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Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders.

ABSTRACT: OBJECTIVE:To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. STUDY DESIGN:A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was "adverse neonatal outcome", including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxic-ischemic encephalopathy, intracranial hemorrhage or respiratory distress. RESULTS:Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2-3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1-4.3). CONCLUSION:When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor.

SUBMITTER: Monari F

PROVIDER: S-EPMC4881909 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders.

Monari Francesca F Pedrielli Giulia G Vergani Patrizia P Pozzi Elisa E Mecacci Federico F Serena Caterina C Neri Isabella I Facchinetti Fabio F

PloS one 20160526 5

<h4>Objective</h4>To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders.<h4>Study design</h4>A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was "adverse neonatal outcome", includin ...[more]

PMID: 27228078

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Project description:ObjectiveCurrently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement.MethodsFollowing third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium).ResultsPlacentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10-12) vessels/mm2 vs. normal outcome 13 (12-15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19-50) nM vs. 12 (6-24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11-50) vs. 55 (24-102) mIU/mg, p = 0.007) and human placental lactogen (11 (6-14) vs. 27 (9-50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13-29) vs. 5 (2-15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue.ConclusionThese data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may improve its prediction.

Project description:Fetal and placental growth disorders are common in maternal human immunodeficiency virus (HIV) infection and can be attributed to both the infection and comorbidities not associated with HIV. We describe placental growth disorders and adverse reproductive outcomes in HIV-infected pregnant women whose delivery occurred between 2001-2014 in Vitoria, Brazil. Cases with gestational age (GA) ? than 22 weeks validated by ultrasonography, with placental and fetal weight dimensions at birth, were studied. Outcomes were summarized as proportions of small (SGA), appropriate (AGA), and large (LGA) for GA when the z-score values were below -1.28, between -1.28 and +1.28, or above +1.28, respectively. Of 187 fetal attachment requisitions, 122(65.2%) women and their newborns participated in the study. The median maternal age was 28 years and 81(66.4%) underwent ? 6 prenatal visits. A total of 81(66.4%) were diagnosed before current pregnancy; 68(55.7%) exhibited criteria for acquired immunodeficiency syndrome (AIDS); 64(52.4%) had detectable viral load; 25(20.5%) cases presented SGA placental weight and 6(4.9%) SGA placental thickness. SGA placental area was observed in 41(33.6%) cases, and among the SGA placental weight cases 12(48%) were also SGA fetal weight. Preterm birth (PTB) occurred in 15.6%(19/122) of cases; perinatal death in 4.1%(5/122) and HIV vertical transmission in 6 of 122 (4.9%). Women, ?36 years old, were 5.7 times more likely to have PTB than those under 36. Also, patients with AIDS-defining criteria were 3.7 times more likely to have PTB. Prenatal care was inversely associated with PTB. Statistically significant associations were observed between AGA placental area and Protease Inhibitor usage and between SGA placental weight and SGA area. We found a prevalence of placental growth disorders in HIV-infected pregnant women and values higher than international reference values. The restriction of placental growth was a common disorder, possibly attributed to virus effects or a combination of antiretroviral regimens.

