Accuracy of prenatal culture in predicting intrapartum group B streptococcus colonization status

Abstract

Objective: To evaluate the positive predictive value (PPV) of group B Streptococcus (GBS) cultures at 35–37 weeks of gestation relative to GBS colonization status at delivery.

Methods: Rectovaginal swabs from 221 women at labor in four Lisbon hospitals were collected for GBS screening according to the CDC guidelines.

Results: The PPV was 24.4%. IAP was administered to 100% of prenatally GBS positive women. There was no case of early onset GBS disease (EOD).

Conclusions: Poor accuracy of prenatal cultures in identifying true candidates for IAP highlights the need for Portuguese clinical and laboratory guidelines to prevent EOD and antibiotic overtreatment of pregnant women.     

The usefulness of the universal culture-based screening and the efficacy of intrapartum prophylaxis of group B Streptococcus infection

Abstract

Objective: To evaluate the usefulness of universal culture-based GBS screening at 35–37?weeks of gestation, assess the efficacy of intrapartum antibiotic administration (IAP) and investigate factors influencing the infection rate in neonates.

Methods: Out of 1653 pregnant women 304 (18.4%) further analyzed were GBS positive directly before the delivery, among them 69 were false GBS negative on antenatal screening. Various variables regarding parturients’ and newborns’ characteristics were taken into account in order to achieve the objective of the study.

Results: Out of 304 GBS-positive patients directly before the delivery, culture-based screening was positive in 72.4%, while 22.7% presented with GBS-negative screening and received no IAP. No single culture-confirmed early-onset GBS disease was observed.

Conclusions: IAP is an effective way of early-onset GBS disease prevention, however prenatal screening would be most efficient if performed intrapartal.     

Acute and chronic respiratory diseases in pregnancy: Associations with spontaneous premature rupture of membranes

Objective. To examine whether acute and chronic respiratory diseases are associated with an increased risk of spontaneous premature rupture of the membranes (PROM).

Methods. We used the 1993–2004 National Hospital Discharge Survey data of singleton deliveries in the USA (N = 41 250 539). The International Classification of Diseases Ninth Revision was utilized to identify acute (acute upper respiratory diseases, viral/bacterial pneumonia, and acute bronchitis/bronchiolitis) and chronic (chronic bronchitis and asthma) respiratory conditions and spontaneous PROM. All analyses were adjusted for potential confounders.

Results. The incidence of PROM was 5%, and rates of acute and chronic respiratory conditions were 2.1 and 9.5 per 1000 pregnancies, respectively. Chronic bronchitis was associated with a reduced risk of PROM (RR 0.39, 95% CI 0.31, 0.48). Asthma was significantly associated with PROM at preterm (RR 1.15, 95% CI 1.14, 1.17) and term (RR 1.27, 95% CI 1.23, 1.30). Stratification by race showed that acute upper respiratory disease was associated with preterm PROM in whites (RR 1.90, 95% CI 1.71, 2.11) and blacks (RR 6.76, 95% CI 5.67, 8.07). Viral/bacterial pneumonia was associated with preterm PROM in blacks and term PROM in both races. Asthma was associated with term PROM in blacks but not whites.

Conclusions. Acute respiratory diseases and asthma during pregnancy are associated with spontaneous PROM, with substantially stronger association among blacks than whites. We speculate that timely diagnosis and treatment, coupled with closely mentoring of pregnant women may help reduce the rate of PROM and associated complications.     

A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection

Objective: Preterm prelabor rupture of membranes (preterm PROM) accounts for 30–40% of spontaneous preterm deliveries and thus is a major contributor to perinatal morbidity and mortality. An amniotic fluid (AF) interleukin-6 (IL-6) concentration is a key cytokine for the identification of intra-amniotic inflammation, patients at risk of impending preterm delivery and adverse pregnancy complications. The conventional method to determine IL-6 concentrations in AF is an enzyme-linked immunosorbent assay (ELISA). However, this technique is not available in clinical settings, and the results may take several days. A lateral flow-based immunoassay, or point of care (POC) test, has been developed to address this issue. The objective of this study was to compare the performance of AF IL-6 determined by the POC test to that determined by ELISA for the identification of intra-amniotic inflammation in patients with preterm PROM.

