Implanon contraceptive implants: effects on carbohydrate metabolism.

The objective of the study was to assess the possible differences in effects of Implanon and Norplant implants on carbohydrate metabolism. This is a 2-year open randomized study of 80 implant (Implanon and Norplant) acceptors. Oral glucose tolerance test (OGTT) was performed before implant insertion and at 6, 12, and 24 months after implant insertion. Glycosylated hemoglobin A(1)C was measured in fasting samples and plasma samples during OGTT were tested for glucose and insulin levels. There was a significant increase in the area under the curve for both glucose and insulin during OGTT within each group with increasing duration of use. However, there was no significant change in the fasting plasma glucose values. There was no significant difference in the carbohydrate parameters between the two groups during implant use, except for a minimal but statistically significant rise in fasting glycosylated hemoglobin A(1)C levels at 24 months in the Implanon group. Both implants appear to induce mild insulin resistance but no significant change in serum glucose levels. These alterations in carbohydrate metabolism should have no clinical significance in healthy women.

Effect of Implanon use on selected parameters of thyroid and adrenal function.

In this article, the effects of Implanon implant use on thyroid and adrenal function was compared with those of Norplant implants. In this 2-year open randomized study of 80 implant acceptors, we found that both implants may induce minimal changes in thyroid hormones and cortisol levels, possibly secondary to alterations in the respective binding globulins in the serum. These alterations in thyroid and adrenal function would have no clinical significance in healthy women. In the Norplant group, sex hormone-binding globulin levels decreased, whereas increased levels were found in the Implanon users at the end of 2 years. These findings lend support to the fact that etonogestrel, released from Implanon implants, is significantly less androgenic than levonorgestrel, released from the Norplant implants.

A prospective study on the effects of reformulated 2-rod Norplant implant on haemostasis after five years of use.

OBJECTIVE: To evaluate the long-term effects of the new reformulated 2-rod Norplant implant on haemostasis in a prospective group of subjects who have completed 5 years of use. METHODS: Data from 11 women who have completed 5 years' use of the new reformulated 2-rod subdermal implant from the original 16 women who were recruited and randomized to receive this new improved implant in a comparative study were analysed. Clinical assessment and serial blood sampling were done prior to insertion of implant and after 1, 3, 12, 18, 24, 36, 48 and 60 months of implant use. Each subject served as its own control and Analysis of Variance with Student-Newman-Kuels test was used for statistical analysis. The following parameters were determined: plasminogen activators (t-PA, u-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, beta-thromboglobulin (beta-TG), thrombin-antithrombin (TAT)-complex, fibrinogen, Factor VII, platelets, haematocrit and haemoglobin levels. RESULTS: No significant change was observed for t-PA levels in prolonged implant use. u-PA antigen showed a significant decrease whilst D-dimer were significantly elevated at only 24 months of implant use compared to pre-implant level. PAI-1 levels were not significantly changed but fibrinogen and FVII levels increased at 36 months and 42 months of use with enhanced platelet activation shown by beta-TG levels at 24 months. Platelet numbers were not affected by prolonged implant use. Haemoglobin concentration and haematocrit level showed significant fluctuations and then return to pre-implant level by 54 and 60 months. CONCLUSION: Enhanced fibrinolysis with platelet activation at 24 months of implant use were seen during the 60 months of 2-rod reformulated Norplant implant use. Hypercoagulable state was not observed although fibrinogen and FVII levels remain above the pre-implant levels as coagulation activation was not enhanced. The increased haemoglobin and haematocrit levels seen indicate enhanced bone marrow activity. There was no association between the use of reformulated 2-rod Norplant implant over 60 months of use and prothrombotic state.

Effects on hemostasis after two-year use of low dose combined oral contraceptives with gestodene or levonorgestrel.

