Epigenetic Modification in Methylene Tetrahydrofolate Reductase (MTHFR) Gene of Women with Pre-eclampsia.

BACKGROUND: Genetic and epigenetic factors play significant roles in the aetio-pathogenesis of pre-eclampsia (PE). The effects may vary across racial and geographical boundaries. The role of epigenetic modification in pre-eclampsia was studied among African populations in Lagos, Nigeria. AIM AND OBJECTIVES: This study aimed to determine the pattern of Methylene tetrahydrofolate reductase gene (MTHFR) CpG island methylation in pre-eclampsia, and evaluate associated covariates. METHODOLOGY: This study was an observational, cross-sectional, study conducted at the Lagos University Teaching Hospital and the Lagos State Island Maternity Hospital. A total of 400 pregnant women consisting of 200 pregnant women diagnosed with pre-eclampsia (study group) and 200 pregnant normotensive and apparently healthy women (control group) were recruited for the study. Demographic and clinical histories were obtained through questionnaires. The DNA Methylation status of the CpG Island in promoter region of the MTHFR gene was assessed using bisulphite conversion and methylation specific PCR method. The biochemical parameters measured in the study were: red cell folate, vitamin B12, plasma homocysteine (Hcy) and methylene tetrahydrofolate reductase enzyme level. RESULTS: Homozygous MTHFR CpG island hypomethylation pattern was significantly associated with pre-eclampsia (χ 2 = 22.96; p = 0.000), Mean values of plasma homocysteine in PE women with homozygous hypomethylation (26.1 ± 9.1 umol/L) were significantly higher than (20.1 ± 4.2 umol/L) observed in PE subjects with homozygous hypermethylation (p = 0.008). Homozygous CpG island hypomethylated pattern of the MTHFR promoter region, was associated with the lowest median MTHFR enzyme level (72.8 ± 39.8 pmol/L) compared with heterozygous methylated pattern (91.3 ± 60.9 pmol/L; p = 0.047) and homozygous methylated pattern (82.3 ± 31.0 pmol/L; 0.047). Red cell folate and Vitamin B12 levels were not significantly associated with CpG island methylation status. CONCLUSION: Epigenetic modification plays significant role in the pathogenesis of pre-eclampsia.

Prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer.

AIMS: This study was aimed at investigating the prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer (EOC) patients in Lagos, Nigeria. METHODS: This was a retrospective cohort study involving the review of the clinical record of 72 patients with histologically confirmed EOC who were managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. Information on the sociodemographic data and platelet counts at diagnosis of EOC were retrieved from the patients' medical records. Descriptive statistics were then computed for all baseline patients' characteristics. Survival analyses were carried out using the Kaplan-Meier estimates. Multivariate analysis of these data was performed with the Cox proportional hazards model. RESULTS: This study revealed that the prevalence of pretreatment thrombocytosis was 41.7% among the women with EOC. Fifty-three (73.6%) of the women had the advanced-stage disease (FIGO stage III-IV) while 52 (72.2%) had high-grade disease (II-III). The majority (66.7%) of the women had a serous histological type of EOC while 76.4% had documented recurrence. Pretreatment thrombocytosis was significantly associated with the women's parity (P = 0.009), serum carbohydrate antigen 125 levels (P = 0.018), median progression-free survival (PFS) (P < 0.001), 3-year median overall survival (OS) (P < 0.001), type of primary treatment (P = 0.002), extent of cytoreduction (P < 0.001), presence of ascites (P = 0.002), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.008), and histological type (P = 0.011). Pretreatment thrombocytosis was negatively associated with PFS (hazard ratio [HR] = 0.25; 95% CI 0.83, 0.75; P = 0.014) and 3-year OS (HR = 0.03; 95% CI 0.03, 0.27; P = 0.002). CONCLUSIONS: The study suggests that pretreatment thrombocytosis may be a useful predictor of survivals in EOC patients.

Prevalence of abnormal cervical smears among patients with HIV in Lagos, Nigeria.

