Anthony Shanks

Evaluation of polymerase chain reaction for group B Streptococcus detection using an improved culture method

OBJECTIVE: The administration of antibiotic prophylaxis to laboring women who harbor Group B streptococci (GBS) depends on identification of carriers. We sought to evaluate the diagnostic accuracy of real-time polymerase chain reaction (PCR) for detection of GBS using a more stringent culture method. METHODS: Two swabs were used simultaneously to obtain rectovaginal GBS samples from consenting women. One swab was analyzed using a stringent, validated culture technology, which included direct plating onto selective agar and inoculation of a selective broth. The other swab was used for a commercial real-time PCR assay, which uses amplification to detect the presence of the cfb gene sequence of GBS DNA. We calculated the assay accuracy using sensitivity and specificity. RESULTS: A total of 233 samples were available. Both the culture and PCR methods were positive for 59 and negative for 157 patients. The culture method was positive and PCR was negative in 9 patients. The culture was negative and the PCR positive for 8 patients. The sensitivity of the PCR assay was 86.8% and specificity was 95.2%. The positive predictive value was 88.1% and the negative predictive value was 94.6%. CONCLUSION: Although a rapid PCR assay may be useful to determine GBS status in the urgent intrapartum setting, the false-negative rate of 13.2% for the real-time PCR assay prohibits its use for standard GBS screening in the office. LEVEL OF EVIDENCE: II-1

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

Hypoxia in Human Trophoblasts Stimulates the Expression and Secretion of Connective Tissue Growth Factor

The mechanisms underlying cellular injury when human placental trophoblasts are exposed to hypoxia are unclear. Connective tissue growth factor (CTGF) mediates cell injury and fibrosis in diverse tissues. We hypothesized that hypoxia enhances the production of CTGF in primary term human trophoblasts. Using cultured term primary human trophoblasts as well as villous biopsies from term human placentas, we showed that CTGF protein is expressed in trophoblasts. When compared with cells cultured in standard conditions (FiO2 = 20%), exposure of primary human trophoblasts to low oxygen concentration (FiO2 = 8% or <or= 1%) enhanced the expression of CTGF mRNA in a time-dependent manner, with a significant increase in CTGF levels after 16 h (2.7 +/- 0.7-fold; P < 0.01), reaching a maximum of 10.9 +/- 3.2-fold at 72 h. Whereas exposure to hypoxia had no effect on cellular CTGF protein levels, secretion of CTGF to the medium was increased after 16 h in hypoxia and remained elevated through 72 h. The increase in cellular CTGF transcript levels and CTGF protein secretion was recapitulated by exposure of trophoblasts to agents that enhance the activity of hypoxia-inducible factor (HIF)1alpha, including cobalt chloride or the proline hydroxylase inhibitor dimethyloxaloylglycine, and attenuated using the HIF1alpha inhibitor 2-methoxyestradiol. Although all TGFbeta isoforms stimulated the expression of CTGF in trophoblasts, only the expression of TGFbeta1 mRNA was enhanced by hypoxia. We conclude that hypoxia increases cellular CTGF mRNA levels and CTGF protein secretion from cultured trophoblasts, likely in a HIF1alpha-dependent manner.

Administration of steroids after 34 weeks of gestation enhances fetal lung maturity profiles

OBJECTIVE To estimate the effect of antenatal glucocorticoid administration on fetal lung maturity in pregnancies with known fetal lung immaturity between the 34th and 37th weeks of gestation. STUDY DESIGN Pregnancies between 34(0/7) and 36(6/7) weeks undergoing amniocentesis to determine fetal lung maturity were targeted. Women with negative results (TDx-FLM-II <45 mg/g) were randomly assigned to intramuscular glucocorticoid injection or no treatment. A repeat TDx-FLM-II test was obtained 1 week after enrollment. RESULTS Thirty-two women who met inclusion criteria were randomly assigned. Seven women delivered within a week of testing for fetal lung maturity, and were excluded from the analysis. Ten received glucocorticoid and 15 did not. Women assigned to glucocorticoids had a mean increase TDx-FLM-II in 1 week of 28.37 mg/g. Women assigned to no-treatment had an increase of 9.76 mg/g (P < .002). CONCLUSION A single course of intramuscular glucocorticoids after 34 weeks in pregnancies with documented fetal lung immaturity significantly increases TDx- FLM-II.

Clinical accuracy of estimated fetal weight in term pregnancies in a teaching hospital

Abstract Objective: To evaluate whether clinical characteristics alter the accuracy of clinical estimation of fetal weight (EFW) in term pregnancies in a teaching hospital. Methods: Secondary analysis of a retrospective cohort study of patients presenting for labor at term. Clinical EFW was performed using Leopold maneuvers. A Spearman’s rank correlation coefficient (r) was used to evaluate the linear relationship between clinical EFW and actual birth weight (BW). Body mass index (BMI), gestational age, fetal station, and admission diagnosis were evaluated with respect to their impact on clinical EFW. The primary outcome was an absolute error between clinical EFW and actual BW >500 g. Results: Of 3797 patients, 941 (24.8%) had an absolute error in clinical EFW exceeding 500 g. The overall correlation between clinical EFW and actual BW was weak (r = 0.4). There was a significant trend of improved accuracy of clinical EFW with increasing gestational age; however, BMI, fetal station, and admission diagnosis did not have significant effects. Of 221 cases of macrosomia (>4000 g), 181 (81.9%) were undetected by clinical EFW. Conclusion: The correlation between clinical EFW and actual BW is overall weak, particularly in patients with macrosomic fetuses; however, BMI, admission diagnosis, and fetal station do not have a significant impact.

Uterine synechiae and pregnancy complications.

