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.

Erythropoietin stimulates a rise in intracellular free calcium concentration in single early human erythroid precursors.

Erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulate the differentiation and proliferation of erythroid cells. To determine the cellular mechanism of action of these growth factors, we measured changes in intracellular free calcium concentration [( Cac]) in single human erythroid precursors in response to recombinant erythropoietin and GM-CSF. [Cac] in immature erythroblasts derived from cultured human cord blood erythroid progenitors was measured with fluorescence microscopy digital video imaging. When stimulated with erythropoietin, [Cac] in the majority of erythroblasts increased within 3 min, peaked at 5 min, and returned toward baseline at 10 min. The percentage of cells that responded to erythropoietin stimulation increased in a dose-dependent manner. Additional stimulation with GM-CSF in cells previously exposed to erythropoietin resulted in a second [Cac] increase. Immature erythroblasts treated with GM-CSF followed by erythropoietin responded similarly to each factor with a rise in [Cac]. The source of transient calcium is intracellular since erythroblasts were incubated in medium devoid of extracellular calcium. Our observations suggest that changes in [Cac] may be an intracellular signal that mediates the proliferative/differentiating effect of hematopoietic growth factors.

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.

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.

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.

Calculating radiation absorbed dose for pheochromocytoma tumors in 131-I MIBG therapy.

A protocol for calculating radiation absorbed dose to pheochromocytoma tumors during treatment with 131I-labeled metaiodobenzylguanidine (MIBG) is described. The technique calls for (a) obtaining tumor volumes from Computed Tomography and/or Magnetic Resonance Imaging, (b) computing energy absorbed by assuming complete beta-particle absorption and a standard shape for gamma-ray absorption and (c) scaling from tracer to therapy dose rate by the ratio of administered activities. Also a 131I time-activity curve is obtained from planar, Anger-camera, conjugate-view images of the tumor and a known-strength source, both over a series of days. In addition, to correct for any systematic errors in the calculated uptakes, a larger activity of 123I MIBG is administered separately and quantitative Single Photon Emission Computed Tomography (SPECT) is undertaken. A known-strength source also undergoes SPECT to calibrate the tomograms. Correction for Compton scattering is accomplished by the dual-energy-window technique. The subtraction fraction was found to be 0.7 for the 1/2" crystal camera and the mean reduction in tumor counts for seven tumors from Compton correction was 0.76. The normalization factor needed to bring the conjugate-view activities into agreement with the SPECT values ranged from 0.74 to 1.06. A test study on an anthropomorphic phantom indicated that the error in resultant activities might be estimated as +/- 13%. Application of the protocol led to the calculation of real, or potential (when decision was finally made to not administer therapy) radiation absorbed dose to seven tumors in three patients from an administration of about 8 GBq of MIBG. For two metastatic tumors in a 19-year old patient who did not have her primary cancer resected, the calculated radiation absorbed dose was 170 and 180 Gy. For the four metastatic deposits evaluated in two older patients, both of whom had their primary tumor surgically removed, the values ranged from 18 to 31 Gy.

The clinical significance of placental villous edema.

A study was undertaken to determine why there is such variability in morbidity and mortality in neonates exposed to antenatal chorioamnionitis. Villous edema provides a clue. It was present in 72/83 placentas with chorioamnionitis. The extent and severity of the edema had a strong, positive correlation with cord arterial blood pH values, low Apgar scores, the need to resuscitate vigorously at birth, the subsequent need for assisted ventilation, the frequency of hyaline membrane disease, and neonatal mortality. Most of the difference in morbidity and mortality between preterm and full-term infants was related to the greater severity and extent of villous edema in those born prematurely.

Dynamic variable background subtraction: a simple means of displaying radiolabeled monoclonal antibody scintigrams.

