Maternal educational level and preterm birth: Exploring inequalities in a hospital-based cohort study.

Preterm birth has been related to inequalities in maternal educational level, but the causal mechanism is not entirely known. Some factors associated with preterm birth and low educational level such as chronic medical conditions, pregnancy complications and related-health behaviours could have a mediation role in the pathway. This study aimed to evaluate the association between maternal educational level and preterm birth, analysing the mediation role of these factors. We performed a retrospective cohort study based on hospital electronic records of 10467 deliveries that took place in the Hospital Clínic of Barcelona between 2011 and 2017. Poisson regression was used to obtain crude and adjusted relative risk of preterm birth in women with different educational level and the percentage of change in relative risk was calculated when mediation variables were included in the model. Women with a lower educational level had a higher risk of preterm birth (RR 1.57, 95% CI 1.21, 2.03). The loss of association after the inclusion of body mass index in the model suggests an important mediation role of maternal overweight. Other variables such as smoking, drug use, preeclampsia and genitourinary infections also appear to play a role in the observed inequality between women with different levels of education. Efforts to promote health literacy and to improve preventive interventions, before and during pregnancy, could decrease preterm birth rates and perinatal health inequalities.

Outpatient management of preterm prelabor rupture of membranes before 34 weeks: Maternal and neonatal outcomes.

OBJECTIVE: To evaluate the maternal, fetal, and neonatal outcomes of pregnant women complicated with preterm prelabor rupture of membranes (PPROM) eligible for outpatient care. METHODS: This study included a retrospective cohort of patients with singleton pregnancies with PPROM between 23+0 to 34+0 weeks who remained pregnant after the first 72 h. Outpatient management was considered in women with clinical, ultrasound and analytical stability, and easy access to hospital. Maternal, fetal, and neonatal results were compared between women managed as inpatients versus those managed as outpatients. RESULTS: Women eligible for the outpatient management had a better prognostic profile (no anhydramnios, longer cervical length, less intraamniotic infection, and clinical, ultrasound, and analytical stability) and presented a lower gestational age at admission and longer latency to delivery, resulting in a similar gestational age at delivery as the inpatient group. Postpartum curettage, uterine atony, respiratory distress syndrome, and bronchopulmonary dysplasia were less frequent in the outpatient group. Composite maternal-fetal morbidity and mortality outcomes were similar in both groups, while composite neonatal morbidity and mortality outcomes were significantly lower in the outpatient group. CONCLUSION: Outpatient management may be an option for women presenting stable PPROM before 34 weeks when adequate selection criteria are fulfilled. Differences in perinatal outcomes in the outpatient group compared with the inpatient group are probably attributable to baseline characteristics. Further prospective randomized studies are needed to confirm the benefits of outpatient management in PPROM.

Influence of perinatal inflammation on the neurodevelopmental outcome of premature infants.

OBJECTIVE: To evaluate the influence of perinatal inflammation on neurodevelopmental outcome of premature infants. STUDY DESIGN: From a retrospective cohort study of women with preterm labor with intact membranes or preterm prelabor rupture of membranes (PPROM) with an amniocentesis to rule out intra-amniotic inflammation (IAI) and microbial invasion of the amniotic cavity (MIAC), we evaluated neurodevelopmental outcome of their infants born between 24.0 and 34.0 weeks gestation. Women with clinical chorioamnionitis at admission were excluded. Neurodevelopmental outcome was screened with the Ages & Stages Questionnaire (ASQ)-3. We analyzed the relationship between an altered ASQ-3 and antenatal, intra-partum and post-partum factors related to perinatal inflammation. RESULT: Among 98 infants evaluated, 22% had an abnormal score. Amniotic fluid interleukin-6 levels and early-onset sepsis (EOS) were independent factors of an altered ASQ-3 with delivery <26.0 weeks being the strongest predictor. CONCLUSIONS: In premature infants, the presence of IAI, delivery <26.0 weeks and EOS were found to be independent factors of an altered ASQ-3.

