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There is increasing interest in measuring metals concentrations in human placentas to better understand physiology, disease, and toxic and diagnostic exposures. For these purposes, formalin-fixed paraffin embedded (FFPE) tissues obtained at clinical pathology examination represent a valuable potential store of well-characterized tissues for analysis. However, the limited data that exist comparing metal concentrations in FFPE tissue to recently collected frozen tissues paints a confusing picture, and there is no published data directly comparing frozen and FFPE placental villus tissues.Paired samples of fresh frozen and FFPE tissue from 22 rapidly processed human singleton placentae were weighed and digested using standard clean laboratory procedures and subsequently analyzed for a suite of 13 metals using a PerkinElmer DRC II ICP-MS. The analytical results were compared using either a paired t-test or a sign test depending on data normality.Concentrations of metals (aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), gadolinium (Gd), mercury (Hg), manganese (Mn), lead (Pb), strontium (Sr), and zinc (Zn)) measured in both types of tissue preparations (frozen and FFPE) displayed a consistent range with other studies and did not display significantly different values from each of the paired specimens for any of the 13 specific metals analyzed.Within placentae, metals concentrations of measured trace, toxic and diagnostic elements (Al, As, Ba, Cd, Cr, Cu, Fe, Gd, Hg, Mn, Pb, Sr, and Zn) are consistent between FFPE and fresh placental villus tissue, without indications of systematic element loss or bias. FFPE from archived pathology specimens may offer an important and convenient alternative for measuring trace metals in human frozen placental tissues.

Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and baby, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. While it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathological examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetric and neonatal provider based on publications and the expert opinion of sixteen placental pathologists and a pathologists' assistant using a modified Delphi approach. These criteria include those indications in which placental pathology has clinical relevance such as pregnancy losses, maternal infection, suspected abruption, fetal growth restriction, preterm birth, non-reassuring fetal heart testing requiring urgent delivery, preeclampsia with severe features, or neonates with early evidence of multiorgan system failure including neurological compromise. We encourage a focused gross examination by the provider or an attendant at delivery for all placentas and provide guidance for this examination. We recommend that any placenta which is abnormal on gross examination undergo a complete pathology examination. Additionally, we suggest practice criteria for placental pathology services including a list of critical values to be called in to the relevant provider. We hope these sets of triage indications, criteria, and practice suggestions will facilitate appropriate submission of placentas for pathologic examination and improve their relevance to clinical care.

Aims This study aimed to investigate the potential of tocilizumab therapy in minimizing mortality and mechanical ventilation (MV) requirements among hospitalized COVID-19 patients. Methods A single-center, retrospective, observational cohort study of 375 patients with severe COVID-19 (March 1 and April 22, 2020) included 150 patients treated with Tocilizumab and 225 consecutive control patients adjusted for age and gender. Both groups received concomitant standard of care treatments in addition to Tocilizumab. The statistical methods relied on survival analyses, conditional logistic regression models, and contingency analyses. The primary outcomes included in-hospital mortality and the MV requirement. Results Tocilizumab associated with improved in-hospital mortality (34.7% vs 46.7%, P = 0.0136) and lower requirement for MV on days 1, 3, and 5 after treatment (P = 0.005, P

Exposures to environmental chemicals and psychosocial stressors during pregnancy have been individually associated with adverse perinatal outcomes related to birthweight and gestational age, but are not often considered in combination. We review types of psychosocial stressors and instruments used to assess them and classes of environmental chemical exposures that are known to adversely impact perinatal outcomes, and identify studies relevant studies. We discuss the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) program that has combined existing longitudinal cohorts that include more than 50,000 children across the U.S. We describe future opportunities for investigators to use this important new resource for addressing relevant and critical research questions to maternal health. Of the 84 cohorts in ECHO, 38 collected data on environmental chemicals and psychosocial stressors and perinatal outcomes. The diverse ECHO pregnancy cohorts provide capacity to compare regions with distinct place-based environmental and social stressors.

