Histological villous maturation in placentas of complicated pregnancies.

Chorioamnionitis and preeclampsia account for the majority of preterm births worldwide. Thus far, adequate methods for early detection or prevention of these diseases are lacking. In preeclampsia, accelerated villous maturation is believed to compensate placental insufficiency. However, little is known about the effects of placental inflammation in chorioamnionitis on villous maturation. Therefore, we established a set of morphological parameters to evaluate histological villous maturity in pregnancies complicated by chorioamnionitis and preeclampsia. Preterm placentas complicated by chorioamnionitis or preeclampsia were compared to idiopathic preterm placentas and term controls. Histological villous maturation was analyzed by means of 17 histological markers. Fourteen of these markers provided information on absolute and relative numbers of the terminal villi (TV), the extent of their vascularization (using CD31-stained sections) and their exchange capacities. In addition, the numbers of syncytial bridges, syncytial apoptotic knots and shed syncytiotrophoblasts were counted. Accelerated villous maturation in preeclampsia was demonstrated by means of histological villous remodeling and confirmed by 11 relevant markers. Chorioamnionitis, however, only showed increased area of fetal capillaries. In preeclampsia, placentas may transition from growth to maturation earlier than placentas in normal pregnancies, whereas in chorioamnionitis placental changes are more acute and therefore less elaborated at a structural level. Regression analysis suggests the number of all villi and the number of terminal villi as a percentage of all villi as parameters to evaluate histological villous maturity in preeclamptic placentas and to assist diagnosis. However, we would recommend to analyze all 11 relevant parameters to judge placental maturity in detail.

Risk of adverse pregnancy outcomes in women with periodontal disease and the effectiveness of interventions in decreasing this risk: protocol for systematic overview of systematic reviews.

BACKGROUND: Periodontal disease is an inflammatory disease of the tissues supporting the teeth. Women who have periodontal disease while pregnant may be at risk of adverse pregnancy outcomes. Although the association between periodontal disease and adverse pregnancy outcomes has been addressed in a considerable number of systematic reviews and meta-analyses, there are important differences in the conclusions of these reviews. Systematic reviews assessing the effectivity of various therapeutic interventions to treat periodontal disease during pregnancy to try and reduce adverse pregnancy outcomes have also arrived at different conclusions. We aim to provide a systematic overview of systematic reviews comparing the frequency of adverse pregnancy outcomes between women with and without periodontal disease and/or evaluating the effect of preventive and therapeutic interventions for periodontal disease before or during pregnancy on adverse pregnancy outcomes. METHODS: We will include systematic reviews reporting on studies comparing adverse pregnancy outcomes: (i) between women with or without periodontal disease before (<6 months) or during pregnancy and/or (ii) according to preventive or therapeutic interventions for periodontal disease. Eligible interventions include (combinations of) the following: oral hygiene education, use of antibiotics, subgingival scaling, and root planing. For preventive and/or therapeutic reviews, the following comparisons will be considered: no intervention, a placebo intervention, or an alternative intervention. Our primary adverse pregnancy outcomes of interests are maternal mortality, preterm delivery, and perinatal mortality. Two reviewers will independently identify eligible published and unpublished systematic reviews from six electronic databases and using hand searching of reference lists and citations. Data items extracted from included systematic reviews are based on the Cochrane Effective Practice and Organization of Care checklist and the preferred reporting items for systematic review and meta-analysis (PRISMA) statement. In our narrative data synthesis, we will consider risk of bias of individual reviews, focusing mainly on the conclusions of the highest quality reviews using the assessment of multiple systematic reviews (AMSTAR) checklist. Disagreements during search, selection, data extraction, and risk of bias assessment will be resolved through discussion and/or consultation of a third reviewer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015030132.

Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome.

Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48-0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15-14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31-36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy outcomes.

Automated auditory brainstem response in preterm newborns with histological chorioamnionitis.

OBJECTIVE: We investigated whether histological chorioamnionitis is associated with an adverse neonatal hearing outcome. METHODS: Two cohorts of very preterm newborns (n = 548, gestational age ≤ 32.0 weeks) were linked to placental histology and automated auditory brainstem response (AABR) outcome. RESULTS: In multivariable analyses, an abnormal AABR was not predicted by the presence of histological chorioamnionitis, either with or without fetal involvement (OR 1.4, 95% CI 0.5 - 3.8, p = 0.54 and OR 1.1, 95% CI 0.4-3.0, p = 0.79, respectively). Significant predictors of abnormal AABR included, e.g. birth weight (per kg increase: OR 0.2, 95% CI 0.0-0.6, p = 0.006), umbilical cord artery pH (per 0.1 increase: OR 0.7, 95% CI 0.5-0.9, p = 0.005) and mechanical ventilation (OR 3.7, 95% CI 1.2-11.6, p = 0.03). CONCLUSIONS: Histological chorioamnionitis was not associated with an adverse neonatal hearing outcome in two cohorts of very preterm newborns. Indicators of a complicated neonatal clinical course were the most important predictors of an abnormal hearing screening.

A clinical prediction rule for histological chorioamnionitis in preterm newborns.

BACKGROUND: Histological chorioamnionitis (HC) is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns. AIM: Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF) in preterm newborns. METHODS: Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤ 32.0 weeks) born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216) or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206). HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth. RESULTS: HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92-0.98), a positive predictive value of 80% (95%CI = 74-84%), and a negative predictive value of 93% (95%CI = 88-96%). Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88-0.96), positive predictive value 59% (95%CI = 52-62%), and negative predictive value 97% (95%CI = 93-99%). External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values. CONCLUSION: Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation.

Sex differences in lung gas volumes after lipopolysaccharide-induced chorioamnionitis in fetal sheep.

BACKGROUND: Preterm female infants have a survival advantage and enhanced lung development, which is an important determinant of preterm survival. OBJECTIVE: Given the modulation of lung development by fetal exposure to infection/inflammation, we hypothesized that female fetuses have enhanced lung maturational responses to chorioamnionitis compared with male fetuses. METHODS: Time-pregnant ewes received intra-amniotic injections with saline (n = 60) or lipopolysaccharide (LPS) at 2 days (n = 30) or 7 days (n = 45) before surgical delivery at 123 to 125 days of gestation (term: ∼147 days). We assessed inflammatory responses in bronchoalveolar lavage fluid and cord blood, lung maturation with pressure-volume curves, and lung structure. RESULTS: Lung gas volume showed differences between the sexes after 2 days LPS (male 4.6 [1.2] mL/kg, female 7.7 [4.4] mL/kg; P = 0.02) and 7 days LPS (male 20.5 [9.3] mL/kg, female 27.0 [7.0] mL/kg; P = 0.01). The control group was not different by sex (male 8.0 [3.6] mL/kg, female 8.9 [3.9] mL/kg; P > 0.05). No difference in lung structure and in pulmonary and systemic inflammatory response was evident by sex. CONCLUSION: Preterm female sheep fetuses had increased lung gas volumes after exposure to LPS, without any detectable differences in fetal inflammatory responses.