Uterine Cervical Length Measurement to Reduce Length of Stay in Patients Admitted for Threatened Preterm Labor: A Randomized Trial.

OBJECTIVE: To study whether knowledge of cervical length (CL) is useful in reducing the length of hospital stay in women admitted because of threatened preterm labor. METHODS: We performed a single-center, parallel, randomized trial at the Hospital Clínic of Barcelona. Inclusion criteria were single pregnancy, gestational age (GA) between 24+0 and 35+6 weeks, Bishop score <6, no parturition within 24-48 h after admission, and no clinical signs of chorioamnionitis, vaginal bleeding, or nonreassuring fetal status. CL measurement was performed 24-48 h after admission. In the control group, the patient and the physician in charge were blinded. In the study group, this information was given; if CL was >25 mm, early discharge within 12-24 h from randomization was recommended. Length of hospital stay was the main outcome. RESULTS: After randomization, 149 patients had complete follow-up (control group, n = 74; study group, n = 75). The mean (SD) length of stay was significantly shorter - 3.0 (2.2) vs. 4.0 (2.0) days (p = 0.004) - in the study group, with a higher proportion of women remaining hospitalized ≤3 days (relative risk [95% confidence interval] 0.43 [0.26-0.70]), with no differences in GA at delivery or preterm birth rate. CONCLUSIONS: Knowledge of CL in women admitted because of threatened preterm labor is useful in reducing length of stay, with no impact on GA at delivery or preterm birth rate.

Cervical Alpha-Actinin-4 Is Upregulated in Women with Threatened Preterm Labor and Microbial Invasion of the Amniotic Cavity.

OBJECTIVE: To characterize the proteome profile of women with threatened preterm labor (PTL) below 34;0 weeks with and without microbial invasion of the amniotic cavity (MIAC) using mass spectrometry in the amniotic fluid (AF) and Western blot analysis in the cervical mucus and the vaginal fluid. SUBJECTS AND METHODS: In the discovery phase, a case-control study including 8 women with MIAC and 7 without matched for gestational age at sampling was performed. Proteomic profile characterization was done using the LTQ VELOS Orbitrap mass spectrometer in the AF. In the validation phase, a selection of the proteins differentially expressed by mass spectrometry in the genital samples of a prospective cohort of 109 women was validated by Western blot analysis. RESULTS: In the discovery phase, the mass spectrometry analysis identified a total of 444 proteins. Sixteen were chosen for validation, being involved in defense (calgranulin A, B, C, C-reactive protein), cytoskeletal remodeling (alpha-actinin-4 [ACTN-4], plastin-2, α2-antiplasmin, vitronectin), metabolism (cystatin-ß, glucose 6 phosphate isomerase, glutathione S-transferase, prostaglandin D2 synthase, corticosteroid-binding globulin), and vascular (α1-antichymotrypsin, hemopexin, endosialin) pathways. In the validation phase, cervical ACTN-4 was the only significantly upregulated protein in women with MIAC with an odds ratio of 6.8 (p = 0.002). CONCLUSIONS: Cervical ACTN-4 was significantly upregulated in the group of women with PTL with MIAC.

Systemic and local inflammatory response in women with preterm prelabor rupture of membranes.

OBJECTIVE: To evaluate the inflammatory pattern in maternal circulation, amniotic cavity, cervix and vagina from women with preterm prelabor rupture of membranes (PPROM) considering the occurrence of microbial invasion of the amniotic cavity (MIAC). METHODOLOGY: A prospective study was performed in 58 women with PPROM before 34+0 weeks of gestational age. Twenty-six proteins were analyzed by a multiple immunoassay in samples of amniotic fluid, serum, cervix and vagina. Association of an inflammatory response in the invasive and non-invasive samples with MIAC was investigated. RESULTS: The rate of MIAC was 36.2% (21/58). Both amniotic fluid IL-6 and cervical C-reactive protein (CRP) showed to be independent predictors of MIAC. A cut-off level of cervical CRP≥1836 pg/mL showed a detection rate of 75%, false positive rate of 19% and positive and negative predictive values to predict MIAC of 67% and 87%, respectively. There were no independent biomarkers of MIAC either in the serum or vaginal compartment. CONCLUSION: A cervical inflammatory response mediated by CRP was observed in PPROM women with MIAC. Evaluation of serum or vaginal samples did not add valuable information regarding the outcome evaluated.

