Chronic Placental Inflammation Research Articles

The frequency and type of placental histologic lesions in term pregnancies with normal outcome.

Objective To determine the frequency and type of histopathologic lesions in placentas delivered by women with a normal pregnancy outcome. Methods This retrospective cohort study included placental samples from 944 women with a singleton gestation who delivered at term without obstetrical complications. Placental lesions were classified into the following four categories as defined by the Society for Pediatric Pathology and by our unit: (1) acute placental inflammation, (2) chronic placental inflammation, (3) maternal vascular malperfusion and (4) fetal vascular malperfusion. Results (1) Seventy-eight percent of the placentas had lesions consistent with inflammatory or vascular lesions; (2) acute inflammatory lesions were the most prevalent, observed in 42.3% of the placentas, but only 1.0% of the lesions were severe; (3) acute inflammatory lesions were more common in the placentas of women with labor than in those without labor; (4) chronic inflammatory lesions of the placenta were present in 29.9%; and (5) maternal and fetal vascular lesions of malperfusion were detected in 35.7% and 19.7%, respectively. Two or more lesions with maternal or fetal vascular features consistent with malperfusion (high-burden lesions) were present in 7.4% and 0.7%, respectively. Conclusion Most placentas had lesions consistent with inflammatory or vascular lesions, but severe and/or high-burden lesions were infrequent. Mild placental lesions may be interpreted either as acute changes associated with parturition or as representative of a subclinical pathological process (intra-amniotic infection or sterile intra-amniotic inflammation) that did not affect the clinical course of pregnancy.

Chronic Placental Inflammation as a Risk Factor of Severe Retinopathy of Prematurity

BackgroundChronic placental inflammation (CPI) has been implicated in the pathogenesis of diseases in premature infants, whereas retinopathy of prematurity (ROP) is a major complication primarily affecting preterm and very low-birth-weight (VLBW) infants. This study aims to investigate the association between CPI and ROP in VLBW infants.MethodsWe performed a retrospective review of clinical records of VLBW infants born between 2013 and 2016. Placental pathology findings including CPI cases were analyzed using logistic regression to study infants’ morbidities and other clinical characteristics.ResultsA total of 402 infants with a mean (standard deviation) gestational age of 28.5 (2.8) weeks and birth weight of 1,027.2 (304.4) g were included. The incidence of ROP was 24.1%. CPI was found in 90 infants (22.4%), among which 28.9% (26 of 90) developed ROP, and 21.1% (19 of 90) underwent laser photocoagulation. Lower gestational age, lower birth weight, longer duration of oxygen supply, and presence of CPI were associated with the development of ROP. After adjustment for gestational age, birth weight, sex, duration of oxygen supply, and other overlapping placental pathology, CPI was associated with the odds for type 1 ROP that required laser photocoagulation (adjusted odds ratio, 2.739; 95% confidence interval, 1.112 to 6.749; p = .029).ConclusionsCPI was associated with severe ROP requiring treatment with laser photocoagulation in VLBW infants.

The Association between Fetal Fibronectin, Cervical Length, and Amniotic Fluid Sludge with Histological Indicators of Placental Inflammation in Twin Gestations.

The objective of this study was to evaluate the association of screening tests for preterm birth (short cervical length [CL], positive fetal fibronectin (FFN), and amniotic fluid [AF] sludge) in twin gestations with histologic evidence of placental inflammation. Historical cohort study of 596 twin gestations delivered in a single maternal-fetal medicine practice with CL and FFN testing from 22 to 256/7 weeks. A short CL was defined as ≤25 mm. Placental lesions evaluated were chronic and acute membrane inflammation and funisitis. Fischer's exact test and logistic regression were used. None of the screening tests was associated with chronic inflammation. All were associated with acute inflammation. On regression analysis, a short CL and positive FFN remained independently associated with acute inflammation (adjusted odds ratio [aOR]: 5.66 and 2.51, respectively) and funisitis (aOR: 5.66 and 7.17, respectively). AF sludge was not independently associated with acute inflammation nor funisitis. In twin gestations, a short CL and a positive FFN at 22 to 26 weeks are associated with acute but not chronic inflammation on placental histology. These findings imply that mechanisms underlying preterm birth in twins that result in positive screening tests weeks prior to delivery are not reflected as chronic placental inflammation. Therefore, pathologic interpretation of etiologic mechanisms for preterm birth may be limited using solely histologic reports.

