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Aims: To describe the effect of subsequent pregnancies (SSP) on left ventricular (LV) function and outcomes in patients with peripartum cardiomyopathy (PPCM). Methods: Among146 women with PPCM who were prospectively followed at two medical centres in Israel (2007–2019), 75 SSPs (in 50 women) were identified: 8 miscarriages, 8 terminations, and 59 life birth. Results: Forty‐five patients with 59 full‐term SSPs [mean age was 32.9 ± 4.1 years, LV ejection fraction (LVEF) 57.7 ± 5.1%] were analysed. Data on LVEF at 1‐month post‐delivery were available in 46 and at 6 months in 36 SSPs. There was a small decrease in the mean LVEF, mostly at third trimester (57.2 ± 5.6 vs. 54.4. ± 7.3, P < 0.001); and at 1‐mont (57.9 ± 5.7% vs. 55.4 ± 6.1%, P = 0.001) and at 6‐month post‐delivery (57.4 ± 6.1 vs. 55.3 ± 7.9%, P = 0.03). In patients with pre‐SSP LV LVEF ≥55%, a mild reduction in the mean group LVEF was seen at 1‐month post‐delivery (P = 0.009). One patient with pre‐SSP LVEF ≥55% developed severe relapse. In patients with pre‐SSP LVEF <55%, a mild reduction in LVEF was obtained mostly at third trimester (51.1 ± 5.6 vs 47.0 ± 7.4%, P < 0.001), which persisted at 6 months (P = 0.03). A relapse was observed in three (25%) women with LVEF <55%. There was no maternal mortality, 32 patients delivered by caesarean section, and there were no foetal complications. Conclusions: Our study indicates a favourable outcome and low likelihood of maternal mortality associated with SSP in women with a history of PPCM and recovered LV systolic function. SSP was associated with a slight reduction in LVEF mostly during the third trimester, which persisted up to 6 months after delivery. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Lamont R, Sobel J, Carrington D, Mazaki-Tovi S, Kusanovic J, Vaisbuch E, Romero R. Varicella-zoster virus (chickenpox) infection in pregnancy. BJOG 2011; DOI: 10.1111/j.1471-0528.2011.02983.x. Congenital varicella syndrome, maternal varicella-zoster virus pneumonia and neonatal varicella infection are associated with serious fetomaternal morbidity and, not infrequently, mortality. Vaccination against varicella-zoster virus can prevent the disease, and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella-zoster immunoglobulin administration before rash development, with or without antiviral medication, can modify the progression of the disease. [ABSTRACT FROM AUTHOR]

Citation Romero R, Kadar N, Vaisbuch E, Hassan SS. Maternal death following cardiopulmonary collapse after delivery: amniotic fluid embolism or septic shock due to intrauterine infection? Am J Reprod Immunol 2010; 64: 113–125 Problem The amniotic fluid embolism (AFE) syndrome is a catastrophic complication of pregnancy frequently associated with maternal death. The causes and mechanisms of disease responsible for this syndrome remain elusive. Method of study We report two cases of maternal deaths attributed to AFE: (1) one woman presented with spontaneous labor at term, developed intrapartum fever, and after delivery had sudden cardiovascular collapse and disseminated intravascular coagulation (DIC), leading to death; (2) another woman presented with preterm labor and foul-smelling amniotic fluid, underwent a Cesarean section for fetal distress, and also had postpartum cardiovascular collapse and DIC, leading to death. Results Of major importance is that in both cases, the maternal plasma concentration of tumor necrosis factor-α at the time of admission to the hospital and when patients had no clinical evidence of infection was in the lethal range (a lethal range is considered to be above 0.1 ng/mL). Conclusion We propose that subclinical intraamniotic infection may be a cause of postpartum cardiovascular collapse and DIC and resemble AFE. Thus, some patients with the clinical diagnosis of AFE may have infection/systemic inflammation as a mechanism of disease. These observations have implications for the understanding of the mechanisms of disease of patients who develop cardiovascular collapse and DIC, frequently attributed to AFE. It may be possible to identify a subset of patients who have biochemical and immunological evidence of systemic inflammation at the time of admission, and before a catastrophic event occurs. [ABSTRACT FROM AUTHOR]