PurposeExtensive research suggests that maternal prenatal distress is reliably related to perinatal and child health outcomes—which may persist into adulthood. However, basic questions remain regarding mechanisms involved. To better understand these mechanisms, we developed the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort study, which has several distinguishing features, including repeated assessments across trimesters, analysis of multiple biological pathways of interest, and incorporation of placental structure and function as mediators of child health outcomes.ParticipantsWomen with normal risk pregnancies were recruited at Findings to dateWe recruited 326 pregnancies; 294 (90%) were retained through birth. Success rates for prenatal biospecimen collection were high across all trimesters (96%–99% for blood, 94%–97% for urine, 96%–99% for saliva, 96% of placentas, 88% for cord blood and 93% for buccal swab). Ninety-four per cent of eligible babies (n=277) participated in a birth examination; postnatal visits are ongoing.Future plansThe current phase of the study follows children through age 4 to examine child neurodevelopment and physical development. In addition, the cohort participates in the National Institutes of Health’s Environmental influences on Child Health Outcomes programme, a national study of 50 000 families examining early environmental influences on perinatal outcomes, neurodevelopment, obesity and airway disease. Future research will leverage the rich repository of biological samples and clinical data to expand research on the mechanisms of child health outcomes in relation to environmental chemical exposures, genetics and the microbiome.

Summary Objective Providing effective dietary counselling so that pregnancy weight gain remains within the 2009 Institute of Medicine (IOM) guidelines requires accurate maternal energy intake measures. Current practice is based on self-reported intake that has been demonstrated unreliable. This study applies an objective calculation of energy intake from a validated mathematical model to identify characteristics of individuals more likely to misreport during pregnancy. Methods A validated maternal energy balance equation was used to calculate energy intake from gestational weight gain in 1,368 subjects. The difference between self-reported and model-predicted energy intake was tested for demographics, economic status, education level and maternal health status. Results A weight gain of 15.2 kg resulted in model-predicted intake during pregnancy of 2,882.97 ± 135.71 kcal day−1, which differed from self-reported intake of 2,180.5 ± 856.0 kcal day−1. The achieved weight gain exceeded the IOM guidelines; however, the model predicted weight gain from self-reported energy intake was below IOM guidelines. Higher income (p = 0.004), education (p = 0.003), birth weight (p = 0.017), gestational diabetes (p = 0.008) and pre-existing diabetes (p

Matrix metalloproteinases (MMPs), specifically MMP-9 plays a role in human placentation. The enzyme confers an invasive ability to cytotrophoblasts and degrades the endometrial matrix as the cells infiltrate the decidua to keep up with placental growth. Since tumor necrosis factor-α (TNF-α) can induce the synthesis of MMP-9, we investigated the patterns of changes in and correlation between placental villous MMP-9 and TNF-α expressions throughout normal human gestation. Placentas were obtained from 179 normal pregnant women who underwent elective abortion or term delivery. Chorionic villi isolated from placental samples were grouped as first, second, and third trimester (70/7-130/7, 131/7-236/7, and 370/7-424/7 weeks, respectively). Chorionic villous TNF-α and MMP-9 proteins were assayed using enzyme immunoassay kits. There were significant differences in MMP-9 and TNF-α protein expressions among the trimester groups ( P = .001). The MMP-9 protein increased progressively with an increase in gestational age (GA), but TNF-α peaked in the second trimester. Within each trimester group, we searched for the effects of variation of GA in days on the 2 variables. A significant positive correlation between MMP-9 and GA was noted in the first trimester ( r = 0.364, P = .005). No other comparisons were significant. When GA was controlled for, partial correlation revealed a significant positive correlation between TNF-α and MMP-9 only in the second trimester ( r = 0.300, P = .018). We hypothesize that the TNF-α peak and the positive correlation between TNF-α and MMP-9 in the second trimester of normal human gestation could contribute toward a successful pregnancy outcome.

To determine the rate and factors associated with the successful Induction of Labor (IOL) in nulliparous patients undergoing scheduled IOL at 41 weeks of gestational age (GA) with an unfavorable cervix. This was a retrospective analysis that included nulliparous patients who presented to the Labor and Delivery unit at the Bronx Lebanon Hospital Center between 2011 and 2012 for elective IOL at 41 weeks of GA. The Bishop score was assessed upon admission and IOL agents were used in compliance with ACOG guidelines in different combinations, based on the obstetrical team preference. Labor and Delivery Unit of the Bronx Lebanon Hospital. Nulliparous patients with 41 weeks of pregnancy for elective induction of labor. Seventy-six patients were included in the study. GA was confirmed using a combination of the last menstrual period and a dating sonogram during pregnancy. This was a retrospective chart review that included nulliparous patients who presented to the Labor and Delivery unit at the Bronx Lebanon Hospital Center between October 2011 and October 2012 for elective IOL at 41 weeks of gestational age with an unfavorable cervix defined as a Bishop score of 6 or less. The overall successful rate of IOL in a combination of different maternal factors with different agents for induction in nulliparous patients undergoing scheduled IOL with an unfavorable Bishop score at 41 weeks of GA was 51.32 %. Factors associated with successful IOL were younger age [22.3 years vs. 25.1(p = 0.015)], lower BMI [25 vs. 28.1(p = 0.46)] and lower maternal weight [64.75 kg vs. 74.02 (p = 0.28)]. Maternal height was not a contributing factor; the artificial rupture of membranes, epidural anesthesia and the prostaglandins used did not contribute. Use of cervical balloon and oxytocin was associated with failed IOL. Patients undergoing IOL at 41 weeks with an unfavorable cervix had a successful rate of 51.32 %. Younger maternal age, lower weight, and lower BMI were associated with successful IOL.

