Harnessing alveolar macrophages for sustained mucosal T-cell recall confers long-term protection to mice against lethal influenza challenge without clinical disease.

Vaccines that induce T cells, which recognize conserved viral proteins, could confer universal protection against seasonal and pandemic influenza strains. An effective vaccine should generate sufficient mucosal T cells to ensure rapid viral control before clinical disease. However, T cells may also cause lung injury in influenza, so this approach carries inherent risks. Here we describe intranasal immunization of mice with a lentiviral vector expressing influenza nucleoprotein (NP), together with an NFκB activator, which transduces over 75% of alveolar macrophages (AM). This strategy recalls and expands NP-specific CD8+ T cells in the lung and airway of mice that have been immunized subcutaneously, or previously exposed to influenza. Granzyme B-high, lung-resident T-cell populations persist for at least 4 months and can control a lethal influenza challenge without harmful cytokine responses, weight loss, or lung injury. These data demonstrate that AM can be harnessed as effective antigen-presenting cells for influenza vaccination.

Facial motor function monitored by hand held calipers versus computer-assisted photography.

BACKGROUND: It is essential to have easy to use, reliable tools to assess and compare facial function for clinical records, audit and research purposes. In this study, two different techniques were examined, Hand held calipers (HHC, as described by Burres), and computerised analysis of digital photographs (CAOP) using Adobe Photoshop 7. The aim of this study was to determine the level of agreement between two operators (physiotherapist) using HHC to measure the distance between facial landmarks, and the level of agreement between two operators (photographers) using CAOP to measure the same distance between facial landmarks and explore whether these two techniques can be used interchangeably. METHOD: The distance between facial landmarks was measured, with the face at rest and following four standard facial expressions. All measurements were repeated one week later to permit inter/intra-rater reliability over time to be assessed. Nine female volunteers with normal facial function were included in the study. RESULTS: The intra- and inter-rater agreement using CAOP was high whereas the agreement was low when using HHC. CONCLUSION: Hand held calipers proved to be an unreliable technique for monitoring facial function. However digital photography when combined with Adobe Photoshop 7 provides a highly reliable objective measurement tool. It was simple to use, low cost and suitable for use in a clinical environment.

Formation of LID vector complexes in water alters physicochemical properties and enhances pulmonary gene expression in vivo.

There is currently an urgent need to develop efficient gene-delivery systems for the lung that are free of inflammatory effects. The LID vector is a synthetic gene delivery system, comprised of lipofectin (L), an integrin-targeting peptide (I) and DNA (D) that has previously been shown to have high transfection efficiency in the lung. We have assessed the effect of alternative methods of complex preparation on structural features of the complex, levels and duration of reporter gene expression and the host response to the LID vector. We have demonstrated that making the complex in water affects the structure of the LID complexes making them smaller and more stable with a more cationic surface charge than complexes prepared in phosphate-buffered saline (PBS). When the LID vector was constituted in water and instilled intratracheally into the lungs of mice there was a 10-fold increase in luciferase activity compared with preparation in PBS. Furthermore, luciferase activity was still evident 1 week following vector instillation. This enhancement may be because of altered complex structure, although effects of the hypotonic vector solution on the lung cannot be excluded. The inflammatory effects of instilling the LID vector in water were minimal, even after three administrations of the LID vector, with only mild alterations in cytokine and broncho-alveolar lavage fluid (BALF) cell profiles. These results demonstrate that the LID vector can generate high, and prolonged, levels of gene expression in the lung from small quantities of DNA and that careful attention to synthetic polyplex structure may be important to optimize efficiency of gene expression in vivo.

Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity.