A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid.

OBJECTIVE: To determine the best prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes (PPROM) using selected candidate proteins in the amniotic fluid (AF). MATERIAL AND METHODS: Prospective cohort study. Twenty-six AF proteins were assayed by a multiple immunoassay from 107 women with membranes rupture from 23+0 to 36+6 weeks. The Czech Republic policy is active management, and the majority of women were delivered within 72 h after the rupture of membranes, except for women with PPROM <28+0 weeks who were managed conservatively. The best predictive models to diagnose histological chorioamnionitis and funisitis were calculated by logistic regression depending on the gestational age (GA) at membrane rupture. RESULTS: Both IL-6 and a combination of IL-10, and migration inhibiting factor (MIF) were the best predictive models of histological chorioamnionitis and funisitis, respectively, with sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (LR+) of 62, 83, 37, 93 and 3.6 and of 63, 91, 53, 94 and 7.0, respectively. Depending on whether GA at membrane rupture was <32 or ≥ 32 weeks, IL-10, alone or in combination with MIF and triggering receptor expressed on myeloid cells-1, was the strongest inflammatory biomarker for funisitis (LR+10.6 and 36.6, respectively). CONCLUSION: Regardless of the GA at membrane rupture, IL-6 from the AF was the best predictor of histological chorioamnionitis. Amniotic fluid IL-10 was notably accurate in the prediction of funisitis.

Association of HIV infection with spontaneous and iatrogenic preterm delivery: effect of HAART.

OBJECTIVES: To assess the association between HIV infection and both spontaneous and iatrogenic preterm delivery (PTD), and to explore the impact of HAART on both entities. METHODS: A matched retrospective cohort study was carried out on 517 HIV-infected pregnant women who consecutively attended a university referral hospital between 1986 and 2010. Two controls were assigned for each case. They were matched by ethnicity, smoking, maternal age and educational level. Exclusion criteria were multiple pregnancy and active injection drug use (IDU). PTD was defined as delivery less than 37.0 weeks. Spontaneous PTD included preterm premature rupture of membranes. Iatrogenic delivery was considered if medically indicated. Factors associated with PTD among HIV-infected women were analyzed by logistic regression. RESULTS: A total of 1557 pregnant women were analyzed (519 HIV-infected and 1038 noninfected). The incidence of PTD was 19.7% in HIV-infected women and 8.5% in controls [odds ratio (OR) 2.6; 95% CI 1.9-3.6]. There was a significantly higher incidence of both spontaneous [adjusted OR (AOR) 2.1; 95% confidence interval (CI) 1.5-3.0] and iatrogenic prematurity (AOR 3.2; 95% CI 1.8-5.7). Iatrogenic PTD was significantly associated with the use of HAART during the second half of pregnancy, whereas spontaneous PTD was not related to HAART. CONCLUSION: There is a significant association of HIV infection with PTD, both spontaneous and iatrogenic PTD. HAART use was predominantly associated with iatrogenic PTD.

Clinical and inflammatory markers in amniotic fluid as predictors of adverse outcomes in preterm premature rupture of membranes.