BACKGROUND: There are over four million people living with HIV/AIDS in Nigeria. Cervical cancer is the most common genital cancer in Nigeria. There are many reports on the association of HIV with increased risk of cervical dysplasia. OBJECTIVE: To determine the prevalence of abormal cervical smears in Nigerian women who are HIV positive in Lagos. METHODS: Cervical smears were taken from 233 HIV positive women and 235 HIV negative women who attended the HIV clinic and the family planning clinic respectively of the Lagos University Teaching Hospital during the period January-April 2004. Proportions were compared with the X2 test. RESULTS: Data were complete for analysis in 227 of HIV positive and 228 of HIV negative women. Mean (SD) ages of HIV positive and HIV negative patients were respectively 35.2 (9.81) and 34.5 (7.37) years. Prevalence of squamous intraepithelial lesion (SIL) was higher in those who were HIV positive than in those who were HIV negative, 10.9% vs 4.3% (X2, 7.04; p=0.00798). Prevalence of high grade SIL was higher in HIV positive than HIV negative subjects, 7.9% vs 2.6% (X2, 6.38; p=0.0115). There was no significant difference in the prevalence of inflammatory smears, 15.7% in HIV positive vs 16.2% in HIV negative. CONCLUSION: Prevalence of cervical dysplasia is high in women who harbour HIV.

Low cost methods for secondary prevention of cervical cancer in developing countries.

BACKGROUND: Cervical cancer is both a preventable and a curable disease- preventable because the pre-invasive stage can be detected by screening and curable because the very early stage can be cured. It is the commonest genital cancer among females in Nigeria. The incidence and mortality from this disease in developing countries is very high. This is due to the unavailability of organised screening programmes. To address this problem, effective and practical alternatives to cytology are being investigated in many studies. OBJECTIVE: To examine the strengths and limitations of new methods currently undergoing evaluation for secondary prevention of cervical cancer in developing countries. MATERIAL AND METHODS: We conducted a computerised literature search for published articles. Mesh phrases used for the search were cervical cancer screening, cervical cancer screening in developing countries, cervical cancer screening- new techniques. Hand searches of journals and the proceedings of major conferences were also done. RESULTS: The visual tests for screening for cervical cancer was found to be highly sensitive and can be performed by not only physician but also other trained health care providers. The "single visit approach" to prevention of cervical cancer also referred to as "see and treat" has been tried in some countries in Asia and Africa and found to be effective and acceptable to women and their partners. CONCLUSION: Several studies conducted in many developing countries have shown that low cost methods for cervical cancer prevention do have a place in reducing the incidence of this deadly disease.

Cervical cancer screening practices among general practitioners in Lagos Nigeria.

Cervical cancer is the most common genital cancer in women in Nigeria. We studied the cervical cancer screening practices of 503 general practitioners in two urban and two rural areas of Lagos state. Only 60 (11.9%) ever informed their patients about cervical cancer screening and female doctors did this more often than their male counterparts (chi(2) = 4.74, p = 0.001). A total of 89 (17.8%) had facilities for Pap smears but only 27(5.4%) screened their patients. A total of 6 out of 27 (22.2%) did routine screening and 21 (77.8%) did selective screening. Only 6 out of 503 (1.2%) therefore did routine screening. Some 126 (25.0%) and 109 (21.7%) would do Pap smears for patients with post-coital bleeding and post-menopausal bleeding. Screening services were more available in the urban than in the rural areas (p = 0.0000). Thus, cervical cancer screening practices and services in Lagos are inadequate, which is no different from other parts of Nigeria and sub-Saharan Africa. Cervical cancer should be accorded the same attention as HIV, malaria, TB and childhood immunisations.

Sociodemographic factors in anaemia in pregnancy at booking in Lagos, Nigeria.

Anaemia in pregnancy is a common problem in many developing countries. In Nigeria, it is responsible for 11.0% of maternal deaths. This study examined the sociodemographic factors associated with anaemia in pregnancy. Anaemia was defined as a haemoglobin (Hb) level <11 g/dl. Proportions were compared using the chi2 test. A total of 35.3% of the 374 women studied were anaemic. Anaemia was more common in primigravidae than in parous women of parity 2 - 4 (chi2 = 6.87; p = 0.0087). Low socioeconomic status, (chi2 = 24.67, p = 0.00090), short interval between pregnancies (chi2 = 20.34, p = 0.000144), booking in the third trimester (chi2 = 15.4, p = 0.00045) and recent febrile illness (chi2 = 6.80; p = 0.0091) were associated with anaemia. Women who only used haematenics were more anaemic than those who also used anti-malarial chemo-prophylaxis (chi2 = 57.32, p = 0.00001). Anaemia in pregnancy is associated with several social and demographic factors. To reduce the prevalence of anaemia women need to have a good formal education, be economically empowered and good antenatal care must be made available, accessible and affordable to all women.

