Jason K. Baxter

Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double‐blind, placebo‐controlled trial

Women with a sonographic short cervix in the mid‐trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.

Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes

OBJECTIVE The purpose of this study was to compare intraamniotic inflammation vs microbial invasion of the amniotic cavity (MIAC) as predictors of adverse outcome in preterm labor with intact membranes. STUDY DESIGN Interleukin-6 (IL-6) was measured in prospectively collected amniotic fluid from 305 women with preterm labor. MIAC was defined by amniotic fluid culture and/or detection of microbial 16S ribosomal DNA. Cases were categorized into 5 groups: infection (MIAC; IL-6, ≥11.3 ng/mL); severe inflammation (no MIAC; IL-6, ≥11.3 ng/mL); mild inflammation (no MIAC; IL-6, 2.6-11.2 ng/mL); colonization (MIAC; IL-6, <2.6 ng/mL); negative (no MIAC; IL-6, <2.6 ng/mL). RESULTS The infection (n = 27) and severe inflammation (n = 36) groups had similar latency (median, <1 day and 2 days, respectively) and similar rates of composite perinatal morbidity and mortality (81% and 72%, respectively). The colonization (n = 4) and negative (n = 195) groups had similar outcomes (median latency, 23.5 and 25 days; composite morbidity and mortality rates, 21% and 25%, respectively). The mild inflammation (n = 47) groups had outcomes that were intermediate to the severe inflammation and negative groups (median latency, 7 days; composite morbidity and mortality rates, 53%). In logistic regression adjusting for gestational age at enrollment, IL-6 ≥11.3 and 2.6-11.2 ng/mL, but not MIAC, were associated significantly with composite morbidity and mortality rates (odds ratio [OR], 4.9; 95% confidence interval [CI], 2.2-11.2, OR, 3.1; 95% CI, 1.5-6.4, and OR, 1.8; 95% CI, 0.6-5.5, respectively). CONCLUSION We confirmed previous reports that intraamniotic inflammation is associated with adverse perinatal outcomes whether or not intraamniotic microbes are detected. Colonization without inflammation appears relatively benign. Intraamniotic inflammation is not simply present or absent but also has degrees of severity that correlate with adverse outcomes. We propose the designation amniotic inflammatory response syndrome to denote the adverse outcomes that are associated with intraamniotic inflammation.

Gestational age at cervical length measurement and incidence of preterm birth.

OBJECTIVE: To estimate the risk of spontaneous preterm birth based on transvaginal ultrasound cervical length and gestational age at which cervical length was measured. METHODS: Women at high risk for spontaneous preterm birth and with transvaginal ultrasound cervical length measurements between weeks 12 and 32 were identified at one institution between July 1995 and June 2005. Inclusion criteria for women at high risk for spontaneous preterm birth were prior spontaneous preterm birth at 14 to 35 weeks, cone biopsy, müllerian anomaly, or two or more dilation and evacuations. Women with multiple gestations, cerclage, indicated preterm birth, or fetal anomalies were excluded. Logistic regression was used to estimate the spontaneous preterm birth risk before 35, 32, and 28 weeks. RESULTS: Seven hundred five women received 2,601 transvaginal ultrasound measurements for cervical length. The incidences of spontaneous preterm birth before 35, 32, and 28 weeks were 17.7, 10.6, and 6.7%, respectively. The risk of spontaneous preterm birth before 35 weeks decreased by approximately 6% for each additional millimeter of cervical length (odds ratio 0.94, 95% confidence interval, 0.92–0.95, P=.001) and by approximately 5% for each additional week of pregnancy at which the cervical length was measured (odds ratio 0.95, 95% confidence interval 0.92–0.98, P=.004). Similar results were obtained for spontaneous preterm birth before 32 and 28 weeks. CONCLUSION: Gestational age at which transvaginal ultrasound cervical length is measured significantly affects the calculation of risk of spontaneous preterm birth. The spontaneous preterm birth risk increases as the length of the cervix declines and as the gestational age decreases. These spontaneous preterm birth risks are important for counseling and management for women with various degrees of short cervical length at different gestational ages. LEVEL OF EVIDENCE: II

Thoracoamniotic Shunts: Fetal Treatment of Pleural Effusions and Congenital Cystic Adenomatoid Malformations