Fetal death: an extreme manifestation of maternal anti-fetal rejection.

The aim of this study was to determine the association between chronic placental inflammation and amniotic fluid (AF) markers of maternal anti-fetal rejection as well as the presence of microorganisms in the AF fluid of patients with fetal death. This cohort study included 40 patients with fetal death whose placentas were examined for chronic inflammatory lesions and whose AF chemokine ligand (CXCL)10 and interleukin (IL)-6 concentrations were determined by immunoassays. AF was processed for bacteria, mycoplasmas and viruses using cultivation and molecular microbiologic techniques (i.e. PCR-ESI/MS). (1) The most prevalent placental findings were maternal vascular underperfusion (63.2%, 24/38), followed by chronic inflammatory lesions (57.9%, 22/38); (2) chronic chorioamnionitis (18/38) was three times more frequent than villitis of unknown etiology (6/38); (3) an elevated AF CXCL10 concentration (above the 95th centile) was present in 60% of the cases, and a receiver operating characteristics (ROC)-derived cut-off of 2.9 ng/mL had a sensitivity of 73% and a specificity of 75% in the identification of chronic placental inflammatory lesions; (4) only five cases had microbial invasion of the amniotic cavity, and the presence of microorganisms did not correlate with chronic placental inflammation. In women with unexplained fetal death, there is an association between elevated AF CXCL10 and chronic placental inflammatory lesions. Therefore, we conclude that a subset of patients with fetal death may have endured a breakdown of maternal-fetal tolerance, which cannot be attributed to microorganisms in the amniotic cavity.

Maternal Income during Pregnancy is Associated with Chronic Placental Inflammation at Birth.

Objective This study aims to examine whether maternal household income is associated with histological evidence of chronic placental inflammation. Study Design A total of 152 participants completed surveys of household income and consented to placenta collection at delivery and postpartum chart review for birth outcomes. Placental inflammatory lesions were evaluated via histological examination of the membranes, basal plate, and villous parenchyma by a single, experienced pathologist. Associations between household income and the presence of inflammatory lesions were adjusted for known perinatal risk factors. Results Overall, 45% of participants reporting household income below $30,000/y had chronic placental inflammation, compared with 25% of participants reporting income above $100,000 annually (odds ratio [OR] = 4.23, 95% confidence interval [CI] = 1.25, 14.28; p = 0.02). Middle-income groups showed intermediate rates of chronic inflammatory lesions, at 40% for those reporting $30,000 and 50,000 (OR = 3.60, 95% CI = 1.05, 12.53; p = 0.04) and 38% for those reporting $50,000 to 100,000 (OR = 1.57, 95% CI = 0.60, 4.14; p = 0.36). Results remained significant after adjustment for maternal age, race, and marital status. Conclusion Chronic placental inflammation is associated with maternal household income. Greater occurrence of placental lesions in low-income mothers may arise from a systemic inflammatory response to social and physical environmental factors.

Maternal obesity leads to increased proliferation and numbers of astrocytes in the developing fetal and neonatal mouse hypothalamus

Maternal obesity during pregnancy is associated with chronic maternal, placental, and fetal inflammation; and it elevates the risk for offspring obesity. Changes in the development of the hypothalamus, a brain region that regulates body weight and energy balance, are emerging as important determinants of offspring risk, but such changes are only beginning to be defined. Here we focused on the hypothesis that the pathological exposure of developing hypothalamic astrocytes to cytokines would alter their development.A maternal high-fat diet (mHFD) mouse model was used to investigate changes in hypothalamic astrocytes in the fetus during late gestation and in early neonates by using immunochemistry, confocal microscopy, and qPCR.The number of astrocytes and the proportion of proliferating astrocytes was significantly higher in the arcuate nucleus (ARC) and the supraoptic nucleus (SON) of the hypothalamus at both ages compared to control offspring from normal weight pregnancies. Supplemental to this we found that cultured fetal hypothalamic astrocytes proliferated significantly in response to IL6 (10ng/ml), one of the cytokines significantly elevated in fetuses of obese dams, via the JAK/STAT3 signaling pathway.Thus, maternal obesity during pregnancy stimulated the proliferation and thereby increased numbers of astrocytes in the fetal as well as early neonatal hypothalamus, which may be driven, during fetal life, by IL6.