Glucocorticoids (GCs) are the mainstay of asthma therapy; however, major side effects limit their therapeutic use. GCs influence the expression of genes either by transactivation or transrepression. The antiinflammatory effects of steroids are thought to be due to transrepression and the side effects, transactivation. Recently, a compound, RU 24858, has been identified that demonstrated dissociation between transactivation and transrepression in vitro. RU 24858 exerts strong AP-1 inhibition (transrepression), but little or no transactivation. We investigated whether this improved in vitro profile results in the maintenance of antiinflammatory activity (evaluated in the Sephadex model of lung edema) with reduced systemic toxicity (evaluated by loss in body weight, thymus involution, and bone turnover) compared with standard GCs. RU 24858 exhibits comparable antiinflammatory activity to the standard steroid, budesonide. However, the systemic changes observed indicate that transactivation events do occur with this GC with similar potency to the standard steroids. In addition, the GCs profiled showed no differentiation on quantitative osteopenia of the femur. These results suggest that in vitro separation of transrepression from transactivation activity does not translate to an increased therapeutic ratio for GCs in vivo or that adverse effects are a consequence of transrepression.

The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth. STUDY DESIGN: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at >/=37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score. RESULTS: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of >/=1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r =.51; P =.0001), sialidase activity (r =.38; P =.0001), and bacterial vaginosis (r =.38; P =.0001), were weakly related to fetal fibronectin (r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5. 5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4). CONCLUSIONS: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity.

Severe oligohydramnios with intact membranes: an indication for diagnostic amnioinfusion.

OBJECTIVE: To quantify the improvement in ultrasonographic fetal imaging following diagnostic amnioinfusion for the indication of unexplained midtrimester oligohydramnios. METHODS: Patients referred for unexplained midtrimester oligohydramnios were retrospectively reviewed. Videotapes of those undergoing diagnostic antenatal amnioinfusion were analyzed for quality of visualization of routinely imaged structures before and after the infusion procedure. RESULTS: The overall rate of adequate visualization of fetal structures improved from 50.98 to 76.79% (p < 0.0001). In fetuses having preinfusion-identified obstructive uropathy, there was improvement in identification of associated anomalies from 11.8 to 31.3%. CONCLUSIONS: Several authors have suggested that diagnostic amnioinfusion can facilitate fetal imaging and increase diagnostic precision in the setting of unexplained severe oligohydramnios. We have quantified the improvement in the rate of optimal visualization of fetal structures which likely translates, in experienced hands, into this observed improved diagnostic precision. Of particular importance is the improvement in appreciation of associated anomalies in cases of obstructive uropathy in which such findings may determine whether or not invasive fetal therapy is indicated.

Obstetrical determinants of neonatal neurological morbidity in < or = 1000-gram infants.

The purpose of this study is to identify obstetrical factors associated with adverse neurological outcome in < or =1000-g infants. In a 1-year (1992-1993) observational study, the NICHD MFMU Network collected obstetrical risk factors for 486 infants who weighed < or =1000 g at birth and who survived > 2 days. Infants' records were abstracted for seizures, intraventricular hemorrhage, and an abnormal neurological evaluation. Seventy-nine (16%) infants had a Grade III or IV intraventricular hemorrhage, 46 (9%) developed seizures and 57 (14%) had an abnormal neurological evaluation. Both lower birth weight and earlier gestational age correlated (P <0.01) with an increasing incidence of all three outcomes. Several other factors appeared to be associated with neurological morbidity, however, after controlling for potential confounders in the multivariate analyses, most of these factors were no longer significant. African-American race, odds ratio (OR) 0.6 (0.3-1.0), and severe preeclampsia, OR 0.2 (0.1-0.7), were protective against intraventricular hemorrhage. Maternal treatment with corticosteroids did not impact neurological outcome in this study population. We conclude that, in a population of < or =1000-g infants, lower birth weight and earlier gestational age were the only consistently significant predictors of all three adverse neurological outcomes.

Induction of labor in patients with term premature rupture of membranes. Effect on perinatal outcome.

