Molly J. Stout

Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations

OBJECTIVE Bacteria have been identified in different regions of the placenta. Here, we tested the hypothesis that the maternal basal plate of the placenta harbors microbes that may be associated with adverse pregnancy outcomes. STUDY DESIGN We performed a cross-sectional study of pregnancies from a single tertiary care hospital. Maternal medical and obstetric characteristics were obtained and pregnancies followed up prospectively for outcomes and placental collection. After delivery, systematic random sampling of the placental basal plate was performed. Paraffin sections of basal plates were stained with 4 histologic stains and scored for morphological evidence of bacteria. RESULTS Of 195 total patients in the study, Gram-positive and -negative intracellular bacteria of diverse morphologies were documented in the basal plates of 27% of all placentas. Of the patients, 35% delivered preterm. No difference was noted between placental basal plates from preterm or term gestations. Intracellular bacteria were found in the placental basal plates of 54% spontaneous preterm deliveries <28 weeks, and in 26% of term spontaneous deliveries (P = .02). Intracellular bacteria were also documented in placentas without clinical or pathologic chorioamnionitis. CONCLUSION A total of 27% of placentas demonstrated intracellular bacteria in the placental basal plate using morphological techniques. Thus, the maternal basal plate is a possible source of intrauterine colonization and placental pathological examination could include examination for bacteria in this important maternal-fetal interface.

Diagnosing pulmonary embolism in pregnancy using computed-tomographic angiography or ventilation-perfusion.

OBJECTIVE: To estimate the rate of nondiagnosis for patients who initially undergo computed-tomographic angiography compared with those who undergo ventilation–perfusion imaging to diagnose pulmonary embolism in pregnancy. METHODS: This was a retrospective cohort study of all women consecutively evaluated from 2001–2006 for clinical suspicion of pulmonary embolism who were pregnant or 6 weeks postpartum and underwent at least computed-tomographic angiography or ventilation–perfusion scan. Charts were abstracted for history, clinical presentation, examination, imaging, and pregnancy and maternal outcomes. Women who underwent computed-tomographic angiography for initial diagnosis were compared with women who underwent ventilation–perfusion. Primary outcome was defined as a nondiagnostic study: nondiagnostic for pulmonary embolism in the computed-tomographic angiography group, or “low or intermediate probability” in the ventilation–perfusion group. Univariable, bivariable, and multivariable analyses were performed. RESULTS: Of 304 women with a clinical suspicion of pulmonary embolism, initial diagnosis was sought by computed-tomographic angiography in 108 (35.1%) and by ventilation–perfusion in 196 (64.9%) women. Women who underwent computed-tomographic angiography tended to have a slightly higher rate of nondiagnostic study (17.0% compared with 13.2%, P=.38). Examining the subgroup of women with a normal chest X-ray, computed-tomographic angiography was much more likely to yield a nondiagnostic result than ventilation–perfusion, even after adjusting for relevant confounding effects (30.0% compared with 5.6%, adjusted odds ratio 5.4, 95% confidence interval 1.4–20.1, P<.01). CONCLUSION: Pregnant or postpartum women with clinical suspicion of a pulmonary embolism and a normal chest X-ray are more likely to have a diagnostic study from a ventilation–perfusion scan compared with a computed-tomographic angiography. Evidence supports computed-tomographic angiography as a better initial test than ventilation–perfusion in patients with an abnormal chest X-ray. LEVEL OF EVIDENCE: II

Leiomyomas at routine second-trimester ultrasound examination and adverse obstetric outcomes.

OBJECTIVE: To estimate the risk of adverse pregnancy outcomes associated with the presence of leiomyomas. METHODS: This was a retrospective cohort study of all consecutive singleton pregnancies from 1990 to 2007 undergoing routine second-trimester fetal anatomic ultrasound survey. The presence or absence of leiomyomas was noted at second-trimester ultrasound examination. Primary and secondary obstetric outcomes were obtained as the individual progressed to delivery. Women with at least one leiomyoma at the time of second-trimester anatomic survey were compared with women without leiomyomas. Primary outcomes were intrauterine fetal death, breech presentation, placenta previa, cesarean delivery, placental abruption, preeclampsia, intrauterine fetal growth restriction, preterm premature rupture of membranes, and preterm birth. Univariable and multivariable analyses were performed. RESULTS: Of 72,373 women who underwent routine second-trimester anatomic survey, 64,047 women had complete obstetric follow-up data. The incidence of leiomyomas was 3.2% (n=2,058). Breech presentation (5.3% compared with 3.1%, adjusted odds ratio [OR] 1.5, 95% confidence interval [CI]1.3–1.9), placenta previa (1.4% compared with 0.5%, adjusted OR 2.2, 95% CI 1.5–3.2), cesarean delivery (33.1% compared with 24.2%, adjusted OR 1.2, 95% CI 1.1–1.4), placental abruption (1.4% compared with 0.7%, adjusted OR 2.1, 95% CI 1.4–3.0), preterm premature rupture of membranes (3.3% compared with 2.4%, adjusted OR 1.3, 95% CI 1.0–1.7), preterm birth less than 37 weeks (15.1% compared with 10.5%, adjusted OR 1.5, 95% CI 1.3–1.8), and less than 34 weeks (3.9% compared with 2.8%, adjusted OR 1.4, 95% CI 1.0–1.8), and intrauterine fetal death in women with a fetus with growth restriction (3.9% compared with 1.5%, adjusted OR 2.5, 95% CI 1.2–5.0) were significantly associated with the presence of leiomyomas. CONCLUSION: Women with leiomyomas are at low risk for obstetric complications compared with women without leiomyomas. LEVEL OF EVIDENCE: II