We studied 67 healthy women who were randomly allocated to receive third generation gestodene (Gynera) or second generation levonorgestrel (Microgynon 30) combination of low-dose estrogen oral contraceptives (OCs) for their hemostatic effects over 2 years. Hemostatic changes were apparent within 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb) concentration decreased by 18 months. Shortened prothrombin time (PT) and activated plasma thromboplastin time (APTT) were associated with elevated fibrinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the 18 months of use. Enhanced thrombin-antithrombin (TAT)-complex level was seen at 18 months of Gynera use. Prothrombin fragment1+2 (F1+2) rise was seen at 3 months with Micro 30. Reduced antithrombin III (ATIII) activity was seen at 18 months with Gynera and at 24 months with Micro 30. Increased protein C activity was seen at 3 months and reduced protein S occurred at 18 months of Gynera use. Tissue plasminogen activator (t-PA) activity was enhanced for 6 months in both OCs with raised D-dimer levels for 12 months with Gynera and 6 months with Micro 30. Decreased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enhanced u-PA activity was only seen in Gynera users. Elevated plasminogen levels were apparent throughout both OCs use. PAI-1 levels were significantly decreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at 18 months and PAI-1 antigen at 12 months. No change in platelets and von Willebrand factor (vWF) were seen in long-term OC use except that beta-thromboglobulin (beta-TG) showed decreased trends reaching statistical significance by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A further significant decrease in beta-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage compared with pretreatment levels. Activated protein C resistance (APCR) was negative in all subjects before and during OC use. The study indicated dynamic balance between coagulation and fibrinolysis with no endothelial activation. However, because some hemostatic markers showed wide fluctuations during OC use, a longer term study is warranted to investigate any adverse hemostatic changes that might enhance the risks of venous thromboembolism in Asian subjects known to be less prone to thrombosis.

Symptomatic gastro-oesophageal reflux in pregnancy: a prospective study among Singaporean women.

The present study was undertaken to estimate the prevalence and time course of reflux-type symptoms in Singaporean women and to determine if these symptoms were associated with nausea and vomiting of pregnancy. Consecutive pregnant women in the first trimester of pregnancy were recruited during attendance at an antenatal clinic in a Singapore teaching hospital. Each was interviewed, using a reliable questionnaire detailing demographic characteristics and symptoms, at four time points during the first, second and third trimesters of pregnancy and postpartum period. A total of 35 of 47 women originally enrolled (response rate 74%) completed the study. Heartburn alone, acid regurgitation alone and both heartburn and acid regurgitation were reported by 5.7, 17.1 and 17.1% of the subjects, respectively. Subjects who had these symptoms were more likely to suffer daily nausea and/or vomiting (78.6%) than those who did not (33.3%, P<0.05). In the majority of subjects, heartburn and/or acid regurgitation began in the first trimester (78.6%) and disappeared during the second trimester (71.4%). Nausea alone and in combination with vomiting similarly came on in the first trimester (100%) and subsided by the second trimester (85.7%) in the majority of the subjects studied. The reported prevalence of heartburn and/or acid regurgitation among Western pregnant women were 48-96% and 62%, respectively. Our data, therefore, showed that reflux-type symptoms were less common in Singaporean pregnant women. Reflux-type symptoms were related to nausea and vomiting, both in frequency and time pattern of onset and disappearance of symptoms. The association suggested either a common mechanism or a cause and effect relationship.

Antiphospholipids and pregnancy--a review.

The presence of antiphospholipid antibodies is associated with a clinical syndrome characterised by thrombocytopenia, recurrent arterial and venous thromboses and recurrent fetal loss. The etiology is unknown but leads to an abnormal autoimmune response. Platelet aggregation and thrombosis follow. The mainstay of treatment is low dose aspirin, heparin and corticosteroids.

Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants.

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

The effects of reformulated 2-rod Norplant implant on hemostasis after three years.