Materials and methods: This retrospective cohort study includes 56 women with singleton pregnancies who presented with preterm PROM. Amniocentesis was performed at the time of diagnosis, and AF was analyzed using cultivation techniques for aerobic and anaerobic bacteria as well as genital mycoplasmas. AF Gram stain and AF white blood cell counts were determined. AF IL-6 concentrations were measured using both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation defined as AF ELISA IL-6?≥?2600?pg/ml. A previously determined cut-off of 745?pg/ml was used to define a positive POC test.

Results: (1) The POC test for AF IL-6 concentrations had 97% sensitivity and 96% specificity for the identification of intra-amniotic inflammation, as defined using ELISA among patients with preterm PROM and (2) the diagnostic performance of the POC test for IL-6 was strongly correlated to that of an ELISA test for the identification of intra-amniotic inflammation and was equivalent for the identification of acute inflammatory placental lesions and microbial invasion of the amniotic cavity (MIAC).

Conclusion: A POC AF IL-6 test can identify intra-amniotic inflammation in patients with preterm PROM. Results can be available within 20?min – this makes it possible to implement interventions designed to treat intra-amniotic inflammation and improve pregnancy outcomes.     

The negative predictive value of cervical interleukin-6 for the risk assessment of preterm birth

Abstract

Objective: To determine the potential clinical use of cervical interleukin-6 (IL-6) as a negative predictor of preterm birth in symptomatic women.

Study design: Observational prospective study carried out in a tertiary hospital.

Patients and methods: We studied 100 singleton pregnant women with threatened preterm delivery and intact membranes, between 24 and 34 weeks, recruited during the period 2006–2008. A cervical swab for IL-6 detection was taken and a transvaginal ultrasound scan was performed for measuring the cervical length.

Results: Five women delivered within 2?d and six women within 7?d. A high cervical IL-6 concentration was found in these women. The area under the ROC curve for cervical IL-6 was 0.97 for deliveries within 2?d after the test, and 0.85 for deliveries within 7?d. The optimal cut-off point was a cervical IL-6 concentration of 210?pg/ml. The negative predictive value (NPV) was 100% for deliveries within 2?d, and 98.5% for deliveries within 7?d (when considering a prevalence of preterm birth of 8%). Cervical IL-6 and sonographic measurement of cervical length showed similar NPV.

Conclusion: A low-cervical IL-6 concentration can accurately identify symptomatic women with a very low chance to progress to preterm birth within 2–7?d.     

Intrapartum antibiotic prophylaxis failure and group-B streptococcus early-onset disease

Objectives.?To determine factors influencing intrapartum antibiotic prophylaxis (IAP) failure in the prevention of group B streptococcus (GBS) early-onset disease (EOD).

Methods.?GBS EOD case is defined as isolation of GBS from a normally sterile body site (e.g. blood or cerebrospinal fluid) in infants aged?≤7 days. During a consecutive 93-month period, GBS EOD cases and care data were reviewed.

Results.?Seventy-nine GBS EOD cases were registered; 67 infants were born to women who received no i.v. antibiotics during labor. The 12 EOD cases exposed to IAP were more likely to be associated with emergency caesarean section (p?=?0.0015), maternal obstetric risk factors (ORFs) (p?=?0.0061), particularly intrapartum fever (p?=?0.0002), and to present with signs of illness at birth (p?=?0.0015). Correct dosages, agents, and timing were registered in three cases only; of which two were associated with intrapartum fever.

Conclusions.?ORFs, emergency caesarean section, and signs of illness at birth are significantly associated with GBS EOD in infants exposed to IAP. This study also suggests that recommended IAP agents, dosages, and timing are infrequently associated with EOD. Strict protocol adherence is recommended in all cases.     

Cervical dilatation thresholds for initiation of group B streptococcus antibiotic prophylaxis for women with spontaneous preterm labor

Objective: To determine the optimal time for initiating group B streptococcus (GBS) antibiotic prophylaxis for women in spontaneous preterm labor.

