Genetic and epigenetic analysis of recurrent hydatidiform mole.

Familial biparental hydatidiform mole (FBHM) is a maternal-effect autosomal recessive disorder in which recurrent pregnancy failure with molar degeneration occurs. The phenotype mimics molar pregnancy due to androgenesis, despite the normal genetic makeup of the conceptus. FBHM appears to result from a failure to establish correct maternal epigenetic identity at imprinted loci during oogenesis. Several women affected with FBHM have previously been shown to have biallelic mutations in the NLRP7 gene (NALP7). Here, we present the results of epigenetic and mutational analysis on FBHM patients from 11 families, 10 of them novel. We demonstrate a methylation defect at imprinted loci in tissue from four new FBHM cases. Biallelic NLRP7 mutations, including eight previously undescribed mutations, were found in all but one family. These results indicate for the first time that maternal imprints at some loci may be correctly specified in FBHM conceptions, since differential methylation of SGCE/PEG10 was preserved in all four cases.

Early neonatal mortality: effects of interventions on survival of low birth babies weighing 1000-2000g.

OBJECTIVE: In order to improve our newborn care, we instituted several changes along with training of medical and nursing staff and compared survival rates in babies < 2000g before and after these changes. We also measured Perinatal Mortality Rate (PMR) and Neonatal Mortality Rate (NMR) in general, percentage of Low Birth Weight (LBW) babies and causes of early neonatal deaths at Lady Dufferin Hospital (LDH). METHODS: It was an intervention study design. All admissions to NICU between 1998 and 2000 were entered in the register. Data included high risk obstetric factors, gestational age, birth weight, APGAR score, gender, need for resuscitation, diagnosis, complications and outcome. Data of rest of the babies was recorded from operation theatre, labour room and postnatal ward registers in a separate register. RESULTS: Of 783 perinatal deaths, 488 were stillbirths and 295 were early neonatal deaths; 2498/14867 (17%) babies were LBW. The main causes of early neonatal mortality included prematurity and related complications (35%), congenital malformations (23%), sepsis 19%), and birth anoxia (16%). Most (27/295 77%) deaths occurred in babies weighing <2500g. Deaths due to prematurity and related complications in babies weighing between 1000-1499g decreased from 17/33 (51%) in 1997 (to 13/33 (39%) 9/45 (20%), 2/38 (5%) in 1998-99 and 2000 respectively. Sepsis related deaths decreased in babies weighing between 1500 to 1999g from 5/57(8.7%) in year 1997 to 7/77 (9%), 3/76 (4%), 4/96 (4%) in 1998, 99, and 2000 respectively. The PMR/NMR decreased from 58/22.4 in year 1997 to 39/15.6, 44.4/18.6, 38.2/12.3 for year 1998, 1999 and 2000 respectively. CONCLUSION: There was a significant reduction in mortality in LBW babies after training of medical and nursing staff. Reduction in overall PMR & NMR was also due to decrease in mortality in LBW babies.