The Human Placenta Project: placental structure, development, and function in real time.

Despite its crucial role in the health of both the fetus and the pregnant woman, the placenta is the least understood human organ. Since a growing body of evidence also underscores the importance of placental development in the lifelong health of both mother and offspring, this lack of knowledge about placental structure and function is particularly concerning. Given modern approaches and technologies and the ability to develop new methods, we propose a coordinated "Human Placenta Project", with the ultimate goal of understanding human placental structure, development, and function in real time.

Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome.

OBJECTIVE: Prenatal alcohol exposure results in fetal death and neurobehavioral complications including learning impairment. Previously synthetic peptides derived from activity-dependent neurotrophic factor have been shown to prevent aspects of alcohol-induced damage in pregnancy. The objective of this work was to evaluate whether activity-dependent neurotrophic factor-12 could prevent alcohol-induced damage in a model of fetal alcohol syndrome. STUDY DESIGN: Using a well-characterized model, C57Bl6/J mice on gestational day 8 were treated with placebo, alcohol (30% volume/volume alcohol 0.03 mL/kg), alcohol plus activity-dependent neurotrophic factor-12 30 minutes prior to alcohol, or activity-dependent neurotrophic factor-12 alone. Fetal death was assessed on gestational day 18 (25 litters were evaluated: alcohol, n = 5; placebo, n = 9; alcohol plus activity-dependent neurotrophic factor-12, n = 11). Neonatal behavior tests were performed on postnatal days 1 through 21 with the offspring of 12 dams (alcohol, n = 16; placebo, n = 46; alcohol plus activity-dependent neurotrophic factor-12, n = 23; and activity-dependent neurotrophic factor-12, n = 35). Adult males were tested in the Morris water maze for learning assessment and with the hole punch activity test for exploratory activity. Statistical analysis included Kruskal-Wallis and analysis of variance. RESULTS: Fetal death was greater in alcohol (67% +/- 13%) vs placebo (8.4% +/- 3%, P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced fetal death (2.2% +/- 8.1%) with levels similar to control (P = .12). Alcohol exposure caused a delay in achieving developmental milestones, with alcohol achieving milestones later than all other groups (all P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced milestone delays. In the Morris water maze, the placebo learned, decreasing their latency to find the hidden platform over 70% (P < .01). Alcohol plus activity-dependent neurotrophic factor-12 also significantly learned, with a learning curve not different from placebo (all P > .5) and significantly better than alcohol on days 4, 6, and 7 (all P < .05). Alcohol exposure resulted in significantly less time in hole punch activity (P < .02) than control. Activity-dependent neurotrophic factor-12 pretreatment prevented the alcohol-induced decline, with levels the same as control (P = .1). CONCLUSION: The novel peptide activity-dependent neurotrophic factor-12 prevents alcohol-induced fetal death and developmental and learning abnormalities in a model of fetal alcohol syndrome. This demonstrates that a single treatment with a peptide is efficacious and may be of value in the prevention of alcohol-induced damage.

Gender differences in amniotic fluid cytokine levels.

OBJECTIVE: Placental trophoblast invasion and amniotic fluid cytokine receptor levels have been reported to vary with fetal gender. We investigated whether fetal gender affects amniotic fluid levels of the inflammatory cytokines interleukin (IL)-6 and IL-10 and the pro-angiogenesis cytokine angiogenin. METHODS: Specimens from singleton gestations undergoing mid-trimester amniocentesis for genetic indications were used. Inclusion criteria were (1) outcome information available, (2) no structural or chromosomal anomaly and (3) no conditions associated with preterm delivery. Amniotic fluid IL-6, IL-10 and angiogenin levels were measured by immunoassay. Statistical analysis included the Mann-Whitney U test and Fisher's exact test with p < 0.05 indicating significance. RESULTS: A total of 74 samples were analyzed. Angiogenin levels were significantly lower in amniotic fluid samples from pregnancies with a male than with a female fetus (median (range): 22.2 (5.9-66.4) vs. 32.0 (11.4-159.2) ng/ml, p=0.007), in contrast to no differences in amniotic fluid IL-6 and IL-10 levels (p=0.4 and p=0.1, respectively). In pregnancies with male fetuses delivering preterm (< 37 weeks), angiogenin was also detected at lower levels (p=0.02). There were no gender differences with respect to race, nulliparity or maternal age. CONCLUSION: Angiogenin levels, but not IL-6 or IL-10 levels, are significantly lower in second-trimester amniotic fluid of women with male compared with female fetuses, including those women delivering preterm.

