Length of the third stage of labor at term pregnancies is shorter if placenta is located at fundus: prospective study

AIM: To investigate how the location of the placenta at term pregnancies affects the duration of the third stage of labor and to discuss the possible mechanisms affecting the duration of the third stage. We believe that this is the first prospective study comparing the duration of the third stage of labor according to placental location. METHODS: The placental implantation was determined as anterior (n = 78), posterior (n = 59), or fundal (n = 64) by ultrasound, in 201 women with singleton pregnancies. After delivery of the newborn, oxytocin infusion was routinely given. Duration of the third stage of labor was compared by anova. P < 0.05 was determined as significant. RESULTS: The duration of the third stage of labor was 10.36 +/- 5.94 min, 10.44 +/- 5.35 min, and 8.12 +/- 4.25 min with placentas located anteriorly, posteriorly, and fundal, respectively. The length of the third stage was significantly shorter in the fundal placenta group. CONCLUSION: In this study, the length of the third stage of labor was approximately 2 min shorter with placentas located at the fundus compared to the other two groups. The mechanism responsible for shorter duration may be the bipolar separation of fundal placentas in contrast to usual unipolar down-up separation of anterior or posterior placentas. Another contributing factor may be the use of oxytocin infusion for the management of the third stage, however this should be investigated by further studies by using real time ultrasonography.     

Study of the third stage of labor by color Doppler sonography

We wanted to evaluate whether improvement in ultrasound equipment in the last 5 years altered our perception of the phases of placental separation during the third stage of labor. We also investigated the influence of active management on the third stage of labor after sonographically verified placental separation. Between January and November 2001, the third stage of labor was examined in 55 women at 37-41 weeks of gestation by color Doppler sonography. The duration of blood flow between the myometrium and the placenta, the latent phase, the detachment phase, and the expulsion phase were measured and compared with the corresponding values of an earlier cohort of 57 patients investigated between November 1994 and August 1995. In the later cohort, both the duration of maternal blood flow and the detachment phase were significantly longer than in the earlier cohort (33 s +/- 48 s vs 0 s, P<0.0001 and 56 s+/-45 s vs 37 s+/-21 s, P<0.01, respectively), whereas the latent phase was significantly shorter (101 s+/-87 s vs 213 s+/-180 s, P<0.0001). There was no statistically significant difference in the length of the expulsion phase or the third stage of labor. The later cohort showed a statistically significantly more frequent multiphasic placental detachment ( P<0.05). Improvement in ultrasound equipment resulted in an earlier detection of the onset of placental separation, leading to a shorter latent phase and consecutively increased duration of the detachment phase, whereas the total duration of the third stage of labor remained unchanged. Furthermore, increased sensitivity of Doppler sonography led to a longer visualization of blood flow between the myometrium and the placenta in the normal third stage of labor.     

Oral misoprostol for the prevention of primary post-partum hemorrhage during third stage of labor

AIM: To assess the effectiveness of oral misoprostol compared with methylergometrine in the prevention of primary post-partum hemorrhage during the third stage of labor. METHODS: This was a randomized controlled trial of 864 singleton low-risk pregnant women. The outcomes were total blood loss, duration of the third stage of labor and peripartal change in hematocrit. Comparisons were by the chi2-test and Student t-test. Relative risks were calculated for side-effects profile. A P-value of less than 0.05 was statistically significant. RESULTS: The biodata of all the participants were similar. The mean blood loss for the misoprostol and methylergometrine groups was 191.6 +/- 134.5 mL and 246.0 +/- 175.5 mL, respectively (95% CI: -79.3 to -39.5 mL). The mean duration of the third stage of labor was 19.6 +/- 2.4 min and 9.4 +/- 3.3 min in the misoprostol and methylergometrine groups, respectively (95% CI: 9.82-10.58 min). More subjects had blood loss >500 mL, 42 (9.7%) versus 6 (1.4%), and peripartal hematocrit change greater than 10%, 38 (8.8%) versus 5 (1.2%), in the methylergometrine group than in the misoprostol group, respectively. Also, more subjects received additional oxytocic in the methylergometrine group, compared to the misoprostol group (80 [18.5%] versus 33 [7.6%] patients, respectively). CONCLUSIONS: Orally administered misoprostol was more effective in reducing blood loss during the third stage of labor than intramuscular methylergometrine. However, there were more subjects in the misoprostol group in whom duration of the third stage of labor was greater than 15 min and who also had manual placental removal than in the methylergometrine group.     