Methods: In total, 227 women delivering singleton infants after presenting with spontaneous preterm labor and intact membranes at 24 0/7–36 6/7 weeks were evaluated, as well as 150 undelivered women with threatened preterm labor during the same time period. The date and time of each cervical examination throughout labor were recorded. We calculated the percentages who would have correctly received at least 4?h of GBS prophylaxis if antibiotics were routinely initiated for various cervical dilatation thresholds during labor, as well as the percentage of undelivered women who would have received unnecessary antibiotic exposure at each cervical dilatation cutoff.

Results: Delaying antibiotics until cervical dilatation reached 2?cm or greater would have resulted in 62.1% receiving four or more hours of antibiotics, compared to 66.5% if antibiotics were started on all women at admission (p?=?0.33), while significantly reducing unnecessary antibiotic exposure in undelivered women from 100% to 62.0% (p?Conclusions: GBS antibiotic prophylaxis may reasonably be withheld for women with suspected preterm labor until the cervix reaches 2?cm or greater at any time during labor.     

Prevention of early onset group B streptococcal disease by universal antenatal culture-based screening in all public hospitals in Hong Kong

Objectives: To determine the prevalence of maternal colonization with group B streptococcus (GBS), and early onset GBS disease (EOGBSD) after implementation of universal screening.

Methods: This was a three-year retrospective cohort study on universal antenatal rectovaginal culture-based screening and intrapartum antimicrobial prophylaxis (IAP) to colonized women in the public sector in Hong Kong. Routinely collected data including maternal colonization and EOGBSD were retrieved.

Results: Of 113,989 GBS screening performed, 21.8% were positive. The colonization rate was higher in the public hospitals (higher risk) than in the Maternal and Child Health Centers (lower risk) (23.7% vs 18.1%, p?p?Conclusions: Maternal GBS colonization rate was higher than previously reported, and varied with different risk populations. EOGBSD reduced after universal screening.     

Screening and management of maternal colonization with Streptococcus agalactiae: an Italian cohort study

Introduction: Streptococcus agalactiae (Group B streptococcus [GBS]) is the most common cause of sepsis and meningitis in infants <3 months of age. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing the transmission of GBS to newborns. The Centers for Disease Control and Prevention (CDC) guidelines suggest vaginal and rectal cultures to assess GBS colonization between 35 and 37 weeks’ gestation.

Methods: Between July and December 2013, we identified 535 women admitted to the Obstetric and Gynecology Unit of Cardarelli Hospital (Campobasso, Italy) for delivery. We evaluated the indications for IAP, complete execution of IAP, and neonatal outcomes.

Results: Our sample included 468 women and 475 live births. Correct screening for GBS was executed in 241 cases (51.5%), the number of women colonized was 96 (30.2%), and 136 women had indications to receive IAP, but only 68 (50%) received adequate treatment.

Conclusions: GBS colonization status should be determined by collecting both vaginal and rectal specimens at 35–37 weeks’ gestation. Inadequate screening for GBS and incorrect IAP led to an increased incidence of early-onset disease in newborns. Local public health agencies should promote surveillance and educational programs to prevent neonatal GBS infections.     

High- but not low-grade histologic chorioamnionitis is associated with spontaneous preterm birth in a Swedish cohort

Objective: To examine whether different grades of placenta inflammation are associated with risk for spontaneous preterm birth, taking into consideration maternal and delivery factors. Placentas from spontaneous preterm births were compared with a control group from full-term deliveries.

Methods: Placentas from 98 full-term, 71 late preterm (gestational week 34–37), and 65 early preterm (gestational week 22–33) singleton deliveries were analysed from the Karolinska University Hospital in Stockholm. The placentas were examined for histologic chorioamnionitis (HCA) grade 1 (low) and 2 (high). Mother, child, and delivery parameters were collected from maternity centre and delivery forms.