Stillbirth in obstetric practice: report of survey findings.

OBJECTIVE: Stillbirth affects a large portion of the population and results in mortality rates comparable to those of preterm delivery and sudden infant death syndrome combined. Despite the large burden, little information is available to offer patients regarding etiology, treatment or prevention for a subsequent pregnancy. METHODS: We surveyed a sample of Fellows of the American College of Obstetricians and Gynecologists to determine the practice patterns in the management of stillbirth. RESULTS: The majority of Fellows agreed on the definition of stillbirth; however, their approach to treatment and prevention varied. A majority of Fellows believed that research on understanding stillbirth was of national importance. CONCLUSIONS: A comprehensive educational effort to include current knowledge regarding causes and management, standardized diagnostic procedures, death registration and case review is recommended to improve obstetric care of those with a stillbirth.

Optimal thresholds of the lecithin/sphingomyelin ratio and lamellar body count for the prediction of the presence of phosphatidyl glycerol in diabetic women.

OBJECTIVE: To assess the optimal thresholds of the lecithin/sphingomyelin (L/S) ratio and lamellar body count for the prediction of the presence of phosphatidyl glycerol (PG) in diabetic pregnant women. METHODS: We accessed a database of clear amniotic fluid specimens obtained by transabdominal amniocentesis in diabetic women with singleton non-malformed fetuses. PG results were classified as 'absent' or 'present'. Receiver operating characteristic (ROC) curve analysis was constructed of different L/S ratios and lamellar body counts to identify the optimal threshold for prediction of the presence of PG. Sensitivity was defined as the rate of L/S ratio and lamellar body count above specific thresholds among cases with present PG. The false-positive rate was that of L/S ratios or lamellar body counts above specific thresholds among cases with absent PG. Statistical analysis included one-way analysis of variance with post-hoc analysis, with p < 0.05 considered significant. RESULTS: A total of 76 consecutive women were included in the analysis, 74% (n = 56) using insulin and the remainder treated by diet alone. L/S and PG results were both available in 72 women. PG was reported as 'present' in 70% (51/73) of specimens. As expected, there was a significant relationship between L/S ratios and presence of PG (area under the curve = 0.932, p < 0.001). An L/S ratio of > or = 3.0 represented the optimal trade-off between sensitivity (68%) and false-positive rate (6%) in the prediction of present PG. Similarly, there was a significant relationship between lamellar body count values and presence of PG (area under the curve = 0.976, p < 0.001). A lamellar body count of > or = 50 000 represented the optimal trade-off between sensitivity (92%) and false-positive rate (0%) in the prediction of present PG. CONCLUSION: In diabetic pregnant patients, the presence of PG in the amniotic fluid more closely corresponded to an L/S ratio of > or = 3.0 or to a lamellar body count of > or = 50,000.

A planned randomized clinical trial of treatment for mild gestational diabetes mellitus.

OBJECTIVE: A planned study is described which will determine whether a benefit exists for the treatment of mild carbohydrate intolerance during pregnancy. METHODS: A randomized clinical trial of women with mild gestational diabetes will compare perinatal outcomes in those receiving diet therapy and insulin as required versus those randomized to no specific treatment. RESULTS: The primary outcome of this study will be a composite of neonatal morbidity in the treatment and control groups. CONCLUSIONS: A randomized treatment trial of mild gestational diabetes mellitus will clarify whether identification and treatment of mild gestational diabetes mellitus reduces perinatal morbidity. This information will aid in selecting appropriate thresholds for the treatment of gestational diabetes mellitus.