OBJECTIVE: We sought to evaluate gestational age, cervical length, amniotic fluid interleukin (IL)-6, and selected proteomic biomarkers as independent predictors of adverse outcome in preterm premature rupture of membranes (PPROM). STUDY DESIGN: This was a prospective cohort study of 65 consecutive women with PPROM (20.0-34.6 weeks). Gestational age, cervical length, amniotic fluid IL-6, and proteomic biomarkers (calgranulins A and C, and neutrophil defensins 1 and 2) were evaluated at diagnosis. The predictive value for intraamniotic infection and neonatal composite morbidity was calculated by logistic regression. RESULTS: Proteomic biomarkers were independent predictors of intraamniotic infection (odds ratio, 22.1; P=.011) and neonatal composite morbidity (odds ratio, 17.6; P=.02). With the exception of a trend between gestational age and neonatal morbidity (P=.054), none of the other parameters were independent predictors of outcome measures. CONCLUSION: Selected proteomic biomarkers were the only independent predictors of adverse outcomes in PPROM. Contrary to what is reported in preterm labor with intact membranes, gestational age, cervical length, and IL-6 were not.

Clinical and biochemical predictors of very preterm birth in twin-to-twin transfusion syndrome treated by fetoscopy.

OBJECTIVE: To evaluate pre- and postoperative predictors of preterm birth in twin-to-twin transfusion syndrome treated with fetoscopic placental laser coagulation. STUDY DESIGN: Prospective cohort study (n = 166) assessing cervical length (pre and postoperatively), amniotic fluid interleukin-6, serum C-reactive protein and duration of surgery. Logistic regression was used to investigate associations with preterm delivery. RESULTS: Preterm delivery within 7 days, before 28.0 and 32.0 weeks occurred in 4.8%, 16.8%, and 28.9%, respectively. The only significant predictor of delivery within 7 days was postoperative cervical length (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.9). Concerning delivery before 32.0 weeks, preoperative cervical length (OR, 0.9; 95% CI, 0.8-1.0), and gestational age (OR, 0.8; 95% CI, 0.4-0.9) were independent risk factors but the association was weak. The presence of a single survivor after surgery was associated with a clear reduction of risk (OR, 0.3; 95% CI, 0.1-0.6). Inflammatory biomarkers and duration of surgery did not discriminate risk of prematurity. CONCLUSION: No strong preoperative predictive factor of preterm birth could be identified. A single survivor was a strong protective factor of very preterm birth.

Acute coronary artery vasospasm associated with misoprostol for termination of pregnancy.

Prostaglandin E(1) analogues, gemeprost and misoprostol, are the most widely used drugs for medical termination of pregnancy within the first two trimesters of pregnancy. Gemeprost has been reported to be associated with acute cardiovascular accidents in a few cases, but no adverse cardiovascular events have been reported with misoprostol. For this reason, misoprostol has been considered a potentially safer drug and is widely recommended as a first-choice drug in combination with mifepristone. We report a case of a 32-year-old woman with active smoking and obesity, who developed an episode of transient acute coronary artery vasospasm following the administration of intravaginal misoprostol. This report illustrates that misoprostol can also be associated with acute coronary events, although it remains to be evaluated whether the risk is similar or lower to gemeprost.

Predictive value of combined amniotic fluid proteomic biomarkers and interleukin-6 in preterm labor with intact membranes.

OBJECTIVE: To assess proteomic biomarkers and interleukin-6 alone or in combination to predict intraamniotic infection, preterm birth, and neonatal morbidity in preterm labor with intact membranes. STUDY DESIGN: Amniotic fluid interleukin-6 and selected proteomic biomarkers were assayed from 86 patients with preterm labor and intact membranes (22-36 weeks). The predictive value of each marker alone or in combination was evaluated for intraamniotic infection, preterm birth, and neonatal composite morbidity. RESULTS: Both interleukin-6 (odds ratio, 19.5; P = .012) and proteomic biomarkers (odds ratio, 25.2; P = .001) were statistically independent predictors of intraamniotic infection with sensitivity, positive predictive value, and false-positive rates of 25%, 17.6%, and 20% when 1 marker was present and of 75%, 75%, and 4.3% when both were detected. Their combination did not improve prediction of preterm birth or neonatal morbidity. CONCLUSION: The combined use of proteomic biomarkers and interleukin-6 to predict intraamniotic infection shows better accuracy than when used alone.