Changes in delivery methods at specialty care hospitals in the United States between 2006 and 2010.

OBJECTIVE: Given the increasing rates of labor induction and cesarean delivery, and efforts to reduce early term births, we examined recent trends in methods and timing of delivery. STUDY DESIGN: We identified delivery methods and medical indications for delivery from administrative hospital discharge data for 231 691 deliveries in 2006 and 213 710 deliveries in 2010 from 47 specialty care member hospitals of the National Perinatal Information Center/Quality Analytic Services. In a subset of 17 hospitals, we examined trends by gestational age. RESULT: From 2006 to 2010, there was an 11% increase in labor induction and a 6% increase in cesarean delivery, largely due to repeat cesareans. There was a 4 per 100 reduction in early term births (37 to 38 weeks), mostly due to a decline in non-medically indicated interventional deliveries. CONCLUSION: We report a shift in deliveries at 38 weeks, which we believe may be attributed to efforts to actively limit non-medically indicated early term deliveries.

Improving perinatal health: a novel approach to improve community and adult health.

Recent trends of increasing infant morbidity and mortality are inconsistent with this nation's vision of advances in adult quality of life and longevity. Infant mortality and weight at birth are important predictors of the health of a society, making these findings all the more disturbing. Infant morbidity could be a reflection or alternatively, a harbinger of increasing national rates of obesity, diabetes mellitus, community violence and widening economic disparities. This paper presents the linkage between perinatal health and adult health using infant morbidities (infant mortality, low birthweight, prematurity) as examples. Infant morbidities/mortalities are social problems with health-care consequences. All social classes suffer the results of poor infant health. Improving perinatal health can improve the health of a community in a cyclic fashion. We propose that improving the health of reproductive age women and infants; will result in a reduction in the incidence of severe/chronic and costly adult health outcomes.

Evolving views in prion glycosylation: functional and pathological implications.

Prion diseases form a group of neurodegenerative disorders with the unique feature of being transmissible. These diseases involve a pathogenic protein, called PrP(Sc) for the scrapie isoform of the cellular prion protein (PrP(C)) which is an abnormally-folded counterpart of PrP(C). Many questions remain unresolved concerning the function of PrP(C) and the mechanisms underlying prion replication, transmission and neurodegeneration. PrP(C) is a glycosyl-phosphatidylinositol-anchored glycoprotein expressed at the cell surface of neurons and other cell types. PrP(C) may be present as distinct isoforms depending on proteolytic processing (full length and truncated), topology(GPI-anchored, transmembrane or soluble) and glycosylation (non- mono- and di-glycosylated). The present review focuses on the implications of PrP(C) glycosylation as to the function of the normal protein, the cellular pathways of conversion into PrP(Sc), the diversity of prion strains and the related selective neuronal targeting.

All-trans retinoic acid down-regulates prion protein expression independently of granulocyte maturation.

The cellular prion protein (PrPc) is a sialoglycoprotein involved in the pathogenesis of prion diseases. It has been identified at the plasma membrane of several cell types. All-trans retinoic acid (ATRA) is known to induce differentiation of human leukemia cell lines in vitro. PrPc messenger ribonucleic acid (mRNA) and protein are down-regulated upon ATRA-induced differentiation of HL60 cells. In this report, we have investigated the regulation of PrPc mRNA and protein expression during ATRA-treatment of maturation-sensitive (NB4) and -resistant (NB4-R1 and NB4-R2) cell lines. In ATRA-induced maturation of NB4 cells, down-regulation of PrPc mRNA and protein were observed. We also show that down-regulation of PrPc mRNA is dependent on protein synthesis. Moreover, the same down-regulation of prion protein by ATRA was observed at the surface of maturation-resistant, ATRA-responsive NB4-R1 cells. In contrast, the maturation-resistant and ATRA-unresponsive NB4-R2 subline showed no variation in membrane prion protein expression. These results demonstrate a dissociation between the regulation of prion protein expression by ATRA and the process of granulocyte maturation. We propose that retinoids should be investigated further as a preventive strategy to slow down prion disease progression.

The cellular prion protein: a new partner of the lectin CBP70 in the nucleus of NB4 human promyelocytic leukemia cells.