A double-blinded, randomized controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage

OBJECTIVE: The objective of this study was to compare the administration of oxytocin at the beginning and end of the third stage of labor for the prevention of postpartum hemorrhage. METHODS: Patients with documented singleton pregnancies were randomly assigned to two groups. The first received 10 units of oxytocin intramuscularly at delivery of the anterior shoulder of the fetus and an identical appearing placebo injection following delivery of the placenta. The second received the opposite medication sequence. The study was double blinded. Blood loss was measured by weighing all fluids collected, visual estimation, and serial blood counts. RESULTS: 27 women received oxytocin at the delivery of the fetal shoulder and 24 after the placenta. Oxytocin given after placenta delivery resulted in lower blood loss (345 vs. 400 ml, p = 0.28), lower collection bag weight (763 vs. 833 g, p = 0.55), lower change in HgB (-1.26 vs. -1.32 g, p = 0.86), lower DeltaHCT (-3.43 vs. -3.64%, p = 0.85), and a shorter third stage of labor duration (8.6 vs. 9.2 min, p = 0.75). The incidence of postpartum hemorrhage, defined as estimated blood loss >500 ml (0 vs. 14.8%) was significantly lowered with oxytocin following placental delivery (p = 0.049). CONCLUSIONS: In our study, postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery.     

Prolonged third stage of labor: morbidity and risk factors

Although retained placenta is a major cause of postpartum hemorrhage, there is no general agreement regarding when manual placental extraction is indicated to prevent hemorrhage. We sought to determine the following: 1) what duration of the third stage of labor is abnormal, 2) what duration is associated with complications, and 3) what antecedent conditions are associated with prolonged third stage. We studied 12,979 consecutive, singleton vaginal deliveries over an 11-year period. Third-stage duration had a log-normal distribution, with a geometric mean of 6.8 minutes, a median of 6 minutes, and an interquartile range of 4-10 minutes. A third stage of 30 minutes or longer occurred in 3.3% of the deliveries. The incidence of postpartum hemorrhage, transfusion, and D&C remained constant in third stages less than 30 minutes, then rose progressively, reaching a plateau at 75 minutes. The increase in these complications after 30 minutes was observed with both spontaneously delivered and manually extracted placentas. In a logistic regression analysis, factors significantly associated with prolonged third stage included: preterm delivery (odds ratio 3.81), delivery in a labor bed (odds ratio 2.17), preeclampsia (odds ratio 1.76), augmented labor (odds ratio 1.47), and nulliparity (odds ratio 1.45). Because there was no increase in hemorrhage until the third stage exceeded 30 minutes, we suggest that in the absence of bleeding, manual placental extraction is not indicated until 30 minutes have elapsed.     

Effects of induced abortion on the third stage of labor in subsequent pregnancy

The aim of the study was to investigate whether the expulsion of the placenta was delayed among women who had previously undergone induced abortion by suction curettage. We studied the duration of the third stage of labor retrospectively by comparing the third stage of labor, recorded in minutes, between 76 second gravida women with previously induced abortions and 95 second para women with previously uncomplicated pregnancies. The duration of the third stage of labor was also compared among a group of primigravidas and a group of second gravidas with previously induced abortions. We excluded women with previous gynecological disorders (e.g. resulting in curettage of the uterine cavity). All patients included presented normal pregnancies and deliveries resulting in full term (greater than 37 weeks), liveborn infants. By the statistical analysis (analysis of variance and Duncan's test), it could be shown that the 3rd stage of labor lasted significantly longer among women with previously induced abortions (mean: 12 minutes), than among the other groups included in the study (mean: 9 minutes). This discrete difference in length of the third stage of labor need not indicate an altered routine for women, who give birth subsequent to an induced abortion.     

