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Biomedical subjects

M W Varner

Publications and source records attributed to M W Varner.

At least 19 recordsLinked to original sources
PubMed2000

A measurement model of perinatal stressors: identifying risk for postnatal emotional distress in mothers of high-risk infants.

A measurement model of perinatal stressors was first evaluated for reliability and then used to identify risk factors for postnatal emotional distress in high-risk mothers. In Study 1, six measures (gestational age of the baby, birthweight, length of the baby's hospitalization, a postnatal complications rating for the infant, and Apgar scores at 1 and 5 min) were obtained from chart reviews of preterm births at two different hospitals. Confirmatory factor analyses revealed that the six measures could be accounted for by three factors: (a) Infant Maturity, (b) Apgar Ratings, and (c) Complications. In Study 2, a modified measurement model indicated that Infant Maturity and Complications were significant predictors of postnatal emotional distress in an additional sample of mothers. This measurement model may also be useful in predicting (a) other measures of psychological distress in parents, and (b) measures of cognitive and motor development in infants.

Adolescent↗
PubMed1998

Maternal mortality in Utah.

OBJECTIVE: To determine trends in maternal deaths in Utah, identify opportunities for preventive intervention, and analyze the mechanism of reporting maternal deaths. METHODS: A retrospective review was performed of maternal death certificates and medical records in Utah from January 1, 1982, through December 31, 1994. RESULTS: Sixty-two maternal deaths were identified. The risk of maternal death increased with maternal age and parity. The classic triad of hemorrhage (n = 8), infection (n = 5), and preeclampsia-eclampsia (n = 3) remains an important contributor (16 of 62 or 25.8%). However, trauma (n = 10), pulmonary embolism (n = 10), and maternal cardiac disease (n = 9) now account for 46.8% (29 of 62) of maternal deaths. A greater number of direct obstetric causes of maternal death (n = 20) were deemed preventable than indirect obstetric causes (n = 1) or nonobstetric causes (n = 4). CONCLUSION: Trauma, pulmonary embolism, and maternal cardiac disease have emerged as the most common identifiable causes of maternal death. Improvements in prevention, earlier diagnosis, and aggressive treatment of these conditions are necessary to achieve the Public Health Service year 2000 objective of a 50% reduction in maternal mortality ratios (using the 1987 ratio as a baseline).

Adolescent↗
PubMed1998

Elevated second-trimester maternal serum hCG: a marker of inadequate angiogenesis.

OBJECTIVE: To measure angiogenin, a potent inducer of neovascularization and interleukin-6, as an indicator of acute inflammation, in second-trimester amniotic fluid of patients with elevated maternal serum hCG. METHODS: In this case-control study, 20 patients with elevated maternal serum hCG (at least 2.0 multiples of median) at triple screen were matched 2:1 with controls on the basis of year of amniocentesis, parity, and race. Inclusion criteria were 1) singleton gestation, 2) no evidence of anomalies, and 3) genetic amniocentesis. Amniotic fluid was immunoassayed for angiogenin and interleukin-6. The immunoassay sensitivity for angiogenin was 0.026 ng/mL, interassay coefficient of variation 4.6%, and intra-assay coefficient of variation 2.9%. For interleukin-6, the immunoassay sensitivity was 2.37 pg/mL, interassay coefficient of variation 2.7%, and intra-assay coefficient of variation 1.9%. Angiogenin and interleukin-6 values were normalized by using natural log transformation for statistical analysis. Statistical analysis included analysis of variance and stepwise regression, with P < .05 significant. RESULTS: After correcting (by multivariate regression) for gestational age at sampling and nulliparity, amniotic fluid angiogenin levels were significantly lower in the study subjects than in controls (26%+/-11% lower, P=.004), whereas the interleukin-6 levels did not change significantly (34%+/-40% lower, P=.3). CONCLUSION: Amniotic fluid angiogenin levels are significantly lower in patients with elevated maternal serum hCG at triple screen, suggesting inadequate angiogenesis, but interleukin-6 values do not differ significantly.

Adult↗
PubMed1998

Medical conditions of the puerperium.

The puerperium is a time of continued, dramatic pregnancy-associated adaptation. Although much less common than in the early part of the century, maternal death can still occur from common postpartum problems such as infection, hemorrhage, and disease. This article reviews the physiologic and emotional changes as well as the clinical management of common problems in the puerperium.

Female↗
PubMed1997

The incidence of the factor V Leiden mutation in an obstetric population and its relationship to deep vein thrombosis.