Severe meconium aspiration syndrome is not caused by aspiration of meconium.

Meconium aspiration syndrome can present clinically with different degrees of severity, ranging from a mild form of respiratory compromise to severe forms that may result in perinatal death despite mechanical ventilation or extracorporeal membrane oxygenation. However, advances in our knowledge concerning meconium aspiration syndrome have revealed that most cases of severe meconium aspiration syndrome are not in fact causally related to the aspiration of meconium but rather are caused by other pathologic processes occurring in utero, primarily chronic asphyxia and infection. Proper understanding of the causative processes underlying fetal or neonatal compromise in these cases is essential to direct future research into preventive or therapeutic treatments and for counseling of the parents of an affected child.

Randomized controlled trial of 50 and 100 mcg of misoprostol for induction of labor at term.

To compare the safety and efficacy of two different regimens of misoprostol for labor induction at term, we conducted a randomized controlled trial on women presenting for induction of labor at > or =37 weeks' gestation. Eligible women were randomized to receive intravaginal misoprostol 50 microg every 4 h or 100 microg every 6 h until any of the following: 1) adequate contraction pattern (3 contractions/10 min); 2) dilatation >3 cm; 3) artificial rupture of membranes; or 4) signs of uterine hyperstimulation. Use of oxytocin during labor was at the discretion of the managing clinician. The main outcome variable considered for analysis was cesarean section rate. Secondary outcome measures were induction to delivery interval and neonatal outcome (Apgar scores, meconium staining, and umbilical artery pH). A total of 58 women were randomized to receive either misoprostol 100 microg (n=26) or 50 microg (n=32). The 100 and 50 microg groups had similar mean Bishop's scores at induction (4.0+/-2.3 vs 4.1+/-2.2, p=0.87), rates of nulliparity, use of epidural anesthesia, and oxytocin augmentation. The number of doses of misoprostol used was similar in the two groups (1.4+/-0.6 vs 1.8+/-1.2). The mean+/-standard deviation time to delivery (hours) (11.9+/-7.3 vs 14.3+/-9.6 h, p=0.30) and cesarean section rate (35% vs 19%, p=0.30, relative risk: 1.8, 95% confidence interval 0.7-5.4) were not different in the 100 vs 50 microg group. Power analysis demonstrated that 132 women would be required in each group to achieve statistical significance in the primary outcome measure (alpha=0.05, beta=0.80). Similarly, rates of 5-minute Apgar scores <7 (4% vs 3%, p=1.0), and of meconium passage (17% vs 25%, p=0.73) were not significantly different between the two groups.

Optimization of cytokine stability in stored amniotic fluid.

OBJECTIVE: Many studies use stored amniotic fluid samples to assay cytokines and other proteins for outcome-based research; however, there is little information on the optimal methods of storage. The objective of our study was to evaluate cytokine stability in amniotic fluid stored at different temperatures both with and without a proteolytic enzyme inhibitor. STUDY DESIGN: Patients undergoing midtrimester genetic amniocentesis for routine indications gave consent for the study. After the sample was centrifuged, the acellular portion of the sample was mixed to homogeneity and aliquoted in 0.5-mL increments and stored for 1 year at 4 degrees C, -20 degrees C, and -80 degrees C with and without the protease inhibitor aprotinin. Enzyme-linked immunoassays for angiogenin, interleukin-6, and vascular endothelial growth factor were performed simultaneously on each aliquot. RESULTS: Thirty samples were assayed for each storage condition. Results were calculated as the percentage of its own sister aliquot stored at -80 degrees C without aprotinin. In all samples, there was a significant relation between storage temperature and cytokine levels, with the lowest levels found at 4 degrees C and the highest at -80 degrees C (angiogenin, P =.004; interleukin-6, P <.001; vascular endothelial growth factor, P =.02). The addition of aprotinin improved stability only for angiogenin at all temperatures (all P <.05). CONCLUSIONS: Degradation of cytokines occurs when amniotic fluid samples are stored for prolonged periods at temperatures greater than -80 degrees C. The addition of a protease inhibitor helps stem the degradation of some cytokines.

