Delivery outcomes in the subsequent pregnancy following the conservative management of placenta accreta spectrum disorder: a systematic review and meta-analysis.

OBJECTIVE: Cesarean hysterectomy is generally presumed to decrease maternal morbidity and mortality secondary to placenta accreta spectrum disorder. Recently, uterine-sparing techniques have been introduced in conservative management of placenta accreta spectrum disorder to preserve fertility and potentially reduce surgical complications. However, despite patients often expressing the intention for future conception, few data are available regarding the subsequent pregnancy outcomes after conservative management of placenta accreta spectrum disorder. Thus, we aimed to perform a systematic review and meta-analysis to assess these outcomes. DATA SOURCES: PubMed, Scopus, and Web of Science databases were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: We included all studies, with the exception of case studies, that reported the first subsequent pregnancy outcomes in individuals with a history of placenta accreta spectrum disorder who underwent any type of conservative management. METHODS: The R programming language with the "meta" package was used. The random-effects model and inverse variance method were used to pool the proportion of pregnancy outcomes. RESULTS: We identified 5 studies involving 1458 participants that were eligible for quantitative synthesis. The type of conservative management included placenta left in situ (n=1) and resection surgery (n=1), and was not reported in 3 studies. The rate of placenta accreta spectrum disorder recurrence in the subsequent pregnancy was 11.8% (95% confidence interval, 1.1-60.3; I2=86.4%), and 1.9% (95% confidence interval, 0.0-34.1; I2=82.4%) of participants underwent cesarean hysterectomy. Postpartum hemorrhage occurred in 10.3% (95% confidence interval, 0.3-81.4; I2=96.7%). A composite adverse maternal outcome was reported in 22.7% of participants (95% confidence interval, 0.0-99.4; I2=56.3%). CONCLUSION: Favorable pregnancy outcome is possible following successful conservation of the uterus in a placenta accreta spectrum disorder pregnancy. Approximately 1 out of 4 subsequent pregnancies following conservative management of placenta accreta spectrum disorder had considerable adverse maternal outcomes. Given such high incidence of adverse outcomes and morbidity, patient and provider preparation is vital when managing this population.

The effect of abnormal placentation on maternal serum fetal fraction of cell-free DNA.

OBJECTIVES: Abnormal placentation may affect the maternal serum fraction of cell-free fetal DNA (fetal fraction) determined as part of non-invasive prenatal screening (NIPS). This study aimed to assess whether the fetal fraction can predict placenta accreta spectrum (PAS) with or without placenta previa (PP). We also investigated the impact of trophoblastic invasion depth on the fetal fraction. METHODS: This is a retrospective case-control study of pregnant women with and without abnormal placentation carrying a singleton and having undergone NIPS prior to 20 weeks of gestation. The eligible subjects were selected from a cohort managed at our institution for PAS suspected antenatally. We compared women with normal placentation (controls) to PAS, PP, or PAS + PP cases. Data were abstracted from electronic medical records, and PAS was confirmed histologically. RESULTS: Of the 146 patients in our cohort, 8 controls, 10 PP, 6 PAS, and 7 PAS + PP cases were eligible for the study. Among the groups, there were no significant differences in baseline demographic and clinical characteristics except the median number of prior uterine surgeries. Also, the groups did not significantly differ in their median fetal fraction. The fetal fraction did not discriminate any group when stratified according to the depth of placental invasion, i.e., no PAS, abnormally adherent, and abnormally invasive placenta. CONCLUSIONS: The maternal serum fraction of cell-free fetal DNA measured before 20 weeks of gestation is not predictive of PAS with or without concurrent PP or the depth of trophoblastic invasion.

Outcomes of pregnancies at high-risk for placenta accreta spectrum following negative diagnostic imaging.