Chronic Placental Inflammation in Twin Pregnancies.

Background:Chronic placental inflammation, such as villitis of unknown etiology (VUE) and chronic chorioamnionitis (CCA), is considered a placental manifestation of maternal anti-fetal rejection. The aim of this study is to investigate its frequency in twin pregnancies compared to singleton pregnancies.Methods:Three hundred twin placentas and 1,270 singleton placentas were consecutively collected at a tertiary medical center in Seoul, Republic of Korea from 2009 to 2012. Hematoxylin and eosin sections of tissue samples (full-thickness placental disc and chorioamniotic membranes) were reviewed.Results:Non-basal VUE was more frequent in twin placentas than in singleton placentas (6.0% vs 3.2%, p < .05). In preterm birth, CCA was found less frequently in twin placentas than in singleton placentas (9.6% vs 14.8%, p < .05), reaching its peak at an earlier gestational age in twin placentas (29–32 weeks) than in singleton placentas (33–36 weeks). CCA was more frequent in twin pregnancies with babies of a different sex than with those with the same sex (13.8% vs 6.9%, p=.052). Separate dichorionic diamniotic twin placentas were affected by chronic deciduitis more frequently than singleton placentas (16.9% vs 9.7%, p<.05).Conclusions:The higher frequency of non-basal VUE in twin placentas and of CCA in twin placentas with different fetal sex supports the hypothesis that the underlying pathophysiological mechanism is maternal anti-fetal rejection related to increased fetal antigens in twin pregnancies. The peak of CCA at an earlier gestational age in twin placentas than in singleton placentas suggests that CCA is influenced by placental maturation.

Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level expression and demonstrate that IgJ expression was largely attributable to the presence of plasma cells as part of chronic deciduitis and that IgA positive plasma cells are associated with chronic deciduitis occurring in combination with chronic chorioamnionitis and chronic villitis of unknown etiology but not with isolated chronic deciduitis.

A "multi-hit" model of neonatal white matter injury: cumulative contributions of chronic placental inflammation, acute fetal inflammation and postnatal inflammatory events.

We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a "multi-hit" model of neonatal white matter injury (WMI). This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) live-born singleton neonates delivered at Hutzel Women's Hospital, Detroit, MI, from 2006 to 2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation. A total of 425 live-born singleton neonates delivered before the 32nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [odds ratio (OR) 4.7; 95% confidence interval (CI) 1.4-15.8 vs. OR 1.3; 95% CI 0.7-2.6]. Similarly, newborns with funisitis who developed neonatal inflammation-initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6 (95% CI 1.5-8.3) vs. OR 1.7 (95% CI 0.5-5.5)]. The greater the number of these three types of inflammation documented, the higher the risk of VE (P<0.0001). Chronic placental inflammation, acute fetal inflammation, and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm.

Characterization of the Fetal Blood Transcriptome and Proteome in Maternal Anti‐Fetal Rejection: Evidence of a Distinct and Novel Type of Human Fetal Systemic Inflammatory Response