OBJECTIVE: A common missense mutation in the factor V gene, the Leiden mutation, renders factor Va resistant to cleavage inactivation by activated protein C and predisposes patients to thrombotic events. We sought to evaluate the prevalence of the Leiden mutation and the associated thromboembolic events in a community hospital's low-risk obstetric population. STUDY DESIGN: Deoxyribonucleic acid was extracted from whole blood of 407 women. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnI 1 for mutation detection. Medical charts were reviewed and patient characteristics, including age, gravidity, parity, obstetric complications, medical complications, and mode of delivery, were recorded. RESULTS: Fourteen of the 407 women carried the factor V Leiden mutation (13 heterozygotes and 1 homozygous mutant) for an allele frequency of 3%, consistent with the published carrier rate. Four of the 14 carriers (28%) had deep venous thrombosis, whereas the frequency of deep venous thrombosis in this obstetric population was <1%. Another patient carrying the mutation had a consumptive coagulopathy of unknown etiology at 20 weeks' gestation, necessitating delivery. CONCLUSIONS: The Leiden mutation is relatively common in the general obstetric population. The high rate of deep venous thrombosis noted in our series suggests the need for genetic testing for this mutation in women with a thrombotic event during pregnancy.

Adult↗
PubMed1997

The risk of preterm birth across generations.

OBJECTIVE: To examine the risk of preterm birth for mothers who themselves were born before term. METHODS: Data were taken from a linked data base of birth certificates composed of two cohorts: 1) a parental cohort of women born between 1947 and 1957 and 2) their offspring born between 1970 and 1992. "Preterm mothers" were women in the parental cohort who were born at less than 37 weeks' gestation. "Term mothers" were women in the parental cohort born at or after 38 weeks' gestation. Preterm mothers and term mothers were matched for birth year, county of birth, marital status, parity, and age. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the risk of preterm delivery in preterm mothers. Multiple logistic regression was used to assess the interaction of concomitant variables with the risk of premature delivery. RESULTS: The risk of preterm birth was significantly higher in preterm mothers than in term mothers (OR 1.18; 95% CI 1.02, 1.37). The risk increased as the gestational age at the mothers' birth decreased (less than 30 weeks'; OR 2.38; 95% CI 1.37, 4.16). The interaction between maternal age and parity increased the risk of preterm delivery at less than 34 weeks in some age and parity strata. CONCLUSION: An increased risk of preterm delivery exists for women who themselves were born before 37 weeks' gestation. The risk is inversely correlated with the maternal gestational age at birth and is influenced by maternal age and parity.

Adolescent↗
PubMed1997

Amniotic fluid interleukin-10 (IL-10) concentrations during pregnancy and with labor.

To determine if amniotic fluid interleukin-10 (IL-10) concentrations are elevated in women with labor, either at term or preterm, and in the setting of infection-associated preterm labor, amniotic fluid samples were collected from women: (1) at term, not in labor (n = 42); at term, in labor (n = 56), preterm contractions, undelivered within 1 week (n = 22), and preterm labor, delivered within 1 week (n = 31). IL-10 concentrations were assayed in each sample via ELISA (Pharmingen, San Diego, CA). In a subsequent analysis, 8 women with preterm labor associated with chorioamnionitis were matched for gestational age with women experiencing preterm contractions (undelivered within 7 days) and preterm labor (delivered within 7 days) and amniotic fluid IL-10 concentrations compared. Approximately 40-70% of amniotic fluid samples obtained from women in each group had detectable IL-10. However, there were no significant differences in amniotic fluid IL-10 concentrations among the patients. While 1 of 8 patients with chorioamnionitis had amniotic fluid IL-10 concentrations greater than 300 pg/ml, there were no statistically significant differences among the matched samples. Amniotic fluid IL-10 concentrations were not elevated in women with term labor, preterm labor, or chorioamnionitis. This finding contrasts with the elevated concentrations of pro-inflammatory cytokines and chemokines such as interleukin-1, tumor necrosis factor-alpha, IL-6, IL-8, MIP-1 alpha, and GRO alpha reported in previous studies. Because we did not detect elevations of the key anti-inflammatory cytokine IL-10 in amniotic fluid of women with infection-associated preterm labor, we suggest that anti-inflammatory processes in this setting may be attenuated.

Adult↗
PubMed1997

Current status of the multicenter randomized clinical trial on fetal oxygen saturation monitoring in the United States.