OBJECTIVES: To assess the pretest and negative post-test probability for placenta accreta spectrum (PAS) in a group of patients with high-risk clinical factors. METHODS: We included patients with suspected and/or confirmed PAS at our institution over 8 years. Sonography performed by maternal-fetal medicine specialists, and selected patients underwent MRI. Imaging was considered positive if either sonography or MRI suggested PAS. Histopathology was the gold standard for diagnosis of PAS. We assessed the pretest and negative imaging-test probability, and resources required. RESULTS: We identified 82 high-risk patients with the following: (1) a history of ≥1 cesarean section and/or intrauterine gynecologic procedure and placenta previa in the index pregnancy; (2) a history of >3 cesarean deliveries and/or gynecologic procedures regardless of placental location; (3) prior PAS disorder, or retained placenta requiring manual extraction and/or curettage, complicated by postpartum hemorrhage; and (4) suspected cesarean section scar pregnancy. Histopathology confirmed PAS in 52 patients, with pretest probability of 63%. Imaging correctly identified 44/50 cases with PAS, and excluded this condition in 24/30 cases. Thus, the positive and negative post-test probability for PAS following negative imaging was 88 and 20%, respectively. Of the six patients with false-negative imaging, all had either surgical complications or required care beyond that for routine cesarean section. CONCLUSIONS: Although diagnostic imaging is sensitive, the negative posttest probability remains high in women with high pretest probability for PAS. Therefore, women at high risk for PAS should be managed in experienced centers by a multidisciplinary team even if imaging is negative.

Improved management of placenta accreta spectrum disorders: experience from a single institution.

OBJECTIVES: To assess the applicability of a standardized multidisciplinary protocol for managing placenta accreta spectrum (PAS) disorders and its impact on the outcomes. METHODS: We compared patients with PAS manage by a standardized multidisciplinary protocol (T2) to historic controls managed on a case-by-case basis by individual physicians between (T1). The primary outcome is composite maternal morbidity. Secondary outcomes were the rates of surgical complications, estimated blood loss, number of blood products transfused, intensive care unit admissions, ventilator use, and birth weight. Multivariate logistic analysis was used to identify independent predictors of composite maternal morbidity. RESULTS: During T1 and T2, we managed 39 and 36 patients with confirmed PAS, respectively. During T2, the protocol could be implemented in 21 cases (58%). Compared to T1, patients managed during T2 had 70% less composite maternal morbidity (95% CI: 0.11-0.82) and lower blood loss (median, 2,000 vs. 1,100 mL, p=0.008). Also, they were 68% less likely to require transfusion of blood products (95% CI: 0.12-0.81; p=0.01), including fewer units of packed red blood cells (median, 2 vs. 0, p=0.02). Management following the protocol was the only independent factor associated with lower composite maternal morbidity (OR: 0.22; 95% CI: 0.05-0.95; p=0.04). Selected maternal and neonatal outcomes were not different among 12 and 15 patients with suspected but unconfirmed PAS disorders managed during T1 and T2, respectively. CONCLUSIONS: Most patients can be managed under a standardized multidisciplinary protocol for PAS disorders, leading to improved outcomes.

The value of amniotic fluid analysis in patients with suspected clinical chorioamnionitis.

Objective To assess the value of incorporating amniotic fluid (AF) analysis in the management of patients with clinical chorioamnionitis. Methods This was a retrospective cohort study of all women carrying a singleton fetus and managed at our center between 2000 and 2009. We included only those women suspected of chorioamnionitis based on one or more of the following: (1) uterine tenderness, (2) maternal fever, (3) maternal and/or fetal tachycardia and (4) purulent discharge. The management was deemed to be justified if (1) pregnancy was terminated <24 weeks and histology confirmed chorioamnionitis; (2) delivery was performed expeditiously after initial assessment and histology confirmed chorioamnionitis; (3) delivery was delayed for 2-7 days and the patient completed a course of antenatal steroids before 34 weeks; and (4) delivery was delayed ≥7 days and histology was not indicative of chorioamnionitis, or delivery occurred after 37 weeks. Univariate and logistic regression analyses were used as appropriate. Results Of the 77 women with suspected chorioamnionitis, AF analysis was performed in 43 (55.8%) cases, and the management was justified in 63 (81.8%) cases based on the aforementioned criteria. Stepwise regression analysis confirmed AF analysis as a predictor of justified management. The rates of composite morbidity, neonatal sepsis, neonatal death and admissions to neonatal intensive care unit were lower in the justified management group. Conclusion Incorporation of AF analysis into clinical assessment does improve the management of suspected chorioamnionitis.