Prion diseases are characterized by the presence of an abnormal isoform of the cellular prion protein (PrPc) whose physiological role still remains elusive. To better understand the function of PrPc, it is important to identify the different subcellular localization(s) of the protein and the different partners with which it might be associated. In this context, the PrPc-lectins interactions are investigated because PrPc is a sialoglycoprotein which can react with lectins which are carbohydrate-binding proteins. We have previously characterized a nuclear lectin CBP70 able to recognize N-acetyl-beta-D-glucosamine residues in HL60 cells. Using confocal immunofluorescence, flow-cytofluorometry, and Western-blotting, we have found that PrPc is expressed in the nucleus of the NB4 human promyelocytic leukemia cell line. It was also found that the lectin CBP70 is localized in NB4 cell nuclei. Moreover, several approaches revealed that PrPc and CBP70 are colocalized in the nucleus. Immunoprecipitation experiments showed that these proteins are coprecipitated and interact via a sugar-dependent binding moiety. In conclusion, PrPc and CBP70 are colocalized in the nuclear compartment of NB4 cells and this interaction may be important to better understand the biological function and possibly the conversion process of PrPc into its pathological form (PrPsc).

Glycosylated nuclear lectin CBP70 also associated with endoplasmic reticulum and the Golgi apparatus: does the "classic pathway" of glycosylation also apply to nuclear glycoproteins?

The subcellular plurilocalization of some lectins (galectin-1, galectin-3, galectin-10, calreticulin, etc.) is an intriguing problem, implying different partners according to their localization, and involvement in a variety of cellular activities. For example, the well-known lectin, galectin-3, a lactose-binding protein, can act inside the nucleus in splicing events, and at the plasma membrane in adhesion, and it was demonstrated that galectin-3 interacts in the cytoplasm with Bcl-2, an antiapoptotic protein. Some years ago, our group isolated a nuclear lectin CBP70, capable of recognizing N-acetylglucosamine residues. This lectin, first isolated from the nucleus of HL60 cells, was also localized in the cytoplasm. It has been demonstrated that CBP70 is a glycosylated lectin, with different types of glycosylation, comparing cytoplasmic and nuclear forms. In this article, we have studied the localization of CBP70 in undifferentiated HL60 cells by electron microscopy, immunofluorescence analysis, and subcellular fractionation. The results obtained clearly demonstrated that CBP70 is a plurilocalized lectin that is found in the nucleus, at the endoplasmic reticulum, the Golgi apparatus, and mitochondria, but not at the plasma membrane. Because CBP70, a nuclear glycoprotein, was found to be associated also with the endoplasmic reticulum and the Golgi apparatus where the glycosylation take place, it raised the question: where does the glycosylation of nuclear proteins occur?

Diagnosis and differentiation of congenital diaphragmatic hernia from other noncardiac thoracic fetal masses.

This retrospective study was designed to evaluate individual sonographic parameters that might help differentiate congenital diaphragmatic hernia (CDH) from other noncardiac thoracic masses such as cystic adenomatoid malformation of the lung (CAML) and congenital lobar emphysema (CLE) prenatally. Twenty-four cases of CDH, CAML, and CLE detected during prenatal ultrasound and documented postnatally (with surgical, autopsy, or radiological proof) were identified through extensive chart and record review. The hard copy gray-scale images were retrospectively reviewed for imaging characteristics that may differentiate the three entities. Additionally, the prospective diagnosis during prenatal ultrasound was also compared with the postnatal diagnosis. The most reliable indicators in our retrospective review included confident visualization of a diaphragmatic defect (92.3/100.0 PPV/NPV, p< or =0.002) and/or localization of the stomach within the chest as well as the presence of severe cardiac deviation (both 92.3/62.5 PPV/NPV, p< or =0.01). Other sonographic indicators (including the presence of cystic areas, side and size of the lesion and the presence of polyhydramnios) offered lower levels of sensitivity and specificity. Prospective diagnosis during real-time assessment was also integral, offering >80% sensitivity and specificity (p< or =0.001). Accurate prenatal diagnosis of CDH is difficult despite the relative frequency of this lesion. The classic triad of a thoracic mass accompanying a displaced heart, absence of a normally positioned fluid-filled stomach and polyhydramnios, although seen with CDH, may not adequately differentiate this entity from other noncardiac fetal thoracic masses. Realtime assessment remains integral to the appropriate diagnosis.