Current clinical methods of intrapartum fetal assessment are sensitive but poorly specific in detecting fetal compromise during labor. These limitations have substantially contributed to the escalating cesarean section rate which occurred in the US during the last several decades. Experimental and clinical research efforts directed towards application of the oxygen saturation monitor (pulse oximeter) to intrapartum fetal assessment have produced encouraging results. If this new method of fetal assessment is to enter the clinical arena, safety and efficacy issues must first be properly evaluated via randomized clinical trials. The purpose of this report is to describe the design of a multicenter randomized clinical trial of intrapartum fetal oxygen saturation monitoring recently begun in the US. Specific aspects of the trial, including purpose, study design, sample size estimates, control and test groups, inclusion and exclusion criteria, fetal heart rate classification, definition of normal fetal arterial oxygen saturation (SpO2), clinical management protocol, and assessment of maternal-fetal outcomes will be addressed.

Female↗
PubMed1997

Progression of pulmonary arteriovenous malformation during pregnancy: case report and review of the literature.

Pulmonary arteriovenous malformations (PAVM) expand during pregnancy because of increases in blood volume, cardiac output, and venous distensibility. More than half of the cases reported during pregnancy are associated with hereditary telangiectasia. In this case a 36-year-old primigravida presented at 24 weeks of gestation with new onset hemoptysis and dyspnea. A PAVM was noted in the right lower lobe during angiography and was successfully treated with embolization. Recurrence of symptoms occurred at 36 weeks of gestation after recanalization of the PAVM. Cesarean delivery was performed because of both this recurrence and breech presentation. The patient's symptoms subsequently resolved after delivery. The patient underwent a segmentectomy without complication 6 months after delivery. Thus, women with known PAVM or a history of hereditary telangiectasia should be followed with serial chest roentgenograms and arterial blood gases to detect acute progression of the PAVM. Embolization can be used during pregnancy if the PAVM is symptomatic.

Adult↗
PubMed1996

Elevations of amniotic fluid macrophage inflammatory protein-1 alpha concentrations in women during term and preterm labor.

OBJECTIVE: To determine whether elevated concentrations of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in amniotic fluid (AF) are related to term and preterm labor. METHODS: Amniotic fluid was obtained from women from five different clinical situations: 1) term cesarean delivery, no labor (n = 29); 2) normal term labor, no infection (n = 36); 3) preterm labor, delivery more than 1 week from sampling, no infection (n = 19); 4) preterm labor, delivery within 1 week from sampling, no infection (n = 18); and 5) preterm chorioamnionitis (n = 8). Amniotic fluid was collected aseptically at the time of amniocentesis, amniotomy, or hysterotomy. Concentrations of MIP-1 alpha were determined by enzyme-linked immunosorbent assay. Statistical analysis was by Wilcoxon rank-sum test, Kruskal-Wallis test, and unpaired t test. RESULTS: Women in normal term labor had significant elevations of AF MIP-1 alpha concentrations when compared with women at term undergoing repeat cesarean delivery (P < .001). In women with term gestation, AF MIP-1 alpha correlated well with cervical dilation (r2 = 0.479, P < .001). In women with preterm labor who later delivered within 1 week of presentation, AF MIP-1 alpha concentrations were higher than those from women who did not deliver within 1 week. Women who presented with clinically evident chorioamnionitis had the highest concentrations of AF MIP-1 alpha (P = .001). CONCLUSION: Women in labor have significantly elevated AF concentrations of MIP-1 alpha, particularly if labor is associated with intrauterine infection. We suggest that MIP-1 alpha is involved in the physiology of normal labor and in the pathogenesis of infection-associated preterm labor.

Amniotic Fluid↗
PubMed1996

A population-based study of congenital diaphragmatic hernia in Utah: 1988-1994.