Umbilical cord arterial lactate compared with pH for predicting neonatal morbidity at term.

OBJECTIVE: To test the hypothesis that umbilical cord arterial lactate is superior to pH for predicting short-term neonatal morbidity at term. METHODS: We conducted a prospective cohort study of all consecutive, non-anomalous, singleton, vertex, term births from 2009 to 2012 at Washington University Medical Center. Umbilical arterial lactate and pH were measured immediately after delivery, before knowledge of neonatal outcomes. The primary outcome was a composite neonatal morbidity consisting of neonatal death, intubation, mechanical ventilation, meconium aspiration syndrome, hypoxic encephalopathy, and need for hypothermic therapy. The predictive ability of lactate and pH were compared using receiver operating characteristic curves. Optimal cutoff values of lactate and pH were estimated based on the maximal Youden index. RESULTS: Of 4,997 term deliveries during the study period, 4,910 met inclusion criteria. The composite neonatal morbidity occurred in 56 neonates (1.1%). The mean lactate level was nearly twofold higher in neonates with the composite morbidity (6.49 compared with 3.26 mmol/L, P<.001), whereas mean pH values were less distinct (7.19 compared with 7.29, P<.001). Lactate was significantly more predictive of neonatal morbidity than pH (receiver operating characteristic curve area: 0.84 compared with 0.78, P=.03). The optimal cutoff value for predicting neonatal morbidity was 3.90 mmol/L for lactate and 7.25 for pH. Corresponding sensitivities and specificities were also higher for lactate (83.9% and 74.1% compared with 75.0% and 70.6%, respectively). CONCLUSION: Results of this large prospective cohort study show that umbilical cord arterial lactate is a more discriminating measure of neonatal morbidity at term than pH. LEVEL OF EVIDENCE: II

Electronic Fetal Monitoring: Past, Present, and Future

Electronic fetal monitoring (EFM) using cardiotocography is a common tool used during labor and delivery for assessment of fetal well-being. It has largely replaced the use of intermittent auscultation and fetal scalp pH sampling. However, data suggesting improved clinical outcomes with the use of EFM are sparse. In this review, the history of EFM is revisited from its inception in the 1960s to current practice, interpretations, and future research goals.

Universal cervical length screening: implementation and outcomes

BACKGROUND Transvaginal measurement of cervical length (CL) has been advocated as a screening tool to prevent preterm birth, but controversy remains regarding the overall utility of universal screening. OBJECTIVE We aimed to evaluate the acceptability of a universal CL screening program. Additionally we evaluated risk factors associated with declining screening and subsequent delivery outcomes of women who accepted or declined screening. STUDY DESIGN This was a retrospective cohort study of transvaginal CL screening at a single institution from July 1, 2011, through December 31, 2014. Institutional protocol recommended transvaginal CL measurement at the time of anatomic survey between 17-23 weeks in all women with singleton, viable pregnancies, without current or planned cerclage, with patients able to opt out. Patients with CL ≤20 mm were considered to have clinically significant cervical shortening and were offered treatment. We assessed acceptance rate, risk factors for declining CL screening, and the trend of acceptance of CL screening over time. We also calculated the prevalence of CL ≤25, ≤20, and ≤15 mm, and estimated the association between CL screening and spontaneous preterm birth. RESULTS Of 12,740 women undergoing anatomic survey during the study period, 10,871 (85.3%; 95% confidence interval [CI], 84.7-85.9%) underwent CL screening. Of those, 215 (2.0%) had a CL ≤25 mm and 131 (1.2%) had a CL ≤20 mm. After the first 6 months of implementation, there was no change in rates of acceptance of CL screening over time (P for trend = .15). Women were more likely to decline CL screening if they were African American (adjusted odds ratio [aOR], 2.17; 95% CI, 1.93-2.44), obese (aOR, 1.18; 95% CI, 1.06-1.31), multiparous (aOR, 1.45; 95% CI, 1.29-1.64), age <35 years (aOR, 1.24; 95% CI, 1.08-1.43), or smokers (aOR, 1.42; 95% CI, 1.20-1.68). Rates of spontaneous preterm birth <28 weeks were higher in those who declined CL screening (aOR, 2.01; 95% CI, 1.33-3.02). CONCLUSION Universal CL screening was implemented successfully with 85% of women screened. Overall incidence of short cervix was low and women with significant risk factors for preterm birth were more likely to decline screening. Patients who declined CL screening were more likely to be African American, obese, multiparous, age <35 years, and smokers. Rates of early, but not late, spontaneous preterm birth were significantly higher among women who did not undergo CL screening.

