Publications by authors named "Mittendorf R"

109 Publications

Umbilical cord serum ionized magnesium level and total pediatric mortality.

Obstet Gynecol 2001 Jul;98(1):75-8

Department of Obstetrics and Gynecology, Loyola University Medical Center, Maywood, Illinois 60153, USA.

Objective: To estimate whether higher magnesium levels in umbilical cord blood at delivery are associated with increased total pediatric (fetal + neonatal + postneonatal) mortality.

Methods: During the Magnesium and Neurologic Endpoints Trial, in addition to randomizing mothers having preterm labor into arms containing magnesium sulfate, other tocolytic agents, or saline controls, we obtained biologic specimens at delivery, including umbilical cord venous blood on which was determined the serum ionized magnesium level using the AVL 988-4 analyzer (Graz, Austria). Laboratory results were then matched with the pediatric mortalities. The study power was based on the anticipated reductions in neonatal intraventricular hemorrhage related to magnesium usage from 18.9% to 4.4%. For alpha =.05, 1-beta (power)=80%, two tailed, the total number of infants needed would be 140.

Results: Of 149 mothers who gave permission for randomization, ionized magnesium levels were available for 82 children. Seven deaths occurred (one immediately before delivery, three as neonates, and three in the postneonatal period). The median level of ionized magnesium among the seven dead children was 0.76 mmol/L; among the 75 survivors, the median level of ionized magnesium was 0.55 mmol/L (Mann-Whitney U test, P =.03). Using multivariable logistic regression analysis, the association remained statistically significant when controlling for possible confounding factors (adjusted odds ratio 7.7, 95% confidence interval 1.2, 47.6, P =.03).

Conclusion: These findings of a dose response between serum ionized magnesium and deaths in children increase our concern about the improper use of tocolytic magnesium.
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http://dx.doi.org/10.1016/s0029-7844(01)01398-9DOI Listing
July 2001

Presurgical plasma exchange for severe factor V deficiency.

J Clin Apher 2001 ;16(1):29-30

Department of Pathology (Blood Bank), The University of Chicago, Chicago, Illinois, USA.

We report two patients with severe congenital factor V deficiency, one of whom also had a factor V inhibitor, who required correction of their coagulopathy prior to surgical procedures. They underwent plasma exchange (PE) with fresh frozen plasma or solvent/detergent treated plasma (S/DP), with achievement of factor V levels satisfactory for hemostasis for their procedures. PE makes it possible to raise factor levels quickly and sufficiently without volume overload. In addition, transient reduction of inhibitor titers by PE may improve the level of correction achievable during the perioperative period. The advent of S/DP promises to provide an added increment of safety in patients exposed to significant volumes of plasma during PE.
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http://dx.doi.org/10.1002/jca.1005DOI Listing
July 2001

The association of coagulase-negative staphylococci isolated from the chorioamnion at delivery and subsequent development of cerebral palsy.

J Perinatol 2001 Jan-Feb;21(1):3-8

Department of Obstetrics and Gynecology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.

Objective: To find out whether there is an association between cultures positive for coagulase negative staphylococci (CONS) taken from babies in the Neonatal Intensive Care Unit (NICU) and a subsequent outcome of cerebral palsy.

Study Design: At delivery, we obtained cultures from the chorioamnion space and, when medically indicated, we obtained bacterial cultures from children in the NICU. Surviving neonates underwent final examination for cerebral palsy at age 18 months.

Results: Of six children in the Magnesium and Neurologic Endpoints Trial who had cerebral palsy, chorioamnion cultures had been obtained for five of six. Four of these five children (80%) had CONS-positive cultures, whereas 26 of 102 (25%) children without cerebral palsy were CONS positive (p = 0.02). In the NICU, of children with cerebral palsy, the prevalence of culture-proven CONS was 80% (4/5); for those without cerebral palsy, the prevalence was 17% (15/86) (p = 0.01). Using multivariable logistic regression to control for confounding, CONS in the chorioamnion remained significant (adjusted odds ratio [OR] 37.7, 95% confidence interval [CI] 3.0 to +infinity; p = 0.003). However, when controlled for extremely low birth weight, nonvertex presentation, and being on a ventilator > or = 20 days, the association between culture-proven CONS in the NICU and cerebral palsy became insignificant (adjusted OR 3.0, 95% CI 0.2 to +infinity; p = 0.42).

Conclusion: CONS in the chorioamnion space are associated with cerebral palsy, but in these data, CONS in the NICU are not found to be associated with cerebral palsy.
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http://dx.doi.org/10.1038/sj.jp.7200474DOI Listing
July 2001

Association between funisitis and elevated interleukin-6 in cord blood.

Obstet Gynecol 2001 Feb;97(2):220-4

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.

Objective: [corrected] To determine whether elevated plasma interleukin-6 (IL-6) in umbilical venous cord blood at delivery is associated with funisitis and whether IL-6 can be used to screen for funisitis in preterm neonates.