Prediction of spontaneous preterm birth by fetal fibronectin and uterine activity.

OBJECTIVE: To evaluate the usefulness of fetal fibronectin and home uterine contraction assessment in predicting preterm birth (before 34 weeks) in at-risk asymptomatic women. METHODS: One hundred fifty women were enrolled prospectively; five were lost to follow-up, leaving 145 women available for analysis. Because patients with preterm labor before 34 weeks' gestation most commonly develop this problem after 28 weeks, the period of 26-28 weeks' gestation was selected prospectively as the first window for prediction and study analysis. Eighty-five of 145 asymptomatic women at high risk for preterm birth had both home uterine contraction assessment of 2 hours per day and one or more cervical sampling(s) for fetal fibronectin measurement at 26-28 weeks. A positive home uterine contraction assessment was defined as contractions exceeding two per hour averaged over the 2-week study interval. Positive fetal fibronectin was defined as greater than 50 ng/mL. RESULTS: Fourteen of the 85 women (16.5%) delivered before 34 weeks. Home uterine contraction assessment alone had a sensitivity, specificity, positive predictive value, and negative predictive value for preterm birth of 64, 85, 45, and 92%, respectively; fetal fibronectin alone was associated with values of 43, 89, 43, and 89%, respectively. A positive home uterine contraction assessment was associated with a relative risk (RR) for preterm birth of 5.9% (95% confidence interval [CI] 2.4-14.2), whereas a positive fetal fibronectin demonstrated an RR of 3.8 (95% CI 1.5-9.4). When both assessments were positive, all patients delivered before 34 weeks and there was an RR of 27.0 (95% CI 8.7-84.1) compared with those with both tests being negative. Only two patients with both tests negative delivered before 34 weeks (negative predictive value 96%). CONCLUSION: Both the home uterine contraction assessment and fetal fibronectin accurately predicted preterm birth before 34 weeks. When both tests were combined, the predictive ability improved substantially.

Sequential longitudinal evaluation of cardiac growth and ventricular diastolic filling in fetuses of well controlled diabetic mothers.

Hypertrophic cardiomyopathy and abnormal ventricular diastolic filling in the infant of the diabetic mother is related to poor maternal glycemic control. Evaluation of fetuses of well controlled diabetic mothers has not been examined. Eleven fetuses of nondiabetic mothers (normals) and 9 fetuses of well controlled insulin-dependent diabetic mothers (FODMs) underwent serial evaluation of cardiac growth and ventricular diastolic filling using M-mode and Doppler echocardiography at 20-26 weeks' (period 1), 27-33 weeks' (period 2), 34-40 weeks' (period 3),m and 48-72 hours after birth (period 4). Indices of right and left ventricular diastolic filling included time velocity integral ratios (E/A and %E/E+A). Cardiac growth and birth weight in the two groups were similar consistent with "good" glycemic control. This conclusion was supported by similar maternal glycosylated hemoglobin (%A1C) prenatally and newborn %A1C and C-peptide values postnatally. Heart rate before and after birth and placental resistance prenatally were similar. Both normals and FODMs demonstrated an increase in left ventricular E/A and %E/E+A ratios from period 1 to 4 (p < 0.0001). This shift occurred earlier (by period 2) in normals (p < 0.01). Right ventricular filling ratios increased by period 4 in normals only (p < 0.01). No differences were noted between the groups during any period. Good glycemic control in FODMs results in normal cardiac growth and ventricular diastolic filling. Progression of diastolic filling is abnormally delayed, however, and is presumably more exaggerated in poorly controlled diabetics.

Occult intraamniotic infection at the time of midtrimester genetic amniocentesis: a reassessment.