OBJECTIVE: Uterine synechiae have generally been considered benign findings in pregnancy. We used a large perinatal database to test the hypothesis that uterine synechiae are associated with pregnancy complications. METHODS: We performed a retrospective cohort study of women with singleton pregnancies presenting for routine ultrasonographic examinations at 17–22 weeks from 1990–2009. Pregnancies with multiple fetuses, amniotic bands, and congenital uterine anomalies were excluded. We compared pregnancy outcomes between women with and without uterine synechiae. Multivariable logistic regression was used to adjust for confounders. RESULTS: Of 65,518 pregnancies meeting inclusion criteria, 296 (0.45%) were diagnosed with uterine synechiae. Women with uterine synechiae were significantly more likely to have placental abruption (2.1% compared with 0.6%, adjusted odds ratio [OR] 3.25, 95% confidence interval [CI] 1.43–7.36), preterm premature rupture of membranes (PROM) (5.5% compared with 2.3%, adjusted OR 2.51, 95% CI 1.51–4.18), and cesarean delivery for malpresentation (5.1% compared with 3.0%, adjusted OR 1.75, 95% CI 1.04–2.95). The risks of placenta previa, fetal growth restriction, stillbirth, and preterm delivery were not significantly different. CONCLUSION: Uterine synechiae are associated with significant increase in the risk of preterm PROM, placental abruption, and cesarean delivery for malpresentation. The notion of uterine synechiae as benign findings in pregnancy should be re-evaluated. LEVEL OF EVIDENCE: II

Impact of chorionicity on risk and timing of intrauterine fetal demise in twin pregnancies

OBJECTIVE We sought to estimate the association between chorionicity and intrauterine fetal demise (IUFD) of one or both fetuses in twin pregnancies. STUDY DESIGN In a retrospective cohort of twins undergoing anatomic survey, risk of IUFD in monochorionic and dichorionic twins was compared. The primary outcome was IUFD of one or both fetuses; secondary outcomes included nonanomalous fetal deaths. RESULTS Of 2161 twin pregnancies meeting inclusion criteria, 86 had at least 1 IUFD and 32 experienced a double fetal loss. Monochorionic pregnancies had an increased risk of a single demise (adjusted odds ratio, 1.69; 95% confidence interval, 1.04-2.75) and a double demise (adjusted odds ratio, 2.11; 95% confidence interval, 1.02-4.37). Of all double demises, 70% occurred <24 weeks. CONCLUSION Monochorionic twins carry an increased risk of fetal death compared to dichorionic twins. Double demise occurs primarily <24 weeks, regardless of chorionicity.

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.

Nasal Bone in Prenatal Trisomy 21 Screening

The definitive diagnosis of fetal chromosomal abnormalities is only accomplished through tests that sample fetal tissue. These procedures—amniocentesis, chorionic villus sampling and cordocentesis—are invasive and carry with them the risks of bleeding, rupture of membranes, and even pregnancy loss. Current recommendations from the American College of Obstetricians and Gynecologists state that all women should be offered screening, regardless of maternal age. However, the exact screening test to apply to pregnant women is still a matter of debate. The goal of any screening method should be high detection (sensitivity) at low screen positive rates. Recent attention has focused on additional ultrasound markers to potentially improve the detection rate. Given that mid-face hypoplasia and a flattened nose are characteristic features of Down syndrome, investigators have tried to utilize its prenatal appearance—or more specifically, its absence—to enhance the detection of trisomy 21 (T21). The purpose of this document is to review the data on the utility of the nasal bone as a marker for T21. Particular attention will focus on its use in the first trimester versus second trimester as well as future directions for its potential incorporation into screening strategies. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to relate the prenatal and postnatal nasal phenotypes for Down syndrome, identify the potential role and pitfalls of nasal bone characteristics in screening for Down syndrome, and describe 3 different methods to define fetal nasal bone hypoplasia.

Stillbirth risk among fetuses with ultrasound-detected isolated congenital anomalies.

OBJECTIVE: To estimate the risk of stillbirth among pregnancies complicated by a major isolated congenital anomaly detected by antenatal ultrasonography and the influence of incidental growth restriction. METHODS: A retrospective cohort study of all consecutive singleton pregnancies undergoing routine anatomic survey between 1990 and 2009 was performed. Stillbirth rates among fetuses with an ultrasound-detected isolated major congenital anomaly were compared with fetuses without major anomalies. Stillbirth rates were calculated per 1,000 ongoing pregnancies. Exclusion criteria included delivery before 24 weeks of gestation, multiple fetal anomalies, minor anomalies, and chromosomal abnormalities. Analyses were stratified by gestational age at delivery (before 32 weeks compared with 32 weeks of gestation or after) and birth weight less than the 10th percentile. We adjusted for confounders using logistic regression. RESULTS: Among 65,308 singleton pregnancies delivered at 24 weeks of gestation or after, 873 pregnancies with an isolated major congenital anomaly (1.3%) were identified. The overall stillbirth rate among fetuses with a major anomaly was 55 per 1,000 compared with 4 per 1,000 in nonanomalous fetuses (adjusted odds ratio [OR] 15.17, 95% confidence interval [CI] 11.03–20.86). Stillbirth risk in anomalous fetuses was similar before 32 weeks of gestation (26/1,000) and 32 weeks of gestation or after (31/1,000). Among growth-restricted fetuses, the stillbirth rate increased among anomalous (127/1,000) and nonanomalous fetuses (18/1,000), and congenital anomalies remained associated with higher rates of stillbirth (adjusted OR 8.20, 95% CI 5.27–12.74). CONCLUSION: The stillbirth rate is increased in anomalous fetuses regardless of incidental growth restriction. These risks can assist practitioners in designing care plans for anomalous fetuses who have elevated and competing risks of stillbirth and neonatal death. LEVEL OF EVIDENCE: II