OBJECTIVE: To define the natural history of congenital diaphragmatic hernia and to determine the potential impact of fetal therapy. METHODS: This retrospective case series consisted of all fetuses and neonates with congenital diaphragmatic hernia born between 1988 and 1994 in the state of Utah that could be identified through genetic counseling referrals, delivery logs, and neonatal intensive care unit discharge diagnosis records. Maternal and neonatal hospital records were reviewed for antepartum, intrapartum, and postpartum variables. Based on existing recommendations, fetuses who might have benefited from fetal therapy were identified. RESULTS: Ninety-six cases were identified, for a frequency of one case in 2710 live births per year. Five pregnancies were terminated before 21 weeks' gestation. The overall survival rate excluding these five cases was 58.2%. Among the remaining 91 cases, survival was significantly better for infants diagnosed in the neonatal period than for those diagnosed prenatally (78% versus 35%; P < .001). The frequency of associated anomalies was similar for antepartum and postpartum cases. Sixty-two percent of nonsurvivors had some type of other anomaly, but no pattern was apparent. There were no accurate prenatal predictors for lethal pulmonary hypoplasia, but preterm birth and the presence of severe cardiac anomalies were predictors of neonatal death. Only two of 96 fetuses would have potentially benefited from fetal therapy. CONCLUSION: The outcome of infants with congenital diaphragmatic hernia is worse with preterm birth and if diagnosed prenatally. The survival rate we found was better than that reported in earlier studies, suggesting improved perinatal and neonatal management. Fetal therapy based on current eligibility criteria would have a minimal impact on survival of fetuses with congenital diaphragmatic hernia.

Congenital Abnormalities↗
PubMed1996

The intergenerational predisposition to operative delivery.

OBJECTIVE: To determine the risk of cesarean delivery for women who themselves were born via operative delivery. METHODS: A linked data base was constructed between the birth certificates of individuals born in Utah during 1947-1957 (parental cohort) and who subsequently became a parent of offspring born in Utah between 1970-1991 (offspring cohort). Parental cohort women (cases) who had been delivered operatively (cesarean delivery, mid- or high forceps) as well as women who had a sibling delivered by an operative procedure were matched (1:2) with parental-cohort women born by spontaneous vaginal delivery (controls). Both cases and controls were selected based on having a record of at least one delivery in Utah during 1970-1991. RESULTS: Women who were delivered by cesarean were at increased risk of subsequently delivering their children by cesarean (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.18-1.70; P < .001). Progressive risk was associated with parental delivery by mid- or high forceps (OR 1.72, 95% CI 1.20-2.47; P = .004), parental cesarean because of cephalopelvic disproportion alone (OR 1.83, 95% CI 1.16-2.88; P = .01), or parental cesarean for dysfunctional labor (OR 5.97, 95% CI 1.5-23.6; P < .001). The attributable risk for cesarean delivery to the contemporary population is 3.5%. CONCLUSION: An intergenerational predisposition to cesarean delivery exists.

Cesarean Section↗
PubMed1996

Dose-related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy.

BACKGROUND: The purpose of this study was to determine which low dose of low dose aspirin (LDA) optimized the urinary prostacyclin (PGI2)/thromboxane (TXA2) ratio and minimized evidence of platelet aggregation during normal late pregnancy. METHODS: Twelve women with uncomplicated singleton pregnancies between 28 and 34 weeks gestation participated in a randomized blinded study. Blood samples for salicylate levels were obtained pretreatment, 4 hours and 7 days after administration of placebo, 20mg, 40mg or 80mg of aspirin. Twenty-four hour urine specimens collected at the same intervals were assayed for PGI2 and TXA2 metabolites. In addition, bleeding time and platelet aggregation studies were performed prior to and after 7 days of LDA or placebo. RESULTS: A dose-related increase in bleeding time occurred with 40 mg and 80 mg of LDA, but not with the 20 mg dose or placebo. Platelet aggregation studies changed progressively from a normal baseline to abnormal with an increasing dose of LDA. The PGI2/TXA2 ratio increased with aspirin doses as low as 20mg, with a decrease in TXA2 metabolites but not in PGI2 metabolites. Serum salicylate was not detectable in any sample from any patient. CONCLUSION: There are dose-related changes in platelet aggregation and bleeding times with progressively increasing doses of LDA. A lower dose of LDA, such as 20-40 mg per day, may be as efficacious as higher doses in the prophylaxis of pre-eclampsia in high risk populations.

Adolescent↗
PubMed1996

Elevations of serum interleukin-12 concentrations in women with severe pre-eclampsia and HELLP syndrome.