Placental tumor necrosis factor-α (TNF-α) is a cell signaling protein. During pregnancy, TNF-α induces synthesis of matrix metalloproteinases (MMPs) which allows cytotrophoblasts to reach the spiral arteries deeper within the uterine decidua. TNF-α also augments apoptosis of vascular smooth muscle cells surrounding these arteries. In this study, chorionic villi TNF-α protein expression throughout normal human gestation were investigated.Placental chorionic villi tissues obtained from elective surgical terminations of pregnancy and from uncomplicated term births were assayed using EIA kits (Cayman Chemicals, Ann Arbor, MI, Item # 589201).The median, 25th percentile and 75th percentile values in the first (N = 99), second (N = 58) and third trimester (N = 42) were: 36.46, 27.25, 45.90 pg/100 mg tissue; 55.43, 40.09, 110.88 pg/100 mg tissue; and 16.63, 9.32, 31.92 pg/100 mg tissue, respectively.Variations in placental TNF-α protein expression noted at different trimesters may suggest gestational age specific roles for the cytokine. The increase in TNF-α protein expression observed in the second trimester may be involved in upregulating synthesis of MMP and in augmenting apoptosis of vascular smooth muscle cells of the spiral arteries. A failure in this second trimester increase in TNF-α protein could contribute to gestational compromise.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, three of which are summarized in this report. These workshops related to vascular systems and circulation in the mother, placenta and fetus, and were divided in to 1) angiogenic signaling and regulation of fetal endothelial function; 2) placental and fetal circulation and growth; 3) spiral artery remodeling.

BACKGROUND: An important contributor to fetal growth is growth of the placenta, the fetus' sole source of nutrients and oxygen. Here we use placental growth measures (larger and smaller disk diameters, reflecting the laterally expanding chorionic plate, and disk thickness) to test the hypothesis that placental growth patterns, while associated with placental weight and birth weight, measure placental functional efficiency, and will have independent effects on the feto-placental weight ratio (FPR). METHODS: Placental measures were available from 23,313 participants in the Collaborative Perinatal Project delivered between 34 and 43 completed weeks. Continuous variables were analyzed by regression for associations with placental weight, birth weight, and FPR, to further explore effects of placental growth patterns on the FPR (lateral chorionic plate growth and chorionic disk thickness were grouped as low, normal, and high values). The relationships of the nine resultant combinations of placental growth categories to the FPR using birth weight adjusted for gestational age, infant gender, parity, and African American race were analyzed (ANOVA). RESULTS: As chorionic disk area and thickness increased, birth weight and placental weight increased, and the FPR decreased (each p < .0001) after adjustment for gestational age, parity, race, and infant gender. Small, thin placental disks had an adjusted FPR of 8.46; the largest, thickest placentas had an adjusted FPR of 6.33. The nine categories of FPRs were significantly different, consistent with chorionic plate area and disk thickness combining to determine the FPR. CONCLUSIONS: Patterns of placental growth, relating to different functional dimensions of the placenta, deliver a different birth weight for a given placental weight. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc.

Introduction Infants born below 2500 g are classified as low birth weight. Excess in utero exposure to cortisol has been linked to restricted fetal growth. Placental production of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) inactivates cortisol before passage into the fetus. The present study tested the hypothesis that placental 11β-HSD2 expression is positively correlated with an individualized birth weight centile and raw birth weight, and examines the relationship between metal concentrations in placental tissue and 11β-HSD2 expression. Methods Placentae from 191 births were collected and samples preserved to maintain mRNA profile. Placental 11β-HSD2 expression was measured via qRT-PCR. Addition samples were collected from placental tissues and uniformly dried in order to quantify 18 metals via ICP-MS (n = 160). Results A significant, positive correlation between 11β-HSD2 expression and individualized birth weight centile (p = 0.0321) and birth weight (p = 0.0243) was found. Additionally, maternal age and gestational age were positivity correlated with each other (p = 0.0321). Birth weight was significantly different with race, marital status, education and maternal tobacco use. Four metals (Co, Mn, Ni, Zn) demonstrated significant positive correlations (p 11β-HSD2 expression. Sex specific differences were found; Co, Cu, Fe, Zn, and Ni were positively correlated with 11β-HSD2 expression in males only, no significant correlations were found in the female only sample. Conclusion These data indicate that the growth potential of a fetus is related to the 11β-HSD2 expression in the placenta, and that 11β-HSD2 expression is related to the trace metals status of the mother.

