Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.

AIM: Genetic thrombophilias are known to contribute to adverse pregnancy outcomes. Studies in Western populations show that 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and Factor V (F5) 1691G>A (Leiden) polymorphisms are commonly associated with pre-eclampsia and recurrent spontaneous pregnancy loss. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133); 1298A>C (rs1801131) and F5 1691G>A (rs6025); 4070A>G (rs1800595) polymorphisms with pre-eclampsia and recurrent pregnancy loss among Sinhalese women in Sri Lanka. MATERIAL AND METHODS: Genotype and allele frequencies at each polymorphic site in the MTHFR and F5 genes and the haplotypes defined by them were determined in 175 Sinhalese women with pre-eclampsia, 171 normotensive controls, 200 Sinhalese women with two or more recurrent pregnancy losses and 200 controls with two or more living children and no pregnancy losses. Genotyping was done by polymerase chain reaction/restriction fragment length polymorphism. Odds ratios and χ(2) -testing were performed to compare genotype/haplotype frequencies at each polymorphic site for both cases and controls. RESULTS: The genotype frequencies at each polymorphic site in the MTHFR 677C>T; 1298A>C; F5 1691G>A and 4070A>G genes and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss. There was no significant association of genetic thrombophilia with either early or late pregnancy losses. CONCLUSIONS: The MTHFR and F5 polymorphisms and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss in this group of Sinhalese women.

Modified anchored B-Lynch uterine compression suture for post partum bleeding with uterine atony.

A prospective observational study was performed to evaluate the performance of a modified uterine compression suturing technique for the management of refractory post partum hemorrhage (PPH) at two leading tertiary referral centers in Colombo, Sri Lanka. An modified anchored B-Lynch suture was done in 17 women with PPH due to uterine atony. In 13 of the women (76%), bleeding was arrested and the uterus conserved. Four women (24%) did not respond to the anchored compression sutures, necessitating emergency post partum hysterectomy. Mean age was 31.2 years. Nine of the women (53%) were primiparous and eight (47%) parous. Mean estimated blood loss was 1994 ml (range 1200-3300 ml). This newly modified anchor B-Lynch compression suture appeared effective in controlling about 75% of PPH due to uterine atony, which allowed uterine conservation. This simple modification can provide a first line surgical step to control PPH.

Tracking progress towards safe motherhood: meeting the benchmark yet missing the goal? An appeal for better use of health-system output indicators with evidence from Zambia and Sri Lanka.

OBJECTIVES: Indicators of health-system outputs, such as Emergency Obstetric Care (EmOC) density, have been proposed for monitoring progress towards reducing maternal mortality, but are currently underused. We seek to promote them by demonstrating their use at subnational level, evaluating whether they differentiate between a high-maternal-mortality country (Zambia) and a low-maternal-mortality country (Sri Lanka) and assessing whether benchmarks are set at the right level. METHODS: We compared national and subnational density of health facilities, EmOC facilities and health professionals against current benchmarks for Zambia and Sri Lanka. For Zambia, we also examined geographical accessibility by linking health facility data to population data. RESULTS: Both countries performed similarly in terms of EmOC facility density, implying this indicator, as currently used, fails to discriminate between high- and low-maternal-mortality settings. In Zambia, the WHO benchmarks for doctors/midwives were met overall, but distribution between provinces was highly unequal. Sri Lanka overshot the suggested benchmarks by three times for midwives and over 30 times for doctors. Geographical access in Zambia--which is much less densely populated than Sri Lanka--was poor, less than half the population lived within 15 km of an EmOC facility. CONCLUSIONS: Current health-system output indicators and benchmarks on EmOC need revision to enhance discriminatory power and should be adapted for different population densities. Subnational disaggregation and assessing geographical access can identify gaps in EmOC provision and should be routinely considered. Increased use of an improved set of output indicators is crucial for guiding international efforts towards reducing maternal mortality.

A study of three candidate genes for pre-eclampsia in a Sinhalese population from Sri Lanka.