Results: There was a relatively low incidence of HCA in the preterm groups (26.7% and 38.5% in the late and early preterm groups, respectively). HCA 2 was most common in the early preterm group and HCA 1 was most common in the full-term group. The odds of early preterm birth was lower for placentas with HCA 1 compared to HCA 2 (OR?=?0.17) and higher for placentas with HCA 2 compared to no HCA (OR?=?2.17).

Conclusions: Despite a relatively low incidence of HCA in the preterm groups, HCA 2 seems to be associated with early preterm birth whereas HCA 1 seems to be part of the full-term delivery.     

Predictors for prolonged interval from premature rupture of membranes to spontaneous onset of labor at term

Objective: To identify predictors for prolonged interval from premature rupture of membranes (PROM) to spontaneous onset of labor in women presenting with PROM and low Bishop score at term.

Methods: A retrospective study of women presenting with PROM and Bishop score?Results: Among 625 women who met inclusion criteria, 155 (24.8%) had a prolonged interval to onset of labor. In multivariate analysis, prolonged PROM was associated with (OR, 95%CI) cervical dilatation (0.35, 0.24–0.52, p?p?p?=?0.004). A multivariable prediction model including maternal age, parity, cervical dilatation and effacement, gestational age and neonatal birthweight was associated with an AUC of receiver–operator characteristic curve of 0.739 (0.631–0.847, p?Conclusion: Uterine contractions and cervical examination parameters can be used for prediction of prolonged interval to spontaneous onset of labor in women with term PROM.     

Group B Streptococcal Colonization and Preterm Labour

Summary: Recent publications have highlighted the controversy regarding the significance of Lancefield Group B Streptococcal (GBS) colonization in pregnancy and preterm delivery. In this prospective study vaginal swabs from 692 women at approximately 24 weeks' gestation were cultured for GBS. GBS was detected in 91 (13.2%) women. The rate of preterm labour (PTL) (<37 weeks) was significantly higher in GBS positive women than in GBS negative women (18.7% versus 5.5%; p< 0.001). This association remained significant even when patients with other recognized factors predisposing to PTL were excluded (11.5% versus 3.9%; p< 0.001). The rate of premature rupture of membranes (PROM) was also significantly higher in GBS positive women (9.9% versus 2.7%; p < 0.005) and remained significantly higher when patients with other recognized risk factors were excluded (6.1% versus 1.8%; p < 0.025). These results unequivocably show that pregnant women who are vaginal carriers of GBS have a significantly increased risk of PROM and PTL.     

Pentraxin 3 in maternal circulation: An association with preterm labor and preterm PROM,but not with intra-amniotic infection/inflammation

Objective.?Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM).

Study design.?This cross-sectional study included women in the following groups: (1) nonpregnant (n?=?40); (2) uncomplicated pregnancies in the first (n?=?22), second (n?=?22) or third trimester (n?=?71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor (n?=?49); (4) PTL and intact membranes who delivered at term (n?=?49); (5) PTL without IAI who delivered preterm (n?=?26); (6) PTL with IAI (n?=?65); (7) preterm PROM without IAI (n?=?25); and (8) preterm PROM with IAI (n?=?77). Maternal plasma PTX3 concentrations were determined by ELISA.

Results.?(1) Maternal plasma PTX3 concentrations increased with advancing gestational age (r?=?0.62, p?<?0.001); (2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29?ng/ml vs. 5.98?ng/ml, p?=?0.013); (3) patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term had a higher median plasma PTX3 concentration than normal pregnant women (p?<?0.001 for all comparisons); (4) similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women (p?<?0.001 for both comparisons); and (5) among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations.

Conclusions.?The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm.     

Use of beta subunit of human chorionic gonadotropin assay as a diagnostic tool for prelabor rupture of membranes

Purpose: The study aimed at assessment of the accuracy of the β-hCG test in vaginal washing fluid for diagnosis of prelabor rupture of membranes (PROM).