Management of isoimmunization in the presence of multiple maternal antibodies.

OBJECTIVE: Evaluation and management of patients with multiple maternal antibody isoimmunization is unclear. The presence of > or = 1 maternal antibody may suggest a worse scenario. The objective of this study was 2-fold: first, to determine whether the presence of multiple antibodies predicts a more severe course than single antibodies and second, to determine the utility of the Queenan curves/protocol in evaluating multiple-antibody isoimmunization. STUDY DESIGN: Amniotic fluid DeltaOD(450) measurements were obtained from the antenatal testing logbook and confirmed by chart review. Cases were categorized by antibody type and clinical outcomes obtained by chart review. RESULTS: Twenty-four pregnancies with isoimmunization and multiple maternal antibodies were identified; of these, 17 had 2 antibodies (anti-D and -C in 13; anti-D and -E in 1; anti-D and -Jka in 1; anti-c and -E in 1; and anti-c and -Jka in 1), and 7 had > 2 antibodies (anti-D, -C, and -E in 4; anti-D, -C, and -N in 1; anti-c, -E, and -FYA in 1; and anti-E, -K, -Fya, -S, and -C in 1). Eleven patients (46%) required at least 1 intrauterine fetal transfusion (mean initial fetal hematocrit, 15%; range, 4.9%-24%). In those not transfused, no DeltaOD(450) measurements occurred in the Queenan "fetal death risk" zone. Poorest outcomes (multiple transfusions/hydrops/fetal demise) were in patients with anti-D and anti-C, with or without anti-E. The absence of anti-D was associated with no need for fetal transfusions. The overall transfusion rate was significantly higher compared with a group of 57 isoimmunization patients with only anti-D (46% vs. 25%, P < or =.05). CONCLUSIONS: The presence of anti-D appears to be the most significant factor guiding the course of isoimmunization with multiple antibodies. The presence of another antibody with anti-D appears to significantly increase the need for intrauterine fetal transfusions. The Queenan protocol can successfully treat patients with multiple maternal red blood cell antibodies.

Amniotic fluid index in the uncomplicated term pregnancy. Prediction of outcome.

OBJECTIVE: To establish whether an association between oligohydramnios and pregnancy outcome is present in the uncomplicated term pregnancy. STUDY DESIGN: Pregnancies with a singleton fetus in cephalic presentation at term (> or = 37 weeks), a reactive non-stress test and an antepartum amniotic fluid index performed within four days of delivery between January 1994 and September 1998 were identified. Excluded were those with any maternal or fetal complication or unavailable outcome information. The primary outcome measure was rate of operative vaginal or abdominal delivery for a nonreassuring fetal heart rate tracing. Statistical analysis included Fisher's exact test and one-way analysis of variance, with a two-tailed P < .05 considered significant. RESULTS: Two hundred thirty-two women met the inclusion criteria; of them, 44 (19%) had an amniotic fluid index < or = 5 cm. There was no difference in the operative delivery rate for a nonreassuring fetal heart tracing between those with a normal amniotic fluid index > 5 cm vs. < or = 5 cm (39 [21%] vs. 5 [11%], P > .05). In addition, there were no differences between the two groups in rates of neonatal intensive care unit admissions or five-minute Apgar scores < 7. Patients with a normal amniotic fluid index had a significantly lower labor induction rate (96 [51%] vs. 42 [98%], P < .001) and higher rate of meconium-stained amniotic fluid (65 [35%] vs. 7 [16%], P = .01) than those with a low amniotic fluid index. CONCLUSION: In the uncomplicated pregnancy at term, an amniotic fluid index < or = 5 cm increases the incidence of labor induction but does not appear to affect the rate of operative delivery for abnormal fetal heart rate tracings.