Evaluation of Serum Fetuin-A and Osteoprotegerin Levels in Patients with Psoriasis.

Psoriasis patients are determined to have a high ratio of coronary artery calcification. Fetuin-A and osteoprotegerin are systemic calcification inhibitors and related to vascular calcification and cardiovascular mortality. In this study we investigated the relationship between fetuin-A and osteoprotegerin levels in psoriasis patients. The study included 40 healthy volunteers and 40 psoriasis patients. Venous blood were collected from healthy volunteers and psoriasis patients in order to search the fetuin-A and osteoprotegerin levels. Disease severity were grouped as mild, moderate and severe according to psoriasis area and severity index (PASI). The relationship between fetuin-A and osteoprotegerin levels and clinical features as sex, PASI and presence of psoriatic arthritis were analyzed. Fetuin-A levels in psoriasis patients were statistically lower than the control group (p < 0.001). In serum osteoprotegerin levels, no statistically significant difference was found in two groups (p > 0.05). Serum fetuin-A and osteoprotegerin level differences were not statistically significant between patients with psoriatic arthritis history and those without. When we grouped patients in respect of their sexes fetuin-A and osteoprotegerin levels of males and females were not significantly different (p > 0.05). No correlation was detected between the ages and PASI scores and the fetuin-A and osteoprotegerin levels of patients. As a result fetuin-A levels in psoriasis patients are found to be low but not related to disease severity. In the light of our results we concluded that fetuin-A may have a role in psoriasis pathogenesis and may contribute to the calcification process developed in psoriasis.

Differential utilization of expanded genetic screening tests in patients of reproductive ages from private and academic practices.

OBJECTIVE: We sought to evaluate the types of genetic screening tests that are performed in women of childbearing ages in New Jersey. METHOD: Data from patients who had a reproductive genetics consultation between January 1, 2012, and July 31, 2012, were stratified according to the referring providers, i.e., those from academic or private practices, and descriptive analyses performed. Unconventional genetic screening was defined as any test ordered by the referring health care provider outside the recommendations from the American Congress of Obstetricians and Gynecologists or the American College of Medical Genetics and Genomics. RESULTS: Overall, 30% of 371 patients referred for a genetic consultation underwent unconventional screening. As compared to patients from academic practices, the relative rate of unconventional screening was 10-fold higher among patients from private practices, resulting in a relative 34-fold increase in the estimated cost in genetic screening (P<0.01). CONCLUSION: This set of preliminary observations highlight the need for further state, nationwide, and international studies to understand the financial, personal, and societal impact that this discrepancy health care system in the use of genetic carrier screening portends.

Serum prolidase activity in psoriasis patients.

This study aimed to evaluate serum prolidase activity and the effects of gender, body mass index (BMI), disease severity and duration, and therapy type on prolidase activity in patients with psoriatic as well as the relationship between serum NO· and prolidase levels in these patients. The study included 29 clinically documented plaque patients with psoriasis and 24 healthy volunteers. Data such as age, sex, BMI, duration and severity of disease, and type of therapy were assessed. NO· levels were determined by the Griess reaction. Serum prolidase assay is based on a colorimetric determination of proline by Chinard's reagent. We did not determine any difference in serum NO· levels of psoriatic patients when compared to controls. Serum prolidase levels in psoriasis patients were significantly higher than those in controls. There was no significant difference in prolidase activity between male and female. No statistically significant correlations were found between serum prolidase levels and BMI, PASI and disease duration. When compared between topical treatment group and systemic treatment group, there was no significant difference in serum prolidase activity. In conclusion, patients with psoriasis exhibit higher serum prolidase activity independent of gender, BMI, disease severity or duration, type of treatments or NO· level. However, further studies are needed to verify these findings as well as altered collagen synthesis in patients with psoriasis.