The human fetus is able to mount a systemic inflammatory response when exposed to microorganisms. This stereotypic response has been termed the 'fetal inflammatory response syndrome' (FIRS), defined as an elevation of fetal plasma interleukin-6 (IL-6). FIRS is frequently observed in patients whose preterm deliveries are associated with intra-amniotic infection, acute inflammatory lesions of the placenta, and a high rate of neonatal morbidity. Recently, a novel form of fetal systemic inflammation, characterized by an elevation of fetal plasma CXCL10, has been identified in patients with placental lesions consistent with 'maternal anti-fetal rejection'. These lesions include chronic chorioamnionitis, plasma cell deciduitis, and villitis of unknown etiology. In addition, positivity for human leukocyte antigen (HLA) panel-reactive antibodies (PRA) in maternal sera can also be used to increase the index of suspicion for maternal anti-fetal rejection. The purpose of this study was to determine (i) the frequency of pathologic lesions consistent with maternal anti-fetal rejection in term and spontaneous preterm births; (ii) the fetal serum concentration of CXCL10 in patients with and without evidence of maternal anti-fetal rejection; and (iii) the fetal blood transcriptome and proteome in cases with a fetal inflammatory response associated with maternal anti-fetal rejection. Maternal and fetal sera were obtained from normal term (n = 150) and spontaneous preterm births (n = 150). A fetal inflammatory response associated with maternal anti-fetal rejection was diagnosed when the patients met two or more of the following criteria: (i) presence of chronic placental inflammation; (ii) ≥80% of maternal HLA class I PRA positivity; and (iii) fetal serum CXCL10 concentration >75th percentile. Maternal HLA PRA was analyzed by flow cytometry. The concentrations of fetal CXCL10 and IL-6 were determined by ELISA. Transcriptome analysis was undertaken after the extraction of total RNA from white blood cells with a whole-genome DASL assay. Proteomic analysis of fetal serum was conducted by two-dimensional difference gel electrophoresis. Differential gene expression was considered significant when there was a P < 0.01 and a fold-change >1.5. (i) The frequency of placental lesions consistent with maternal anti-fetal rejection was higher in patients with preterm deliveries than in those with term deliveries (56% versus 32%; P < 0.001); (ii) patients with spontaneous preterm births had a higher rate of maternal HLA PRA class I positivity than those who delivered at term (50% versus 32%; P = 0.002); (iii) fetuses born to mothers with positive maternal HLA PRA results had a higher median serum CXCL10 concentration than those with negative HLA PRA results (P < 0.001); (iv) the median serum CXCL10 concentration (but not IL-6) was higher in fetuses with placental lesions associated with maternal anti-fetal rejection than those without such lesions (P < 0.001); (v) a whole-genome DASL assay of fetal blood RNA demonstrated differential expression of 128 genes between fetuses with and without lesions associated with maternal anti-fetal rejection; and (vi) comparison of the fetal serum proteome demonstrated 20 proteins whose abundance differed between fetuses with and without lesions associated with maternal anti-fetal rejection. We describe a systemic inflammatory response in human fetuses born to mothers with evidence of maternal anti-fetal rejection. The transcriptome and proteome of this novel type of fetal inflammatory response were different from that of FIRS type I (which is associated with acute infection/inflammation).

“Trophoblast islands of the chorionic connective tissue” (TICCT): A novel placental histologic feature

IntroductionWe found isolated or clustered trophoblasts in the chorionic connective tissue of the extraplacental membranes, and defined this novel histologic feature as the “trophoblast islands of the chorionic connective tissue” (TICCT). This study was conducted to determine the clinical significance of TICCT. MethodsImmunohistochemistry for cytokeratin-7 was performed on the chorioamniotic membranes (N = 2155) obtained from singleton pregnancies of 1199 uncomplicated term and 956 preterm deliveries. The study groups comprised 1236 African–American and 919 Hispanic women. Gestational age ranged from 24+0 weeks to 41+6 weeks. Multiple logistic regression analysis was performed to investigate the magnitude of association between patient characteristics and the presence of TICCT. ResultsThe likelihood of TICCT was significantly associated with advancing gestational age both in term (OR: 1.29, 95% CI: 1.16–1.45, p < 0.001) and preterm deliveries (OR: 1.19, 95% CI: 1.07–1.32, p = 0.001). Hispanic women were less likely than African–American women to have TICCT across gestation in term (OR: 0.23, 95% CI: 0.18–0.31, p < 0.001) and preterm pregnancies (OR: 0.41, 95% CI: 0.29–0.58, p < 0.001). Women with a female fetus were significantly more likely to have TICCT than women with a male fetus, in both term (OR: 1.64, 95% CI: 1.28–2.11, p < 0.001) and preterm gestations (OR: 2.04, 95% CI: 1.46–2.85, p < 0.001). TICCT was 40% less frequent in the presence of chronic placental inflammation [term (OR: 0.60, 95% CI: 0.45–0.81, p = 0.001) and preterm gestations (OR: 0.58, 95% CI: 0.40–0.84, p = 0.003)] and in parous women at term (OR: 0.60, 95% CI: 0.44–0.81, p = 0.001). ConclusionsOur findings suggest that the duration of pregnancy, fetal sex, and parity may influence the behavior of extravillous trophoblast and placental mesenchymal cells.