Prolonged use of reformulated and the original 2-rod Norplant implants showed similar changes in most hemostatic parameters studied. Raised hemoglobin concentration and hematocrit values with not enhanced platelet activation or significant changes in platelet numbers were seen. Factor VII showed an increase from 18 months compared to the first 12 months of original Norplant implant use, while with reformulated Norplant implant, the level at 36 months was significantly higher than the first 24 months of implant use. Fibrinogen levels were significantly elevated by 36 months of both implant use. No evidence of enhanced activation of coagulation, fibrinolysis/inhibitor were observed during prolonged implant use. Overall, no significant changes in tissue plasminogen activator (t-PA) levels were observed but urokinase-like plasminogen activator (u-PA) levels were significantly reduced, indicating no enhancement of tissue breakdown. Plasminogen activation inhibitor (PAI-1) antigen levels were significantly reduced from 12 to 36 months with original Norplant implant use compared to the pre-insertion levels, while a nonsignificant decreased trend was seen with prolonged reformulated Norplant implant use. The increased levels of fibrinogen and FVII at the end of 36 months of implant use require further observation as these factors are known markers of hypercoagulation and associated with increased arteriosclerotic and cardiovascular risks. This study is on-going to evaluate the effects of levonorgestrel-containing subdermal reformulated Norplant implants on hemostasis after five years of use.

PIP: Researchers compared data on women using the 2-rod Norplant implant system formulated with the Silastic elastomer 4092 (original system) with those using the 2-rod Norplant made with a different elastomer (Q74910) (reformulated system) to examine their hemostatic effects during 36 months of use. All 33 women lived in Singapore. Both systems released the same amount of levonorgestrel at the same rate. In most hemostatic parameters, prolonged use of both 2-rod Norplant implant systems effected similar changes: increased hemoglobin concentration and hematocrit values, increased fibrinogen levels, no increased platelet activation, no increased activation of coagulation or fibrinolysis/inhibitor, no significant changes in platelet numbers, no significant changes in tissue plasminogen activator, and decreased urokinase-like plasminogen activator. Factor VII was higher after 18 months than it was during the first 12 months in original Norplant users (p 0.001). The factor VII level at 36 months during reformulated Norplant use was significantly higher than it was during the first 24 months of use (p 0.001). None of the changes common to both systems suggested tissue breakdown. Plasminogen activator inhibitor antigen levels were significantly lower during 12-36 months than preinsertion levels in original Norplant users, while they fell insignificantly in reformulated Norplant users. The increased levels of fibrinogen and factor VII at 36 months are areas of concern since they are markers of hypercoagulation and are linked to increased arteriosclerotic and cardiovascular risks. Researchers of this on-going study will later publish the two systems' effects on hemostasis after 5 years of use.

Menstrual bleeding patterns in Norplant-2 implant users.

The objective of the present study was to analyze the patterns of menstrual bleeding in Singaporean women using Norplant-2 contraceptive implants over a five-year period. Of the 100 women recruited for the study, 62 were still using the implant at the end of five years. Only 9 women discontinued for menstrual reasons and they did so within the first 21 months of implant use. Although a normal menstrual bleeding pattern was uncommon during the first three months of use, 69.4% had normal menstruation at the end of five years. Irregular bleeding was the most common form of menstrual abnormality throughout the study period. Infrequent periods and amenorrhoea were distinctly uncommon, especially after the first two years of use. The pattern of bleeding with Norplant-2 was not significantly different from that previously observed with Norplant.

PIP: To investigate the menstrual bleeding patterns among long-term users of Norplant-2 implants, 100 Singaporean women were followed for 5 years. All participants had delivered at least one child prior to implant insertion and had a history of regular menstrual periods. Monthly menstrual diaries indicating days of bleeding or spotting were collapsed into successive 90-day reference periods and analyzed for evidence of amenorrhea, prolonged bleeding (10 days or more), frequent bleeding (over four bleeding/spotting episodes per month), infrequent bleeding (less than two episodes), and irregular bleeding (bleeding-free interval exceeding 17 days). At the end of the 5-year study period, 62 women still had their implants, 9 had discontinued within 21 months after insertion for menstruation-related reasons, while 24 requested removal to achieve pregnancy. There were no pregnancies during Norplant use. Although only 9% of users experienced normal menstrual bleeding in the first three months of use, this statistic increased to 32.6%, 43.6%, 37.8%, 52.3%, and 69.4% after 1, 2, 3, 4, and 5 years of use, respectively. The most common menstrual irregularities were irregular bleeding and prolonged bleeding. Although more women had regular cycles with time, there was only minimal improvement in intraindividual variability in those who continued to have irregular bleeding. Overall, the bleeding disturbances recorded by Norplant-2 acceptors did not differ substantially from those found among users of the original Norplant delivery system.