OBJECTIVE: The objective of this study was to reevaluate the incidence of occult early midtrimester intraamniotic infection in asymptomatic patients at the time of genetic amniocentesis. METHODS: A total of 177 amniotic fluid (AF) specimens from patients referred for genetic amniocentesis between 15 and 20 postmenstrual weeks were evaluated for the presence of bacteria by detailed light microscopy, after Gram and Wright stain, and by cultures for aerobic and anaerobic baceria, Mycoplasma sp., and Ureaplasma urealyticum. Seventy-seven AF specimens were also tested for the presence of bioactive leukoattractants by a leukotaxis bioassay. RESULTS: All fluids were negative for bacteria and bioactive leukoattractants [95% confidence interval (CI), 0-1.9%; 99% CI, 0-2.9%]. This is significantly less than a recently reported incidence of 5.09% (P = 0.002). Incidentally, artifacts with light microscopic morphology consistent with spermatozoa were found during the detailed light microscopic evaluation of AF Gram stains from 2 (1.1%) AF samples in otherwise uneventful pregnancies, a previously unreported finding. Scanning electron microscopy was used to confirm the light microscopic findings. CONCLUSIONS: Occult intraamniotic infection in the second trimester is not as high as recently reported. AF culture in all cases of second-trimester amniocentesis is not necessary. The identification of spermatozoa on Gram stain of second-trimester AF specimens needs further confirmation.

Neutrophil attractant/activating peptide-1/interleukin-8: association with histologic chorioamnionitis, preterm delivery, and bioactive amniotic fluid leukoattractants.

OBJECTIVES: The goals of this study were (1) to determine immunoreactive neutrophil attractant/activating peptide-1/interleukin-8 levels in amniotic fluid from patients with preterm labor and (2) to compare neutrophil attractant/activating peptide-1/interleukin-8 levels, amniotic fluid culture, Gram stain, and the leukotaxis bioassay for their ability to predict histologic chorioamnionitis and clinical outcome. STUDY DESIGN: Amniotic fluid was collected by amniocentesis from 55 patients with idiopathic preterm labor and three patients with preterm labor and clinical chorioamnionitis. Gram stain, culture (aerobic, anaerobic, and Mycoplasma species), leukotaxis bioassay, and a commercially available neutrophil attractant/activating peptide-1/interleukin-8 enzyme-linked immunosorbent assay (sensitivity 1 ng/ml) were performed on the amniotic fluid samples. Placentas and chorionic membranes were evaluated for evidence of histologic chorioamnionitis in patients delivered preterm. RESULTS: All patients with detectable leukoattractants by the leukotaxis bioassay had neutrophil attractant/activating peptide-1/interleukin-8 levels above the threshold of the assay. The presence of amniotic fluid neutrophil attractant/activating peptide-1/interleukin-8 is a more sensitive marker for histologic chorioamnionitis and delivery before 34 weeks than is amniotic fluid culture (100% vs 59%, p < 0.01; and 95% vs 56%, p < 0.01, respectively). Also, of patients in idiopathic preterm labor those without amniotic fluid leukoattractants (group 1) had the lowest amniotic fluid levels, followed by patients with amniotic fluid leukoattractants and a negative culture (group 2) and patients with amniotic fluid leukoattractants and a positive culture (group 3) who had the highest levels (group 1 vs group 2, p < 0.001; group 2 vs group 3, p < 0.01). CONCLUSIONS: Amniotic fluid neutrophil attractant/activating peptide-1/interleukin-8, like the leukotaxis assay, is an accurate antepartum predictor of histologic chorioamnionitis and subsequent early delivery in patients with preterm onset of labor. This study supports the role of neutrophil attractant/activating peptide-1/interleukin-8 in the recruitment of neutrophils into chorionic membranes and placenta during developing intrauterine infection.

The presence of amniotic fluid leukoattractants accurately identifies histologic chorioamnionitis and predicts tocolytic efficacy in patients with idiopathic preterm labor.