Methods: At the time of delivery, umbilical venous cord blood samples were collected from 92 infants for whom placental pathology results were also available. Interleukin-6 concentrations in the umbilical venous cord blood plasma were measured by immunoassay. Histologic examinations of the placenta and umbilical cord were done to determine the presence or absence of funisitis and chorioamnionitis. For a power of 90% with an alpha of.05, 12 subjects were required in each group.

Results: We found a significant association between the presence of histologic funisitis and elevated umbilical venous cord blood plasma IL-6 concentrations (defined as 10 pg/mL or greater). Of 15 infants whose umbilical cords showed funisitis, 93% (14 of 15) had elevated umbilical venous cord blood plasma IL-6 concentrations. Of 77 infants without funisitis, 32% (25 of 77) had elevated IL-6 concentrations in their cords (P <.001, two-sided Fisher exact test). The negative predictive value of IL-6 as a screening test for funisitis was 98%.

Conclusion: In preterm neonates, screening for funisitis by using the immunoassay for IL-6 appears to be valid. In the near future, elevated umbilical venous cord blood IL-6 concentrations at delivery could be clinically useful to identify children who might benefit from early treatment for systemic fetal inflammatory syndrome.
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http://dx.doi.org/10.1016/s0029-7844(00)01149-2DOI Listing
February 2001

Age at any full-term pregnancy and breast cancer risk.

Am J Epidemiol 2000 Apr;151(7):715-22

School of Public Health and Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei.

The authors analyzed data from two multistate, population-based case-control studies to investigate the association between age at any full-term pregnancy (FP) and breast cancer risk. Study subjects included breast cancer cases aged 20-79 years identified from four statewide cancer registries and randomly selected controls interviewed from 1988 to 1996. Complete information on a comprehensive set of risk factors for breast cancer was available for 9,891 cases and 12,271 controls. The large number of subjects enabled simultaneous adjustment of the covariates and efficient application of various modeling approaches. Overall, each 5-year increase in age at first FP was associated with an odds ratio of 1.07 (95% confidence interval (CI): 1.01, 1.13) for breast cancer. The corresponding estimates were odds ratio = 1.02 (95% CI: 1.00, 1.05) for age at second through ninth FPs. For age at last FP, the effect estimate (odds ratio = 1.01, 95% CI: 0.97, 1.06) was indistinguishable from that for other FPs after the first. In this analysis, a modest and transient increase in breast cancer risk after childbirth was also observed. The relatively greater effect of age at first FP is consistent with the existence of a long-term effect of early first FP on the differentiation of mammary cells, causing them to become less susceptible to carcinogenesis.
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http://dx.doi.org/10.1093/oxfordjournals.aje.a010266DOI Listing
April 2000

Ethnic differences in the impact of advanced maternal age on birth prevalence of Down syndrome.

Am J Public Health 2000 Nov;90(11):1778-81

Department of Pediatrics, University of Chicago, Ill., USA.

Objectives: This study explored whether ethnic differences in the impact of advanced maternal age on the risk of Down syndrome might reflect differences in use of prenatal diagnostic technologies.

Methods: Maternal age-specific odds of Down syndrome and amniocentesis use were compared among African Americans, Mexican Americans, and non-Hispanic Whites via birth data for the years 1989 to 1991.

Results: The odds ratio and population attributable risk of Down syndrome due to maternal age of 35 years or older were highest for Mexican Americans, intermediate for African Americans, and lowest for non-Hispanic Whites.

Conclusions: Advanced maternal age has a greater impact on the risk of Down syndrome for African American and, particularly, Mexican American women than for non-Hispanic White women. This difference in impact might reflect lower availability or use of prenatal diagnostic technologies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1446403PMC
http://dx.doi.org/10.2105/ajph.90.11.1778DOI Listing
November 2000

An overview of the possible relationship between antenatal pharmacologic magnesium and cerebral palsy.

J Perinat Med 2000 ;28(4):286-93

Department of Obstetrics and Gynecology, Loyola University Medical Center, Maywood, IL, USA.

Magnesium sulfate is currently being used in obstetric practice for either eclamptic seizure prophylaxis or for tocolysis, in some countries. Evidence for its use in preeclampsia is credible, whereas the evidence for its use as a tocolytic is limited, if not absent. Of interest, the findings of two epidemiologic studies have suggested a third possible use for antenatal pharmacologic magnesium sulfate, namely, as a neuroprotectant against the later development of cerebral palsy in the newborn. In support of this hypothesis are laboratory data, much of which have to do with the modulation of cellular membrane receptors. Unfortunately, during the Magnesium and Neurologic Endpoints Trial (MagNET), while attempting to confirm the neuroprotective effect of magnesium sulfate, the occurrence of excess total pediatric mortality in those children exposed to magnesium led to early termination of the trial. Nonetheless, despite the alarming findings in MagNET, it is conceivable that exposures to doses of magnesium sulfate less than those often used for aggressive tocolysis may be neuroprotective without being lethal. Other randomized controlled trials now underway may answer this important question.
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http://dx.doi.org/10.1515/JPM.2000.035DOI Listing
January 2001

Perinatal death and tocolytic magnesium sulfate.