Levels of interleukin-6 in second-trimester amniotic fluid are not predictive of adverse neonatal outcome.

OBJECTIVE: Elevation of interleukin (IL)-6 in the amniotic fluid (AF) during the second trimester is associated with increased risk of preterm deliver

Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

Does exposure to magnesium sulfate in utero decrease the risk of necrotizing enterocolitis in premature infants?

BACKGROUND: The objective of this study is to assess whether antenatal exposure to magnesium sulfate may decrease the risk of necrotizing enterocolitis in preterm infants. METHODS: We have compared the rate of magnesium sulfate exposure before birth among 23 consecutive infants diagnosed with necrotizing enterocolitis with that of 46 controls matched by gestational age at delivery and gender. Relevant obstetric and neonatal variables were compared between the two groups using chi-square and Fisher's exact test for categorical data, and one-way analysis of variance for continuous variables, with a two-tailed p-value <0.05 considered significant. RESULTS: No significant differences were present between the two groups in mode of delivery (p=0.9), rate of Apgar score at five minutes below seven (p=0.4), prenatal exposure to indocin (p=0.5) or steroids (p=0.6), or neonatal administration of surfactant (p=0.1). Similar proportions of babies with necrotizing enterocolitis and controls were diagnosed with respiratory distress syndrome (p=0.5), intraventricular hemorrhage grades three or four (p=0.9), and sepsis (p=0.6). Babies with necrotizing enterocolitis had a significantly longer hospital stay (74.6+/-64.0 vs. 41.9+/-37.0 days, p=0.01) and intubation period (31.4+/-24.1 vs. 16.8+/-15.6 days, p=0.01) than controls. The rates of prenatal exposure to magnesium sulfate were similar in the necrotizing enterocolitis and control groups (30% vs. 39% respectively, p=0.4). Power analysis demonstrated that 385 babies would be required in each group to reach statistical significance (alpha=0.05, beta=80%). CONCLUSION: In this retrospective case-control study, maternal administration of magnesium sulfate prior to delivery does not appear to confer a significant protective effect for the neonatal occurrence of necrotizing enterocolitis.

Preterm premature rupture of the fetal membranes complicated by oligohydramnios.

Preterm premature rupture of the fetal membranes complicated by oligohydramnios may have significant impact and sequelae on pregnancy outcome. In this article the role of amniotic fluid in fetal development, especially lung development, is reviewed; complications resulting from oligohydramnios are outlined; and the evaluated therapeutics and management schemes are delineated.

Maternal estrogen receptor-beta expression during mouse gestation.

PROBLEM: Although estrogen receptor (ER)-alpha has been well characterized, the recently identified novel ER-beta has not. In some tissues, there is overlap of the ERs, which allows for rescue in cases of deficiency; in other tissues, the ERs appear to have opposite effects. The objective of this study was to evaluate the expression of ER-beta during pregnancy. METHOD OF STUDY: Pregnant mouse uteri (embryonic days 6-14, 16, 18) were studied. ER-alpha and ER-beta oligonucleotide probes were end-labeled and in situ hybridization histochemistry was performed. RESULTS: ER-beta was strongly expressed in maternal ovaries; there was no other evidence of strong expression during gestation. ER-alpha was expressed in the uterus throughout gestation, with decreasing intensity as gestation progressed, and in maternal ovarian tissue. CONCLUSIONS: Differential expression of the two ERs was apparent during pregnancy, with ER-alpha playing a dominant role. This may have implications for selective drug treatment targeting estrogen receptors.

Magnesium sulfate therapy affects attention and working memory in patients undergoing preterm labor.