OBJECTIVES: We tested these hypotheses: (1) that amniotic fluid from patients with idiopathic preterm labor and histologic chorioamnionitis contains leukoattractants and (2) that the detection of amniotic fluid leukoattractants is an accurate predictor of tocolytic efficacy. STUDY DESIGN: Amniotic fluid from 86 patients in idiopathic preterm labor was evaluated by microbiologic tests and leukotaxis assay. The tests' ability to predict histologic chorioamnionitis and response to tocolysis (51 tocolytic candidates) is established. Statistical analysis was performed with Fisher's exact test and unpaired Student t test. RESULTS: The detection of amniotic fluid leukoattractants was a better predictor of histologic chorioamnionitis (97%) than were amniotic fluid microbiologic tests (62%) (p less than 0.01). Also, in patients with detectable amniotic fluid leukoattractants tocolysis failed significantly more often than in patients without detectable leukoattractants (93% vs 7%, p less than 0.01). CONCLUSION: The presence of leukoattractants in amniotic fluid detected by the leukotaxis assay accurately identifies histologic chorioamnionitis and can additionally predict tocolytic efficacy in patients with idiopathic preterm labor.

Amniotic fluid levels of substance P.

The presence of substance P (SP) in the amniotic fluid (AF) from 88 obstetric patients was determined with a radioimmunoassay. AF was collected from each patient in EDTA-coated tubes. Cross-reactivity of anti-SP antibody with methionine, met-enkephalin, leu-enkephalin, beta-endorphin, eledoisen and physalemin was less than 1%. The SP levels during the midtrimester were not significantly lower than those of late gestation. Data on the late-gestation group were evaluated further as per the clinical problem. The only statistically significant finding was between the diabetics with fetal maturity and the non-diabetic group. This preliminary study identified the presence of SP in AF in mid and late gestation.

Intracellular events are responsible for the differential expression of fibronectin on the fibroblast surface during chick embryo development.

We previously showed that differences in the adhesive behaviour of fibroblasts obtained from 8-day-old (8-day CEF) and 16-day-old chick embryos (16-day CEF) were not due to alterations of cell surface fibronectin receptors. Herein we show that fibronectin (FN) was expressed more rapidly on the 8-day CEF surface (30 min) than on the 16-day CEF surface (60 min). In order to elucidate the mechanism responsible for these differences in the expression of cell surface FN we investigated the biosynthesis and the post-translational modifications of FN in 8- and 16-day CEF. Pulse-chase experiments revealed that FN was processed more slowly to an endo-beta-N-acetylglucosaminidase H (endo H)-resistant form in 16-day CEF than in 8-day CEF, whereas the kinetic of FN biosynthesis was similar in both cell populations. This difference was not related to a differential retention of FN in endoplasmic reticulum (ER) as determined after saponin-permeabilization. These results suggested that the rate-limiting step in the transport of FN to the cell surface in 16-day cells occurred between the ER and the medial part of the Golgi apparatus. It seems that the delay in the processing of endo H-resistant N-glycans was sufficient to account for differences between 8- and 16-day CEF in the rate of surface expression of FN and CEF adhesion to a plastic substratum.

Alterations in transfer and lipid distribution of arachidonic acid in placentas of diabetic pregnancies.

Placental tissue from nondiabetic term pregnancies and pregnancies complicated by maternal insulin-dependent diabetes mellitus (IDDM) was perfused in vitro to compare the transfer and lipid distribution of arachidonic acid (AA). Radiolabeled albumin-bound AA was administered into the maternal afferent circulation, and samples of fetal and maternal effluent were collected at 10-min intervals. Perfused placental tissue was collected at the end of each experiment. The effluent was analyzed for total radioactivity, and extracts were subjected to thin-layer chromatography for the assessment of radioactivity associated with various lipid fractions. Placental AA uptake was significantly increased in perfused tissue from diabetic pregnancies (0.88 vs. 1.72 nM.min-1.g-1 in nondiabetic and IDDM, respectively; P less than 0.01), as was AA transfer (0.22 vs. 0.42 ml/min in nondiabetic and IDDM, respectively; P less than 0.01). However, transfer of the highly diffusible marker substance antipyrine was significantly reduced in IDDM placentas (1.79 vs. 2.49 ml/min in IDDM and nondiabetic, respectively; P less than 0.01). Compared with nondiabetic placentas, incorporation of AA into triglyceride was significantly increased in both maternal and fetal effluents and in placental tissue from IDDM pregnancies, whereas the percentage of AA remaining unesterified was reduced in both placental tissue and fetal effluent. Incorporation of AA into phosphoglycerides was significantly reduced in placental tissue but increased in fetal effluent in placentas from IDDM pregnancies. The results of these studies suggest that transfer and lipid distribution of AA are significantly altered in placentas from IDDM pregnancies. These findings may be relevant to the increased incidence of abnormal fetal growth and development associated with IDDM pregnancies.