Obstet Gynecol 2000 Aug;96(2):178-82

Pritzker School of Medicine, Biological Sciences Division, University of Chicago, Chicago, Illinois, USA.

Objective: To determine whether there is a significant association between perinatal mortality and exposure to total doses of tocolytic magnesium sulfate larger than 48 g.

Methods: We did a case-control study in which cases were defined as neonates or fetuses who died after being exposed to tocolytic magnesium sulfate and controls were those who survived exposure. The study included fetuses and neonates who weighed between 700 and 1249 g and whose mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital between January 1, 1986, and March 31, 1999. We excluded women who received prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on chronic hypertension, and fetuses or neonates with major congenital anomalies. Data were analyzed by Fisher exact test, chi(2) test, Student t test, Mann-Whitney U test, multivariable logistic regression, and Cochrane-Armitage trend test.

Results: Controlling for birth weight or gestational age, year of delivery, receipt of betamethasone, acute maternal disease, and maternal race in a multivariable model, we found that exposure to total doses of tocolytic magnesium sulfate exceeding 48 g was significantly associated with increased perinatal mortality (adjusted odds ratio 4. 7; 95% confidence interval 1.1, 20.0; P =.035). Using the Cochrane-Armitage trend test, we found that a significant dose response was present (P =.03), but one that was most consistent with a threshold effect.

Conclusion: Our findings support the hypothesis that high doses of tocolytic magnesium sulfate are associated with increased perinatal mortality among fetuses and neonates weighing 700-1249 g.
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http://dx.doi.org/10.1016/s0029-7844(00)00893-0DOI Listing
August 2000

Early-life physical activity and postmenopausal breast cancer: effect of body size and weight change.

Cancer Epidemiol Biomarkers Prev 2000 Jun;9(6):591-5

University of Wisconsin Comprehensive Cancer Center, Madison 53706, USA.

It is not yet known whether early-life physical activity reduces the risk of developing breast cancer. Subgroup analyses according to menopausal status and body mass may help clarify this association. Data from a population-based case-control study of female residents of Wisconsin, Massachusetts, Maine, and New Hampshire were used to examine associations between body mass and breast cancer risk. Cases (n = 4614) were identified by each state's tumor registry; controls (n = 5817) were randomly selected from population lists. Frequency of participation in strenuous physical activity when 14-22 years of age, weight at age 18 and 5 years before interview, height, and other factors were ascertained through structured telephone interviews. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression. Reductions in postmenopausal breast cancer risk associated with strenuous physical activity were greatest for women in the fourth quartile of body mass index at age 18; the OR for women with the highest activity frequency on average (> or =once/day) was 0.45 (95% CI = 0.26-0.79). Associations with frequency of activity also varied by weight change. Compared to women with no activity and little adult weight gain, frequent physical activity was associated with reduced postmenopausal breast cancer risk in women who had lost weight since age 18 (OR = 0.19, 95% CI = 0.05-0.70) or had gained little or modest amounts of weight (weight gain: first tertile, OR = 0.36, 95% CI = 0.05-0.85; second tertile, OR = 0.31, 95% CI = 0.14-0.66). Weighted MET score analyses yielded similar but less inverse results. These findings suggest that the reduced risk of postmenopausal breast cancer associated with frequent, early-life physical activity may be greatest in women who, over the adult years, either lost weight or gained only modest amounts.
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June 2000

The control of labor.

N Engl J Med 1999 Dec;341(27):2098-9

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http://dx.doi.org/10.1056/NEJM199912303412716DOI Listing
December 1999

Association between cerebral palsy and coagulase-negative staphylococci.

Lancet 1999 Nov;354(9193):1875-6

Coagulase-negative staphylococci were cultured from the space between the placental membranes at delivery in four of five neonates who were later diagnosed with cerebral palsy, and in 26 of 102 neonates who were not found to have the disorder (p=0.02).
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http://dx.doi.org/10.1016/S0140-6736(99)01111-3DOI Listing
November 1999

Length of pregnancy in African Americans: validation of a new predictive rule.

J Natl Med Assoc 1999 Sep;91(9):523-7

Department of Obstetrics and Gynecology, Pritzker School of Medicine, University of Chicago, IL, USA.