OBJECTIVE: Patients commonly consent to undergoing invasive procedures while receiving magnesium sulfate therapy. This study evaluated the effects of magnesium sulfate on attention, comprehension, and memory in patients undergoing preterm labor. STUDY DESIGN: Consenting patients were studied while receiving(study) and not receiving (control) intravenous magnesium sulfate tocolysis for preterm labor. Excluded were patients with possible preeclampsia, imminent delivery, sedative administration, or prior mental illness. Patient comprehension was assessed with the Boston Diagnostic Aphasia Examination. Level of attention and working memory were evaluated with the Paced Auditory Serial Addition Test. Verbal learning, short-term memory, and recognition were determined with the Hopkins Verbal Learning Test. Gross mental-neurologic deficits were evaluated with the Mini-Mental Status Examination. The tests were administered by the same examiner. Control testing was performed >24 hours after intravenous magnesium sulfate was discontinued. Magnesium levels were obtained at the time of testing. The primary outcome measure was the Paced Auditory Serial Addition Test score because of its ability to elicit subtle differences in attention capacity. Statistical analysis included the paired t test and the McNemar test. RESULTS: Fifteen patients completed the study. Paced Auditory Serial Addition Test scores were significantly higher (ie, more errors were made) during magnesium sulfate therapy than periods without therapy (14 +/- 8 vs 7 +/- 7; P <.05). Comprehension (Boston Diagnostic Aphasia Examination score) was not different between the groups (P =.7). There was no difference in short-term memory (Hopkins Verbal Learning Test) or gross mental-neurologic deficits between the 2 groups (all P >.1). CONCLUSIONS: Magnesium sulfate therapy appears to have an effect on attention and working memory but not on long-term memory or comprehension. The significant differences in Paced Auditory Serial Addition Test scores reveal deficits in information-processing ability in patients on a regimen of magnesium sulfate therapy.

Protective peptides derived from novel glial proteins.

In studying the mediators of VIP neurotrophism in the central nervous system, two glial proteins have been discovered. Both of these proteins contain short peptides that exhibit femtomolar potency in preventing neuronal cell death from a wide variety of neurotoxic substances. Extension of these peptides to models of oxidative stress or neurodegeneration in vivo have indicated significant efficacy in protection. These peptides, both as individual agents and in combination, have promise as possible protective agents in the treatment of human neurodegenerative disease and in pathologies involving oxidative stress.

Biophysical profile in predicting acute ascending infection in preterm rupture of membranes before 32 weeks.

OBJECTIVE: To assess the performance of the biophysical profile (BPP) and its components within 24 hours of delivery in predicting histopathologic evidence of severe acute placental inflammation in women with premature rupture of membranes (PROM) before 32 weeks' gestation. METHODS: We examined placentas from a series of consecutive, nonanomalous, live-born, singleton infants delivered before 32 weeks' gestation after PROM. In 166 cases, biophysical profiles (BPP) were done within 24 hours of birth. Histologic evidence of acute inflammation was assessed in the maternal (amnion) and fetal (chorionic and umbilical cord vessels) compartments, and scored on a severity scale of 0-4 by a single pathologist masked to clinical data. The presence and severity of acute inflammation was related to BPP results and its individual components. RESULTS: The overall prevalence of severe acute inflammation, ie, a score of 3 or 4, was 59% (98 of 166). In 30 (18%) cases it was present in the amnion, in 49 (30%) cases in chorionic or umbilical cord vessels, and in 19 (11%) cases in maternal and fetal compartments. There was no association between abnormal BPP score and presence or absence of severe acute placental inflammation (48% versus 46%, P =.7). Our study had a 90% power to detect a 0.26 difference between them. When rates of abnormal BPP scores were compared in cases with different degrees of acute inflammation in the maternal, fetal, or both compartments, no association was found. When the individual components of the BPP were analyzed in relation to site and severity of acute inflammation, no association was detected. CONCLUSION: We did not find evidence of a dose-response relationship between acute placental inflammation and BPP score or its individual components in cases of PROM with infants delivered before 32 weeks. Mediators other than infection might affect BPP in preterm PROM.