Biological Markers of Stress in Pregnancy: Associations with Chronic Placental Inflammation at Delivery

To estimate the association between biomarkers of chronic stress during pregnancy and chronic placental inflammation. African-American and Caucasian pregnant women were recruited between May 2008 and July 2009. Blood samples were collected between 14 and 226/7 weeks and between 28 and 326/7 weeks of gestation. Samples were analyzed for serum C-reactive protein (CRP), Epstein-Barr virus (EBV) antibody, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH). Placentas were collected at delivery and evaluated for chronic inflammation. Placentas were available from 88 of the 112 women enrolled in the study. EBV antibody levels were significantly higher during both the second and third trimester in women whose placentas demonstrated chronic villitis. CRP values also were significantly higher during the third trimester when chronic villitis was present. No association between placental chronic inflammation and CRH or ACTH was found. Chronic placental inflammation is associated with elevated serum EBV antibody and CRP levels during pregnancy.

Both Acute and Chronic Placental Inflammation Are Overrepresented in Term Stillbirths: A Case-Control Study

Objective. To elucidate differences in the frequency and severity of acute chorioamnionitis (CAM) and chronic villitis in placentas from stillborns compared with liveborns at term and to evaluate other risk factors and placental findings. Design. Case-control study. Setting. All delivery wards in major Stockholm area. Population or Sample. Placentas from stillborn/case (n = 126) and liveborn/control (n = 273) neonates were prospectively collected between 2002 and 2005. Methods. CAM was assessed on a three-grade scale based on the presence and distribution of polymorphonuclear leucocytes in the chorion/amnion. The presence of vasculitis and funisitis was recorded separately. Chronic villitis was diagnosed by the presence of mononuclear cells in the villous stroma. Relevant clinical data were collected from a specially constructed, web-based database. The statistic analyses were performed using multivariable logistic regression. Results. CAM (especially severe, AOR: 7.39 CI: 3.05–17.95), villous immaturity (AOR: 7.17 CI: 2.66–19.33), villitis (<1 % AOR: 4.31 CI: 1.16–15.98; ≥1 %, AOR: 3.87 CI: 1.38–10.83), SGA (AOR: 7.52 CI: 3.06–18.48), and BMI >24.9 (AOR: 2.06 CI: 1.21–3.51) were all connected to an elevated risk of term stillbirth. Conclusions. We found that CAM, chronic villitis, villous immaturity, SGA, and maternal overweight, but not vasculitis or funisitis are independently associated with risk for stillbirth at term.

Risk factors for uteroplacental vascular compromise and inflammation

The purpose of this study was to identify potentially modifiable risk factors of placental injury that reflect maternal uteroplacental vascular compromise (UPVC) and acute and chronic placental inflammation. A prospective epidemiologic study was conducted. A total of 1270 placentas were characterized by gross and microscopic examination. Placental pathologic condition was coded for features of amniotic fluid infection syndrome (AFIS), chronic villitis, UPVC, and fetal vascular obstructive lesions. Odds ratios between UPVC, the acute and the chronic inflammatory lesions, and risk factors of interest were calculated. After adjustment for confounders, we found that women with a history of preterm birth had 1.60 times the odds of chronic inflammation (95% CI, 1.10, 2.55). Women with a previous elective termination had 3.28 times the odds of acute inflammation (95% CI, 1.89, 5.70). The odds of chronic villitis increased with parity; the odds of AFIS decreased with parity. We have identified several predictors of UPVC, AFIS, and chronic villitis. Further studies are needed to examine whether interventions to alter UPVC, AFIS, and chronic villitis will lead to improved pregnancy outcomes.

