary TXB2, while not necessarily originating from the pregnant uterus, appears to reflect the uterine activity of labor and may be the expression of a general stimulation of prostanoid production during parturition.

Vaginal and abdominal delivery increases maternal urinary 6-keto-prostaglandin F1 alpha excretion.

To study the role of the antiaggregatory and vasodilatory prostacyclin (PGI2) during human delivery, serial urine samples collected from 13 women delivered vaginally and from eight delivered abdominally were assayed for 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, a breakdown product of PGI2) by high-performance-liquid-chromatography and radioimmunoassay. In women delivered vaginally the mean urinary 6-keto-PGF1 alpha concentration was 41.9 (SE 8.3) ng/mmol creatinine, before the onset of labour and increased progressively to a maximum of 186.5 (SE 47.6) ng/mmol creatinine 2 h after delivery irrespective of the use of oxytocin and epidural analgesia. In women delivered by caesarean section under epidural anaesthesia, the urinary 6-keto-PGF1 alpha rose from 33.4 (SE 4.2) ng/mmol creatinine to 2153 (SE 314) ng/mmol creatinine 2 h after section. In both groups the increased levels had fallen by 24 h postpartum to levels below those found before delivery. In neonatal urine 6-keto-PGF1 alpha concentrations were some 12-30 times higher than those in postpartum urine. Thus, vaginal and abdominal delivery is accompanied by significant increases in maternal PGI2 release, perhaps in the myometrium and/or intrauterine tissues. This may be of significance in the regulation of fetoplacental blood flow and in the prevention of intra- and postpartum thrombosis.