Vascular reactivity to angiotensin II and eicosanoid production in the human placenta from term and preterm pregnancy

Isolated human placental cotyledons from normal term (37-40 weeks of gestation) and preterm (26-36 weeks of gestation) labor were perfused in vitro, and the effect of angiotensin II (ANG II) and its interaction with prostanoids was measured. In the preterm group, ANG II caused greater maximal increases in perfusion pressure than in normal term pregnancies without affecting sensitivity. Also, preparations from normal term pregnancies showed a marked development of tachyphylaxis compared to placentae from preterm pregnancies. Indomethacin (10(-6) M) increased the maximum pressor response to ANG II by 33.6% in normal term, however, in preterm placentas a 39.2% reduction was observed. Infused ANG II 10(-6) M) decreased the concentrations of thromboxane B(2) and 6-keto-PGF(1alpha) in both pregnancy groups, but this effect was not statistically different from the baseline values. In the current study, we show that the placenta of preterm pregnancies in basal conditions produce 7.6 times as much thromboxane as the normal term placenta (2,800+/-470 vs. 366.5+/-62 pg/min, respectively), without significant change in prostacyclin levels (preterm 88.6+/-11.0 vs. Term 100.6+/-30.7 pg/min). These observations provide evidence that the contribution of basally released thromboxane from placental tissue appears to contribute to abnormalities in the regulation of fetoplacental hemodynamics in premature pregnancies.     

Placental implantation as the cause of breech presentation

The ultrasonographic study of 5294 singleton pregnancies between the 16 and 41 gestational weeks and 47 breech presentations at term revealed the following: The placenta was found in the mid-anterior or mid-posterior region of the uterus in 60.9 to 74.0%. In 12.8 to 18.7% of cases, the placenta was implanted in the fundal region before gestational week 28, but thereafter it was found in the cornual region in 13.8 to 19.1%. Of 47 cases with breech presentation at term, the placenta was implanted in the cornual region in 28, in the fundus in 7, in the lateral in 6, and in the mid-anterior or mid-posterior in another 6. In gestational weeks from 16 to 19, the breech presentation was found in 38% when the placenta was implanted in the cornual region, in 50% when it was implanted in the lateral region, 52.8% in the fundus, and 47.2% in the middle, with no significant difference in the incidence of occurrence. However in gestational weeks from 36 to 41, the incidence was 20.2, 6.4, 9.0 and 1.1% respectively and the spontaneous version rate was significantly higher when the placenta was implanted in the middle region than in others (p less than 0.01). The author has concluded that the breech presentation in single pregnancy is caused by the placental position; when it markedly indents and changes the inverted pear shape of the amniotic cavity, the spontaneous fetal cephalic version is inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)     

正常单胎及双胎妊娠妇女子宫动脉血流变化的比较

目的探讨正常单胎和双胎妊娠妇女子宫动脉血流搏动指数（ＰＩ）在孕期中的变化,并研究子宫动脉血流ＰＩ与胎盘位置的关系。方法采用Ｄｏｐｐｌｅｒ超声诊断仪,对９９例正常单胎妊娠和２４例正常双胎妊娠妇女的子宫动脉血流ＰＩ进行了检测,并同时探测胎盘的位置。结果单胎妊娠妇女的子宫动脉血流ＰＩ无论是胎盘侧或是对侧,均随孕周增加至分娩呈逐渐下降,孕２９周时子宫动脉血流ＰＩ平均值０．７８±０．１３。但双胎妊娠妇女的子宫动脉血流ＰＩ值随孕周逐渐下降至孕２７周后,则维持在一平台水平。孕２９周时子宫动脉血流ＰＩ平均值０．６７±０．１１,无论是单胎妊娠还是双胎妊娠,胎盘侧子宫动脉血流ＰＩ值均较对侧为低。结论单胎或双胎妊娠胎盘侧子宫动脉均较对侧血流丰富;且双胎妊娠时子宫动脉血流阻力较单胎为低。     

A randomized controlled trial comparing oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage

