Enhanced surveillance for pregnancy-associated mortality--Maryland, 1993-1998.

CONTEXT: Deaths occurring among women who are pregnant or who have had a recent pregnancy have a devastating impact on the family and community. It is important to understand the magnitude and causes of pregnancy-associated mortality so that comprehensive strategies can be formulated to prevent such deaths. OBJECTIVE: To ascertain the number and causes of pregnancy-associated deaths using enhanced surveillance techniques. DESIGN, SETTING, AND SUBJECTS: Retrospective, cross-sectional analysis of death certificate data of reproductive-age women, live birth and fetal death records, and medical examiner records in Maryland during 1993-1998. MAIN OUTCOME MEASURE: Number of pregnancy-associated deaths, defined as death from any cause during pregnancy or within 1 year of delivery or pregnancy termination, by source of data and cause of death. RESULTS: A total of 247 pregnancy-associated deaths were ascertained. Twenty-seven percent (n = 67) were identified through cause-of-death information obtained from death certificates, 70% (n = 174) through linkage of death records with birth and fetal death records, and 47% (n = 116) through review of medical examiner records. Homicide was the leading cause of pregnancy-associated death (n = 50; 20%), and cardiovascular disorders were the second-leading cause (n = 48; 19%). CONCLUSIONS: In this Maryland sample, comprehensive identification of pregnancy-associated deaths was accomplished only after collecting information from multiple sources and including all deaths occurring up to 1 year after delivery or pregnancy termination. This enhanced pregnancy mortality surveillance led to the disturbing finding that a pregnant or recently pregnant woman is more likely to be a victim of homicide than to die of any other cause. By broadening pregnancy mortality to include all possible causes, previously neglected factors may assume increased importance in prenatal and postpartum care.

Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability.

Loss of imprinting (LOI) is an epigenetic alteration of some cancers involving loss of parental origin-specific expression of imprinted genes. We observed LOI of the insulin-like growth factor-II gene in twelve of twenty-seven informative colorectal cancer patients (44%), as well as in the matched normal colonic mucosa of the patients with LOI in their cancers, and in peripheral blood samples of four patients. Ten of eleven cancers (91%) with microsatellite instability showed LOI, compared with only two of sixteen tumors (12%) without microsatellite instability (P < 0.001). Control patients without cancer showed LOI in colonic mucosa of only two of sixteen cases (12%, P < 0.001) and two of fifteen blood samples (13%, P < 0.001). These data suggest that LOI in tumor and normal tissue identifies most colorectal cancer patients with microsatellite instability in their tumors, and that LO! may identify an important subset of the population with cancer or at risk of developing cancer.

Limited up-regulation of DNA methyltransferase in human colon cancer reflecting increased cell proliferation.

Epigenetic alterations in the genome of tumor cells have attracted considerable attention since the discovery of widespread alterations in DNA methylation of colorectal cancers over 10 years ago. However, the mechanism of these changes has remained obscure. el-Deiry and coworkers [el-Deiry, W. S., Nelkin, B. D., Celano, P., Yen, R. C., Falco, J. P., Hamilton, S. R. & Baylin, S. B. (1991) Proc. Natl. Acad. Sci. USA 88, 3470-3474], using a quantitative reverse transcription-PCR assay, reported 15-fold increased expression of DNA methyltransferase (MTase) in colon cancer, compared with matched normal colon mucosa, and a 200-fold increase in MTase mRNA levels compared with mucosa of unaffected patients. These authors suggested that increases in MTase mRNA levels play a direct pathogenetic role in colon carcinogenesis. To test this hypothesis, we developed a sensitive quantitative RNase protection assay of MTase, linear over three orders of magnitude. Using this assay on 12 colorectal carcinomas and matched normal mucosal specimens, we observed a 1.8- to 2.5-fold increase in MTase mRNA levels in colon carcinoma compared with levels in normal mucosa from the same patients. There was no significant difference between the normal mucosa of affected and unaffected patients. Furthermore, when the assay was normalized to histone H4 expression, a measure of S-phase-specific expression, the moderate increase in tumor MTase mRNA levels was no longer observed. These data are in contrast to the previously reported results, and they indicate that changes in MTase mRNA levels in colon cancer are nonspecific and compatible with other markers of cell proliferation.

Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour.

The insulin-like growth factor-II (IGF2) and H19 genes are imprinted in mouse and human, with expression of the paternal IGF2 and maternal H19 alleles. IGF2 undergoes loss of imprinting (LOI) in most Wilms' tumours (WT). We now show that: (i) LOI of IGF2 is associated with a 80-fold down regulation of H19 expression; (ii) these changes are associated with alterations in parental-origin-specific, tissue-independent sites of DNA methylation in the H19 promoter; and (iii) loss of heterozygosity is also associated with loss of H19 expression. Thus, imprinting of a large domain of the maternal chromosome results in a reversal to a paternal epigenotype. These data also suggest an epigenetic mechanism for inactivation of H19 as a tumour suppressor gene.

Birth weights among infants born to adolescent and young adult women.

Birth weights of 422 infants born to primigravid patients under the age of 16 years were compared with the birth weights of 422 infants born to a racially comparable group of primigravid patients 20 to 24 years old. No significant difference in birth weights was found between the two groups. Although infants of adolescents were born of shorter gestations than infants of older women, overall mean birth weights were similar, since the infants of adolescents were heavier at gestations of less than 37 weeks. Race and sex of the infant were more important predictors of birth weight among the adult group, whereas the maternal gain in weight was a more important factor among the adolescent group. Reduced birth weights reported in previous studies among infants of adolescents may have been due to overrepresentation of risk factors among these mothers rather than to maternal age, per se.