Project description:ObjectiveTo assess the value of in utero placental assessment in predicting adverse pregnancy outcome after reported reduced fetal movements (RFM).MethodA non-interventional prospective cohort study of women (N = 300) with subjective RFM at ≥28 weeks' gestation in singleton non-anomalous pregnancies at a UK tertiary maternity hospital. Clinical, sonographic (fetal weight, placental size and maternal, fetal and placental arterial Doppler) and biochemical (maternal serum hCG, hPL, progesterone, PlGF and sFlt-1) assessment was conducted. Multiple logistic regression identified combinations of measurements (models) most predictive of adverse pregnancy outcome (perinatal mortality, birth weight <10th centile, five minute Apgar score <7, umbilical arterial pH <7.1 or base excess <-10, neonatal intensive care admission). Models were compared by test performance characteristics (ROC curve, sensitivity, specificity, positive/negative predictive value, positive/negative likelihood ratios) against baseline care (estimated fetal weight centile, amniotic fluid index and gestation at presentation).Results61 (20.6%) pregnancies ended in adverse outcome. Models incorporating PlGF/sFlt-1 ratio and umbilical artery free loop Doppler impedance demonstrated modest improvement in ROC area for adverse outcome (baseline care 0.69 vs. proposed models 0.73-0.76, p<0.05). However, there was little improvement in other test characteristics (baseline vs. best proposed model: sensitivity 21.7% [95% confidence interval 13.1-33.6] vs. 35.8%% [24.4-49.3], specificity 96.6% [93.4-98.3] vs. 94.7% [90.7-97.0], PPV 61.9% [40.9-79.3] vs. 63.3% [45.5-78.1], NPV 82.8% [77.9-86.8] vs. 85.2% [80.0-89.2], positive LR 6.3 [2.8-14.6] vs. 6.7 [3.4-3.3], negative LR 0.81 [0.71-0.93] vs. 0.68 [0.55-0.83]) and wide confidence intervals. Negative post-test probability remained high (16.7% vs. 14.0%).ConclusionAntenatal placental assessment may improve identification of RFM pregnancies at highest risk of adverse pregnancy outcome but further work is required to understand and refine currently available outcome definitions and diagnostic techniques to improve clinical utility.

Project description:BackgroundStudies have revealed associations between preceding short and long birth-to-birth or birth-to-pregnancy intervals and poor pregnancy outcomes. Most of these studies, however, have examined the effect of intervals that began with live births. Using data from Bangladesh, we examined the effect of inter-outcome intervals (IOI) starting with a non-live birth or neonatal death, on outcomes in the next pregnancy. Pregnancy spacing behaviors in rural northeast Bangladesh have changed little since 2004.MethodsWe analyzed pregnancy histories for married women aged 15-49 years who had outcomes between 2000 and 2006 in Sylhet, Bangladesh. We examined the effects of the preceding outcome and the IOI length on the risk of stillbirth, neonatal death and spontaneous abortion using multinomial logistic regression models.ResultsData included 64,897 pregnancy outcomes from 33,495 mothers. Inter-outcome intervals of 27-50 months and live births were baseline comparators. Stillbirths followed by IOI's <=6 months, 7-14 months or overall <=14 months had increased risks for spontaneous abortion with adjusted relative risk ratios (aRRR) and 95% confidence intervals = 29.6 (8.09, 108.26), 1.84 (0.84, 4.02) and 2.53 (1.19, 5.36), respectively. Stillbirths followed by IOIs 7-14 months had aRRR 2.00 (1.39, 2.88) for stillbirths. Neonatal deaths followed by IOIs <=6 months had aRRR 28.2 (8.59, 92.63) for spontaneous abortion. Neonatal deaths followed by IOIs 7-14 and 15-26 months had aRRRs 3.08 (1.82, 5.22) and 2.32 (1.38, 3.91), respectively, for stillbirths; and aRRRs 2.81 (2.06, 3.84) and 1.70 (1.24, 3.84), respectively, for neonatal deaths. Spontaneous abortions followed by IOIs <=6 months and 7-14 months had, respectively, aRRRs 23.21 (10.34, 52.13) and 1.80 (0.98, 3.33) for spontaneous abortion.ConclusionIn rural northeast Bangladesh, short inter-outcome intervals after stillbirth, neonatal death and spontaneous abortion were associated with a high risk of a similar outcome in the next pregnancy. These findings are aligned with other studies from Bangladesh. Two studies from similar settings have found benefits of waiting six months before conceiving again, suggesting that incorporating this advice into programs should be considered. Further research is warranted to confirm these findings.