Levels of lupus autoantibodies in pregnant SLE patients: correlations with disease activity and pregnancy outcome.

OBJECTIVE: To follow the levels of lupus autoantibodies throughout pregnancy in a large cohort of pregnant SLE patients, and to examine whether they correlate with disease activity and pregnancy outcome. METHODS: 54 pregnancies in 46 SLE patients, and 70 control pregnant women were followed in the study. All patients were receiving steroid treatment. Titers of antibodies to ssDNA, dsDNA, histones, cardiolipin (CL) and phosphatidylserine (PS) were determined at the first, second, and third trimester and post-partum by ELISA. RESULTS: Overall the average levels of autoantibodies in all the patients were within the normal range, except for the average levels of anti-dsDNA antibodies which were elevated during the second trimester. Eight women (14.5%) had active disease during pregnancy, and there was a significant correlation between the levels of anti-dsDNA and the risk of disease activity (p = 0.0225). There were 7 fetal losses. There was a tendency for correlation between elevated anti-dsDNA levels, and anti-CL levels and the risk of fetal loss; however, this did not reach statistical significance (p = 0.0685, and 0.0881, respectively). There was a significant correlation between the levels of anti-dsDNA antibodies and the risk of preterm delivery (p = 0.0331). CONCLUSIONS: Pregnancy in SLE patients is associated with significant complications to both the mother and the fetus. Anti-dsDNA levels seem to correlate with the risk of disease exacerbation, and prematurity. Elevated levels of anti-dsDNA and anti-CL may suggest an increased risk of fetal loss.

Maternal congenital heart disease and pregnancy outcome.

OBJECTIVE: To study the obstetrics and neonatal outcome of women with congenital heart disease. METHOD: This is a retrospective study of 85 women with congenital cardiac disease. Data collected include maternal characteristics, New York Heart Association Class, cardiac complications and obstetric and neonatal outcome. RESULTS: The maternal and neonatal outcomes were excellent with no maternal and perinatal mortality. The main cardiac lesions were mitral valve prolapse (60.8%), atrial septal defect (8.6%), ventricle septal defect (6.5%) and aortic regurgitation (4.3%) and 2.1% each of tricuspid regurgitation, pulmonary regurgitation, Ebstein's anomaly, coarctation of aorta, patent ductus arteriosus, and Eisenmenger's syndrome. Six deliveries were associated with New York Heart Association deterioration. Compared to the general obstetric population, more women in the study group were primigravida, had pregnancy induced hypertension, underwent instrumental vaginal deliveries and caesarean sections and had more babies with lower birth weights. CONCLUSION: Despite potential difficulties and complications associated with congenital heart disease, careful cardiac and obstetric management in a tertiary referal centre resulted in good maternal and fetal outcomes.

Ethnicity and obstetric performance in Singapore.

The influence of ethnicity on obstetric performance in Singapore was assessed by retrospective analysis of all deliveries in the National University Hospital over a 7-year period. Malay mothers were younger, shorter, less educated, of higher parity, were more likely to have had no antenatal care, and had the highest incidence of premature labour. However, mothers of Indian origin had the smallest babies, the highest incidence of low birth weight and significantly higher perinatal mortality rates. Chinese mothers fared better than their Malay and Indian counterparts in all parameters assessed. The ethnic origin of the mother has an important bearing on perinatal performance. This emphasises the importance of designing appropriate strategies to improve perinatal health in the different ethnic groups.