Subtraction of a nonspecific radionuclide is frequently used to enhance visualization of tumors imaged by radiolabeled monoclonal antibodies. Determining the optimal amount of the nonspecific radionuclide image to subtract can be difficult. We have developed a computer program that generates a closed-loop cinematic display in which a continuously varying amount of the nonspecific radionuclide image is subtracted from the specific antibody image. Through examination of this dynamic display, a broad range of background-subtracted images can be viewed expeditiously in an effort to select the optimal level of background subtraction. This method may be useful in routinely displaying such background-subtracted studies.

Variations of biologic activity of low-dose prostaglandin E2 on cervical ripening.

The effect of low-dose prostaglandin E2 vaginal gel specially prepared from commercially available materials, on subsequent indicated oxytocin induction of labor, was investigated in a randomized, double-blind, placebo-controlled clinical trial. The stability of the gel after preparation was documented by radioimmunoassay in vitro. No differences between the treated and placebo groups were noted in subsequent modified Bishop scores, length of labor, use of analgesia or anesthesia, success of induction, mode of delivery, or perinatal outcome. Comparisons of this clinical trial with those previously reported are offered.

Thermoregulation during aerobic exercise in pregnancy.

To characterize maternal thermal balance during pregnancy, the authors recorded the thermal response to moderate weight bearing exercise stress in four aerobically conditioned pregnant women. Studies were performed in a climate-controlled environment in each trimester of pregnancy and postpartum after modifying the exercise protocol for changes in maternal exercise condition. Core, vaginal, and mean skin temperatures were recorded at rest and during maximum exercise. Mean resting skin temperature increased during pregnancy; mean resting core and vaginal temperatures did not change. Core temperatures did not exceed 39C during exercise. Heat storage (heat content/kg) was not increased as a result of exercise with advancing pregnancy. According to these findings, thermal balance can be maintained with advancing gestation when exercise prescriptions are appropriately modified for conditioned women.

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.

Placental microbiology and histology and the pathogenesis of chorioamnionitis.

The present study was undertaken to determine the proportion of cases of chorioamnionitis that was caused by microbiologic agents. Seventy-five placentas were processed to isolate aerobic and anaerobic bacteria and chlamydia. Results were correlated with the presence or absence of histologic and clinical chorioamnionitis. Bacteria were recovered from 72% (18 of 25) of placentas with histologic chorioamnionitis and from nine of 11 cases (82%) of clinical chorioamnionitis, all of which had histologic chorioamnionitis. Bacteria were recovered from only 15% (six of 39) of placentas without histologic chorioamnionitis. Nearly 50% of the bacteria recovered from placentas were anaerobes, often fastidious in their growth requirements. Often two to three such anaerobes were recovered from a placenta. Findings of the present study increase the possibility that bacteria are responsible for most cases of chorioamnionitis.

Nonimmunologic hydrops fetalis: a review of 19 cases.

Nineteen cases of nonimmunologic hydrops fetalis occurring during a nine-year period were reviewed. The pregnancies were complicated by hydramnios (78%) and preterm delivery (84%). Hydramnios appears to be the most useful indicator of the pregnancy at risk; its occurrence should prompt ultrasonographic investigation for evidence of hydrops. Modalities available for antenatal diagnosis of underlying fetal abnormalities include amniocentesis, serologic tests, fetal cardiac monitoring, radiography, hemoglobin electrophoresis and glucose tolerance testing. A specific cause for the hydrops may not be detectable (42% of our cases were idiopathic). Management of affected pregnancies is influenced by the frequent occurrence of fetal asphyxia and premature delivery. Outcome is poor: only 32% of the babies survived beyond the neonatal period. Symptomatic treatment for the neonate includes fluid restriction, maintenance of blood sugar, support of ventilation and attention to the complications of asphyxia.

Role of prenatal genetic counseling before amniocentesis. A survey of genetics centers.

