Is Group B Streptococcus Colonization Associated with Maternal Peripartum Infection in an Era of Routine Prophylaxis?

OBJECTIVE: This study aimed to assess whether colonization with group B streptococcus (GBS) is associated with maternal peripartum infection in an era of routine prophylaxis. STUDY DESIGN: This study presented a secondary analysis of women delivering ≥37 weeks who underwent a trial of labor from the U.S. Consortium on Safe Labor (CSL) study. The exposure was maternal GBS colonization and the outcome was a diagnosis of chorioamnionitis, and secondarily, analyses were restricted to deliveries not admitted in labor and measures of postpartum infection (postpartum fever, endometritis, and surgical site infection). Logistic regression with generalized estimating equations was used accounting for within-woman correlations. Models adjusted for maternal age, parity, race, prepregnancy body mass index, pregestational diabetes, insurance status, study site/region, year of delivery, number of vaginal exams from admission to delivery, and time (in hours) from admission to delivery. RESULTS: Among 170,804 assessed women, 33,877 (19.8%) were colonized with GBS and 5,172 (3.0%) were diagnosed with chorioamnionitis. While the frequency of GBS colonization did not vary by chorioamnionitis status (3.0% in both groups), in multivariable analyses, GBS colonization was associated with slightly lower odds of chorioamnionitis (adjusted odds ratio [AOR]: 0.89; 95% confidence interval [CI]: 0.83-0.96). In secondary analyses, this association held regardless of spontaneous labor on admission; and the odds of postpartum infectious outcomes were not higher with GBS colonization. CONCLUSION: In contrast to historical data, GBS colonization was associated with lower odds of chorioamnionitis in an era of routine GBS screening and prophylaxis. KEY POINTS: · Data in an era prior to routine group B streptococcus (GBS) screening and prophylaxis showed that maternal GBS colonization was associated with a higher frequency of maternal peripartum infection.. · In the current study, GBS colonization was associated with lower odds of chorioamnionitis in an era of routine GBS screening and prophylaxis.. · The results highlight potential benefits of GBS screening and intrapartum antibiotic prophylaxis beyond neonatal disease prevention, including mitigating the risk of maternal infectious morbidity..

Association of Treatment of Chorioamnionitis with Non-Beta Lactam Antibiotics and Postcesarean Infectious Morbidity.

OBJECTIVE: Chorioamnionitis (CAM) is associated with postcesarean (CS) infectious morbidity (IM). Beta-lactam antibiotics (BLA) are used to treat CAM. It is uncertain if women who cannot receive BLA attain similar benefit from treatment of CAM with non-BLA. STUDY DESIGN: Retrospective cohort of women with CAM is delivered by CS in the maternal-fetal medicine units CS registry. We compared IM in women who received BLA versus women who received non-BLA. The primary outcome was a composite of endometritis, wound complication, necrotizing fasciitis, septic pelvic thrombophlebitis, and pelvic abscess. Multivariable logistic regression estimated odds ratios for the association of non-BLA treatment with IM outcomes. RESULTS: A total of 3,063 (93%) women received BLA, and 232 (7%) received non-BLA. Groups had similar rates of composite post-CS IM (10.6 vs. 12.1%, p = 0.5). After adjusting for confounders, treatment of CAM with non-BLA was not associated with post-CS IM (adjusted odds ratio [AOR] 1.1, 95% confidence interval [CI] 0.6-1.7), endometritis (AOR 1.1, 95% CI 0.7-1.8), or wound complications (AOR 1.2, 95% CI 0.5-3.2). CONCLUSION: Women with CAM who receive non-BLA and require CS may not be at increased risk of postoperative infections complications, compared to women who receive BLA.

Association Between Features of Spontaneous Late Preterm Labor and Late Preterm Birth.