OBJECTIVE: To determine if the timing of the administration of prophylactic oxytocin influences the incidence of postpartum hemorrhage caused by uterine atony, retained placenta, and third-stage duration. STUDY DESIGN: Parturients who presented for vaginal delivery were randomized in a double-blinded fashion to receive oxytocin, 20 units in a 500-mL crystalloid intravenous bolus, beginning upon delivery of either the fetal anterior shoulder or placenta. For all patients, the third stage of labor was managed with controlled cord traction until placental expulsion, followed by at least 15 seconds of fundal massage. Patients were excluded if they had a previous cesarean section, multiple gestation, antepartum hemorrhage, or bleeding disorder. RESULTS: A total of 1486 patients were enrolled: 745 in the before-placenta group and 741 in the after-placenta group. The groups were similar with respect to gestational age, fetal weight, labor duration, maternal age, parity, and ethnicity. The incidence of postpartum hemorrhage did not differ significantly between the two groups (5.4% vs 5.8%; crude OR, 0.92; 95% CI, 0.59 to 1.43). There were no significant differences between the two groups with respect to incidence of retained placenta (2.4% vs 1.6%; OR, 1.49; 95% CI, 0.72 to 3.08), or third-stage duration (7.7 minutes vs 8.1 minutes; P =.23). CONCLUSIONS: The administration of prophylactic oxytocin before placental delivery does not reduce the incidence of postpartum hemorrhage or third-stage duration, when compared with giving oxytocin after placental delivery. Early administration, however, does not increase the incidence of retained placenta.     

Increased immunoreactive erythropoietin in cord serum after labor

Since several hours of hypoxemia in fetal animals is sufficient to cause an increase in the plasma erythropoietin level and since labor may be associated with fetal hypoxemia, this study was undertaken to determine if erythropoietin levels in cord blood were higher in fetuses subjected to labor. Two groups of term (37 to 41 weeks) singleton pregnancies were compared: (1) those delivered by elective repeat cesarean section without prior labor (n = 18) and (2) those delivered vaginally (n = 23). Erythropoietin was measured by a radioimmunoassay in which a highly purified human erythropoietin (70,000 U/mg of protein) was used and which has a sensitivity limit of 4 to 5 mU/ml. The mean cord serum erythropoietin level was higher in pregnancies with labor (46 +/- 34 mU/ml, mean +/- SD) compared to those without (26 +/- 10, p less than 0.02). There were no differences between the two groups for maternal age, gestational age, birth weight, infant sex, or Apgar scores. No association of erythropoietin with either gestational age or sex was found. In 11 pregnancies without labor, comparisons were made among simultaneously obtained samples of umbilical arterial plasma, umbilical venous plasma, and mixed cord serum. Although there were no differences between umbilical arterial and umbilical venous plasma erythropoietin levels (21.3 +/- 9.3 versus 19.0 +/- 7.8 mU/ml), mixed cord serum was inexplicably higher (24.4 +/- 9.5 mU/ml, p less than 0.01). We concluded that in uncomplicated pregnancies the duration and intensity of labor are sufficient to cause an increase in the fetal erythropoietin level at delivery.     

Forty weeks and beyond: pregnancy outcomes by week of gestation

OBJECTIVE: To assess pregnancy outcomes at 40, 41, and 42 weeks' gestation when labor induction is done routinely at 42 but not 41 weeks. METHODS: We reviewed all singleton pregnancies delivered at 40 or more weeks' gestation between 1988 and 1998 at Parkland Memorial Hospital, Dallas, Texas. We excluded women with hypertension, prior cesarean, diabetes, malformations, breech presentation, and placenta previa. Labor characteristics and neonatal outcomes of pregnancies at 41 and 42 weeks' gestation were compared with pregnancies that ended at 40 weeks. Women with certain dating criteria had induction of labor at 42 weeks. Gestational age was calculated from the last menstrual period (LMP), sonography when available, and clinical examination. If the fundal height between 18 and 30 weeks was within 2 cm of gestational age, the reported LMP was accepted as correct. Sonogram was used to calculate gestational age if a discrepancy was identified. Statistical analysis consisted of chi(2) and analysis of variance. RESULTS: We studied 56,317 pregnancies: 29,136 at 40 weeks, 16,386 at 41 weeks, and 10,795 at 42 weeks. Labor complications increased from 40 to 42 weeks, including oxytocin induction (2% versus 35%, P <.001), length of labor (5.5 +/- 4.9 versus 8.8 +/- 6. 5 hours, P <.001), prolonged second stage of labor (2% versus 4%, P <.001), forceps use (6% versus 9%, P <.001), and cesarean delivery (7% versus 14%, P <.001). Neonatal outcomes were similar in the three groups, including 5-minute Apgar score less than 4, admission to the neonatal intensive care unit (NICU), umbilical artery pH less than 7, seizures, and perinatal mortality. Sepsis was more frequent in the 42-week group than the other groups (0.1 versus 0.3%, P =. 001), as was admission to the NICU (0.4 versus 0.6%, P =.008). CONCLUSION: Routine labor induction at 41 weeks likely increases labor complications and operative delivery without significantly improving neonatal outcomes.     