The effects of gestational age on placental oxidative balance throughout gestation were investigated in women with uncomplicated pregnancies. Placental tissues were obtained from normal pregnant women who delivered at term or underwent elective pregnancy termination at 6 to 23 + 6 weeks of pregnancy. Placental tissues were analyzed for total antioxidant capacity (TAC) and lipid peroxide (malondialdehyde, MDA) levels using commercially available kits. Two hundred and one placental tissues were analyzed and the mean ± SD MDA (pmol/mg tissue) and TAC (µmol Trolox equivalent/mg tissue) levels for first, second, and third trimester groups were 277.01 ± 204.66, 202.66 ± 185.05, and 176.97 ± 141.61,P< 0.004 and 498.62 ± 400.74, 454.90 ± 374.44, and 912.19 ± 586.21,P< 0.0001 by ANOVA, respectively. Our data reflects an increased oxidative stress in the placenta in the early phase of normal pregnancy. As pregnancy progressed, placental antioxidant protective mechanisms increased and lipid peroxidation markers decreased resulting in diminution in oxidative stress. Our findings provide a biochemical support to the concept of a hypoxic environment in early pregnancy. A decrease in placental oxidative stress in the second and third trimesters appears to be a physiological phenomenon of normal pregnancy. Deviations from this physiological phenomenon may result in placental-mediated disorders.

The placenta, as the vector for all maternal-fetal oxygen and nutrient exchange, is a principal influence on birthweight. Placental weight summarizes laterally expanding growth of the chorionic disc, and villous arborization yielding the nutrient exchange surface. These different growth dimensions alter fetoplacental weight ratio and ponderal index, and thus may modify placental functional efficiency. The placenta may show a range of histopathologies, some of which are also associated with fetal growth restriction. Different fetal intrinsic abilities to compensate for gross and histo-pathology may clarify the imperfect relationships between fetal growth and both intrauterine pathology, and the long-term health risks associated with poor fetal growth.

Background. The aim of this study was to evaluate whether particular placental histopathology lesions are associated with recurrent preterm birth. Methods. We analyzed a database of 413 consecutive singleton pregnancies delivered at

Summary Current data strongly support that a wide variety of adult health risks are influenced by intrauterine life events. Twins may have the same (identical, monozygous) or different (fraternal, dizygous) genes, but their relationship to their outside world, via their placentas, is rarely equal. Monochorionic twins and dichorionic twins both resemble and differ from singletons. In the balance between the similarities and the differences, we may find the answer to the interpretation of twin studies, and appropriately apply them to the ‘fetal origins’ hypothesis.

The use of illicit and licit drugs during pregnancy is a major public health concern because of potential adverse effects on the fetus and the risk to maternal health. Because the placenta is the primary link between the mother and the conceptus and is essential for the growth and survival of the fetus, abnormalities in placental formation and function resulting from drug use could have a major influence on pregnancy outcome. At present, little information is available on the impact of abused drugs on placental biology alone or in combination with other "host" factors (eg, stress, infections). This prompted the National Institute on Drug Abuse (NIDA) to convene a meeting of experts in placental biology to review cutting-edge research with the mission to translate existing information to new clinical and research initiatives in the drug abuse field. This report summarizes the presentations and research recommendations resulting from the workshop discussions.