This study evaluated whether a new predictive rule is more accurate for estimating the length of pregnancy in African Americans than Nägele's rule, the accepted standard. After identifying women in early pregnancy, telephone interviews were conducted to obtain information about 16 previously established determinants of gestational length. Based on these data, a linear multivariate regression model was used to predict an estimated delivery date (EDD) for each mother. In addition, the EDD was determined using Nägele's rule. Later, the actual delivery date was compared with the EDD predicted by the new rule and with the EDD predicted by Nägele's rule. Each pregnancy was assigned to its better prediction group, either the new rule's group or the Nägele's rule group. Fifty-seven pregnancies were identified prospectively and monitored. The new rule predicted the actual delivery date more accurately in 66% (37/56) of pregnancies, Nägele's rule was a better predictor in 34% (19/56) of pregnancies, and both rules were equally accurate in predicting the delivery date for one pregnancy. The new rule was more precise than Nägele's rule (P = .022) when the binomial distribution was used. When using the linear regression model rule, a more accurate EDD can be determined for African-American women. Moreover, it is possible to predict the risk of preterm delivery (those occurring > 3 weeks earlier than the EDD).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2608540PMC
September 1999

Epidural analgesia and cesarean delivery.

JAMA 1999 Jun;281(22):2084-5; author reply 2086-7

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http://dx.doi.org/10.1001/jama.281.22.2084DOI Listing
June 1999

Maternal second trimester serum tumor necrosis factor-alpha-soluble receptor p55 (sTNFp55) and subsequent risk of preeclampsia.

Am J Epidemiol 1999 Feb;149(4):323-9

Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, USA.

Preeclampsia is characterized by diffuse vascular endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha), which plays a key role in the cytokine network responsible for immunoregulation, is also known to contribute to endothelial dysfunction and other metabolic disturbances noted in preeclampsia. Results from cross-sectional studies and one longitudinal study indicate that TNF-alpha (or its soluble receptor, sTNFp55) is increased in the peripheral circulation and amniotic fluid of women with preeclampsia as compared with normotensive women. Between December 1993 and August 1994, prediagnostic sTNFp55 concentrations (a marker of excessive TNF-alpha release) were measured in 35 women with preeclampsia and 222 normotensive women to determine whether elevations precede the clinical manifestation of the disorder. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Mean second trimester (15-22 weeks' gestation) serum sTNFp55 concentrations, measured by enzyme-linked immunosorbent assay, were 14.4% higher in preeclamptic women than in normotensive controls (716.6 pg/ml (standard deviation 193.6) vs. 626.4 pg/ml (standard deviation 158.0); p = 0.003). The relative risk of preeclampsia increased across successively higher quintiles of sTNFp55 (odds ratios were 1.0, 1.3, 2.1, and 3.7, with the lowest quintile used as the referent; p for trend = 0.007). After adjustment for maternal age, adiposity, and parity, the relative risk between extreme quintiles was 3.3 (95% confidence interval 0.8-13.4). These findings indicate that the level of TNF-alpha in maternal circulation is increased prior to the clinical manifestation of the disorder, and they are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia. Further work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy, and to assess whether lowering of TNF-alpha concentrations in pregnancy alters the incidence and severity of preeclampsia.
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http://dx.doi.org/10.1093/oxfordjournals.aje.a009816DOI Listing
February 1999

Relationship of cesarean delivery to lower birth weight-specific neonatal mortality in singleton breech infants in the United States.

Obstet Gynecol 1998 Nov;92(5):769-74

University of Chicago Children's Hospital, University of Chicago, Illinois 60637, USA.

Objective: The preferred route of delivery for breech presentation has been controversial. We compared the birth weight-specific neonatal mortality of vaginal births to cesarean births in singleton births with breech presentation.

Methods: A total of 371,692 singleton live births with breech presentation were selected for the study from the United States birth cohorts for the years 1989-1991. Differences in birth weight specific mortality were compared using a z-statistic for differences in proportions and by logistic regression.

Results: Compared to primary vaginal births, primary cesarean births had significantly lower neonatal mortality for all birth weight groups, despite increased prevalence of fetal malformations in the cesarean as compared with vaginally delivered group. This mortality difference was greatest in the first hour of life. Difference in overall neonatal (less than 28 days) mortality rate ranged from a low of 1.6-fold in the 500-749 g group (726.6 per 1000 vaginal births compared with 456.3 per 1000 cesarean births, P < .001) to as high as about three-fold in the 1250-1499 g group (232.9 per 1000 vaginal births compared to 72.5 per 1000 cesarean births, P < .001). In the group with birth weights over 2500 g, neonatal mortality in the primary vaginal births was 5.3 per 1000 and in the primary cesarean births, 3.2 per 1000 (P < .001). Similarly, repeat cesarean births had significantly lower birth weight-specific neonatal mortality, compared with vaginal births after previous cesarean.

Conclusion: Singleton live births with breech presentation delivered by cesarean had lower birth weight-specific neonatal mortality as compared with vaginal births.
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http://dx.doi.org/10.1016/s0029-7844(98)00291-9DOI Listing
November 1998

Short interpregnancy intervals and the risk of adverse birth outcomes among five racial/ethnic groups in the United States.