Pregnancy in a woman with chronic neutrophilic leukemia.

BACKGROUND: Chronic neutrophilic leukemia is a rare myeloproliferative disorder in women of reproductive age. CASE: A pregnant woman with an established diagnosis of chronic neutrophilic leukemia presented at 26 weeks of gestation with splenomegaly, thrombocytopenia, leukocytosis, and anemia. Thrombocytopenia was refractory to medical treatment and, in part, was attributed to splenic sequestration. She delivered a healthy neonate at 35 weeks of gestation by repeat cesarean delivery under general anesthesia. Her preoperative platelet count was 30,000/mL and she was transfused platelets throughout the perioperative period. Her postpartum course was complicated by intraabdominal hemorrhage and severe preeclampsia. She recovered with intensive medical and surgical management. CONCLUSION: Chronic neutrophilic leukemia poses difficult challenges during pregnancy and requires a multidisciplinary approach.

Innate immune system gene polymorphisms in maternal and child genotype and risk of preterm delivery.

OBJECTIVE: There is little information about the combination of genetic variability in pregnant women and their children in relation to the risk of preterm delivery (PTD). In a sub-cohort of 487 non-Hispanic white and 288 African-American mother/child pairs, the Pregnancy Outcomes and Community Health Study assessed 10 functional polymorphisms in 9 genes involved in innate immune function. METHODS: Race-stratified weighted logistic regression models were used to calculate odds ratios for genotype and PTD/PTD subtypes. Polymorphisms significantly associated with PTD/PTD subtypes were tested for mother/child genotype interactions. RESULTS: Three maternal polymorphisms (IL-1 receptor antagonist intron two repeat (IL-1RN), matrix metalloproteinase- -C1562T, and TNF receptor two M196R (TNFR2)) and three child polymorphisms (IL1-RN, tumor necrosis factor-alpha -G308A, and TNFR2) were associated with PTD, but associations varied by PTD subtype and race. Two interactions were detected for maternal and child genotype. Among non-Hispanic white women, the odds of PTD was higher when both mother and child carried the IL-1RN allele two (additive interaction p < 0.05). Among African-American women, the odds of PTD were higher when both mother and child carried the TNFR2 R allele (multiplicative interaction p < 0.05). CONCLUSION: These results highlight the importance of assessing both maternal and child genotype in relation to PTD risk.

Optimized amniotic fluid analysis in patients suspected of intrauterine infection/inflammation.

OBJECTIVE: To determine the combination of amniotic fluid (AF) tests with the best diagnostic accuracy for predicting intrauterine infection/inflammation (IUI) in patients with clinical suspicion of chorioamnionitis. STUDY DESIGN: This is a retrospective study of 34 pregnant women who presented with uterine tenderness, maternal fever, maternal tachycardia, and/or fetal tachycardia and underwent AF analysis. IUI diagnosis was based on placental histology, positive AF bacterial cultures, and/or Gram stain. RESULT: Logistic regression analysis revealed a significant relationship between IUI and AF glucose. Glucose is more sensitive than culture or Gram stain (64% vs. 40% and 20%, respectively). Culture and glucose combined achieved the best diagnostic accuracy (sensitivity, 71%; specificity, 100%; positive and negative predictive values, 100-83%, respectively). CONCLUSION: Positive AF Gram stain or glucose <15 mg/dL strongly suggests IUI in symptomatic patients. If both tests are negative, the result of culture should aid the management.

The clinical use of inflammatory markers during pregnancy.