To describe the relationship between the degree of placental histologic villous mineralization (VM) and stillbirth in aneuploid and euploid fetuses.The extent of VM for aneuploid and gestational age-matched euploid placentas was graded semiquantitatively on a 0 to 3 scale based on the number of terminal or stem villi containing mineralizations in forty x10 fields of view. The extent of VM was analyzed in relation to fetal status at delivery (liveborn or stillborn) for both aneuploid and euploid fetuses.For 14 available aneuploid placentas, grade 0 or 1 VM was recorded for seven aneuploid specimens, of which two were stillborn. Grade 2 or 3 VM was recorded for seven aneuploid specimens, of which six were stillborn. Fourteen gestational age-matched euploid placentas served as controls. Grade 0 or 1 VM was observed in nine euploid specimens, of which four were stillborn. Grade 2 or 3 VM was observed in five euploid specimens, of which four were stillborn. For aneuploid fetuses, stillbirth was significantly more frequent with grade 2 or 3 VM compared with grade 0 or 1 VM (chi(2) = 4.667, P.05). This relationship did not exist for euploid fetuses (chi(2) = 1.659, P.05).Histologic VM is not a universal finding in, or exclusive to, stillbirths. Aneuploid but not euploid stillbirths show increased histologic VM compared with livebirths. This may implicate impaired placental or circulatory function as a mechanism for death in aneuploid fetuses.

We hypothesized that the altered placental proportions that influence birth weight affect childhood body proportions, and that these effects would be independent of birth weight. We also hypothesized that altered placental proportions might affect the fetal cardiovascular system, and may be reflected in variation in childhood blood pressure. By using linear regression with birth weight as the dependent variable, placental variables were entered as predictors. The predicted birth weights based on placental factors were then obtained. The ratio of the actual birth weight to that predicted by placental parameters (observed/expected ratio, OER) was used as the independent variable in analyses of age 7 year body mass index (BMI) and diastolic blood pressure (DBP) in the 15,902 singleton liveborns delivered between 34 and 43 weeks. The standardized residual birth weight was also used as a variable to examine the effects of birth weight that is not consistent with placental parameters. For each unit increase in the OER, BMI at 7 years increased 1 kg/m2 (P < 0.0001). The OER also had a significant effect on DBP (β = 4.52, P < 0.001) at 7 years of age but only among African-American children. Results for the standardized residual birth weight variable were consistent with the OER. All results were adjusted for gestational age, sex, socioeconomic status, African-American race and maternal pre-pregnancy BMI. Being larger or smaller than predicted by one’s placenta affects childhood body composition and blood pressure. The placental measurements provide insight into pathophysiological mechanisms of the developmental origins of adult disease.

Our previous work suggests that stressors that impact placental vascular growth result in a deformed chorionic surface shape, which reflects an abnormal placental three-dimensional shape. We propose to use variability of placental disk thickness as a reflector of deviations in placental vascular growth at the finer level of the fetal stems. We hypothesize that increased variability of thickness is associated with abnormal chorionic surface shape, but will be a predictor of reduced placental functional efficiency (smaller baby for a given placental weight) independent of shape. These measures may shed light on the mechanisms linking placental growth to risk of adult disease. The sample was drawn from the Pregnancy, Infection and Nutrition Study. In all, 94.6% of the cohort consented to placental examination. Of the 1023 delivered at term, those previously sectioned by the Pathology Department were excluded, leaving 587 (57%) cases with intact placentas that were sliced and photographed. The chorionic surface shape and the shape of a central randomly oriented placental slice were analyzed and measures were compared using correlation. Lower mean placental disk thickness and more variable disk thickness were each strongly and significantly correlated with deformed chorionic plate shapes. More variable disk thickness was strongly correlated with reduced placental efficiency independent of abnormal chorionic surface shape. Variability of placental disk thickness, simple to measure in a single randomly oriented central slice, may be an easily acquired measure that is an independent indicator of lowered placental efficiency, which may in turn program the infant and result in increased risk for development of adult diseases.

We hypothesized that placental villous branching that is measured by disk chorionic plate expansion and disk thickness is correlated with factors also involved in regulation of branching growth of other fetal viscera (e.g. lung, kidney) including neuronal dendrites, and thus may be associated with variation in childhood intelligence quotient (IQ). IQ at age 7 years was assessed using the Wechsler Intelligence Scale for Children. Placental measures [placental weight (g), thickness (mm), chorionic plate surface diameters (cm), area (cm2), shape, and cord length and cord eccentricity] were independent variables in regression analyses of age 7-year IQ in 12,926 singleton term live born infants with complete placental data. Analyses were stratified on gender with adjustment for socioeconomic status, race, parity, gestational age, exact age at testing and centered parental ages. After adjustment for covariates, placental measurements were independently associated with IQ at age 7 years but results varied by gender. Chorionic plate diameters were only associated with higher IQ in girls. Placental thickness was positively associated with higher IQ for boys and girls. We have previously shown that placental measures affect age 7-year body mass index and diastolic blood pressure. Here we demonstrate that specific measures, placental chorionic plate diameters in girls and disk thickness, independent of gender, are correlated with age 7-year IQ. Further exploration of the possible interaction of these factors on the placental villous arborization reflected by the chorionic plate expansion and placental thickness that correlate with age 7-year IQ, as well as other age 7 somatic features as previously addressed, is indicated.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of ‘omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution.