OBJECTIVE: This study aimed to evaluate the association between clinical and examination features at admission and late preterm birth. STUDY DESIGN: The present study is a secondary analysis of a randomized trial of singleton pregnancies at 340/7 to 365/7 weeks' gestation. We included women in spontaneous preterm labor with intact membranes and compared them by gestational age at delivery (preterm vs. term). We calculated a statistical cut-point optimizing the sensitivity and specificity of initial cervical dilation and effacement at predicting preterm birth and used multivariable regression to identify factors associated with late preterm delivery. RESULTS: A total of 431 out of 732 (59%) women delivered preterm. Cervical dilation ≥ 4 cm was 60% sensitive and 68% specific for late preterm birth. Cervical effacement ≥ 75% was 59% sensitive and 65% specific for late preterm birth. Earlier gestational age at randomization, nulliparity, and fetal malpresentation were associated with late preterm birth. The final regression model including clinical and examination features significantly improved late preterm birth prediction (81% sensitivity, 48% specificity, area under the curve = 0.72, 95% confidence interval [CI]: 0.68-0.75, and p-value < 0.01). CONCLUSION: Four in 10 women in late-preterm labor subsequently delivered at term. Combination of examination and clinical features (including parity and gestational age) improved late-preterm birth prediction.

Association between early amniotomy in labour induction and severe maternal and neonatal morbidity.

BACKGROUND: Amniotomy is a commonly used, inexpensive method of labour induction; however, the optimal timing of amniotomy during labour induction is debated. AIMS: To investigate whether artificial rupture of membranes <4 cm dilation is associated with caesarean, severe maternal and neonatal morbidity, and labour induction duration. MATERIALS AND METHODS: Retrospective cohort study of 228 438 deliveries at 19 US hospitals. Women with a viable, singleton gestation undergoing induction ≥37 weeks with cervical dilation <4 cm were included. Women were excluded if membranes spontaneously ruptured <4 cm. Women were compared by early amniotomy (<4 cm dilation) versus not early. The primary outcome was caesarean. Secondary outcomes included severe maternal and neonatal morbidity, and labour duration. Logistic and Cox proportional hazard regression estimated the association between early amniotomy and study outcomes. RESULTS: Of 15 525 eligible women, 10 421 (67%) had early amniotomy. Early amniotomy was associated with higher adjusted odds of caesarean and severe maternal morbidity, but not neonatal morbidity. After accounting for interaction, early amniotomy was associated with increasingly higher odds of caesarean as body mass index increased. Early amniotomy was associated with lower odds of severe maternal morbidity among multiparas with mechanical ripening. Median labour induction was 2.5 h shorter with early amniotomy, significant in hazard regression. CONCLUSIONS: Early amniotomy was associated with increased odds of caesarean among obese women. The association between early amniotomy and severe maternal morbidity varied by maternal characteristics, but early amniotomy was not associated with neonatal morbidity. Early amniotomy in labour induction may be advantageous in certain populations, particularly non-obese women requiring mechanical ripening.

Incidence and Risk Factors for Postpartum Severe Hypertension in Women with Underlying Chronic Hypertension.

OBJECTIVE: To determine risk factors and time to diagnosis of postpartum severe hypertension (PHTN) in women with chronic hypertension (CHTN). STUDY DESIGN: Retrospective cohort of singleton pregnancies with CHTN at a tertiary care center. The primary outcome was PHTN, defined as hypertension ≥160/ ≥ 110 mm Hg during an emergency room (ER) or outpatient visit, or hospitalization within 8 weeks postpartum. Multivariable logistic regression was used to assess independent risk factors for PHTN. RESULTS: Two-hundred thirty-five women had CHTN: 30 (12.8%) were diagnosed with PHTN, and 17 (7.2%) were hospitalized or seen in the ER for PHTN. Women with PHTN had more severe superimposed pre-eclampsia (p < 0.05), higher average systolic blood pressures at discharge (141 vs. 135 mm Hg, p = 0.04), and required antihypertensives after delivery (p < 0.01). The number of antihypertensive medications (adjusted odds ratio [aOR] 1.78, 95% confidence interval [CI], 1.25-2.55) and a systolic blood pressure >135 mm Hg (aOR 4.55, 95% CI, 1.64-12.61) at discharge remained independently associated with PHTN. Median time to diagnosis of PHTN was 10 days (interquartile range [IQR] 6-32 days); time to diagnosis among women requiring readmission or ER evaluation was 8 days (IQR 5-11 days). CONCLUSION: PHTN occurred in 13% of women with CHTN, and was associated with blood pressure level and number of medications at discharge.

