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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
PubMed2006

Placental abruption is more frequent in women with the angiotensinogen Thr235 mutation.

OBJECTIVE: Obstetrical complications such as preeclampsia, fetal growth restriction, and placental abruption are associated with inadequate placental perfusion. Previous studies have shown that the angiotensinogen (AGT) Thr235 mutation is associated with abnormal remodeling of the uterine spiral arteries and occurs at higher frequencies in preeclampsia. This study was done to evaluate whether the AGT Thr235 mutation increases the risk of placental abruption. MATERIALS AND METHODS: We compared 62 placentas from women who had placental abruption with 240 control patients of similar age and ethnicity. DNA was extracted from paraffin blocks from placentas. AGT Met235Thr mutation status was determined by single fluoresceine labeled probe real-time PCR using a LightCycler system. RESULT: AGT genotypes were divided into three groups: MM (homozygous wild), TT (homozygous mutant), and MT (heterozygous). The constituent ratio of AGT genotype in abrupted placentas (MM 14.5%, MT 43.5%, TT 41.9%) was significantly different from in control group (MM42.5%, MT 39.6%, TT 17.9%) (p<0.001). AGT mutant allele frequency in placental abruption (0.637) was significantly higher than in the control group (0.377) (p<0.001). CONCLUSION: The AGT Thr235 mutation was observed more frequently in placental abruption. AGT Thr235 mutation may be considered a risk factor for placental abruption.

Abruptio Placentae↗
PubMed2001

Paternal and maternal components of the predisposition to preeclampsia.

BACKGROUND: There is an inherited maternal predisposition to preeclampsia. Whether there is a paternal component, however, is not known. METHODS: We used records of the Utah Population Database to identify 298 men and 237 women born in Utah between 1947 and 1957 whose mothers had had preeclampsia during their pregnancy. For each man and woman in the study group, we identified two matched, unrelated control subjects who were not the products of pregnancies complicated by preeclampsia. We then identified 947 children of the 298 male study subjects and 830 children of the 237 female study subjects who had been born between 1970 and 1992. These children were matched to offspring of the control subjects (1950 offspring of the male control group and 1658 offspring of the female control group). Factors associated with preeclampsia were identified, and odds ratios were calculated with the use of stepwise logistic-regression analysis. RESULTS: In the group whose mothers had had preeclampsia (the male study group), 2.7 percent of the offspring (26 of 947) were born of pregnancies complicated by preeclampsia, as compared with 1.3 percent of the offspring (26 of 1973) in the male control group. In the female study group, 4.7 percent of the pregnancies (39 of 830) were complicated by preeclampsia, as compared with 1.9 percent (32 of 1658) in the female control group. After adjustment for the offspring's year of birth, maternal parity, and the offspring's gestational age at delivery, the odds ratio for an adult whose mother had had preeclampsia having a child who was the product of a pregnancy complicated by preeclampsia was 2.1 (95 percent confidence interval, 1.0 to 4.3; P=0.04) in the male study group and 3.3 (95 percent confidence interval, 1.5 to 7.5; P=0.004) in the female study group. CONCLUSIONS: Both men and women who were the product of a pregnancy complicated by preeclampsia were significantly more likely than control men and women to have a child who was the product of a pregnancy complicated by preeclampsia.

Adult↗
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↗
PubMed2000

Serial salivary estriol to detect an increased risk of preterm birth.

OBJECTIVE: To evaluate serial measurements of salivary estriol (E3) to detect increased risk of spontaneous preterm labor and preterm birth. METHODS: A masked, prospective, multicenter trial of 956 women with singleton pregnancies was completed at eight United States medical centers. Saliva was collected weekly, beginning at the 22nd week of gestation until birth, and tested for unconjugated E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and low-risk groups using the Creasy scoring system. RESULTS: A single, positive (at or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous preterm labor and delivery in the total population (relative risk [RR] 4.0, P <.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk population (RR 3.4, P =.05). Two consecutive positive tests significantly increased the RR in all study groups, with a dramatic improvement in test specificity and positive predictive value but only a modest decrease in sensitivity. In women who presented with symptomatic preterm labor, salivary E3 identified 61% of those who delivered within 2 weeks, using a threshold of 1.4 ng/mL. CONCLUSION: Elevated salivary E3 is associated with increased risk of preterm birth in asymptomatic women and symptomatic women who present for evaluation of preterm labor.

Adult↗
PubMed2000

A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns.

OBJECTIVE: Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status. STUDY DESIGN: A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation. RESULTS: A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation. CONCLUSION: The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.

Adult↗
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↗