Objective: To determine whether fetuses that underwent thoracoamniotic shunt placement for treatment of pleural effusion (PE) or macrocystic congenital cystic adenomatoid malformation (CCAM) have an improved outcome as compared with an untreated population. Methods: A retrospective review from a single tertiary center was performed using thoracoamniotic shunt placement to treat PE or macrocystic CCAM between 1998 and 2001. Thoracoamniotic shunts were used on 26 occasions in 19 pregnancies. Results: The average gestational age at the diagnosis of PE and CCAM was 22 + 4 and 20 + 0 weeks, respectively. Shunts were offered in pregnancies complicated by hydrops or at significant risk for pulmonary hypoplasia. Shunts were placed at 26 + 2 weeks (average) and 23 + 1 weeks (average) in the PE and CCAM groups, respectively. In CCAM patients, the mean pre- and postshunting mass volumes were 50.5 and 25.7 cm3, representing a 51% reduction in mass volume following shunt placement. In the PE group, the average delivery age was 33 + 5 weeks, with an average shunt placement to delivery time of 7 + 3 weeks. In the CCAM group, the average delivery was 33 + 3 weeks, with an average shunt placement to delivery time of 10 + 2 weeks. The postnatal survival rates were 67% (6/9) and 70% (7/10) in the PE and CCAM groups, respectively. Conclusions: (1) Thoracoamniotic shunts should be considered as a treatment option for selected PE or macrocystic CCAM fetuses with hydrops or a significant risk for pulmonary hypoplasia; (2) the neonatal survival with shunting was similar for PE and CCAM groups and was improved as compared with literature reports, and (3) fetuses with CCAM presented earlier with hydrops than those with PE. Successful shunting resulted in a prolongation of pregnancy into the 3rd trimester in both groups.

HELLP syndrome: the state of the art.

Preeclampsia/eclampsia has been recognized for centuries and continues to plague both the patient and the obstetrician. A severe variant, the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP), has been recognized for 50 years. Although much new data has been elucidated about the condition, only several observations have withstood the test of time. These are the uniqueness of the disease to humans, the progressive nature of the disease, and the fact that delivery is the sole therapy. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to outline the history of HELLP syndrome and describe the pathophysiology of HELLP syndrome, to summarize the clinical presentation and differential diagnosis of HELLP syndrome, and to list the various management options.

Predicting length of treatment for neonatal abstinence syndrome in methadone-exposed neonates.

OBJECTIVE The objective of the study was to identify maternal variables predicting length of treatment for neonatal abstinence syndrome (NAS). STUDY DESIGN This was a retrospective cohort study of infants treated for NAS during 2000-2006 whose mothers were on methadone maintenance at delivery. Mixed-effects linear regression was used to examine the interaction of maternal and neonatal variables with length of treatment. RESULTS Of 204 neonates born to methadone exposed mothers, the average dose at delivery was 127 mg daily (25-340 mg) with median length of treatment 32 days (1-122 days). Trimester of initial exposure (P = .33), methadone dose at delivery (P = .198), body mass index (P = .31), antidepressant use (P = .40), cigarette use (P = .76), race (P = .78), and maternal age (P = .84) did not predict length of treatment. In the multivariate analysis, gestational age at delivery and benzodiazepine use were significant predictors of length of treatment. CONCLUSION Later gestational age and concomitant benzodiazepine use were associated with longer treatment.

Endothelial Differentiation of Amniotic Fluid-Derived Stem Cells: Synergism of Biochemical and Shear Force Stimuli

Human amniotic fluid-derived stem (AFS) cells possess several advantages over embryonic and adult stem cells, as evidenced by expression of both types of stem cell markers and ability to differentiate into cells of all three germ layers. Herein, we examine endothelial differentiation of AFS cells in response to growth factors, shear force, and hypoxia. We isolated human AFS cells from amniotic fluid samples (1-4 cc/specimen) obtained from patients undergoing amniocentesis at 15-18 weeks of gestation (n = 10). Isolates maintained in nondifferentiating medium expressed the stem cell markers CD13, CD29, CD44, CD90, CD105, OCT-4, and SSEA-4 through passage 8. After 3 weeks of culture in endothelial growth media-2 (EGM-2), the stem cells exhibited an endothelial-like morphology, formed cord-like structures when plated on Matrigel, and uptook acetylated LDL/lectin. Additionally, mRNA and protein levels of CD31 and von Willebrand factor (vWF) significantly increased in response to culture in EGM-2, with further up-regulation when stimulated by physiological levels (12 dyne/cm(2)) of shear force. Culture in hypoxic conditions (5% O(2)) resulted in significant expression of vascular endothelial growth factor (VEGF) and placental growth factor (PGF) mRNA. This study suggests that AFS cells, isolated from minute amounts of amniotic fluid, acquire endothelial cell characteristics when stimulated by growth factors and shear force, and produce angiogenic factors (VEGF, PGF, and hepatocyte growth factor [HGF]) in response to hypoxia. Thus, amniotic fluid represents a rich source of mesenchymal stem cells potentially suitable for use in cardiovascular regenerative medicine.