Citation DiGiulio DB, Romero R, Kusanovic JP, Gómez R, Kim CJ, Seok K, Gotsch F, Mazaki-Tovi S, Vaisbuch E, Sanders K, Bik EM, Chaiworapongsa T, Oyarzún E, Relman DA. Prevalence and diversity of microbes in the amniotic fluid, the fetal inflammatory response, and pregnancy outcome in women with preterm pre-labor rupture of membranes. Am J Reprod Immunol 2010; 64: 38–57 Problem The role played by microbial invasion of the amniotic cavity (MIAC) in preterm pre-labor rupture of membranes (pPROM) is inadequately characterized, in part because of reliance on cultivation-based methods. Method of study Amniotic fluid from 204 subjects with pPROM was analyzed with both cultivation and molecular methods in a retrospective cohort study. Broad-range and group-specific polymerase chain reaction (PCR) assays targeted small subunit ribosomal DNA (rDNA), or other gene sequences, from bacteria, fungi, and archaea. Results were correlated with measurements of host inflammation, as well as pregnancy and perinatal outcomes. Results The prevalence of MIAC was 34% (70/204) by culture, 45% (92/204) by PCR, and 50% (101/204) by both methods combined. The number of bacterial species revealed by PCR (44 species-level phylotypes) was greater than that by culture (14 species) and included as-yet uncultivated taxa. Some taxa detected by PCR have been previously associated with the gastrointestinal tract (e.g., Coprobacillus sp.), the mouth (e.g., Rothia dentocariosa), or the vagina in the setting of bacterial vaginosis (e.g., Atopobium vaginae). The relative risk for histologic chorioamnionitis was 2.1 for a positive PCR [95% confidence interval (CI), 1.4–3.0] and 2.0 for a positive culture (95% CI, 1.4–2.7). Bacterial rDNA abundance exhibited a dose relationship with gestational age at delivery ( R2 = 0.26; P < 0.01). A positive PCR was associated with lower mean birthweight, and with higher rates of respiratory distress syndrome and necrotizing enterocolitis ( P < 0.05 for each outcome). Conclusion MIAC in pPROM is more common than previously recognized and is associated in some cases with uncultivated taxa, some of which are typically associated with the gastrointestinal tract. The detection of MIAC by molecular methods has clinical significance. [ABSTRACT FROM AUTHOR]

Citation Mazaki-Tovi S, Vaisbuch E, Romero R, Kusanovic JP, Chaiworapongsa T, Kim SK, Ogge G, Yoon BH, Dong Z, Gonzalez JM, Gervasi MT, Hassan SS. Hyperresistinemia – a novel feature in systemic infection during human pregnancy. Am J Reprod Immunol 2010 Problem Resistin, originally described as an adipokine, has emerged as a potent pro-inflammatory protein associated with both acute and chronic inflammation. Moreover, resistin has been proposed as a powerful marker of sepsis severity, as well as a predictor of survival of critically ill non-pregnant patients. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma resistin concentrations. Methods of study This cross-sectional study included the following groups: (i) normal pregnant women ( n = 85) and (ii) pregnant women with pyelonephritis ( n = 40). Maternal plasma resistin concentrations were determined by ELISA. Non-parametric statistics was used for analyses. Results (i) The median maternal plasma resistin concentration was higher in patients with pyelonephritis than in those with a normal pregnancy ( P < 0.001); (ii) among patients with pyelonephritis, the median maternal resistin concentration did not differ significantly between those with and without a positive blood culture ( P = 0.3); (iii) among patients with pyelonephritis who were diagnosed with systemic inflammatory response syndrome (SIRS), those who fulfilled ≥3 criteria for SIRS had a significantly higher median maternal plasma resistin concentration than those who met only two criteria; and (iv) maternal WBC count positively correlated with circulating resistin concentration ( r = 0.47, P = 0.02). Conclusion Hyperresistinemia is a feature of acute pyelonephritis during pregnancy. The results of this study support the role of resistin as an acute-phase protein in the presence of bacterial infection during pregnancy. [ABSTRACT FROM AUTHOR]

Citation Vaisbuch E, Romero R, Erez O, Mazaki-Tovi S, Kusanovic JP, Soto E, Dong Z, Chaiworapongsa T, Kim SK, Ogge G, Pacora P, Yeo L, Hassan SS. Activation of the alternative pathway of complement is a feature of pre-term parturition but not of spontaneous labor at term. Am J Reprod Immunol 2010; 63: 318–330 Problem Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous pre-term delivery <34 weeks of gestation. The aim of this study was to determine whether spontaneous pre-term labor (PTL) with intact membranes, intra-amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations. Method of study This cross-sectional study included women in the following groups: (i) non-pregnant ( n = 40); (ii) normal pregnancy (gestational age range 20–36, 6/7 weeks, n = 63); (iii) women at term not in labor ( n = 70); (iv) women at term in spontaneous labor ( n = 59); (v) patients with an episode of PTL who delivered at term ( n = 62); (vi) PTL without IAI who delivered pre-term ( n = 30); and (vii) PTL with IAI who delivered pre-term ( n = 67). Maternal plasma FBb concentrations were determined by ELISA. Results (i) Among patients with PTL, those who had a pre-term delivery either with IAI (1.21 μg/mL, IQR 0.77–2.16) or without IAI (1.13 μg/mL, IQR 0.92–2.08) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 μg/mL, IQR 0.64–1.57; P = 0.007 and P = 0.026, respectively); (ii) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered pre-term ( P = 0.9); (iii) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration ( P = 0.8); (iv) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non-pregnant controls ( P = 0.8) and were not correlated with advancing gestational age ( r = −0.28, P = 0.8). Conclusion (i) Pre-term parturition is associated with activation of the alternative complement pathway in maternal circulation; (ii) such activation is not detectable in spontaneous labor at term; (iii) IAI does not explain the activation of the alternative pathway of complement in PTL. Collectively, these observations suggest that pre-term and term labors have fundamental differences in the regulation of innate immunity. [ABSTRACT FROM AUTHOR]