Immunohistochemical and biochemical investigations on glutathione S-transferases in the human placenta

GST-pi can be purified as a major molecular form of glutathione S-transferase (GST) in human placenta. In this paper, the localization of GST-pi as well as of neutral and basic GSTs in the first, second and third trimester placental tissues (10, 3 and 14 samples, respectively) was investigated immunohistochemically using antibodies to acidic GST-pi from the placenta, neutral GST-mu and basic GST-I from the liver. Total GST activity was assayed using 1-chloro-2,4-dinitrobenzene as a substrate, and the relative activity and content of GST-pi were determined by activity inhibition test and single radial immunodiffusion, respectively, on 4 first and 5 third trimester placental tissues. The results obtained were as follows. In early placenta, cytotrophoblasts were strongly stained by anti-GST-pi antibody, while in third placenta mainly syncytiotrophoblasts were stained. GST-mu was stained only in syncytiotrophoblast in early placenta, while basic GST-I was weakly stained in the various cells in early to term placenta. Total GST activity in early and term placentas was 5.8 +/- 2.0 units/g of tissue (mean +/- S.D.) and 14.8 +/- 3.4 units/g, respectively. GST-pi relative activities were 90 +/- 4% and 85 +/- 6%, and GST-pi content was 41 +/- 31 micrograms/g and 106 +/- 29 micrograms/g, respectively. These results indicate that GST-pi is a major form of GST and localized mainly in trophoblasts at any developmental stage of the placenta, and it increases with development.     

Second trimester placental location as a predictor of an adverse pregnancy outcome.

OBJECTIVE: To determine if the second trimester placental location is associated with perinatal outcomes. MATERIALS AND METHODS: Observational study of placental location and the subsequent risk of an adverse pregnancy outcome. Placental location was divided into three categories, low, high lateral and high fundal. RESULTS: There were 3336 pregnancies analyzed in this study. Low implantation sites had a greater risk of preterm labor (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.38 to 2.90, P<0.001), preterm delivery (OR 1.86, 95% CI 1.36 to 2.54, P<0.001), fewer fetuses with macrosomia (OR 0.56, 95% CI 0.38 to 0.83, P=0.010) and reduced risk of postpartum hemorrhage (OR 0.56, 95% CI 0.46 to 0.95, P=0.026). High lateral implantations had a greater risk of low 1-min (OR 1.80, 95% CI 1.11 to 2.93, P=0.017) and 5-min (OR 3.49, 95% CI 1.46 to 8.36, P=0.005) Apgar scores. CONCLUSIONS: Low placental implantation was associated with an increased risk of preterm labor, preterm delivery and a reduced risk of postpartum hemorrhage, and of a macrosomic fetus. High lateral implantation was associated with low Apgar scores.     

Uteroplacental blood flow velocity waveforms in the second and third trimesters of normal pregnancy as related to the placenta location

The systolic/diastolic ratios (A/B) of uteroplacental blood flow velocity waveforms as related to the placenta location were investigated by continuous-wave Doppler ultrasound in 67 normal pregnancies at 18-21 weeks, in 111 at 31-33 weeks, and in 34 at 40-41 weeks of gestation. Using real-time ultrasound, the placenta was located laterally in 48%, posteriorly in 30% and anteriorly in 22% of the pregnancies. A/B values decreased slightly with advancing gestational age. With lateral placenta location, statistically significant higher A/B values were found in vessels on the nonplacental side at 31-33 weeks of gestation (2.07 +/- 0.43 versus 1.74 +/- 0.27; p less than 0.05). In the other gestational age groups there were no statistically significant differences between A/B values in the vessels on the placental and nonplacental sides. There were also no differences in A/B values between left and right uteroplacental vessels with anterior or posterior placenta locations in any of the gestational age groups.     