OBJECTIVE: To determine whether delayed induction of labor in patients with premature rupture of membranes (PROM) at term has beneficial effects on the mother or the infant. STUDY DESIGN: Retrospective analysis of our database revealed 576 patients >37 weeks of gestation with PROM, who delivered live-born infants without major congenital anomalies. We analyzed the frequencies of primary cesarean, neonatal intensive care unit (NICU) admissions, and oxytocin use by time since hospital admission and interval until onset of labor. RESULTS: NICU admission increased from 1.9% in <3 h between admission to onset of labor to 13.3% after >18 h. Admission-onset of labor interval, birth weight of <2,500 or >4,000 g and meconium were all more important determinants of NICU admission than gestational age, duration of labor, PROM, and ROM. Prolonged admission-onset of labor interval was associated with an increased risk of variable decelerations (p < 0.001). Primary cesarean rates increased progressively with longer intervals between admission and onset of labor. Stepwise discriminant function analysis revealed that labor duration, admission-onset of labor interval, gestational age, and birth weight of <2,500 g were all more important determinants of primary cesarean delivery than the durations of PROM or ROM. CONCLUSIONS: The increased frequencies of NICU admission, variable decelerations, and primary cesarean suggest that delayed labor induction after hospital admission was linked to worsened perinatal outcomes. These results may have been influenced by usually performing a single digital examination as part of initial evaluation of term patients who present with PROM. Based on our data, we suggest immediate induction for PROM at term, especially if digital examination has been performed.

Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants.

OBJECTIVE: The aim of the study was to compare clinical and ultrasonographic variables obtained before delivery as predictors of neonatal survival and morbidity in infants weighing

Benefits of maternal corticosteroid therapy in infants weighing

OBJECTIVE: The aim of the study was to determine the effects of antenatal maternal corticosteroid treatment on selected neonatal outcomes in infants weighing

Indicated versus spontaneous preterm delivery: An evaluation of neonatal morbidity among infants weighing

OBJECTIVE: The aim of the study was to determine whether infants weighing 20 weeks who were not produced as the result of an induced abortion were included. Our analysis was further limited to infants without major congenital anomalies who survived >2 days, were deemed potentially viable by the obstetrician, and would have undergone a cesarean delivery for fetal indications (N = 411). The primary reason for delivery was categorized as indicated delivery, spontaneous preterm labor, or spontaneous preterm premature rupture of membranes. Selected neonatal outcomes were evaluated among infants born to women in each of these groups. Logistic regression analyses were used to control for the effects of other potentially confounding variables. RESULTS: A total of 156 of the 411 infants were born to women who underwent an indicated preterm delivery, whereas 160 were born after spontaneous preterm labor and 95 were delivered after preterm premature rupture of membranes. Univariate analyses revealed significantly lower incidences of grade III or IV intraventricular hemorrhage, grade III or IV retinopathy of prematurity, and seizure activity among infants born in an indicated preterm delivery than among those born after spontaneous preterm labor or preterm premature rupture of membranes. However, infants of women who underwent indicated preterm delivery had a more advanced mean gestational age at birth than did those born after spontaneous preterm labor or preterm premature rupture of membranes (28 +/- 2 weeks, 26 +/- 2 weeks, and 26 +/- 1 weeks, respectively, P <.001). Multiple logistic regression analysis was therefore used to control for the disparity in gestational age. Multivariate analyses did not confirm the apparent improvement in neonatal outcome in the indicated delivery group. CONCLUSION: In this population of infants weighing

Plasma ferritin, premature rupture of membranes, and pregnancy outcome.