Evidence-based surgery for cesarean delivery: an updated systematic review

The objective of our systematic review was to provide updated evidence-based guidance for surgical decisions during cesarean delivery (CD). We performed an English-language MEDLINE, PubMed, and COCHRANE search with the terms, cesarean section, cesarean delivery, cesarean, pregnancy, and randomized trials, plus each technical aspect of CD. Randomized control trials (RCTs) involving any aspect of CD technique from Jan. 1, 2005, to Sept. 1, 2012, were evaluated to update a previous systematic review. We also summarized Cochrane reviews, systematic reviews, and metaanalyses if they included additional RCTs since this review. We identified 73 RCTs, 10 metaanalyses and/or systematic reviews, and 12 Cochrane reviews during this time frame. Recommendations with high levels of certainty as defined by the US Preventive Services Task Force favor pre-skin incision prophylactic antibiotics, cephalad-caudad blunt uterine extension, spontaneous placental removal, surgeon preference on uterine exteriorization, single-layer uterine closure when future fertility is undesired, and suture closure of the subcutaneous tissue when thickness is 2 cm or greater and do not favor manual cervical dilation, subcutaneous drains, or supplemental oxygen for the reduction of morbidity from infection. The technical aspect of CD with high-quality, evidence-based recommendations should be adopted. Although 73 RCTs over the past 8 years is encouraging, additional well-designed, adequately powered trials on the specific technical aspects of CD are warranted.

A Universal Transvaginal Cervical Length Screening Program for Preterm Birth Prevention

OBJECTIVE: To evaluate a universal transvaginal ultrasonogram cervical length screening program on the incidence of a cervical length 20 mm or less and adherence to the management protocol for a cervical length less than 25 mm. METHODS: We conducted a prospective cohort study of women with singleton gestations 18 0/7 to 23 6/7 weeks of gestation eligible for universal transvaginal ultrasonogram cervical length screening over an 18-month period. Only women receiving antenatal care at our institution were included. Women with a prior spontaneous preterm birth and without delivery data available were excluded. A transvaginal ultrasonogram cervical length of less than 25 mm was managed according to a predetermined protocol. Primary outcomes were the incidence of a cervical length 20 mm or less and adherence to the management protocol for a cervical length less than 25 mm. Secondary outcomes were the incidences of spontaneous preterm birth at less than 37, less than 34, or less than 32 weeks of gestation among women undergoing transvaginal ultrasonogram cervical length screening compared with those not screened. RESULTS: One thousand five hundred sixty-nine of 2,171 (72.3%) eligible women underwent transvaginal ultrasonogram cervical length screening. Overall, 17 (1.1%, 95% confidence interval [CI] 0.66–1.74) women had a cervical length 20 mm or less before 24 weeks of gestation. Management protocol deviations occurred in nine women with a cervical length less than 25 mm (43%, 95% CI 24.3–63.5). There was no difference in the incidence of spontaneous preterm birth at less than 37 weeks of gestation (4.1 compared with 4.7%, adjusted odds ratio [OR] 0.91, 95% CI 0.57–1.45), less than 34 weeks of gestation (1.5 compared with 1.3%, adjusted OR 1.19, 95% CI 0.52–2.74), or less than 32 weeks of gestation (0.8 compared with 0.8%, adjusted OR 0.0.76, 95% CI 0.26–2.25) among women receiving transvaginal ultrasonogram cervical length screening compared with those not screened. CONCLUSION: In a universal transvaginal ultrasonogram cervical length screening program, the incidence of a cervical length 20 mm or less was 1.1% in women with singleton gestations without prior spontaneous preterm birth. Protocol deviations occurred in 43% of women with a cervical length less than 25 mm. The incidence of spontaneous preterm birth was similar among women undergoing transvaginal cervical length screening compared with those not screened. LEVEL OF EVIEDENCE: II

Relationship between maternal methadone dose at delivery and neonatal abstinence syndrome.

OBJECTIVE To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS). STUDY DESIGN We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (<or=80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d). The primary outcome was treatment for NAS. Symptoms of NAS were objectively measured with the Finnegan scoring system, and treatment was initiated for a score>24 during the prior 24 hours. RESULTS A total of 330 women treated with methadone and their 388 offspring were included. Average methadone dose at delivery was 117+/-50 mg/d (range, 20-340 mg/d). Overall, 68% of infants were treated for NAS. Of infants exposed to methadone doses<or=80 mg/d, 81-120 mg/d, 121-160 mg/d, and >160 mg/d, treatment for NAS was initiated for 68%, 63%, 70%, and 73% of neonates, respectively (P=.48). The rate of maternal illicit opiate abuse at delivery was 26%, 28%, 19%, and 11%, respectively (P=.04). CONCLUSION No correlation was found between maternal methadone dose and rate of NAS. However, higher doses of methadone were associated with decreased illicit opiate abuse at delivery.