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.

Role of pathological cardiotocography in evaluating fetal well-being.

OBJECTIVE: To determine the frequency of pathological pattern of cardiotocography (C.T.G) in antepartum and intrapartum period and to evaluate the significance of those patterns in determining fetal well-being. DESIGN: Analytical study. PLACE AND DURATION OF STUDY: The study was conducted at Lady Dufferin Hospital, Karachi from February 2000 to January 2001. PATIENTS AND METHODS: All women with singleton pregnancies of >35 weeks gestation and cephalic presentations were electronically monitored in antepartum and intrapartum period and those with pathological trace were identified according to International Federation of Obstetricians and Gynaecologists (FIGO) classification. After delivery, Apgar score, fetal cord, blood gas values and neonatal intensive care unit admission duration were examined as the main outcome measures. RESULTS: Among the 3701 patients who qualified for the study, 60 (1.62%) had tracing, classified as pathological, of which 44 (73%) were in the intrapartum and 16 (27%) in the antepartum period. Out of these 60 patients, 53 (88.33%) were delivered alive while neonatal death (NNDs) occurred in 9 (16.9%) of the live born babies. There were 07 (11.6%) still births. In 53 of live born babies, Apgar score was <7 at 1 minute in 34 (64.15 %), while it was >7 at 1 minute in 19 (35.84%). Low Apgar score persisted at 5 minutes in 10 (18.86%) cases of pathological CTG. Out of these 10, there were 3(30%) NNDs, while 6 (13.95%) NNDs occurred in those whose apgar had improved to >7 at 5 minute (P=0.9). Cord pH results were available in 31 (58.49 %) cases and were acidotic (<7.20) in 16 (51.61%), pre-acidotic (7.20-7.25) in 9 (29.03%) and normal (7.25-7.35) in 6 (19.35 %). All alive born babies with a pathological CTG tracing were admitted in NICU as per hospital policy. The duration of admission was less than 24 hours in 15 (28.30 %), 2-4 days in 26 (49%) and more than 4 days in 12 (22.64%). CONCLUSION: In this series, an increased frequency of detectable hypoxia on CTG was observed during the intrapartum period as compared to the antepartum period, however, no significant association was found between a pathological CTG recording, fetal APGAR score and acidemia, if a pathological trace is used alone to assess fetal well-being. An increased cesarean section rate in babies with a pathological CTG stresses on the need for additional tests to differentiate hypoxic from non-hypoxic fetuses thus avoiding unnecessary intervention.

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.