OBJECTIVE: The objective of this study was to determine whether plasma ferritin levels predict maternal or neonatal outcomes in women with preterm rupture of membranes at <32 weeks' gestation. METHODS: Plasma from 223 women with premature rupture of membranes at <32 weeks' gestation who had participated in a randomized antibiotic trial were analyzed for ferritin at random assignment and at delivery, and the results were compared with the development of clinical chorioamnionitis, latency until delivery, neonatal sepsis, and a composite adverse neonatal outcome variable. RESULTS: The mean plasma ferritin level rose from 19.2 +/- 29.1 microgram/L on admission to 38.3 +/- 54.3 microgram/L at delivery, with a mean latency of 9.3 +/- 14.6 days. Plasma ferritin levels were significantly higher at both times in mothers whose infants acquired sepsis than in those whose infants did not, especially at delivery (68.5 +/- 96.3 microgram/L vs 32.5 +/- 40.5 microgram/L, P =.01), and neonatal sepsis was 2 to 3 times more common among women with plasma ferritin levels above the median than among those with levels below the median. CONCLUSIONS: Among women with premature rupture of membranes at <32 weeks' gestation, plasma ferritin levels were significantly associated with neonatal sepsis. These data suggest that higher plasma ferritin levels may serve as a marker of infection among women with premature rupture of membranes; however, the clinical utility of plasma ferritin levels in predicting neonatal outcome appears limited.

Limited usefulness of fetal weight in predicting neonatal brachial plexus injury.

OBJECTIVE: The objectives were to determine the neonatal morbidity rate from vaginal birth and examine fetal weight-based injury-prevention strategies. STUDY DESIGN: Selected neonatal morbidities were categorized by birth weight for all vertex vaginal deliveries occurring during a 12-year period. Sensitivity, specificity, and predictive values for brachial palsy were calculated at increasing birth weight cutoff levels. A policy of cesarean delivery for macrosomic infants was evaluated. RESULTS: There were 80 cases of brachial palsy among 63,761 infants (0.13%). In mothers without diabetes, rates in the 4500- to 4999-g and >5000-g groups were 3.0% and 6.7%, respectively. A threshold of 3700 g had a sensitivity of 71% and a specificity of 86%; the positive predictive value was 0.56%. To prevent a single case of permanent injury, 155 to 588 cesarean deliveries are required at the currently recommended cutoff weight of 4500 g. CONCLUSIONS: The rates of lasting morbidity do not justify routine cesarean delivery for infants without diabetic complications weighing <5000 g.

The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: We sought to estimate the risk of spontaneous preterm birth in parous women by use of obstetric history, fetal fibronectin, and sonographic cervical length. STUDY DESIGN: The probability of spontaneous preterm birth before 35 weeks' gestation was estimated from a logistic regression model with data from 1282 parous women analyzed according to gestational age at the most recent prior delivery (prior preterm birth at 18 to 26 weeks, 27 to 31 weeks, 32 to 36 weeks, and > or = 37 weeks' gestation), fetal fibronectin status (positive = > or = 50 ng/dl), and cervical length by percentile groups (< or = 10th = < or = 25 nm, 10th to 50th = 26 to 35 mm, and > 50th = > 35 mm) measured at 22 to 24 weeks' gestation. Fibronectin and cervical length results were blinded for clinical care. RESULTS: Among fetal fibronectin positive women with a prior preterm birth, the estimated recurrence risk of preterm birth < 35 weeks' gestation was approximately 65% when the cervix was < or = 25 mm, 45% when the cervix was 26 to 35 mm, and 25% when the cervix was > 35 mm at 24 weeks' gestation. For fetal fibronectin negative women with a prior preterm birth, the recurrence risk was 25% when the cervix was < or = 25 mm, 14% when the cervix was 26 to 35 mm, and 7% when the cervix was > 35 mm. The risk of preterm birth was increased among women with a history of preterm delivery but was not influenced by the gestational age at delivery of the most recent preterm birth. CONCLUSION: The recurrence risk of spontaneous preterm birth varies widely according to fetal fibronectin and cervical length. Cervical length and fetal fibronectin results had distinct and significant effects on the recurrence risk of preterm birth. Predicted recurrence risk is increased by twofold to fourfold in women with a positive compared with a negative fetal fibronectin, and it increases as cervical length shortens in both fetal fibronectin-positive and fetal fibronectin-negative women. These data may be useful to care for women with a history of preterm birth and to design studies to prevent recurrent premature delivery.