AIM: The aim of these investigations was to study three candidate genes for pre-eclampsia--epidermal growth factor (EGF), transforming growth factor alpha, and angiotensinogen--in pregnant Sinhalese women from Sri Lanka, the first such study undertaken in this ethnic group. Reproducibility of results of genetic association studies of candidate genes for pre-eclampsia has not been consistent across populations. One of the factors that may contribute to such inconsistencies is genetic stratification due to population admixture. We therefore compared the allele frequencies of these candidate genes in healthy Sri Lankan subjects from three ethnic groups--Sinhalese, Sri Lankan Tamils and Moors--and in white Western Europeans. METHODS: Allele frequencies were established in 80 subjects from each of four populations (Sinhalese, Sri Lankan Tamils, and Moors in Sri Lanka and white Western Europeans in the U.K.). A further 175 Sinhalese women with pre-eclampsia and 171 normotensive Sinhalese controls were genotyped at eight single nucleotide polymorphisms in the candidate genes. RESULTS AND DISCUSSION: In all genes haplotype and allele frequencies were comparable within the three Sri Lankan populations, but differed significantly from those in the white Western European population. Consequently cryptic population stratification is unlikely to have significant effects on allele or haplotype frequencies of the genes examined in this case-control study of Sinhalese women which showed a marginal association for EGF haplotypes and genotypes with pre-eclampsia (P = 0.031). This association requires replication in other populations.

Morbidity and mortality associated with pre-eclampsia at two tertiary care hospitals in Sri Lanka.

AIM: To report the occurrence of morbidity and mortality associated with carefully phenotyped pre-eclampsia in a sample of nulliparous Sinhalese women with strictly defined disease. METHODS: A phenotyping database of 180 nulliparous women with pre-eclampsia and 180 nulliparous normotensive pregnant women who were recruited for a study into genetics of pre-eclampsia was analyzed. RESULTS: Women who developed pre-eclampsia had significantly higher systolic blood pressure (SBP; P = 0.002) and diastolic blood pressure (DBP; P = 0.002) at booking (at approximately 13 weeks of gestation). 38.3%, 28.3% and 33.3% of women delivered at <34 weeks, at 34-36 weeks, and at term, respectively. 78% required a cesarean section. Complications included SBP > or = 160 mmHg (75.5%); DBP > or = 110 mmHg (83.8%); proteinuria > or =3 + (150 mg/dL) in the urine protein heat coagulation test (87%); renal failure requiring dialysis (2%); platelet counts <100 x 10(9)/L (13%); > or =70 U/L in aspartate and/or alanine aminotransaminase (15%); placental abruption (4%); eclampsia (9%); and one maternal death. Maternal complications indicative of severe disease, apart from the incidence of SBP > or = 160 mmHg and DBP > or = 110 mmHg, were not significantly different in early and late-onset pre-eclampsia; fetal outcome was better with late-onset disease. 48% of babies were small for gestational age. Only 80 of 135 babies of women with pre-eclampsia whose condition could be confirmed at 6 weeks post-partum were alive. CONCLUSIONS: Pre-eclampsia in Sinhalese women is associated with severe maternal morbidity and fetal morbidity and mortality, suggesting that modification of the Western diagnostic criteria and/or guidelines for medical care may be necessary. There is an urgent need to improve neonatal intensive care services in Sri Lanka.

The urine protein heat coagulation test--a useful screening test for proteinuria in pregnancy in developing countries: a method validation study.

In many parts of the developing world, the urine protein heat coagulation test is routinely used to screen for proteinuria in pregnancy. The aim of this study was to determine whether > or =1+ on a standardised heat coagulation test reliably detects significant proteinuria and to compare it with the dipstick test for urinary protein. Heat coagulation test, dipstick test and 24-hour urine protein excretion results of 102 women were compared. > or =1+ on heat coagulation test is as sensitive and specific as > or =2+ on the dipstick test in detecting proteinuria of > or =500 mg/day. The heat coagulation test, however, is less sensitive than > or =1+ on dipstick in detecting lesser degrees of proteinuria.