Sex-Specific Differences in Late Preterm Neonatal Outcomes.

OBJECTIVE: To estimate sex-specific differences in late preterm outcomes and evaluate whether betamethasone modifies this association. STUDY DESIGN: We conducted a secondary analysis of a multicenter trial of women at risk for late preterm birth randomized to receive betamethasone or placebo. We included women who delivered at 34 to 37 weeks and excluded major fetal anomalies. The primary outcome was severe neonatal morbidity (mechanical ventilation, respiratory distress syndrome, bronchopulmonary dysplasia, sepsis, necrotizing enterocolitis, and intraventricular hemorrhage). Maternal characteristics were compared using chi-square test, t-test, or Mann-Whitney U-test. Multivariable logistic regression estimated the association between sex and morbidity, and likelihood ratio testing assessed for effect modification by betamethasone. RESULTS: Of 2,831 women in the primary trial, 2,331 met the inclusion criteria: 1,236 delivered males and 1,095 delivered females. Betamethasone modified the association between sex and severe morbidity (p = 0.047). Among those who received betamethasone, male sex was associated with higher odds of severe morbidity (adjusted odds ratio: 1.95, 95% confidence interval: 1.25-3.05), compared with female sex. Among those who did not receive betamethasone, there was no significant association between sex and morbidity. CONCLUSION: Male sex is a risk factor for adverse late preterm outcomes, including severe neonatal morbidity after betamethasone receipt.

The Association of Metabolic Dysfunction with Breastfeeding Outcomes in Gestational Diabetes.

OBJECTIVE: To evaluate the relationship between prenatal metabolic markers and breastfeeding outcomes in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Secondary analysis of a cluster-randomized trial of a lifestyle intervention to improve metabolic health among women with GDM. Women were enrolled between 22 and 36 weeks' gestation and followed through 10 months postpartum. Metabolic markers were measured at enrollment. Women reported when they stopped breastfeeding, whether they breastfed as long as desired, and when they introduced formula. We evaluated the association of tertiles of metabolic markers with undesired weaning and time to breastfeeding cessation using Cox proportional hazards models and Mantel-Haenszel chi-square tests, respectively. RESULTS: Eighty-two women were eligible for analysis. There was a statistically significant difference in time to breastfeeding cessation among tertiles of fasting glucose, hemoglobin A1c (A1c), body mass index (BMI), and skinfolds (all p < 0.05). Women with higher fasting glucose, BMI, or skinfolds were also more likely to report undesired weaning; women with higher fasting glucose introduced formula earlier. CONCLUSION: Higher fasting glucose, A1c, BMI, and subscapular skinfolds were associated with earlier breastfeeding cessation in women with GDM. These markers may identify mothers in need of enhanced postpartum support to achieve their breastfeeding goals.

Examining the Starting Dose of Glyburide in Gestational Diabetes.

