Michael Cackovic

Ultrasound evaluation of the uterine scar after cesarean delivery: a randomized controlled trial of one- and two-layer closure.

OBJECTIVE: To survey the uterine scar thickness by ultrasonography in women randomly assigned to one- or two-layer hysterotomy closure after primary cesarean delivery. METHODS: This was a randomized, blinded trial of uterine scar closure with ultrasonographic follow-up. Thirty consecutive patients undergoing primary cesarean delivery were enrolled and randomly assigned to one- or two-layer closure of the hysterotomy. Ultrasound surveillance of the uterine scar thickness was performed at baseline (before surgery) and 48 hours, 2 weeks, and 6 weeks post partum. RESULTS: Patient compliance with the postpartum surveillance protocol was 90%, and the uterine scar was visualized in 99% of attempted ultrasonographic examinations. There were no differences between groups at baseline or at any of the follow-up evaluations. An initial 5- to 6-fold increase in uterine scar thickness was observed, followed by a gradual decrease with the 6-week measurements still thicker than baseline. Repeated measures analysis of variance showed significant variation across time points starting either at baseline (P<.001) or at 48 hour postoperatively (P<.001), but this variation did not depend on closure type (P=.79 for all visits and P=.81 beginning with 48-hour postoperative time point). CONCLUSION: The process of uterine scar remodeling can be successfully monitored by ultrasonography. Uterine scar thickness diminishes progressively after both one- or two-layer closure but does not vary with mode of hysterotomy closure. The uterine scar thickness remains increased even at 6 weeks post partum, suggesting that the process of uterine scar remodeling extends beyond the traditional postpartum period. CLINCAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00224250 LEVEL OF EVIDENCE: I

Fractional Excretion of Tumor Necrosis Factor-α in Women With Severe Preeclampsia

OBJECTIVE: Proinflammatory cytokines of placental or systemic origin are thought to play a central role in the pathophysiology of preeclampsia. We sought to estimate the fractional excretion of tumor necrosis factor (TNF)-&agr; in relationship to proteinuria in women with severe preeclampsia. METHODS: In a cross-sectional study, we evaluated the serum and urine levels of TNF-&agr; in 45 women diagnosed with severe preeclampsia (mean±standard error of the mean, gestational age 29.1±0.5 weeks). Forty-five healthy pregnant women matched for parity, maternal age, and gestational age at recruitment (30.1±0.4 weeks) made up the control group. Urinary concentrations were normalized to creatinine. The fractional excretion of TNF-&agr; was interpreted in relationship to that of total proteins and soluble fms-like tyrosine kinase-1 (sFlt-1). RESULTS: We found that the women with preeclampsia had significantly higher serum TNF-&agr; concentrations compared with the women in the control group (mean±standard error of the mean, preeclampsia: 1.39±0.09 versus control: 0.93±0.07 pg/mL, P<.001). In contrast, urinary levels of TNF-&agr; were significantly decreased in the women with preeclampsia compared with the healthy women (median [interquartile range], preeclampsia: 0.26 [0.10–0.91] versus control: 0.58 [0.21–1.29] pg/mg creatinine, P=.003), even though the hypertensive women had higher levels of proteinuria. In contrast to sFlt-1, urinary TNF-&agr; did not correlate with the degree of proteinuria. Additionally, in preeclampsia, the fractional excretion of TNF-&agr; was significantly lower (preeclampsia: 1.92% [0.46–4.20] versus control: 7.2% [2.44–12.07], P<.001). CONCLUSION: The fractional excretion of TNF-&agr; is significantly reduced in women with severe preeclampsia despite proteinuria. The decreased clearance and altered renal excretion of this cytokine may contribute to the exaggerated inflammatory response observed in preeclampsia. LEVEL OF EVIDENCE: II

Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis.

OBJECTIVE The objective of the study was to test the hypothesis that inflammation modulates fetal erythroblastosis and/or the release of nucleated red blood cells (NRBCs) independent of hypoxia or fetal stress. We sought to determine whether fetal inflammation is associated with an elevation in neonatal NRBC count in the setting of inflammation-associated preterm birth. STUDY DESIGN The relationships between peripheral NRBC count, histological chorioamnionitis, umbilical cord interleukin (IL)-6, erythropoietin (EPO), cortisol, and acid-base status were analyzed in 68 preterm singletons, born to mothers who had an amniocentesis to rule out infection. Proteomic profiling of amniotic fluid identified presence of intraamniotic inflammation according to established parameters. NRBC counts were assessed within 1 hour of birth. Early-onset neonatal sepsis (EONS) was established based on hematological and microbiological indices. IL-6, EPO, and cortisol levels were measured by immunoassays. Fetal acid-base status was determined within 10 minutes of delivery. Parametric or nonparametric statistics were used. RESULTS Fetuses with EONS (n = 19) were delivered at earlier gestational ages (mean +/- SD: 27.1 +/- 2.8 weeks, P = .001) and more often by mothers with intraamniotic inflammation (P = .022) and histological chorioamnionitis (P < .001). Neonates with EONS had higher absolute NRBC counts (P = .011). NRBC counts were directly correlated with cord blood IL-6 levels (P < .001) but not with EPO, cortisol or parameters of acid-base status levels regardless of EONS status. These relationships remained following correction for gestational age, diabetes, intrauterine growth restriction, and steroid exposure. CONCLUSION In the setting of inflammation-associated preterm birth and in the absence of hypoxia, elevations in NRBCs in the early neonatal period may be a direct response of exposure to inflammatory mediators in utero.

Effect of 2 stitches vs 1 stitch on the prevention of preterm birth in women with singleton pregnancies who undergo cervical cerclage.