Am J Epidemiol 1998 Oct;148(8):798-805

Department of Pediatrics, University of Chicago Children's Hospital, IL 60637, USA.

The authors studied the effects and population-level impact of short (< or = 12 months) interpregnancy intervals on the risks for low (<2.5 kg) birth weight and preterm (<37 weeks) delivery of liveborn singleton infants to US African American, Mexican, Native American, non-Hispanic white, and Puerto Rican mothers (n = 4,841,418) from 1989 to 1991. Statistical analyses were done by using the Mantel-Haenszel correlation statistic chi-square test and logistic regression. The proportion of livebirths associated with < or =12-month interpregnancy intervals was the lowest among non-Hispanic whites (18.5%, 95% confidence interval 18.5-18.5) and the highest among Native Americans (29.7%, 95% confidence interval 29.2-30.2). As compared with mothers with >12-month intervals, mothers with <6-month intervals had an approximately 50% to 80% increased risk of very low (<1.5 kg) birth weight delivery and a 30% to 90% increased risk of very preterm (<32 weeks) delivery. Logistic regression analyses showed that the adverse effects of short intervals were reduced by about 10% but remained for the most part significant after controlling for potential confounding by maternal age, education, parity, marital status, prenatal care, smoking, and previous preterm delivery.
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http://dx.doi.org/10.1093/oxfordjournals.aje.a009701DOI Listing
October 1998

Menstrual factors in relation to breast cancer risk.

Cancer Epidemiol Biomarkers Prev 1998 Sep;7(9):783-9

Department of Community and Family Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.

We evaluated menstrual factors in relation to breast cancer risk in a large, population-based, case-control study. Case women were ascertained through state-wide registries covering Wisconsin, Western Massachusetts, Maine, and New Hampshire; control women were randomly selected from driver's license and Medicare lists in each state. Information regarding menstrual characteristics was obtained through a telephone interview. The study population comprised 6888 breast cancer cases and 9529 control women. Because exogenous hormones influence menstrual cycle patterns, we repeated our analyses in a subgroup of women who had never used oral contraceptives or hormone replacement therapy. Our results indicate decreased breast cancer risk with menarcheal age of 15 years or more, relative to menarche at age 13; the relation was stronger among premenopausal [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.57-0.91] as opposed to postmenopausal women (OR, 0.90; 95% CI, 0.80-1.03). Risk was slightly reduced among premenopausal women whose menstrual cycles did not become regular until at least 5 years after onset of menses, relative to those whose cycles became regular within 1 year (OR, 0.80; 95% CI, 0.63-1.02). There was no clear relation between breast cancer risk and irregular menstrual cycles, episodes of amenorrhea, or menstrual cycle length. Early menopause, whether natural or surgical, was associated with decreased breast cancer risk; surgical menopause before age 40 conferred the strongest protective effect (OR, 0.57; 95% CI, 0.47-0.71). We found no evidence of increased risk with late natural menopause (OR, 0.92; 95% CI, 0.80-1.06). Results in the subgroup of women who never used exogenous hormones were similar to those for the entire group.
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September 1998

Cancer risk in women exposed to diethylstilbestrol in utero.

JAMA 1998 Aug;280(7):630-4

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7362, USA.

Context: The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero.

Objective: To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up.

Design: A cohort study with mailed questionnaires and medical record review of reported cancer outcomes.

Participants: A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s.

Main Outcome Measures: Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters.

Results: To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result.

Conclusions: Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.
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http://dx.doi.org/10.1001/jama.280.7.630DOI Listing
August 1998

If tocolytic magnesium sulfate is associated with excess total pediatric mortality, what is its impact?

Obstet Gynecol 1998 Aug;92(2):308-11

Department of Obstetrics and Gynecology, Pritzker School of Medicine, University of Chicago, Illinois, USA.

The Magnesium and Neurologic Endpoints Trial was a randomized controlled trial (RCT) done to learn whether or not receiving magnesium sulfate during preterm labor could prevent cerebral palsy. Unexpectedly, in the tocolytic arms of the trial, seven (including one set of twins) of 46 cases assigned to receive magnesium ended in total pediatric mortality (fetal + neonatal + postneonatal), compared to none of 47 cases assigned to other tocolytics ending in death. The difference between the two treatment arms is highly statistically significant (risk difference 15.2%; 95% confidence interval 4.8, 25.6; P = .006). If this relationship is confirmed by experimentation with animals or through the conduct of a large RCT at other institutions, it is possible that tocolytic magnesium will be found to be associated with the deaths of several thousand newborns in the United States annually. If the true excess total pediatric mortality is 10%, and if magnesium accounts for 40% of all tocolytics used, then tocolytic magnesium increases the absolute number of infant deaths by about 4800 every year.
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http://dx.doi.org/10.1016/s0029-7844(98)00163-xDOI Listing
August 1998

Fetal congenital malformations. Biophysical profile evaluation.