OBJECTIVE: The aim of this study was to determine the impact of initial glyburide dosing on pregnancy outcomes. STUDY DESign: Retrospective cohort of singleton pregnancies complicated by gestational diabetes mellitus (GDM) from 2007 to 2013. Women who received glyburide were compared by initial dose: 2.5 mg (n = 170) versus 5 mg (n = 154) total daily dose. The primary maternal outcome was hypoglycemia, defined as a blood glucose < 60 mg/dL. The primary neonatal outcome was birth weight. Secondary maternal outcomes included time to blood glucose control, preeclampsia, and cesarean delivery. Secondary neonatal outcomes included macrosomia (>4,000 g), hypoglycemia (<40 mg/dL), shoulder dystocia, and preterm delivery. RESULTS: The 5 mg/day glyburide dose did not increase maternal hypoglycemia (26% in the 2.5 mg/day group vs. 27% in the 5 mg/day group; adjusted odds ratio [AOR] 0.67; confidence interval [CI] 0.30-1.49). An increase in macrosomia in the 5 mg/day group was not significant after adjusting for maternal obesity (AOR 2.16; CI 0.96-4.88). Differences in preterm birth and large for gestational age were not significant after adjusting for prior preterm birth and maternal obesity, respectively. CONCLUSIONS: A higher starting dose of glyburide for the management of GDM was not associated with increased maternal hypoglycemia or decreased adverse neonatal outcomes.

Elevated midtrimester maternal plasma cytokines and preterm birth in patients with cerclage.

BACKGROUND: Cerclage is used for the prevention of spontaneous preterm birth; however, many patients at high risk of spontaneous preterm birth who have a cerclage in place eventually deliver before term. Although inflammation, measured by biomarkers (eg, cytokines), is a known risk factor for preterm delivery, evaluation of inflammation to determine pregnancy outcomes among patients with cerclage is poorly understood. OBJECTIVE: We sought to examine levels of maternal plasma inflammatory cytokines in the midtrimester among asymptomatic patients with a cervical cerclage (placed for any indication, including history, ultrasound, and examination indications) to evaluate the association between cytokine levels and preterm birth. STUDY DESIGN: This was a prospective cohort study of singleton, nonanomalous pregnancies who had a cerclage placed at <24 weeks of gestation from 2015 to 2018 at a single tertiary institution. Maternal plasma was collected perioperatively whenever possible. A custom magnetic bead Luminex cytokine assay was used to measure plasma inflammatory cytokine levels from these stored samples. The primary outcome was preterm birth at <37 weeks of gestation. A statistical cut point was calculated for each cytokine level to assess its optimal sensitivity and specificity for spontaneous preterm birth prediction. Patients were classified as having a "high" or "low" result for each cytokine based on this cut point. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and positive and negative predictive values for spontaneous preterm birth prediction. Cox proportional-hazards regression modeled the association between the number of "high" inflammatory cytokines and gestational age at delivery, adjusting for confounders. Additional analyses were performed on the subgroup of patients with history-indicated cerclage and those with an ultrasound- or examination-indicated cerclage. RESULTS: A total of 43 patients participated in this study: 20 (46.5%) had spontaneous preterm birth (median, 30.9 weeks of gestation; interquartile range, 28.4-35.0). Plasma samples were collected at a median of 0 (interquartile range, -2 to 17) days concerning cerclage placement and a median of 18 (interquartile range, 13-21) weeks of gestation. Based on the statistical cut point for each cytokine level, 7% of patients had zero, 20.9% had 1, 18.6% had 2, 20.9% had 3, and 32.6% had ≥4 "high" cytokine results. Each additional "high" cytokine level was associated with earlier delivery (hazard ratio, 1.51; 95% confidence interval, 1.25-1.81) even after controlling for ultrasound- or examination-indication for cerclage (hazard ratio, 1.73; 95% confidence interval, 0.95-3.15). The presence of ≥4 "high" cytokine levels was 70% sensitive and 74% specific for predicting spontaneous preterm birth (area under the curve, 0.846; 95% confidence interval, 0.728-0.964; positive predictive value, 70%; negative predictive value, 73.9%). CONCLUSION: Among patients with a cervical cerclage, elevated midtrimester maternal plasma cytokine profiles were associated with subsequent preterm birth and can estimate the probability of preterm birth. Confirmation and refinement of this noninvasive panel may provide insight into improved selection of individuals who may benefit from cerclage placement and investigation of therapeutic strategies to mitigate midpregnancy inflammation.

Risk factors associated with prolonged neonatal intensive care unit stay after threatened late preterm birth.