Spontaneous heterotropic pregnancy in sickle cell disease with survival of the abdominal pregnancy.

A case is presented of a spontaneously conceived heterotopic pregnancy in a 38-year-old Haemoglobin SS woman, with intrauterine foetal demise and survival of the extra-uterine pregnancy, which was an abdominal pregnancy. The diagnosis was not made until delivery. This report should create the awareness of the possibility of abdominal or heterotopic pregnancy in spontaneous cycles, particularly in patients with recurrent severe anaemia in pregnancy, whether or not they have haemoglobinopathies.

Late presentation of patients with cervical cancer to a tertiary hospital in Lagos: what is responsible?

OBJECTIVES: To determine the factors contributing to late presentation of patients with cervical cancer to a tertiary hospital in Lagos. METHODS: Cervical cancer patients who attended the hospital between September 2000 and December 2001 were interviewed to determine the healthcare facilities visited at the onset of symptoms and time interval between presentation and referral. RESULTS: There were 127 patients with a mean age of 54.6 +/- 13.4 years. Common symptoms at onset of disease were post-menopausal bleeding (55.9%) and vaginal discharge (48.8%). Of the patients, 60.7.1% first went to private hospitals. The interval between onset of symptoms and seeking healthcare was 6.10 +/- 9.31 months; time elapsing between seeking healthcare and referral to a tertiary hospital was 9.35 +/- 12.9 months. Stage 3A cervical cancer was diagnosed in 71.8%. CONCLUSION: Patients' delay in seeking healthcare and care providers' delay in referring patients to a tertiary hospital contributed to the late presentation.

Uses and misuse of blood transfusion in obstetrics in Lagos, Nigeria.

UNLABELLED: The objectives of this study were to identify obstetric and medical conditions in transfused patients, appraise the justification for the transfusion and recommend measures for reducing transfusion in obstetrics in Nigeria. Available case records of obstetric patients transfused at the Lagos University Teaching Hospital between the period 1st November 1995 and 31 October 1998 were reviewed retrospectively. Data collected included booking status, mode of delivery, amount of blood-transfused, post transfusion packed cell volume (PCV), and obstetric and medical conditions found in the patients. There were 4,159 cases out of which 503 were transfused. The overall transfusion rate was 12.1%, in booked and unbooked patients, it was 6.6% and 45.8% respectively. Only 231 cases were available for full analysis, mean age was 28.9 +/- 5.2 years (range 16-43 years). Sixty-three (27.3%) had unit-transfusions. Mean post transfusion PCV was 28.4% +/- 4.3% (range 17%-43%). In 63 (27.3%), the post transfusion PCV was above 30%. Some of the obstetric and medical conditions in the transfused patients were caesarean section (68.8%), previous caesarean section (20.4%), antepartum haemorrhage (16.9%), pregnancy induced hypertension (15.6%), anaemia and malaria (14.0%), induction of labour (13.0%), ruptured uterus (8.8%), and sickle cell anaemia (5.2%). Multi-unit transfusions were found in ruptured uterus (5.8 units), sickle cell anaemia (4.9 units), vaginal and cervical lacerations (4.0 units), forceps delivery (3.9 units) and malaria and anaemia (2.9 units). CONCLUSION: The study shows a high transfusion rate; an appreciable number were unnecessary transfusions. A number of the obstetric and medical factors for blood transfusion were avoidable. A reduction in blood transfusion rate can be achieved by the provision of adequate, available and affordable maternal health services in Nigeria.

Pregnancy outcome in HbSS-sickle cell disease in Lagos, Nigeria.

A retrospective study of pregnancy outcome in 60 HbSS sickle cell disease patients, exclusively managed in accordance with standard management modality, as obtained in the obstetric Unit of the Lagos University Teaching Hospital (LUTH), was carried out over a 3-year period (1995-1997). The study shows an increase in the number HbSS patients seeking antenatal care in the LUTH. Although the patients maintained a stable haematological profile, all through pregnancy and delivery, as reflected by the booking, pre-delivery and post-delivery PCV of 23.2 +/- SD 4.6% and 23.6 +/- SD 4.5% respectively; pregnancy was complicated in 96.6% of cases (n = 58). Sickle cell crises of bone pain (41.4%), acute haemolysis with anaemia (34.4%); malaria (22.4%) and other systemic infections (22.4%) were the major causes of pregnancy complications. Antenatal and postpartum blood transfusion rates were 45.0% and 81.6% respectively. The perinatal and maternal mortality rates were 121 and 67/1000 respectively, while caesarean section rate was 43.2%. It is observed that while more patients with HbSS sickle cell disease are seeking antenatal care in the LUTH, with improved prognosis, pregnancy complications from sickle cell crisis, remain a major problem in the care of these patients.