J Reprod Med 1998 Jun;43(6):521-7

Department of Obstetrics and Gynecology, University of Chicago, IL 60637, USA.

Objective: To study the association between various fetal congenital malformations and the biophysical profile (BPP), we tested the following hypotheses: (1) a specific organ system malformation is associated with the absence of one or more BPP parameters, and (2) four BPP parameters are not affected by the advancement of fetal maturation.

Study Design: From 1985 to 1995, 316 fetuses with congenital malformations and 351 controls were identified in a high-risk population undergoing ultrasound examinations of anatomic structures and biophysical profile evaluations. For investigation of the influence of fetal maturity on biophysical profile evaluations, both the malformed fetuses and the controls were stratified into two gestational-age groups, 26-34 weeks and > 34 completed weeks. Four parameters of the BPP, including (1) fetal breathing, (2) gross fetal movements, (3) fetal muscle tone, and (4) quantitative amniotic fluid volume, were divided into low (0-6) and high (8) total score subgroups. Tests of significance were done using chi 2 analysis, Student's t test or Fisher's exact test, as appropriate. Level of significance was set at P < .05.

Results: When comparing malformed fetuses to controls, the malformed group had a statistically significantly higher percentage of low BPP scores due to absent fluid, tone or breathing. Fetuses with a musculoskeletal anomaly were statistically significantly more likely to lose points for fetal movement (P < .02); fetuses with a genitourinary system anomaly lost points for fluid (P < .001), tone (P < .005) and breathing (P < .005); fetuses with a central nervous system anomaly lost points for tone (P < .02) and breathing (P < .001); and fetuses with a thoracic anomaly lost points for breathing (P < .002). There was no statistically significant difference in BPP scores between fetuses at 26-34 weeks' gestational age and fetuses > 34 completed weeks' gestational age.

Conclusion: The two hypotheses were confirmed by the study results.
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June 1998

Risk factors for breast cancer in women with a breast cancer family history.

Cancer Epidemiol Biomarkers Prev 1998 May;7(5):359-64

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Family history (FH) is an important indicator of a woman's future risk of developing breast cancer. Using data collected in a large population-based case-control study (6705 cases and 9341 controls), we examined the associations of breast cancer with known risk factors in women reporting a first-degree FH (mother or sister), with an emphasis on lifestyle determinants that may be altered to reduce risk. First-degree FH was reported by 18.4% (n = 1234) of cases and 11.3% (n = 1058) of controls; the overall relative risk (RR) for breast cancer associated with a positive history was 1.70 [95% confidence interval (CI), 1.55-1.87] and 2.34 (95% CI, 1.80-3.02) for breast cancer at age 45 years or younger. Among women with a FH, statistically significant inverse associations were observed for increasing parity (RR per birth = 0.90; P < 0.0001), intake of carotene-rich foods (RR for >2000 IU/day = 0.73; P = 0.02), and strenuous activity as a young adult (RR per episode/week = 0.93; P = 0.02). Recent alcohol consumption increased risk (RR per 13 g/week = 1.21; P = 0.02), as did weight gain during adult life in postmenopausal women (RR per 5 kg = 1.08; P = 0.001). Breast-feeding for any duration was associated with a lower RR in parous, premenopausal women (RR = 0.59; P = 0.04). Associations for most risk factors with breast cancer were similar among women with and without a FH of breast cancer; however, a stronger inverse association was observed for parity in women with a positive history (P for interaction = 0.04). Based on these data, women with a FH may reduce their excess risk of breast cancer through adjustments in lifestyle and reproductive choices. The risk associated with FH of breast cancer seems to be largely independent of other known risk factors.
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May 1998

Environmental endocrine modulators and human health: an assessment of the biological evidence.

Crit Rev Toxicol 1998 Mar;28(2):109-227

Environmental Risk Sciences, Washington, D.C. 20007, USA.