OBJECTIVE: To identify risk factors associated with neonatal intermediate or intensive care unit (NICU) stay ≥3 days among women with threatened late preterm birth (PTB). STUDY DESIGN: Secondary analysis of women with nonanomalous, singleton gestations enrolled in multicenter trial of betamethasone versus placebo for late PTB. Maternal and obstetric characteristics at time of presentation with threatened PTB were compared between those with and without NICU stay ≥3 days. Multivariable logistic regression identified risk factors for NICU stay ≥3 days. RESULT: Of 2795 eligible mother-neonate dyads, 962 (34%) had NICU stay ≥3 days. Gestational age and fetal growth restriction as the reason for threatened PTB had the strongest association with NICU stay ≥3 days in the final model (AUC 0.76). CONCLUSION: Maternal and obstetric characteristics at the time of admission for threatened late PTB should be considered when counseling patients about the probability of NICU stay ≥3 days.

Metabolites from midtrimester plasma of pregnant patients at high risk for preterm birth.

BACKGROUND: There is an increased awareness regarding the association between exposure to environmental contaminants and adverse pregnancy outcomes including preterm birth. Whether an individual's metabolic profile can be utilized during pregnancy to differentiate the subset of patients who are ultimately destined to delivered preterm remains uncertain but could have MEANINGFUL clinical implications. OBJECTIVE: We sought to objectively quantify metabolomic profiles of patients at high risk of preterm birth by evaluating midtrimester maternal plasma and to measure whether endogenous metabolites and exogenous environmental substances differ among those who ultimately deliver preterm compared with those who deliver at term. STUDY DESIGN: This was a case-control analysis from a prospective cohort of patients carrying a singleton, nonanomalous gestation who were at high risk of spontaneous preterm birth. Subjects with a plasma blood sample drawn at <28 weeks' gestation and no evidence of preterm labor at the time of enrollment were included. Metabolites were extracted from frozen samples, and metabolomic analysis was performed using liquid chromatography/mass spectrometry. The primary outcome was preterm birth at 16.0 to 36.9 weeks' gestation. RESULTS: A total of 42 patients met the inclusion criteria. Of these, 25 (59.5%) delivered preterm at <37 weeks' gestation, at a median of 30.14 weeks' gestation (interquartile range, 28.14-34.14). A total of 812 molecular features differed between preterm birth cases and term controls with a minimum fold change of 1.2 and P<.05. Of these, 570 of 812 (70.1%) were found in higher abundances in preterm birth cases; the other 242 of 812 (29.9%) were in higher abundance in term birth controls. The identity of the small molecule/compound represented by the molecular features differing statistically between preterm birth cases and term controls was identified as ranging from those involved with endogenous metabolic pathways (including lipid catabolism, steroids, and steroid-related molecules) to exogenous exposures (including avocadyne, diosgenin, polycyclic aromatic hydrocarbons, acetaminophen metabolites, aspartame, and caffeine). Random forest analyses evaluating the relative contribution of each of the top 30 compounds in differentiating preterm birth and term controls accurately classified 21 of 25 preterm birth cases (84%). CONCLUSION: Both endogenous metabolites and exogenous exposures differ in maternal plasma in the midtrimester among patients who ultimately delivered preterm compared with those who deliver at term.

Screening for spontaneous preterm birth and resultant therapies to reduce neonatal morbidity and mortality: A review.

Despite considerable effort aimed at decreasing the incidence of spontaneous preterm birth, it remains the leading cause of perinatal morbidity and mortality. Screening strategies are imperfect. Approaches used to identify women considered by historical factors to be low risk for preterm delivery (generally considered to be women with singleton pregnancies without a history of a previous preterm birth) as well as those at high risk for preterm birth (those with a previous preterm birth, short cervix, or multiple gestation) continue to evolve. Herein, we review the current evidence and approaches to screening women for preterm birth, and examine future directions for clinical practice. Further research is necessary to better identify at-risk women and provide evidence-based management.