The incidence of respiratory distress syndrome does not increase when preterm delivery occurs greater than 7 days after steroid administration.

We sought to determine if the risk of the respiratory distress syndrome (RDS) is increased when preterm delivery occurs greater than 7 days from the last steroid administration. At our hospital, steroids were repeated weekly only on inpatients. Linking pharmacy and delivery records, we analyzed the risk of RDS with preterm delivery by interval since last steroid administration. Discriminant function analysis revealed that adjusted for gestational age, there was a negative correlation between interval since last steroids administration and risk for RDS (p<0.05, n=254). Using analysis of variance to control more precisely for gestational age (28-32 weeks, n=19) we found no difference in the risk for RDS with longer intervals since the last steroid administration. We then used multiway contingency analysis to consider intervals as zero to 7 versus greater than 7 days and similar results were obtained. Our findings suggest that the process of pulmonary maturation induced by steroid administration is permanent rather than transient. Repetitive steroid administration does not appear to be beneficial. Only a large, prospective randomized trial could definitively address the issue of repeat steroid administration. However, on the basis of our findings and review of available literature, we believe there is insufficient data to recommend weekly repeat steroid administration to women at risk for preterm delivery.

The preterm prediction study: risk factors for indicated preterm births. Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development.

OBJECTIVE: Preterm births occur for many different reasons. Most efforts to identify risk factors for preterm births either ignore cause and consider preterm births as a single entity or examine risk factors for spontaneous preterm births. We performed this study to examine risk factors for indicated preterm births, which constitute more than one quarter of all preterm births. STUDY DESIGN: The study included 2929 women evaluated at 24 weeks' gestation at 10 centers. Information was gathered about demographic factors, socioeconomic status, home and work environments, drug and alcohol use, and medical history. In addition vaginal samples were evaluated for fetal fibronectin and bacterial vaginosis and cervical length was measured by transvaginal ultrasonography. Associations with indicated preterm birth were evaluated by univariate tests and by multivariable analysis with logistic regression. RESULTS: Of the women studied at 24 weeks' gestation 15.3% were delivered of their infants at <37 weeks' gestation. Of these deliveries, 27.7% were indicated preterm births. Risk factors in the final multivariable model were, in order of decreasing odds ratios, mullerian duct abnormality (odds ratio 7.02), proteinuria at <24 weeks' gestation (odds ratio 5.85), history of chronic hypertension (odds ratio 4.06), history of previous indicated preterm birth (odds ratio 2.79), history of lung disease (odds ratio 2.52), previous spontaneous preterm birth (odds ratio 2.45), age >30 years (odds ratio 2.42), black ethnicity (odds ratio 1.56), and working during pregnancy (odds ratio 1.49). Alcohol use in pregnancy was actually associated with a lower risk of indicated preterm birth (odds ratio 0.35). CONCLUSION: The risk factors found in this analysis tend to be different from those associated with spontaneous preterm birth.

The preterm prediction study: the value of new vs standard risk factors in predicting early and all spontaneous preterm births. NICHD MFMU Network.

OBJECTIVES: This study was undertaken to determine the relationship between fetal fibronectin, short cervix, bacterial vaginosis, other traditional risk factors, and spontaneous preterm birth. METHODS: From 1992 through 1994, 2929 women were screened at the gestational age 22 to 24 weeks. RESULTS: The odds ratios for spontaneous preterm birth were highest for fetal fibronectin, followed by a short cervix and history of preterm birth. These factors, as well as bacterial vaginosis, were more strongly associated with early than with late spontaneous preterm birth. Bacterial vaginosis was more common--and a stronger predictor of spontaneous preterm birth--in Black women, while body mass index less than 19.8 was a stronger predictor in non-Black women. This analysis suggests a pathway leading from Black race through bacterial vaginosis and fetal fibronectin to spontaneous preterm birth. Prior preterm birth is associated with spontaneous preterm birth through a short cervix. CONCLUSIONS: Fetal fibronectin and a short cervix are stronger predictors of spontaneous preterm birth than traditional risk factors. Bacterial vaginosis was found more often in Black than in non-Black women and accounted for 40% of the attributable risk for spontaneous preterm birth at less than 32 weeks.