Project description:BACKGROUND:Hyperhomocysteinemia may be a risk factor for endothelial dysfunction. Folate and vitamin B12 regulate the homocysteine metabolic process. This study aimed to evaluate the associations between subsequent events of adverse pregnancy outcome and early variables of homocysteine, folate, and vitamin B12 in pregnant women. METHODS:This multicenter, retrospective, case-control study involved 563 pregnant women with adverse pregnancy outcome and 600 controls. Adverse pregnancy outcomes included one or more of the following events: preeclampsia, preterm birth, low birth weight, and stillbirth. The associations between subsequent events of adverse pregnancy outcome and early variables of homocysteine, folate, and vitamin B12; metabolic parameters; inflammatory markers; anthropometrics; and lifestyle habits at 11-12?weeks of gestation were analyzed using the logistic regression model. RESULTS:Compared to the lower quartile homocysteine concentrations, the upper quartile homocysteine concentrations were associated with preeclampsia, preterm birth and low birth weight. On the contrary, the lower quartile folate concentrations were associated with preeclampsia, preterm birth and low birth weight compared with the upper quartile folate concentrations. The incidence of adverse pregnancy outcome increased progressively from the first to fourth homocysteine quartiles but decreased progressively from the first to fourth folate quartiles. After adjusting for confounding factors, multivariate logistic regression analysis showed that besides systolic blood pressure, diastolic blood pressure, body mass index and age, homocysteine (IV vs I quartile, aOR 5.89, 95% CI 4.08-8.51, P?<?0.001), folate (IV vs I quartile, aOR 0.35, 95% CI 0.25-0.50, P?<?0.001), folate supplementation (yes vs no, aOR 0.55, 95% CI 0.35-0.86, P?=?0.010) during early pregnancy were independently associated with subsequent events of adverse pregnancy outcome, and vitamin B12 was rejected. Of these, the homocysteine revealed the highest odds ratio in all risk variables, and folate showed the lowest odds ratio in all protective variables. CONCLUSIONS:Higher homocysteine concentration and lower folate level during early pregnancy were associated with adverse pregnancy outcome. However, no association was found between vitamin B12 and adverse pregnancy outcome. Supplementation with folate in early pregnancy may reduce adverse pregnancy outcome.

Project description: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.

Project description:BackgroundMalaria during pregnancy is a major contributor to the global burden of adverse birth outcomes including fetal growth restriction, preterm birth, and fetal loss. Recent evidence supports a role for angiogenic dysregulation and perturbations to placental vascular development in the pathobiology of malaria in pregnancy. The Angiopoietin-Tie2 axis is critical for placental vascularization and remodeling. We hypothesized that disruption of this pathway would contribute to malaria-induced adverse birth outcomes.MethodsUsing samples from a previously conducted prospective cohort study of pregnant women in Malawi, we measured circulating levels of angiopoietin-1 (Angpt-1) and Angpt-2 by Luminex (n=1392). We used a preclinical model of malaria in pregnancy (Plasmodium berghei ANKA [PbA] in pregnant BALB/c mice), genetic disruption of Angpt-1 (Angpt1+/- mice), and micro-CT analysis of placental vasculature to test the hypothesis that disruptions to the Angpt-Tie2 axis by malaria during pregnancy would result in aberrant placental vasculature and adverse birth outcomes.FindingsDecreased circulating levels of Angpt-1 and an increased ratio of Angpt-2/Angpt-1 across pregnancy were associated with malaria in pregnancy. In the preclinical model, PbA infection recapitulated disruptions to the Angiopoietin-Tie2 axis resulting in reduced fetal growth and viability. Malaria decreased placental Angpt-1 and Tie2 expression and acted synergistically with reduced Angpt-1 in heterozygous dams (Angpt1+/-), to worsen birth outcomes by impeding vascular remodeling required for placental function.InterpretationCollectively, these data support a mechanistic role for the Angpt-Tie2 axis in malaria in pregnancy, including a potential protective role for Angpt-1 in mitigating infection-associated adverse birth outcomes.FundingThis work was supported by the Canadian Institutes of Health Research (CIHR), Canada Research Chair, and Toronto General Research Institute Postdoctoral Fellowship Award. The parent trial was supported by the European & Developing Countries Clinical Trials Partnership and the Malaria in Pregnancy Consortium, which was funded by the Bill & Melinda Gates Foundation. The funders had no role in design, analysis, or reporting of these studies.

Dataset Information

Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders.

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Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders.

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