OBJECTIVE This study investigates whether 2 cerclage stitches are more effective than 1 stitch in the prevention of preterm birth. STUDY DESIGN This is a retrospective cohort study of 150 singleton pregnancies that underwent cervical cerclage. Gestational age at delivery and clinical characteristics were compared. RESULTS One hundred twelve patients (74.7%) received 1 stitch, and 38 patients (25.3%) received 2 stitches. There were no baseline differences between the groups. Analysis showed no significant difference in gestational age at delivery between the 1 vs 2 cerclage groups overall (median, 38.0 vs 38.3 weeks of gestation, respectively; P = .356) or for a given gestational age cut-off (<37 weeks of gestation: 37.4% vs 34.2% [P = .727]; <34 weeks of gestation: 16.8% vs 18.4% [P = .823]; <28 weeks of gestation: 9.4% vs 2.6% [P = .179]). CONCLUSION This study shows no measurable benefit to the placement of 2 stitches over 1 stitch during cervical cerclage in singleton pregnancies; however, further study of preterm birth at <28 weeks of gestation and postcerclage outcomes among a larger cohort is merited.

The Probability of Neonatal Respiratory Distress Syndrome as a Function of Gestational Age and Lecithin/Sphingomyelin Ratio

We sought to define the risk of neonatal respiratory distress syndrome (RDS) as a function of both lecithin/sphingomyelin (L/S) ratio and gestational age. Amniotic fluid L/S ratio data were collected from consecutive women undergoing amniocentesis for fetal lung maturity at Yale-New Haven Hospital from January 1998 to December 2004. Women were included in the study if they delivered a live-born, singleton, nonanomalous infant within 72 hours of amniocentesis. The probability of RDS was modeled using multivariate logistic regression with L/S ratio and gestational age as predictors. A total of 210 mother-neonate pairs (8 RDS, 202 non-RDS) met criteria for analysis. Both gestational age and L/S ratio were independent predictors of RDS. A probability of RDS of 3% or less was noted at an L/S ratio cutoff of > or = 3.4 at 34 weeks, > or = 2.6 at 36 weeks, > or = 1.6 at 38 weeks, and > or = 1.2 at term. Under 34 weeks of gestation, the prevalence of RDS was so high that a probability of 3% or less was not observed by this model. These data describe a means of stratifying the probability of neonatal RDS using both gestational age and the L/S ratio and may aid in clinical decision making concerning the timing of delivery.

Fetal Heart Rate Monitoring Patterns in Women with Amniotic Fluid Proteomic Profiles Indicative of Inflammation

We hypothesized that abnormal fetal heart rate monitoring patterns (FHR-MPs) occur more often in pregnancies complicated by intra-amniotic inflammation. Therefore, our objective was to examine the relationships among FHR-MP abnormalities, intra-amniotic inflammation and/or infection, acute histological chorioamnionitis, and early-onset neonatal sepsis (EONS) in pregnancies complicated by preterm birth. Additionally, the ability of various FHR-MPs to predict EONS was investigated. FHR-MPs from 87 singleton premature neonates delivered within 48 hours from amniocentesis (gestational age, mean +/- SD: 28.9 +/- 3.3 weeks) were analyzed blindly using strict National Institute of Child Health and Human Development criteria. Strips were evaluated at three time points: at admission, at amniocentesis, and prior to delivery. Intra-amniotic inflammation was established based on a previously validated proteomic fingerprint (mass-restricted score). Diagnoses of histological chorioamnionitis and EONS were based on well-recognized pathological, clinical, and laboratory criteria. We determined that fetuses of women with severe intra-amniotic inflammation had a higher FHR baseline throughout the entire monitoring period and an increased frequency of a nonreactive FHR-MP at admission. Of all FHR-MPs, a nonreassuring test at admission had 32% sensitivity, 95% specificity, 73% positive predictive value, 77% negative predictive value, and 76% accuracy in predicting EONS. Although a nonreassuring FHR-MP at admission was significantly associated with EONS after correcting for gestational age (odds ratio, 5.6; 95% confidence interval, 1.2 to 26.2; P = 0.030), the majority of the neonates that developed EONS had an overall reassuring FHR-MP. Nonreassuring FHR-MPs at either amniocentesis or delivery had no association with EONS. We conclude that in cases complicated by preterm birth, a nonreassuring FHR-MP at the initial evaluation is a specific but not a sensitive predictor of EONS. An abnormal FHR-MP can thus raise the level of awareness that a fetus with EONS may be born, but it is not a useful clinical indicator of the need for antibiotic treatment of the neonate.

Hypoxic hepatitis in a pregnant patient: a complication of gastric bypass surgery.

Elevated serum transaminase levels can have many different etiologies, especially in the pregnant patient. Hypoxic hepatitis is a distinct syndrome caused by decreased hepatic blood flow that presents with a marked, but transient, increase in liver enzymes. A 28-year-old woman, gravida 3, para 2 with history of gastric bypass, presented in the second trimester with bright red blood per rectum, syncope, and epigastric pain. Laboratory studies were significant for anemia, elevated liver enzymes, and low platelets, raising concern for hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) and the need for emergent delivery. Complete evaluation included an upper endoscopy, which revealed a bleeding jejunal ulcer that was subsequently cauterized. Shortly after cauterization, the patients laboratory values normalized and her pain resolved. Diagnosis of hypoxic hepatitis was made after exclusion of other liver-toxic entities, thus preventing delivery of a preterm infant. Hypoxic hepatitis may masquerade as other clinical syndromes, especially in the pregnant patient. Meticulous physical examination and assessment of laboratory values is essential for making a proper diagnosis and guiding management.