Citation Mazaki-Tovi S, Vaisbuch E, Romero R, Kusanovic JP, Chaiworapongsa T, Kim SK, Nhan-Chang C-L, Gomez R, Yoon BH, Yeo L, Mittal P, Ogge G, Gonzalez JM, Hassan SS. Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis. Am J Reprod Immunol 2010; 63: 252–262 Problem Visfatin/pre-B-cell-enhancing factor (PBEF) has been implicated in the regulation of the innate immune system, as well as in glucose metabolism. Specifically, visfatin plays a requisite role in delayed neutrophil apoptosis in patients with sepsis. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma visfatin concentration in normal weight and overweight/obese patients. Method of study This cross-sectional study included the following groups: (1) normal pregnant women ( n = 200) and (2) pregnant women with pyelonephritis ( n = 40). Maternal plasma visfatin concentrations were determined by ELISA. Non-parametric statistics was used for analyses. Results (1) The median maternal plasma visfatin concentration was significantly higher in patients with pyelonephritis than in those with a normal pregnancy; (2) among overweight/obese pregnant women, those with pyelonephritis had a significantly higher median plasma visfatin concentration than women with a normal pregnancy; and (3) pyelonephritis was independently associated with higher maternal plasma visfatin concentrations after adjustment for maternal age, pre-gestational body mass index, smoking status, gestational age at sampling, and birthweight. Conclusion Acute pyelonephritis during pregnancy is associated with a high circulating maternal visfatin concentration. These findings suggest that visfatin/PBEF may play a role in the regulation of the complex and dynamic crosstalk between inflammation and metabolism during pregnancy. [ABSTRACT FROM AUTHOR]

Problem Mannose-binding lectin (MBL) is a pattern-recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene that is associated with high MBL serum concentrations is more prevalent among patients with pre-eclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre-eclampsia. Method of study This cross-sectional study included normal pregnant women ( n = 187) and patients with pre-eclampsia ( n = 99). Maternal plasma MBL concentrations were determined by ELISA. Results Women with pre-eclampsia had a higher median maternal plasma MBL concentration than normal pregnant women. MBL concentration distribution curves were three-modal, the subintervals in normal pregnancy were low (<143.7), intermediate (143.7–1898.9) and high (>1898.9 ng/mL). The proportion of normal pregnant women was larger in the low subinterval, while the proportion of patients with pre-eclampsia was larger in the high subinterval ( P = 0.02). Normal pregnant women in the high subinterval had a larger rate of placental underperfusion than those in the low and intermediate subintervals ( P = 0.02). Conclusions The median maternal plasma MBL concentration is elevated in patients with pre-eclampsia and a larger proportion of these patients are in the high subinterval than normal pregnant women, suggesting that this component of the innate immune system is involved in the mechanisms of disease in pre-eclampsia. [ABSTRACT FROM AUTHOR]

Problem CXCL6 is a potent pro-inflammatory neutrophil chemoattractant and activator whose activity during pregnancy is not well-established. The purpose of this study was to determine if CXCL6 is present in amniotic fluid (AF) and if CXCL6 concentrations in AF change with labor (pre-term and term) or intra-amniotic infection/inflammation (IAI). Method of study A cross-sectional study was designed including the following groups: (1) mid-trimester ( n = 65); (2) term no labor ( n = 20); (3) term labor ( n = 44); (4) patients with pre-term labor (PTL) with subsequent term delivery ( n = 57); (5) PTL without IAI who delivered pre-term ( n = 47); and (6) PTL with IAI ( n = 62). AF CXCL6 concentrations were determined by ELISA. Results CXCL6 was present in all term samples, but undetectable in 64/65 mid-trimester specimens. Patients with PTL and IAI had a significantly higher median AF CXCL6 concentration than those with PTL without IAI [228.9 pg/mL (0.0–8344.8) versus 55.7 pg/mL (0–454.4); P < 0.05] and those with PTL and term delivery [41.5 pg/mL (0–279.0); P < 0.05]. The median AF CXCL6 concentration did not change with spontaneous term labor [term no labor: 81.1 pg/mL (8.5–201.7) versus term labor: 75.2 pg/mL (6.7–378.7): P = 0.7]. Conclusion (1) CXCL6 is detectable in AF and its concentration increases with gestational age; (2) IAI results in increased AF CXCL6 concentrations, suggesting that CXCL6 plays a role in the deployment of an inflammatory response; (3) In contrast to related chemokines, specifically IL-8, AF CXCL6 does not appear to be involved in spontaneous term parturition. These observations are novel, and suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity. [ABSTRACT FROM AUTHOR]

Congenital varicella syndrome, maternal varicella-zoster virus pneumonia and neonatal varicella infection are associated with serious fetomaternal morbidity and, not infrequently, mortality. Vaccination against varicella-zoster virus can prevent the disease, and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella-zoster immunoglobulin administration before rash development, with or without antiviral medication, can modify the progression of the disease., (© 2011 No Claim to original US government works BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)