To assess the effects of antenatal corticosteroid use on placental histopathology, we have reviewed a database of 463 consecutive non-anomalous singleton liveborns delivered at less than 32 weeks between April 1988 and December 1994, of which 280 received one or more doses of corticosteroids for promotion of fetal lung maturation. Patients were grouped by the number of corticosteroid doses received (analyzed as none, 1, 2 and 3 or more doses). Clinical and demographic factors were recorded prospectively. Placental histopathology was reviewed blinded to clinical factors except gestational age, and 42 distinct placental lesions were examined and scored for severity. Data were analyzed by contingency tables, one-way analysis of variance, and linear regression analysis. Among clinical variables, univariate analysis showed that the number of corticosteroid doses was significantly related to presence of labour prior to delivery, pre-eclampsia, premature rupture of membranes and clinical suspicion or diagnosis of chorioamnionitis. Using linear regression analysis with these clinical variables as confounders, increased number of doses of antenatal corticosteroids was related to increased severity of villous fibrosis and stromal mineralization, and fewer villous infarcts.

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.

This review examines the major observations and principal controversies relating to the effects of smoking and the constituents of tobacco on ovarian, uterine and placental tissues. Maternal exposure is assessed relative to specific tobacco-related chemicals and the feto-placental impact of mutagenic products, in addition to nicotine replacement as a pharmacological intervention for smoking cessation. Important new information is being learned from clinical in vitro fertilization and assisted reproduction technologies regarding the effects of smoking on fertility. Present evidence supports an adverse effect of smoking on ovarian function which is prolonged and dose-dependent, whereas there appear to be more reversible effects on implantation and ongoing pregnancy. The anti-oestrogenic effect of smoking is reviewed in terms of direct effects of nicotine, cadmium and polyaromatic hydrocarbons on oestrogen synthesis and metabolism, oocytes and granulosa-luteal function. Innovative new models provide evidence that smoking may alter fertility through effects on uterine-fallopian tube functions which mediate gamete and conceptus transport. It is of interest that smoking is associated with a decreased incidence of uterine fibroids, endometriosis and uterine cancer, which may reflect inhibitory effects of smoke constituents on uterine cell proliferation and extracellular matrix interactions. The increased miscarriage rate among mothers who smoke may be related to direct adverse effects of nicotine, cadmium and polyaromatic hydrocarbons on trophoblast invasion and proliferation. In this respect, alterations in trophoblast differentiation along invasive or proliferative pathways may explain the changes in endocrine function and vascular morphology that are observed in smokers. In summary, significant advances are being made in the understanding of cellular and molecular mechanisms which underlie the differential effects of cigarette smoking on reproductive tissues.

PROBLEM: Normal placentation requires modulation of proliferative cytotrophoblast to an invasive phenotype. Preeclampsia is characterized by failed cytotrophoblast invasion and arterial remodeling. Osteopontin (OPN) is an extracellular matrix protein implicated in cell adhesion, spreading, and invasion. METHOD OF STUDY: To investigate gestational age-related OPN expression, placental immunostaining was performed. To investigate the role of OPN in uteroplacental vascular pathology, placental immunostaining from pregnancies with preeclampsia (n = 12), fetal growth retardation (FGR) (n = 8), or both (n = 4) was compared with gestational age-matched controls (n = 24). RESULTS: In non-preeclamptic pregnancies, OPN immunolocalized to basal plate and intervillous cytotrophoblasts from 24-30 weeks (n = 13). In preeclampsia, OPN immunoreactivity was detected from 24-40 weeks. Cytotrophoblasts from FGR placentas were OPN-positive until 30 weeks, unless preeclampsia accompanied the FGR. In this case, cytotrophoblasts were OPN-positive from 24-40 weeks. CONCLUSIONS: The data suggest a role for OPN in cytotrophoblast invasion of the maternal vasculature/extracellular matrix during non-preeclamptic placentation, and OPN may serve as a marker for placental bed remodeling.

It is often believed that the frequency of clinical chorioamnionitis in preterm premature rupture of membranes (PROM) increases with the duration of the interval between membrane rupture and delive...