Episiotomies in Nigeria--should their use be restricted?

Episiotomy continues to be a frequently used procedure in obstetrics despite little scientific support for its routine use. The incidence of episiotomy and perineal tears and also the indications for episiotomy were therefore investigated in 1007 singleton deliveries between January 1, 1997 and December 31, 1997 at the Lagos University Teaching Hospital. The incidence of episiotomy was 54.9% of all deliveries. Episiotomy was more frequently performed in primipara (90.4%). Perineal tears occurred in only 18.8% of all deliveries, with majority in the multipara (93.6%). Most of the team were of first degree (98.4%). No third degree tear was recorded. The commonest indication for episiotomy was that of protecting the perineum from possible tears (80.7%). All the episiotomies were mediolateral. Episiotomy rate was higher among deliveries conducted by doctors. Performance of episiotomy had a positive correlation with increasing foetal weight. No major complication or maternal death attributable to episiotomy was recorded. The results of our study suggest that the use of episiotomy can be restricted to specified indications like instrumental and big babies delivery. It is also useful for the prevention of maternal morbidity through perineal laceration. Randomized control trials will however be necessary to clarify the controversies relating to restrictive episiotomy.

Prevalence of trichomonas vaginalis in patients with vaginal discharge in Lagos, Nigeria.

Trichomonas vaginalis is the most prevalent, non-viral sexually transmitted infection worldwide and probably the most commonly treatable in Africa and worldwide. The purpose of this study was to determine the prevalence of T. vaginalis among women with vaginal discharge attending a gynaecologic clinic in Lagos and to identify the common characteristics of the vaginal discharge in T Vaginalis. High vaginal swabs were taken from consenting adults with vaginal discharge. The quantity, colour and odour of the discharge were noted. Amine (10% KOH) test and pH were determined. Wet-mount microscopy Giemsa staining and culture in Oxoid (R) Trichomonas Medium were performed on each swab. A total of 200 patients were examined. One hundred and forty-nine (74.5%) had T. vaginalis. There was no statistically significant association between age, marital status, parity, number of sexual partners and prevalence of T vaginalis. The colour of the discharge was white in 104 (69.8%), yellow in 30 (20.1), clear in 15 (10.1%). None was frothy or greenish. The discharge was heavy in 50 (33.6%) and malodorous in 51 (34.2%). The pH range was 4-7 and 42 (28.2%) normal pH of4. In 47 (31.5%) the amine test was negative. The prevalence of T vaginalis among women with vaginal discharge is high. Women complaining of vaginal discharge should be thoroughly screened for T. vaginalis using all available methods.

Asymptomatic malaria parasitaemia in pregnant women at booking in a primary health care facility in a periurban community in Lagos, Nigeria.

Malaria can cause severe disease in pregnancy. We determined asymptomatic parasitaemia in 477 consenting consecutive women during their booking visits to a primary health care facility in a peri-urban area in Lagos State. There were 129 primigravidae and 348 multigravidae, with mean ages of 19.8 +/- 2.4 years (range 16-26 years) and 25.7 +/- 3.7 years (range 19-41 years), respectively. Most of the patients, 77.5% of primigravidae and 73.6% of multigravidae booked in the second trimester. Many (79.1%) of the primigravidae and 81.9% of the multigravidae had not taken any form of antimalaria chemoprophylaxis at the time of booking. Parasitaemia was significantly higher in the primigravidae than in the multigravidae 44.2% vs 33.6% (chi2 = 3.89, P < 0.05). In both primigravidae and multigravidae parasitaemia was highest in the second trimester compared with the two other trimesters (chi2 = 7.92, P < 0.02 and chi2 = 8.54, P < 0.01, respectively). There was no significant difference in parasitaemia among those who had anti-malaria chemoprophylaxis prior to booking and those who did not (P > 0.05). Prevalence of anaemia (PCV < 33%) was high, 73.6% in primigravidae and 69.8% in multigravidae, severe anaemia (PCV < 21%) however, was significantly associated with parasitaemia in the primigravidae (chi2 = 115, P < 0.001). Asymptomatic malaria parasitaemia at booking is high, hence we recommend parasites clearance in all patients at booking.