PURPOSE OF REVIEW: There is overwhelming evidence that intrauterine infection and inflammation play an important role in the pathogenesis of spontaneous preterm labor, preterm prelabor rupture of the membranes and fetal injury resulting in long-term sequelae. Early diagnosis of subclinical infection and inflammation may therefore aid clinicians institute interventions focusing on such adverse outcomes. RECENT FINDINGS: Biomarkers of intrauterine inflammation such as interleukin-6, although sensitive, are not specific. Thus, decision to deliver remote from term because of intrauterine infection and/or inflammation should be based on clinical signs and/or bacterial culture or Gram stain of amniotic fluid. In patients with preterm contractions and intact membranes, the risk of delivery is 1% within the week following a negative fetal fibronectin in cervicovaginal secretions. This aids to decide whether antenatal steroids should be administered to patients presenting with preterm contractions between 24 and 34 weeks' gestation. Biomarkers in cervical secretions and amniotic fluid identify those who may benefit from cerclage when the cervix is shortened (<25 mm) and dilated in the second trimester. SUMMARY: So far, few interventions utilizing inflammatory biomarkers have shown clinical benefit. Future efforts should focus on the quest for accurate biomarkers that can be obtained noninvasively and allow early prediction of subclinical disease to initiate appropriate risk-specific intervention.

The role of gene-environment interaction in predicting adverse pregnancy outcome.

This article focuses on the influence of gene-environment interaction on pregnancy outcome. In particular, we focus on those adverse outcomes related to subclinical infection and the resultant inflammation of gestational tissues. We identify genetic association studies on pregnancy-related disorders with an infectious/inflammatory etiology. All studies in this field have focused on spontaneous preterm delivery and/or preterm and premature rupture of membranes. We discuss those articles where an environmental (infectious) exposure was studied in relation to genetic variability. In these studies, infectious exposure was defined as altered vaginal flora or bacterial vaginosis (BV). Maternal genomic variations influence both tumor necrosis factor-alpha and interleukin-1beta response to BV-related organisms (anaerobic Gram-negative bacteria and Gardnerella vaginalis in particular) in the vagina and the risk of spontaneous preterm birth. Further studies are warranted to confirm these associations, stratify disease risk, and delineate interventions for achieving population health benefits.

TNFA-308G>A polymorphism influences the TNF-alpha response to altered vaginal flora.

OBJECTIVE: To investigate the association between a tumor necrosis factor-alpha (TNF-alpha) gene polymorphism, vaginal TNF-alpha level, and microbial flora in pregnant women. METHODS: Vaginal samples from 203 women at 18-22 weeks' gestation were analyzed for microflora. TNFA-308G>A polymorphism was analyzed by polymerase chain reaction and restriction endonuclease analysis and TNF-alpha concentration was determined by ELISA. Outcome data were subsequently obtained. RESULTS: The vaginal TNF-alpha concentration was elevated in TNFA-308A carriers only in the presence of abnormal vaginal flora. A median TNF-alpha level of 10.94 pg/ml in TNFA-308A carriers with bacterial vaginosis (BV) was significantly higher than that of 1.77 pg/ml in TNFA-308A carriers without BV (P=.02), and 1.72 pg/ml in TNF-308G homozygotes with BV (P=.01). CONCLUSION: The TNFA-308G>A polymorphism influences the local TNF-alpha response to altered vaginal microflora. This suggests that the nature of the host response to microbial invasion in the lower female genital is genetically determined.

Vaginal nitric oxide in pregnant women with bacterial vaginosis.

PROBLEM: To evaluate vaginal nitric oxide (NO) production in response to alterations in the vaginal microbial flora. METHOD OF STUDY: Cervicovaginal lavage samples from 206 women at 18-22 weeks of gestation were tested for NO, interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor-alpha and the inducible 70 kDa heat shock protein (hsp70). Bacterial vaginosis (BV) was diagnosed based on gram staining of vaginal smears. RESULTS AND CONCLUSIONS: Elevated NO (>2.14 mmol/L) was associated with a diagnosis of BV (38% versus 11%, P < 0.008) as well as an increased median vaginal IL-1ra concentration (72.5 ng/ml versus 36.6 ng/ml, P = 0.041). Elevated vaginal NO was also associated with vaginal hsp70 and this relationship was independent of BV status or IL-1ra concentrations (P < 0.026). We conclude that vaginal hsp70 release in response to abnormal vaginal microflora may trigger NO production in an attempt to minimize the pathological consequences of this altered milieu.