OBJECTIVE To evaluate whether fetal heart rate (FHR) patterns obtained in nonstress testing within 24 hours of delivery in patients with preterm delivery were associated with histologic acute infection, and if so, whether the associations are with maternal as opposed to fetal acute inflammation (acute amnionitis versus acute umbilical vasculitis). METHODS The data set included 351 consecutive patients delivering from 22 to 32 weeks' gestation (excluding cases of preeclampsia; nonhypertensive abruption; stillbirth; fetal structural and karyotypic anomalies; Rh isoimmunization and hydrops fetalis; and maternal diabetes and hypertension). Severe variable decelerations were defined as FHR 60 seconds, and decreased fetal heart variability included both reduced beat-to-beat variability and long-term heart rate cyclicity. Amniotic fluid volume was graded sonographically as part of a fetal biophysical profile. Acute inflammation of amnion (indicative of maternal inflammation) and umbilical cord (fetal inflammation) were scored by a single pathologist blinded to clinical data. RESULTS Severe FHR variable decelerations were directly related to acute amnionitis (P = .012) and acute umbilical vasculitis (P = .0013). In preterm labor, decreased FHR variability was related to acute amnionitis (P = .005). All observations were independent of amniotic fluid volume or use of tocolytic agents. CONCLUSIONS Severe variable decelerations and decreased FHR variability at < 32 weeks' gestation are related to histologic evidence of acute inflammation.

The fact that the semi-allogeneic conceptus can develop for 9 months, most commonly without harm, shows that protective mechanisms must exist that permit its survival. These mechanisms are so finely tuned or so locally confined that the immune rejection of the conceptus is prevented while maintaining the mother's ability to fight infection. One consequence of this immune silence may be the late onset of systemic manifestations of intrauterine infections, such as chorioamnionitis. This silence may be part of the complexity that has surrounded issues of vertical transmission of infectious disease in general and HIV in particular.

We report on a woman with incontinentia pigmenti (IP), who had two successive term pregnancies. The first pregnancy ended in the birth of a male infant, who is alive and well at 2 years. A second liveborn male had early postnatal distress and died after 1 day of life, after a fulminating clinical course. Polymorphic microsatellite markers, closely linked to the IP gene on the X chromosome, showed that each son inherited a different X chromosome from his mother. Although in most instances IP appears to be prenatally lethal for the male, the phenotype is not completely known. We propose that the neonatal phenotype may be characterized by lethal disturbances in the hematopoietic and immunologic systems.

The objective of this study was to determine if placental histopathology patterns are associated with clinical features of preterm pre-eclampsia. A 1989-1993 database of consecutive non-anomalous singleton livebirths delivered at 22-32 weeks gestation excluding cases of maternal diabetes mellitus and chronic hypertension included 74 cases of pre-eclampsia. Placentae were scored for uteroplacental vascular lesions and lesions of chronic inflammation and coagulation. Thirteen lesion patterns identified by factor analysis were studied in relation to the clinical features. Severe maternal proteinuria was related to placental chronic inflammation, while lower maternal antepartum platelet counts were related to placental abruption and infarct. Lower birthweight percentile and lighter placentae were related directly to uteroplacental vascular lesions. Diagnosis of HELLP and coagulopathy were less common when chronic inflammation scores were high. Serologic studies related to autoimmunity and maternal blood pressures were unrelated to placental histopathology factors. It is concluded that features of maternal and fetal compromise in preterm pre-eclampsia are related to placental histopathology patterns.

Summary Lipoprotein(a) (lp(a)) deposition, a marker of vascular wall damage, was studied in (1) Placental bed biopsies (9 normal term pregnancies and 12 proteinuric preeclampsia); (2) Placental basal plates from consecutive births in March–June, 1995 (14 normal term births, 6 term preeclampsia, 4 preterm preeclampsia, and 11 spontaneous preterm births); and (3) 4 implantation sites obtained at least 2 weeks post partum and 2 peripartum hysterectomies performed due to intractable hemorrhage. Formalin-fixed paraffin-embedded sections were stained for lp(a). Lp(a) was detected in 2/69 (3%) normotensive placental bed uteroplacental or spiral arteries and in 71/179 (40%) preeclamptic placental bed uteroplacental or spiral arteries (p