Recently, a great deal of attention and interest has been directed toward the hypothesis that exposure, particularly in utero exposure, to certain environmental chemicals might be capable of causing a spectrum of adverse effects as a result of endocrine modulation. In particular, the hypothesis has focused on the idea that certain organochlorine and other compounds acting as weak estrogens have the capability, either alone or in combination, to produce a variety of adverse effects, including breast, testicular and prostate cancer, adverse effects on male reproductive tract, endometriosis, fertility problems, alterations of sexual behavior, learning disability or delay, and adverse effects on immune and thyroid function. While hormones are potent modulators of biochemical and physiological function, the implication that exposure to environmental hormones (e.g., xenoestrogens) has this capability is uncertain. While it is reasonable to hypothesize that exposure to estrogen-like compounds, whatever their source, could adversely affect human health, biological plausibility alone is an insufficient basis for concluding that environmental endocrine modulators have adversely affected humans. Diethylstilbestrol (DES) is a potent, synthetic estrogen administered under a variety of dosing protocols to millions of women in the belief (now known to be mistaken) that it would prevent miscarriage. As a result of this use, substantial in utero exposure to large numbers of male and female offspring occurred. Numerous studies have been conducted on the health consequences of in utero DES exposure among the adult offspring of these women. There are also extensive animal data on the effects of DES and there is a high degree of concordance between effects observed in animals and humans. The extensive human data in DES-exposed cohorts provide a useful basis for assessing the biological plausibility that potential adverse effects might occur following in utero exposure to compounds identified as environmental estrogens. The effects observed in both animals and humans following in utero exposure to sufficient doses of DES are consistent with basic principles of dose response as well as the possibility of maternal dose levels below which potential non-cancer effects may not occur. Significant differences in estrogenic potency between DES and chemicals identified to date as environmental estrogens, as well as an even larger number of naturally occurring dietary phytoestrogens, must be taken into account when inferring potential effects from in utero exposure to any of these substances. The antiestrogenic properties of many of these same exogenous compounds might also diminish net estrogenic effects. Based on the extensive data on DES-exposed cohorts, it appears unlikely that in utero exposure to usual levels of environmental estrogenic substances, from whatever source, would be sufficient to produce many of the effects (i.e., endometriosis, adverse effects on the male reproductive tract, male and female fertility problems, alterations of sexual behavior, learning problems, immune system effects or thyroid effects) hypothesized as potentially resulting from exposure to chemicals identified to date as environmental estrogens.
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http://dx.doi.org/10.1080/10408449891344191DOI Listing
March 1998

Neonatal circumcision. Randomized trial of a sucrose pacifier for pain control.

Arch Pediatr Adolesc Med 1998 Mar;152(3):279-84

Department of Pediatrics, University of Chicago Pritzker School of Medicine, Ill, USA.

Objective: To assess the effectiveness of oral sucrose via a nipple compared with no treatment and dorsal penile nerve block (DPNB) for alleviating pain in neonatal circumcision.

Design: Randomized control trial. Data analysis performed by investigators blinded to the 3 treatment groups.

Setting: University teaching hospital, General Care Nursery.

Patients: One hundred nineteen full-term male, normal birth weight neonates, 12 hours old or older.

Interventions: No treatment (our standard care), DPNB, or oral sucrose prior to circumcision.

Main Outcome Measures: Differences between groups in heart rate and oxygen saturation changes from baseline during specified intervals of the circumcision procedure. Differences between groups in loss of data due to episodes of excessive motion.

Results: Sucrose gave significant (P < .001) pain relief compared with the no treatment control throughout most of the circumcision and particularly in the early stages of the procedure. Overall, the average difference in the elevation of heart rates during the circumcision operative procedure among the 3 groups and the 95% confidence intervals (CIs) were as follows: control vs DPNB, 27.1 beats/min (17.6, 36.6) and control vs sucrose, 9.7 beats/min (0.1, 19.3). Furthermore, newborns who received either DPNB or sucrose had less loss of oxygen saturation data due to excessive motion during the procedure than the no-treatment controls. The total percentages of lost data due to excessive motion in the 3 groups were 31% for control, 10% for DPNB, and 8% for sucrose. Relative risk and 95% CIs were: DPNB vs control, 0.32 (0.23, 0.43); sucrose vs control, 0.26 (0.18, 0.36). Differences in oxygen saturation among the 3 groups during the circumcision operative procedure were statistically (P < .001), but perhaps not clinically, significant. However, the analysis did not include missing data due to excessive motion, which occurred predominantly in the no-treatment control group.

Conclusion: Sucrose on a pacifier is an inexpensive and effective method for pain relief in neonatal circumcision when DPNB is not desirable.
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http://dx.doi.org/10.1001/archpedi.152.3.279DOI Listing
March 1998

Intake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer.

Cancer Epidemiol Biomarkers Prev 1997 Nov;6(11):887-92

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.

Intake of fruits, vegetables, vitamin A, and related compounds are associated with a decreased risk of breast cancer in some studies, but additional data are needed. To estimate intake of beta-carotene and vitamin A, the authors included nine questions on food and supplement use in a population-based case-control study of breast cancer risk conducted in Maine, Massachusetts, New Hampshire, and Wisconsin in 1988-1991. Multivariate-adjusted models were fit to data for 3543 cases and 9406 controls. Eating carrots or spinach more than twice weekly, compared with no intake, was associated with an odds ratio of 0.56 (95% confidence interval 0.34-0.91). Estimated intake of preformed vitamin A from all evaluated foods and supplements showed no trend or monotonic decrease in risk across categories of intake. These data do not allow us to distinguish among several potential explanations for the protective association observed between intake of carrots and spinach and risk of breast cancer. The findings are, however, consistent with a diet rich in these foods having a modest protective effect.
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November 1997

Human development index as a predictor of infant and maternal mortality rates.