Patients and methods: Two groups of pregnant women from 17 to 38 weeks of gestation were recruited. The first group (PROM group) included 50 pregnant women with unequivocal PROM. The other group included 50 pregnant women with intact membranes. A sterile speculum examination was performed. If less than 5?cc was collected or no fluid found, 10?cc sterile saline was sprinkled on the vaginal wall and 5?cc were recollected in a sterile syringe. Two drops of collected fluid were used for qualitative testing of β-hCG. The remaining fluid was used for quantitative assessment of β-hCG.

Results: The quantitative β-hCG test results were significantly higher in PROM group (median and range: 138.5 (23–475) versus 13 (1–55); the difference in medians and 95% CI: 105 (91–166); p value: <.001). The qualitative β-hCG test was positive in 42/50 (84%) of the PROM group, while it was negative in 50/50 (100%) of the intact membranes group. Areas under receiver operating characteristics (AUC) for both the quantitative and qualitative β-hCG tests were high (0.97, 95% CI: 0.91–0.99, p value: <.001 and .92, 95% CI: 0.84–0.96, p value: <.001, respectively). The suggested cut-off of β-hCG for the quantitative test was 32 mIU/ml. The sensitivity of quantitative and qualitative tests are: 94, 95% CI: 83.5–98.7% and 84, 95% CI: 70.9–92.8%, respectively. The specificity of quantitative and qualitative tests are: 94, 95% CI: 83.5–98.7% and 100, 95% CI: 92.9–100%, respectively.

Conclusion: β-hCG test (either quantitative or qualitative) in vaginal washing fluid can be used in the diagnosis of PROM in both preterm and term cases.     

Predictive factors for neonatal survival in women with periviable preterm rupture of the membranes

Abstract

Objective: To identify clinical, hematological or instrumental factors available at the time of the diagnosis that may predict neonatal survival in periviable preterm premature rupture of the membranes (PROM).

Methods: We report on a cohort (n?=?85) of women with periviable PROM (14–23.6 weeks’ gestation) occurring over a 10-year period in a single institution. The main outcome chosen was the survival rate beyond the neonatal period. Variables considered were those available at 24?h after admission.

Results: The overall survival rate was 49%. In the multivariate analysis, significant contributions for the prediction of neonatal survival were provided by four variables: genetic amniocentesis-related cause of PROM (p?<?0.001), gestational age at PROM (p?=?0.019), CRP >?1?mg/dl within 24?h after admission (p?=?0.042) and oligohydramnios (largest vertical pocket ≤2?cm) (p?=?0.041). The corresponding adjusted odds ratio (OR)s were 73.9 (95% CI: 7.9–694.7), 1.5 (95% CI: 1.1–2.0) per week, 0.26 (95% CI: 0.07–0.95) and 0.20 (95% CI: 0.04–0.93), respectively.

Conclusions: Genetic amniocentesis-related cause of PROM, gestational age at PROM, C-reactive protein >1?mg/dl and oligohydramnios are significantly associated with survival in women with periviable PROM. The evaluation of these few and easily available variables may help physicians and patients in the decision-making process of this demanding condition.     

The role of cervical length measurement at 11–14 weeks for the prediction of preterm delivery

Objective.?To determine whether cervical length (CL) measurement at 11–14 weeks is predictive of preterm delivery (PTD).

Methods.?This was a prospective study of a low-risk population of 1113 women, who underwent CL measurement at 11–14 weeks. Mean CL was calculated for deliveries at >37, <37 and <34 weeks. Cut-off limits of 27?mm and 30?mm were used to examine the predictive value of CL.

Results.?Mean?±?SD CL for the entire study population was 40.6?±?5.5?mm. CL was analyzed for term and PTD (<37 weeks) and further analyzed for deliveries at 34–37 and <34 weeks. Mean CL was 38.9?±?5.5?mm for PTD and 40.8?±?5.5?mm for deliveries >37 weeks (p?=?0.001). Receiver operating characteristic analysis showed small predictive value of CL for PTD <37 weeks (sensitivity?=?63.3% and specificity?=?51.1%, area under the curve (AUC)?=?0.60, 95% CI: 0.54–0.66) (p?=?0.001) and did not show any predictive value for PTD <35 weeks (AUC?=?0.55, 95% CI: 0.43–0.67, p?=?0.355) or PTD <32 weeks (AUC?=?0.51, 95% CI: 0.30–0.74, p?=?0.851).