The objective is to test the hypothesis that serum IL-12 concentrations would be elevated in women with severe pre-eclampsia and HELLP syndrome. The Methods used were as follows: Serum was obtained from women admitted to our Labor and Delivery unit diagnosed with severe pre-eclampsia or HELLP syndrome and normal control patients. IL-12 concentrations in these samples were determined by the use of two different and specific enzyme-linked immunosorbent assays for the p40 subunit and the intact p75 dimer. It was found that serum IL-12 (p40 subunit) concentrations were elevated in women with both severe pre-eclampsia (p = 0.011) or HELLP syndrome (= 0.004). Similar findings were noted for these patients when matched with control patients for maternal age, gestational age, and parity. Eleven women had elevations of serum IL-12 p75 dimer, and 10 of these 11 patients had severe pre-eclampsia or HELLP syndrome. In conclusion, we found that women with severe pre-eclampsia and HELLP syndrome commonly have detectable concentrations of the IL-12 p40 monomer and were more likely than normal control women to have detectable serum IL-12 p75 dimer. While the exact role of IL-12 in hypertensive disease during pregnancy is unclear, our data support the hypothesis that the regulation of IL-12 production and metabolism is abnormal in women with pre-eclampsia and HELLP syndrome, perhaps contributing to the immunologic alterations characteristic of these disorders.

Adult↗
PubMed1996

Very advanced maternal age: pregnancy after age 45.

OBJECTIVE: Our purpose was to describe the maternal and fetal outcomes of pregnancies in women > or = 45 years old at delivery. STUDY DESIGN: A retrospective review of in-hospital deliveries after 20 weeks of gestation was performed in four Utah tertiary care hospitals for the 10-year period between 1985 and 1994. RESULTS: Seventy-nine cases were identified among 126,500 births, with an incidence of 0.63 per 1000 births. Maternal ages were 45 (n = 44), 46 (n = 21), and > or = 47 (n = 14) years. Three of the conceptions were assisted, including both twin gestations. Thirty-seven (46.8%) had obstetric complications during pregnancy; the most frequent complications were gestational diabetes (12.7%) and preeclampsia (10.1%). Median (range) gestational age at delivery was 39 (22.9 to 41.7) weeks; 12 (15.2%) deliveries occurred before 37 weeks. Eight (9.9%) karyotype abnormalities were diagnosed. The cesarean section rate was 31.7%; the most frequent indications were abnormal lie (n = 9), fetal distress (n = 5), and previous cesarean delivery (n = 5). There were no maternal deaths. Median (range) birth weight was 3466 (397 to 5085) gm; 14 (17.3%) were < 2500 gm and 16 (19.8%) were > 4000 gm. Twelve (14.8%) infants were admitted to the neonatal intensive care unit. The corrected perinatal mortality rate was 1.3% (1/78). CONCLUSIONS: In women > 45 years old at delivery maternal and fetal outcomes were generally good, but there was a high incidence of pregestational (chronic hypertension, hypothyroidism) and gestational (karyotype abnormalities, gestational diabetes, cesarean section, macrosomia) complications. This information may be helpful for counseling women between 45 and 50 years old who are considering pregnancy.

Apgar Score↗
PubMed1996

Elevation of amniotic fluid interleukin-4 concentrations in women with preterm labor and chorioamnionitis.

Preterm labor associated with intrauterine infection is characterized by increased amniotic fluid concentrations of various proinflammatory cytokines, including interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage inflammatory protein-1alpha (MIP-1alpha). The purpose of this study was to determine if preterm labor in women with clinically evident chorioamnionitis is marked by elevations of the anti-inflammatory cytokine interleukin-4 (IL-4) and the T cell growth factor IL-2. Amniotic fluid samples were obtained from (1) women at term, not in labor (n = 10); (2) women at term, in labor (n = 10); (3) women with preterm contractions but undelivered within 1 week of amniotic fluid collection (n = 10); (4) women with preterm labor and delivery without clinically evident chorioamnionitis (n = 10); (5) women with preterm labor associated with chorioamnionitis (n = 8); and (6) women with preterm labor and delivery without infection matched with patients with chorioamnionitis (n = 8). Amniotic fluid concentrations of IL-4 and IL-2 were determined for each sample with a specific and sensitive enzyme-linked immunoassay. We found that women with infection-associated preterm labor and delivery had significantly higher concentrations of IL-4 when compared to appropriately matched controls (p < 0.05). Additionally, women with preterm labor and delivery not associated with infection had higher amniotic fluid IL-4 concentrations than women with preterm contractions but no labor (p < 0.05). Women with term labor had rare modest elevations of amniotic fluid IL-4. No IL-2 was detected in any sample. Our data indicate that amniotic fluid IL-4 is elevated in women with preterm labor and delivery, particularly in association with chorioamnionitis. We suggest that IL-4, although previously considered an anti-inflammatory agent, may have a paradoxical proinflammatory role in the pathogenesis of infection-associated preterm labor.

Adult↗