Gastric dysrhythmias and nausea of pregnancy.

Gastric dysrhythmias have been recorded from patients with a variety of nausea syndromes. The aim of this study was to measure gastric myoelectric activity in women with and without nausea during the first trimester of pregnancy. In 32 pregnant women gastric myoeletric activity was recorded for 30-45 min with cutaneous electrodes that yielded electrogastrograms (EGGs). Frequencies of the EGG waves were analyzed visually and by computer. Subjects rated their nausea at the time of EGG recording on a visual analog scale with 0 representing no nausea and 300 mm severe nausea. Gastric dysrhythmias were found in 26 pregnant subject: Seventeen had tachygastrias (EGG frequencies of 4-9 cpm), five had 1- to 2-cpm EGG waves, and four had flat-line patterns Mean nausea scores of the subjects with tachygastrias, 1- to 2-cpm, and flat-line patterns were 64.8 +/- 13, 93.4 +/- 23, and 77.2 +/- 36, respectively. Six pregnant subjects had normal 3-cpm EGG patterns, and their nausea scores averaged 2.8 +/- 1.1 (P less than 0.05 compared with nausea scores in subjects with tachygastrias, 1- to 2-cpm, and flat-line rhythms). Six subjects with gastric dysrhythmias during pregnancy were restudied after delivery; each of these subjects had normal 3-cpm EGG patterns and none had nausea. Thus, gastric dysrhythmias are objective pathophysiologic events associated with symptoms of nausea reported during the first trimester of pregnancy.

Eicosanoid production and transfer in the placenta of the diabetic pregnancy.

The metabolism of arachidonic acid (AA) and the transfer of its metabolites was determined in in vitro perfused placental tissue from normal pregnancies and those complicated by maternal insulin-dependent diabetes mellitus (IDDM). 14C-labelled AA was recirculated in the fetal circulation for 60 min while 3H-AA was recirculated in the maternal circulation. Placental effluent was subjected to high performance liquid chromatography (HPLC) and analysis of dual-label scintillation counts. Placentae from IDDM pregnancies converted 3-6 times more radiolabelled AA to eicosanoids than did normal placentae. In addition, the transfer of eicosanoids into the opposing circulation was doubled in placentae from IDDM pregnancies compared to normal placentae. The predominant direction of eicosanoid transfer in both groups of placentae was in the fetal-to-maternal direction. The relative amounts of eicosanoids produced was also altered in placentae from IDDM pregnancies. Increased amounts of thromboxane (Tx) B2 and hydroxyeicosatetraenoic acids (HETEs) were present in both circulations of placentae from IDDM pregnancies. Levels of 6-keto prostaglandin F1a (6KPGF1a) were significantly reduced in both circulations in placentae from IDDM pregnancies. Thus, the ratio of TxA2 to PGI2 and the ratio of HETEs to PGI2 were both significantly increased in placentae from IDDM pregnancies. These results suggest an imbalance in eicosanoid production which may be relevant to abnormal placental structure and function in IDDM pregnancies.

Cell spreading on laminin substrate involves Con A-binding proteins.

Concanavalin A (Con A), a tetravalent lectin, was shown to impair 8 chick embryo fibroblast (8 d CEF) spreading on a laminin (LM) substrate but not on a fibronectin substrate (FN), suggesting that cell surface Con A binding proteins could be involved in 8 d CEF spreading on a LM substrate. The interaction of Con A-binding proteins with Con A is dependent upon the carbohydrate moieties of the isolated glycoproteins; since they interact strongly with Con A-Sepharose and are eluted with 0.3 Mol/l alpha-methylmannopyranoside, the isolated Con A binding-proteins inhibit 8 d CEF adhesion to a Con A substrate to the same extent as alpha-methylmannopyranoside. Furthermore, the isolated Con A binding proteins specifically inhibit in a dose-dependent manner 8 d CEF spreading on LM but not on FN.