Our objective was to determine if placental histologic acute inflammation is related to maternal and fetal serum cytokine levels in preterm labor, using a data set previously constructed blinded to histopathologic information. To this goal in 1992, 32 consecutive patients at 20-36 weeks with progressive labor and tocolytic failure were recruited. Maternal serum sampled during the active phase of labor, and fetal (umbilical vein) serum were assayed by ELISA for levels of soluble interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptor (IL-2 R), and interleukin 6 (IL-6) (T-Cell Diagnostics). Acute placental inflammation was scored by two groups blinded to clinical data, and the average scores analyzed for relationships to serum cytokine levels. Weighted kappa values, reflecting interobserver agreement in scoring of acute inflammation, were: amnion 0.84; choriodecidua 0.84; umbilical cord 0.85; and chorionic plate 0.73. Fetal levels of IL-1 beta and IL-2 R were higher with grade 3-4 acute amnionitis than with grades 0-2 (p = 0.022 and p = 0.023). Fetal levels of all three cytokines were higher in grade 3-4 umbilical vasculitis (IL-1 beta p = 0.008, IL-2 R p = 0.01, and IL-6 p = 0.03). In contrast, maternal serum cytokine levels were not associated with presence or severity of histologic evidence of acute placental inflammation. Histologic acute inflammation was not related to duration of labor, interval from membrane rupture to delivery, and presence or duration of antibiotic therapy. We conclude that fetal serum, but not maternal serum cytokine levels, are correlated with histologic evidence of acute placental inflammation, and may reflect a predominant placental origin of the cytokines.

To examine whether changes in nucleated erythrocyte (nRBC) counts in the early neonatal period can distinguish between causes of nRBC release. From a data set of 465 nonanomalous singleton live births delivered at 22–32 weeks, excluding maternal diabetes mellitus, Rh isoimmunization, and chronic hypertension, 125 cases had a complete blood count with an nRBC count within 3 hours of life and at least one other value obtained within 48 hours of the first. The change in nRBC count per deciliter was calculated (ΔnRBC) and was correlated with antenatal fetal assessment, neonatal outcome variables, and placental histopathology infwe categories: 1) histologic acute intrauterine inflammation, 2) uteroplacental vascular lesions, 3) intraplacental vaso-occlusive lesions, 4) chronic inflammation, and 5) coagulation-related lesions. There were 92 cases (74%) of premature rupture of membranes (PROM) and preterm labor/intact membranes (PTL) and 33 cases (26%) of preeclampsia. In PROM/PTL, multivariate analyses demonstrated that a higher uteroplacental vascular lesion score was related to more stable nRBC counts (P =.009), whereas a higher nonmyeloid count in the initial neonatal white blood cell count was related to a more rapid decrease in ΔnRBC (combined r = 0.54, P

The purpose of this study was to quantitatively analyze normal and preeclamptic uteroplacental vasculature. Myometrial arteries from eight placental bed biopsies from uncomplicated term deliveries and 12 from proteinuric preeclampsia were characterized as uteroplacental, spiral, or basal arteries. Basal lumens within 0.2 mm radius and spiral/uteroplacental lumens within 0.4 mm radius were considered as the same artery. The biopsy area, lumen density, and arterial density (after correction for multiple lumens), lumen area, lumen perimeter, mean wall thickness, inflated diameter, and a slant factor, measuring the obliqueness of arterial transection, and ratios of lumen characteristics to mean wall thickness were analyzed. In preeclamptic cases, there were more basal lumens/mm 2 and basal arteries/nun 2 ( P = .003, P = .03), and more spiral lumens/mm 2 and spiral arteries/ mm 2 ( P = .01, P = .03). Basal lumen area ( P = .0003) and wall thickness ( P = .007), and basal and spiral artery lumen perimeters and inflated diameters (for each, P = .0001, P = .048, respectively) and inflated diameter/wall ratios ( P = .04, P = .05) were reduced compared with normal cases. Preeclamptic spiral and basal arteries are more tortuous or densely distributed than normal placental bed arteries, with smaller-caliber lumens and thicker walls. Failure of proper placentation may result in abnormal spatial anatomy in the placental bed. Alternatively, an anatomic variant of spiral and basal arteries may be more susceptible to hemodynamic stresses and endothelial damage and may predispose to preeclampsia.

Human birth weight does not scale linearly with the weight of the placenta: placental mass (PM) is proportional to the fetal mass (FM) raised to the scaling exponent of 0.75 (PM ∼ FM(0.75)) [1,2]. The mouse is a common model for studying genetic and physiological backgrounds of placental development, function and pathologies. However, to date it has not been known how placental weight scales relative to embryo weight in mice. We analyzed E12.5 litters of CD1 wild-type mice, and found that the mouse placental weight demonstrates a power-law scaling relationship with fetal weight; the value of the scaling exponent is approximately 0.72.