Early pregnancy vaginal microbiome trends and preterm birth

Background Despite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions. Objective To characterize vaginal microbial community characteristics in a large, predominantly African‐American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth. Study Design This is a nested case‐control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid‐vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term. Results A total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African‐American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness, diversity, and evenness during pregnancy (P < .01). This change occurred between the first and second trimesters. Within‐subject comparisons across pregnancy showed that preterm birth is associated with increased vaginal microbiome instability compared to term birth. No distinct taxa were associated with preterm birth. Conclusion In a predominantly African‐American population, a significant decrease of vaginal microbial community richness and diversity is associated with preterm birth. The timing of this suppression appears early in pregnancy, between the first and second trimesters, suggesting that early gestation may be an ecologically important time for events that ordain subsequent term and preterm birth outcomes.

Intrapartum magnesium for prevention of cerebral palsy: continuing controversy?

Purpose of review The purpose of the present review is to review the literature regarding the use of antenatal magnesium sulfate (MgSO4) for fetal neuroprotection and prevention of cerebral palsy in women at risk of preterm delivery. Recent findings Cerebral palsy is a nonprogressive disorder of movement and posture and a leading cause of childhood disability. Preterm birth is a major risk factor for the development of cerebral palsy; gestational age at delivery has an inverse relationship to the risk of cerebral palsy. Observational studies over the past 15 years have suggested a possible protective role for MgSO4. In some studies, children born preterm who were exposed prenatally to MgSO4 for obstetric indications such as seizure prophylaxis or tocolysis had decreased rates of cerebral palsy as compared with children born preterm to women who were not exposed to MgSO4. Randomized trials have been conducted to test the hypothesis that maternal MgSO4 exposure had neonatal neuroprotective effects. These studies included women thought to be at risk of preterm delivery within 24 h. The largest of these studies, published in 2008 by Dr Rouse et al., included more than 2000 women and found a decreased rate of moderate-to-severe cerebral palsy in surviving children born to women treated with MgSO4. Summary MgSO4 treatment in women at high risk for preterm birth may reduce the risk of cerebral palsy in children who survive.

Umbilical Cord Venous Lactate for Predicting Arterial Lactic Acidemia and Neonatal Morbidity at Term.

OBJECTIVE: To estimate the utility of umbilical venous lactate, more readily available than umbilical cord arterial lactate, for predicting arterial lactic acidemia and neonatal outcomes at term. METHODS: This was a prospective cohort study of consecutive, nonanomalous, singleton, term births after labor in a large academic medical center (2009–2014). Umbilical arterial and venous lactate were measured immediately after delivery, before knowledge of neonatal outcomes. The outcome measures were arterial lactic acidemia (greater than 3.9 mmol/L) and a composite neonatal outcome consisting of neonatal death and any of a number of neonatal morbidities including intubation, mechanical ventilation, meconium aspiration syndrome, hypoxic–ischemic encephalopathy, and therapeutic hypothermia. Predictive ability of venous lactate was estimated using the area under the receiver operating characteristic curve. RESULTS: Among 7,741 births, venous lactate was strongly predictive of arterial lactic acidemia (area under the curve 0.958). The “optimal” cut point of venous lactate for predicting both arterial lactic acidemia and the composite neonatal outcome was 3.4 mmol/L. This predicted arterial lactic acidemia with sensitivity of 87.0% and specificity of 91.3%. Positive and negative predictive values were 79.9% and 94.7%, respectively. The composite neonatal outcome occurred in 104 neonates (1.3%). Compared with arterial lactate, venous lactate predicted the composite neonatal outcome with comparable sensitivity (75.0% compared with 74.0%, P>.99) but slightly lower specificity (69.7% compared with 72.2%, P<.01). CONCLUSION: Umbilical venous lactate strongly predicts arterial lactic acidemia and is comparable with arterial lactate for predicting neonatal morbidity at term. It could be used as a measure of neonatal morbidity when arterial blood is not available.

The Incidence of Isolated Single Umbilical Artery in Twins And Adverse Pregnancy Outcomes

The aim of this study was to estimate the incidence of single umbilical artery (SUA) in twin pregnancies and to investigate whether SUA in twin gestations is associated with adverse obstetric outcomes.