Faculty Bibliography

OBJECTIVES/OBJECTIVE: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. METHODS:This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. RESULTS:Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups. CONCLUSIONS:The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

Ultrasound machines are nowadays part of the armamentarium of all modern Labor and Delivery Suites. Due to their portability, these machines are ideal for use in emergencies which can occur at any of the labor and delivery rooms. Many of the emergencies in Labor and Delivery can be life threatening; thus, maternal and fetal safety requires efficient and timely ultrasound evaluation. The purpose of this article is to provide guidelines for quick and efficient use of ultrasound based on both the authors' experience and the published literature.

OBJECTIVE:To determine if the histology of placental abruption differs by maternal thrombophilia status. STUDY DESIGN/METHODS:This was a multicentre, case-control study of women with abruption and delivering at >or=20 weeks' gestation, collected as part of the ongoing New Jersey-placental abruption study. Women were identified by clinical criteria of abruption. Maternal blood was collected postpartum and tested for anticardiolipin antibodies, and mutations in the Factor V Leiden and prothrombin genes. Cases were comprised of women with an abruption and a positive thrombophilia screen. Controls were comprised of women with an abruption and a negative thrombophilia screen. All placental histology was systematically reviewed by two perinatal pathologists, blinded to the abruption status. RESULTS:A total of 135 women with placental abruption were identified, of which 63.0% (n = 85) had at least one diagnosed maternal thrombophilia. There were increases in the rates of meconium-stained membranes (7.9%vs. 2.1%, p = 0.015) and decidual necrosis (4.5%vs. 2.1%, p = 0.023) when a maternal thrombophilia was diagnosed. Although there was no difference in the overall presence of infarcts between the two groups (27.0%vs. 38.3%, p = 0.064), the presence of an old infarct was more common among women with a positive thrombophilia screen (83.3%vs. 44.4%, p = 0.003). CONCLUSION/CONCLUSIONS:Placental abruption with a positive maternal thrombophilia screen is associated with higher rates of old placental infarcts and decidual necrosis compared with abruption when thrombophilia is not diagnosed. These lesions suggest a chronic etiology of placental abruption in the presence of a maternal thrombophilia.

PROBLEM/OBJECTIVE:Sulfasalazine (SASP) inhibits lipopolysaccharide-induced nuclear-factor kappa B activation and interleukin-8 (IL-8) production by cultured explants of placenta, amnion and choriodecidua. Bacteria-induced IL-8 production in the cervix is a potential mechanism for premature cervical ripening that may lead to preterm birth. Our objective was to determine if SASP inhibits IL-8 production by endocervical cells stimulated with bacterial pathogens associated with preterm birth. METHOD OF STUDY/METHODS:Human endocervical cells were incubated with 0-1.6 mm SASP and then stimulated with Ureaplasma parvum, Escherichia coli, or Gardnerella vaginalis. Conditioned medium was then harvested and production of IL-8 was quantified by ELISA. Viability of the cells was ascertained at the end of the experiment with the MTT-assay. RESULTS:At the highest concentration tested (1.6 mm), SASP significantly inhibited IL-8 production by cultures stimulated with E. coli (P < 0.001), U. parvum (P < 0.001), and G. vaginalis (P < 0.001). Viability of the cells, however, was significantly reduced by SASP at 0.8 and 1.6 mm in both the presence and absence of bacteria for all experiments. CONCLUSION/CONCLUSIONS:Although high concentrations of SASP inhibit IL-8 production by cultures of endocervical cells stimulated with pathogens associated with preterm birth, this effect may be because of toxicity of the antibiotic on the cells.

Folate deficiency and maternal smoking are strong risk factors for placental abruption. We assessed whether the reduced folate carrier [NM_194255.1: c.80A-->G (i.e., p.His27Arg)] (RFC-1) polymorphism was associated with placental abruption, and evaluated if maternal smoking modified the association between plasma folate and abruption. Data were derived from the New Jersey-Placental Abruption Study--a multicenter, case-control study of placental abruption (2002-2007). Maternal DNA was assayed for the RFC-1 c.80A-->G polymorphism using a PCR-dependent diagnostic test. Maternal folate (nmol/l) was assessed from maternal plasma, collected immediately following delivery. Due to assay limitations, folate levels at > or =60 nmol/l were truncated at 60 nmol/l. Therefore, case-control differences in folate were assessed from censored log-normal regression models following adjustment for potential confounders. Distribution of the mutant allele (G) of the RFC-1 c.80A-->G polymorphism was similar between cases (52.3%; n = 196) and controls (50.5%; n = 191), as was the homozygous mutant (G/G) genotype (OR 1.1, 95% CI 0.6-2.2). In a sub-sample of 136 cases and 140 controls, maternal plasma folate levels (mean +/- standard error) corrected for assay detection limits were similar between placental abruption cases (63.6 +/- 5.1 nmol/l) and controls (58.3 +/- 4.7 nmol/l; P = 0.270), and maternal smoking did not modify this relationship (interaction P = 0.169). We did not detect any association between the RFC-1 c.80A-->G polymorphism and placental abruption, nor was an association between plasma folate and abruption risk evident. These findings may be the consequence of high prevalence of prenatal multivitamin and folate supplementation in this population (over 80%). It is therefore not surprising that folate deficiency may be rare and that the RFC-1 c.80A-->G polymorphism is less biologically significant for placental abruption.

PURPOSE OF REVIEW/OBJECTIVE:Fetal growth restriction is a complicated perinatal condition, with multiple causes. It shares common pathophysiologies with other important disorders, such as preeclampsia and abruption. As a group, these conditions associated with ischemic placental disease are responsible for a large percentage of indicated preterm births. The ability to accurately predict, diagnose and manage these pregnancies has significant and far-reaching implications, including potential effects on long-term adult health. RECENT FINDINGS/RESULTS:Placental ischemia is the most common cause of fetal growth restriction. Alterations in placental development are being linked to various angiogenic mediators, which may be of future use in early risk-determination. Until then, the use of ultrasound to accurately diagnose fetal growth restriction and time delivery is the mainstay of management. Research in this area has revealed some commonalities in the deterioration of the growth restricted fetus, but has also indicated that not every affected fetus will follow the same progression in Doppler and other wellbeing parameters. Most importantly, gestational age at delivery is consistently being documented as a critical factor in perinatal morbidity and mortality. SUMMARY/CONCLUSIONS:Fetal growth restriction is a late manifestation of early abnormal placental development. Once abnormal Doppler velocimetry is present, surveillance and timing of delivery should be based on the antepartum test results and on the gestational age.