Prediction of duration of active labor in nulliparous women at term

We have assessed the independent predictors of duration of active labor in nulliparous women at term. Using a cohort of 1067 nulliparae in spontaneous labor at > 37.0 weeks with singleton fetuses in vertex presentation, multivariate analysis was used to identify independent predictors of duration of active labor. Duration of active labor was 4.1 +/- 2.4 hours. Stepwise linear regression selected 10 independent predictors of duration of active labor: gestational age at delivery ( P < 0.001), race ( P = 0.014), obstetric risk factors ( P = 0.022), amniotomy ( P < 0.001), fundal height ( P = 0.005), cervical dilation on admission ( P < 0.001), frequency of contractions ( P < 0.001), station of presenting part ( P < 0.001), oxytocin ( P < 0.001), and epidural use ( P < 0.001). A prediction formula incorporating the 10 predictors accounted for 51% of the total variance of the observed duration of active labor. Ten variables are independent predictors of duration of active labor; when incorporated in a prediction formula they account for > 50% of the variability of duration of labor in nulliparous women.     

Minimum cord length that allows spontaneous vaginal delivery

OBJECTIVE: To determine the shortest umbilical cord length that will permit spontaneous vaginal delivery. METHODS: This prospective, observational study included 166 randomly chosen women with no apparent antepartum complications who delivered spontaneously at or beyond 37 weeks. The cord was clamped at the maternal introitus immediately after delivery. The cord segment was measured from introitus to placental insertion. We reviewed a recent fetal scan to identify the placental implantation site (fundal or lateral). RESULTS: The mean cord segment from placental insertion to maternal introitus measured 22.4 cm (95% CI 11-32). The segment was 2.1 cm longer (95% CI 0.4-3.7) when the placenta was implanted at the uterine fundus rather than laterally (p < 0.01, 1-sided t test). An excessively short cord segment (<13 cm) was present in 2 cases (1.2%) with lateral placental implantation. There were no cases of fundal implantation with an excessively short cord. CONCLUSION: The uterine axis and birth canal are not long enough to prevent spontaneous vaginal delivery .in the presence of a short umbilical cord. Placental location does not impede delivery except perhaps when fundal in the presence of an excessively short cord.     

Monoamine oxidase activity in the term human placenta

Using a radioenzymatic assay, placental monoamine oxidase (MAO) activity was measured at term after delivery in normal and high-risk pregnancies where decreases in placental blood flow previously were shown. MAO activity in placentas of healthy controls after spontaneous labor was similar to that after elective cesarean section not in labor (mean +/- SE, 133 +/- 18 versus 100 +/- 15 nmol/min/mg protein, respectively). Compared to controls, there was a significant reduction in placental MAO activity in high-risk pregnancies (chronic hypertension, toxemia, and diabetes mellitus), 71 +/- 14, 69 +/- 22, and 69 +/- 7, respectively (P less than 0.05). These differences also were maintained when data were expressed per total placental weight. Effects of antihypertensive drugs on MAO activity in healthy placental tissue were assessed. In homogenates, both hydralazine and magnesium sulfate reduced enzyme activity, while in explants this was not observed. The effects of certain metabolites (which are elevated in plasma of diabetic patients) on healthy homogenates also were studied. Only butyrate reduced enzyme activity. In conclusion, placental MAO activity in vitro is low in term high-risk pregnancies. This may reduce local metabolic inactivation of catecholamines and serotonin and consequently lead to a decrease in blood flow. Such a direct relationship must be confirmed in further studies.     

The determination of basic fibroblast growth factor (bFGF) in human placental tissue and the changes in bFGF during pregnancy]

The purpose of this study is to develop an assay system for quantification of bFGF in human tissue and to investigate the changes in bFGF content in the human placenta during pregnancy. Sixty-two placental tissue samples from various stages of normal pregnancies were collected. Approximately 28 micrograms bFGF was obtained per 1 kg of placental tissue. The recovery rates were 17.1 +/- 7.4%. The purified samples were confirmed as bFGF by SDS-PAGE and enzyme-linked immunoelectrotransfer blot (EITB) with anti-human bFGF monoclonal antibody. The bFGF readings in the human placenta determined by RIA were 11.81 +/- 2.11 fmol/mg protein (first trimester), 20.45 +/- 4.85 (early second trimester), 9.52 +/- 5.02 (late second trimester), 7.41 +/- 2.07 (third trimester), and 7.75 +/- 1.86 (post trimester). The placental bFGF were significantly high in the early stage of second trimester and declined gradually during the remainder of the pregnancy. The RIA values were correlated closely with the values obtained by bioassay. These results demonstrate that our assay system provides a tool for the quantification of bFGF in biological samples and suggest that bFGF, the active mitogen and angiogenic factor, participates in the formation of the human placenta.