Although prenatal genetic amniocentesis is an accepted procedure for certain high-risk pregnancies, there is no standard approach to prenatal counseling, timing of counseling, materials used and location of the procedure. This survey of 126 genetics centers offering prenatal genetic amniocentesis reviewed aspects of 48,502 counseling events and a total of 61,174 samples processed in 1982. Eighty-three percent of the samples were obtained after counseling at the centers. Of the patients counseled, 88.5% chose amniocentesis, but the utilization rates varied widely between the centers. The choice of amniocentesis varied measurably with the educational materials used but not with the center size. Educational materials, written or audiovisual, were used by genetics centers in counseling 82% of the patients. There was a wide variation in center size, counseling methods used, the timing and use of counseling, and patient responses in the survey population.

Skin preparation methods before cesarean section. A comparative study.

Preoperative skin preparation before cesarean section using a one-minute alcohol wash followed by application of an iodophor-impregnated adhesive film was evaluated in a prospective, randomized, controlled study of 79 patients. The iodophor film was as effective as the five-minute iodophor scrub followed by an iodophor wash, as determined by a reduction in skin bacterial counts. Clinical infectious morbidity was no different between the treatment and control groups, although the study was too small to draw statistically significant conclusions in this respect. This study demonstrated the antimicrobial effectiveness of a new, more rapid method of pre-operative skin preparation before cesarean section as compared to a longer, traditional method. This new, rapid method offers advantages for many patients undergoing abdominal delivery.

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.

Encouraging patients to undergo prenatal genetic counseling before the day of amniocentesis. Its effect on the use of amniocentesis.

The purpose of this study was to determine if encouraging in-depth prenatal genetic counseling before the day of possible genetic amniocentesis affected the use of amniocentesis. Five hundred two patients were referred to our center for prenatal genetic services during a 15-month period. All patients were scheduled for genetic counseling before possible amniocentesis. During the initial three months (group I), patients were routinely scheduled for counseling on the same day of the procedure unless they requested earlier counseling. During the subsequent 12 months (group II), patients were encouraged to undergo counseling before the day of planned amniocentesis, and 48% agreed. When early counseling was encouraged, the use of amniocentesis decreased from 85% (group I) to 73% (group II) (P less than .025). Among patients with advanced maternal age as the only indication for testing (n = 375), utilization of amniocentesis decreased from 93% (group I) to 78% (group II) (P less than .005). A policy of encouraging early prenatal genetic counseling appears to be a significant factor in the use of genetic amniocentesis.

New strategies for preterm labor.

Preterm birth is the leading cause of perinatal mortality and morbidity despite the technological advances in neonatology and maternal-fetal medicine. Risk factors have been tabulated that can help identify the woman at risk for preterm birth. Past medical history, present pregnancy events, and demographic/environmental characteristics can help the practitioner select women who need special care to help prevent or reduce the effects of premature delivery. Recently, new concepts of risk have been identified through research, and emphasis needs to shift from intervention to prevention of the low birth weight infant. Past and present management of premature labor is discussed. New research protocols are presented. Strategies for nurses working in family planning or obstetrical areas are discussed, demonstrating areas for interventions from a prevention-oriented nursing base.

PIP: Premature birth is the principal cause of perinatal mortality and morbidity, despite major technological advances in neonatology and maternal-fetal medicine. Tabulation of new risk factors stimulate further research and innovative patient management ideas. These risk factors include the following concepts of risk: 1)stress, physical and psychosocial, 2) uterine irritability, 3) Events triggering uterine contractions, 4) Cervical changes detected before onset of labor, 5) Selected infections such as mycoplasma, C. trachomatis, and possibly bacterial vaginosis, 6) Inadequate plasma volume expansion and 7) Progesterone deficiency. New strategies offered for reduced preterm labor now aim prevention of premature labor rather than utilizing various treatments. Past and present management of premature labor, and new research protocols are recommended for a broader approach to preterm labor. Updated strategies for nurses employed in family planning are stressed, as well as the need for a prevention-oriented nurse base.

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.