Gender differences of placental dysfunction in severe prematurity

Rates of several obstetric complications have been reported to vary with fetal gender. We investigated whether a sex difference exists in findings at placental histology of extreme prematurity. Case-control study. University Hospital. Four hundred and thirty-seven consecutive deliveries before 32 weeks of gestation of singleton, liveborn, non-anomalous infants. Obstetric, neonatal and placental histologic findings were compared between male (n= 232) and female (n= 205) neonates. Histologic evidence of acute placental inflammation, uteroplacental vascular pathology, intraplacental vascular pathology and chronic placental inflammation. Male fetuses had similar racial distributions, rate of nulliparity, maternal age, gestational age at delivery, placental weight and fetoplacental weight ratio as female fetuses, but higher birthweight centiles (41 [27] vs 33 [26]). Placental histology showed no association between fetal gender and lesions of acute inflammation (P= 0.08), intraplacental vascular pathology (P= 0.16) or uteroplacental vascular pathology (P= 0.83). However, lesions of chronic inflammation had a significantly higher score in male than in female fetuses (P= 0.001). When we examined the distribution of chronic placental inflammation, significantly more severe lesions were noted in male than in female fetuses at the implantation site (i.e. the area of interstitial trophoblast invasion of the maternal decidua and maternal endovascular trophoblast remodelling), than within the placental villi (chronic villitis) or in the amniochorionic membranes (where interstitial trophoblast invasion is minimal). In premature deliveries at <32 weeks, male fetal gender is associated with placental lesions suggestive of a maternal immune response against the invading interstitial trophoblast. The immunologic basis of these findings deserves further studies.

Shortened gestational age following multifetal pregnancy reduction: can chronic placental inflammation be the explanation?

This study tests the hypothesis that chronic inflammatory foci in the placentas of siblings that undergo multifetal pregnancy reduction are associated with shortened gestational length. Among 446 patients who underwent multifetal pregnancy reduction (MPR), 56 delivered at Mount Sinai Hospital, 37 (66%) had their placentas referred to surgical pathology and 29 (78%) of the 37 patients had tissue sampled from the placenta of the reduced sibling. Slides were reviewed (by C.M.S.) blinded to clinical data. Lesions were diagnosed using previously published criteria. Specifically, inflammatory lesions were correlated with the various perinatal parameters. Non-parametric testing considered p < 0.05 to be significant. Ten (35%) of 29 patients had chronic inflammation in the reduced placenta. Their gestational age at delivery was 33.1 +/- 3.2 weeks, compared to 35.8 +/- 2.3 weeks in those without chronic inflammation (Z = -2.53, p = 0.01). There was no difference between the cases with and those without chronic inflammation in the reduced placenta, in regard to past reproductive history or clinical assessment of the MPR procedure (e.g. the number of attempts, duration of the procedure, or post-procedural complications). The majority of patients who underwent MPR did not develop a chronic inflammatory response to the process of 'resorbing' the placental tissues of the reduced sibling. However, a significant number (35%) of women who delivered viable offspring after MPR had chronic inflammation in the placenta, and had a shortened gestational length.

Shortened gestational age following multifetal pregnancy reduction: can chronic placental inflammation be the explanation?

Objective : This study tests the hypothesis that chronic inflammatory foci in the placentas of siblings that undergo multifetal pregnancy reduction are associated with shortened gestational length. Methods : Among 446 patients who underwent multifetal pregnancy reduction (MPR), 56 delivered at Mount Sinai Hospital, 37 (66%) had their placentas referred to surgical pathology and 29 (78%) of the 37 patients had tissue sampled from the placenta of the reduced sibling. Slides were reviewed (by C.M.S.) blinded to clinical data. Lesions were diagnosed using previously published criteria. Specifically, inflammatory lesions were correlated with the various perinatal parameters. Non-parametric testing considered p < 0.05 to be significant. Results : Ten (35%) of 29 patients had chronic inflammation in the reduced placenta. Their gestational age at delivery was 33.1 &#45 3.2 weeks, compared to 35.8 &#45 2.3 weeks in those without chronic inflammation ( Z = &#109 2.53, p = 0.01). There was no difference between the cases with and those without chronic inflammation in the reduced placenta, in regard to past reproductive history or clinical assessment of the MPR procedure (e.g. the number of attempts, duration of the procedure, or post-procedural complications). Conclusion : The majority of patients who underwent MPR did not develop a chronic inflammatory response to the process of 'resorbing' the placental tissues of the reduced sibling. However, a significant number (35%) of women who delivered viable offspring after MPR had chronic inflammation in the placenta, and had a shortened gestational length.