Conclusion.?CL at 11–14 weeks does not appear to be predictive of PTD. Statistical analysis of CL did not show any predictive value for PTD <35 weeks, or <32 weeks and although it showed a predictive value for PTD at <37 weeks, the sensitivity was very low.     

Rapid screening for group B Streptococcus in near-term pregnant women by Granada™ biphasic broth

Background: Prenatal screening for group B Streptococcus (GBS) colonization can reduce the incidence of neonatal GBS infections. We aimed to improve the screening-based approach of GBS in a limited resources antenatal care clinic by using Strep B Granada? Biphasic Broth.

Methods: This study included 80 pregnant women between 35 and 37 weeks of gestation, who attended the antenatal care clinic of Kasr El-Aini University Hospital from November 2013 to January 2014. Two high vaginal swabs were collected, then transported using Amies transport medium. One vaginal swab was processed by conventional culture-based methods on 5% sheep blood agar plates. The other swab was immersed in 3?mL selective enrichment broth (Granada? Biphasic Broth bioMérieux).

Results: Among 80 pregnant women, GBS was detected in 9 (11.25%) of the studied cases within 18–24?hours. Detection of orange-red colonies in GBS Granada broth was 100% specific for the presence of beta-hemolytic group B streptococci.

Conclusion: Using Granada biphasic broth media was easy, affordable and shortened the turnaround time needed for the detection of GBS by conventional culture methods. Routine screening of pregnant women for vaginal GBS colonization by Granada? Biphasic broth would allow properly timed prenatal antimicrobial prophylaxis to prevent possible neonatal infections.     

Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes

Objective: The objectives of this study were to: (1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and (2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM.

Methods: AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations and the occurrence of adverse obstetrical/perinatal outcomes.

Results: (1) PCR/ESI-MS, AF culture, and the combination of these two tests each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; (2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; (3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [ 29% (17/59)]: however, the prevalence of each differed according to the gestational age when PROM occurred; (4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; (5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and (6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) versus 38% (6/16); p?=?0.001].

Conclusions: (1) The frequency of microorganisms in preterm PROM is 40% using both cultivation techniques and PCR/ESI-MS; (2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than AF culture; and (3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation.     

Cervicovaginal fetal fibronectin for the prediction of spontaneous preterm birth in multiple pregnancies: a systematic review and meta-analysis

Objective.?To investigate the accuracy of cervicovaginal fetal fibronectin in predicting preterm birth in women with multiple pregnancies.

Methods.?Systematic review and meta-analysis of predictive test accuracy. Cohort or cross-sectional studies were identified through searches in databases, reference lists, proceedings, and reviews. Study selection, quality assessment, and data extraction were performed. We constructed summary receiver operating characteristic curves and calculated pooled sensitivities and specificities using a bivariate, random-effects meta-regression model. We also calculated summary likelihood ratios and post-test probabilities of preterm birth.

Results.?Fifteen studies (11 in asymptomatic women and 4 in women with symptoms of preterm labor) involving 1221 women with multiple pregnancies were included. Among asymptomatic women with multiple or twin pregnancies, the pooled sensitivities, specificities, and positive and negative likelihood ratios for predicting preterm birth before 32, 34, and 37 weeks' gestation ranged from 33% to 45%, 80% to 94%, 2.0 to 5.5, and 0.68 to 0.76, respectively. Among women with twin pregnancies and threatened preterm labor, the test was most accurate in predicting spontaneous preterm birth within 7 days of testing (pooled sensitivity, specificity, and positive and negative likelihood ratios of 85%, 78%, 3.9, and 0.20, respectively).

Conclusions.?Cervicovaginal fetal fibronectin provides moderate to minimal prediction of preterm birth in women with multiple pregnancies. The test is most accurate in predicting spontaneous preterm birth within 7 days of testing in women with twin pregnancies and threatened preterm labor.