The effect of maternal magnesium sulfate treatment on neonatal morbidity in < or = 1000-gram infants.

We evaluated the effect of maternal magnesium sulfate treatment on selected neonatal outcomes in < or =1000-g infants. In a 1-year (1992-1993) observational study, the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units collected outcome data for 799 infants whose birth weights were < or =1000 g. Only singleton infants, with a gestational age >20 weeks who were not the product of an induced abortion were included. Our analysis was further limited to those infants without major congenital anomalies, who were deemed potentially viable by the obstetrician, whose mother would have undergone a cesarean delivery for fetal indications, and who survived greater than 2 days. Outcomes were compared in infants whose mothers did and did not receive magnesium sulfate for labor tocolysis. Among the 124 women who did and the 184 who did not receive magnesium sulfate tocolytic therapy, the frequencies of grade III or IV intraventricular hemorrhage (16 vs. 20%, p = 0.34), seizure activity (7 vs. 10%, p = 0.35), grade III or IV retinopathy of prematurity (21 vs. 18% p = 0.59), abnormal neurological exam (28 vs. 28%, p = 0.91), intact survival to 120 days or to discharge (48 vs. 44%, p = 0.54), and infant mortality (23 vs. 31%, p = 0.10) were similar. Multiple logistic regression analysis was used to control for the effect of potential confounders (specifically, gestational age) and confirmed the lack of a significant association between maternal magnesium sulfate treatment for tocolysis and selected neonatal outcomes in this population of < or =1000-gram infants.

Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

CONTEXT: Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent. OBJECTIVE: To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. PATIENTS: A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization. INTERVENTIONS: Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization. MAIN OUTCOME MEASURES: The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed. RESULTS: In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001). CONCLUSIONS: We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.

In utero progression of isolated renal pelvis dilation.

The objective of this study to determine the risk of in uteroprogression of renal pelvis dilation when detected on antenatal ultrasound examination. We reviewed 230 fetuses with evidence of renal pelvis dilation. At least one exam was subsequently performed prior to delivery in all cases. Renal pelvis dilation was defined as an anterior-posterior renal pelvis measurement > 4 mm at < 32 weeks' and > 7 mm at > or = 32 weeks' gestation. Hydronephrosis was considered to be present when the renal pelvis measured +10 mm independent of gestational age. Multiple gestations and fetuses with additional congenital anomalies were excluded. The mean gestational age at diagnosis was 24 weeks. Renal pelvis dilation progressed to hydronephrosis in a total of 10.9% (25 of 230) of fetuses. There was a 3.3% chance of unilateral renal pelvis dilation progressing to hydronephrosis versus 26.0% in bilateral dilation (OR 10.4 [95% Cl 3.5-33.3]). Of those fetuses with progression, 80% had bilateral dilation (p < 0.0001). There was no difference in progression between right and left kidneys. Additionally, gender, gestational age at diagnosis and delivery, and birth weight did not differ between those fetuses with and without progression. The hydronephrosis in 7 of 25 (28%) regressed to pyelectasis on a subsequent ultrasound exam. Thus, the overall rate of progression of renal pelvis dilation to persistent hydronephrosis was 7.8% (18 of 230). In conclusion, the risk of isolated renal pelvis dilation progressing to hydronephrosis is low. Although bilateral pelvis dilation carries a higher risk for progression, no fetus in our study required in utero intervention. A follow up scan prior to delivery may be considered to identify those fetuses who will require postpartum intervention.