J Pediatr 1997 Sep;131(3):430-3

Department of Pediatrics, Pritzker School of Medicine, University of Chicago, Illinois 60637, USA.

Objective: The United Nations Human Development Index (HDI) is a composite index of life expectancy, literacy, and per capita gross domestic product that measures the socioeconomic development of a country. We estimated infant and maternal mortality rates in the world and assessed how well the HDI and its individual components predicted infant and maternal mortality rates for individual countries.

Materials: Data on mortality rates and values for HDI components were obtained from the United Nations and the World Bank.

Results: For the 1987 to 1990 period, approximately 9 million infant deaths and 349,000 maternal deaths occurred in the world annually, yielding global infant and maternal mortality rates of 67 per 1000 and 250 per 100,000 live births, respectively. HDI is a powerful predictor of both infant and maternal mortality rates. It accounts for 85% to 92% of the variation in infant mortality rates, and 82% to 85% of the variation in maternal mortality rates among countries. Each component of HDI is also strongly correlated with both infant and maternal mortality rates (significance of all values for r, p < 0.001), and eliminating life expectancy from HDI does not decrease significantly the predictive power of HDI for infant or maternal mortality rates.

Conclusion: HDI is not only a useful measure for socioeconomic development, but also a powerful predictor of infant and maternal mortality rates for individual countries.
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http://dx.doi.org/10.1016/s0022-3476(97)80070-4DOI Listing
September 1997

Impact of increased neonatal survival on postneonatal mortality in the United States.

Paediatr Perinat Epidemiol 1996 Oct;10(4):423-31

Department of Pediatrics, Pritzker School of Medicine, University of Chicago 60637, USA.

Neonatal intensive care has increased neonatal survival, but has also led to postponement of some of the neonatal deaths to the postneonatal period, particularly in very low birthweight (< 1.5 kg) infants. Our report assesses the impact of the increased neonatal survival and the accompanying delayed deaths on the crude postneonatal mortality rate of the US, using the national livebirth cohort data of 1960, 1980, and 1986. With increased neonatal survival, very low birthweight infants comprised 0.68% of all neonatal survivors in 1986, compared with only 0.31% in 1960. However, postneonatal mortality was increased in infants with birthweights < 1.0 kg from 69 per 1000 neonatal survivors in 1960 to 116 per 1000 in 1986. All other birthweight groups (> 1.0 kg) showed significant reductions in their postneonatal mortality, although the 1.0-1.5 kg group showed the least improvement. Thus, in 1986, 12.1% of all postneonatal deaths were from the very low birthweight neonatal survivors, as compared with 2.7% in 1960. If there had been no improvement in neonatal survival of very low birthweight infants since 1960, the crude postneonatal mortality rate of the US would have been 5.5% and 7.9% less than the actual rates of 3.65 and 3.45 per 1000 neonatal survivors in 1980 and 1986, respectively. However, the impact of these delayed deaths in very low birthweight infants was far less than the increase in their neonatal survival: an additional 416 per 1000 very low birthweight infants survived to 1 year of age in 1986 as compared with 1960. Delayed deaths in the 1.5-2.5 kg birthweight group had a very small effect on postneonatal mortality and there was no such effect of delayed deaths in the > 2.5 kg birthweight group.
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http://dx.doi.org/10.1111/j.1365-3016.1996.tb00068.xDOI Listing
October 1996

Variation in female breast cancer risk by occupation.

Am J Ind Med 1996 Oct;30(4):430-7

Department of Environmental Health, Boston University School of Public Health, Massachusetts, USA.

Data from a population-based case control study were used to estimate occupation-specific relative risks for female breast cancer, adjusted for established breast cancer risk factors. Breast cancer cases under age 75 were identified from tumor registries in four states. Controls were randomly selected from driver's license and Medicare beneficiary lists. Information on usual occupation and risk factors was obtained by telephone interview. Odds ratios from logistic regression adjusted for age, state, body mass index, benign breast disease, family history of breast cancer, menopausal status, age at menarche, parity, age of first birth, lactation history, education, and alcohol consumption were calculated for each of 26 occupational groups. Complete occupational information was obtained for 6,835 cases and 9,453 controls. Of 26 occupational groups, only "administrative support occupations" had a statistically significantly increased risk of breast cancer (OR = 1.15, 95% CI 1.06-1.24). In these data, no specific occupational group had an unusual risk of breast cancer. Increased risks reported elsewhere for nurses and teachers were not corroborated.
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http://dx.doi.org/10.1002/(SICI)1097-0274(199610)30:4<430::AID-AJIM8>3.0.CO;2-ZDOI Listing
October 1996
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