Pregnancy outcome and mitral valve prolapse.

Mitral valve prolapse (MVP) comprises a large proportion of obstetric cardiac problems and has a general prevalence of 4%. We examined the obstetric outcome of patients with MVP delivered between 1988-1991 at the National University Hospital, Singapore. During this interval, deliveries totalled 16,755 of which 85 (0.51%) had maternal cardiac disease. Of these, 28 (32.9%) had echocardiographic evidence of non-myxomatous MVP. Ten patients (37.5%) had demonstrable mitral regurgitation and 4 (14.3%) had benign ventricular ectopics. All patients remained well throughout pregnancy. Gestation at delivery and use of analgesia did not differ significantly from non-cardiac patients. However, the labour induction rate was twice the department average at 17.9%. Twenty-four (85.7%) patients achieved vaginal delivery and 4 (14.3%) patients were delivered abdominally. All babies were liveborn. Eight patients (28.6%) did not receive antibiotic prophylaxis during labour and postpartum period and remained afebrile. The role of antibiotics in this category of patients is discussed. Patients with MVP without myxomatous valve changes may expect excellent pregnancy outcome.

Influence of circulating D-dimer levels on assays of fibrinogen.

The influence of circulating D-dimer levels on two different assays for fibrinogen was studied in 31 normal female subjects, 18 late pregnant subjects, 8 male subjects with acute myocardial infarction (AMI) and 9 subjects with unstable angina (UA). Both functional and chemical methods for fibrinogen showed significant correlation (r = 0.8171; P < 0.001). However, values for fibrinogen were significantly lower using the functional method in normal females, AMI and UA patients with mean (SD) ratios of 0.88 (0.11), 0.78 (0.17) and 0.84 (0.09) respectively as compared to the chemical assay method. In late pregnancy this was not observed with a mean ratio of 1.09 (0.22) obtained between the two methods. The D-dimer level in normal subjects was mean 194 (95.3) ng/ml whilst in late pregnancy, in AMI and UA, the levels were significantly elevated at 1093 (1034), 382 (216) and 1056 (708) ng/ml respectively. Significant correlation between fibrinogen and D-dimer levels was observed only in AMI and UA patients but not in late pregnancy. In 3 patients with AMI undergoing thrombolysis, no functional fibrinogen was detectable for the first 12 h following intravenous streptokinase (SK) despite the presence of chemically detectable fibrinogen with values of 13% to 30% of pre-treatment levels and evidenced by lytic states evaluated by thromboelastography (TEG). Grossly elevated D-dimer levels of between 25 x 10(3) and over 100 x 10(3) ng/ml were present during this time. Functional fibrinogen was detectable by 24 h following SK therapy but its level in relation to fibrinogen detected chemically remained depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Obstetrical outcome with increasing maternal age.

A retrospective study of 21,442 Singaporean women who gave birth at the National University Hospital, Singapore, between January 1986 and November 1991 is used to assess the effects of increasing age on obstetric performance. The results show that reproduction after the age of 35 years in Singapore is associated with a higher incidence of antenatal complications such as hypertension and diabetes and a higher rate of obstetric intervention. However, given the current level of obstetric and neonatal care in Singapore, these adverse features do not prejudice the obstetric and neonatal outcomes.

PIP: Physicians compared data on 2410 women, 35 years old and older, with 19,032 women younger than 35 years old, all of whom delivered at the National University Hospital in Singapore between January, 1986, and November, 1991, to examine the effects of advanced maternal age on pregnancy outcome. Older women were more likely to suffer from pregnancy-induced hypertension and diabetes mellitus than the younger women (odds ratio [OR] = 2.32 and 2.92 for primiparity; OR = 2.17 and 2.22 for multiparity, respectively; p .05 for all but diabetes among primiparae). Breech delivery occurred more frequently among the older mothers than younger, but it was significant only for primiparae (OR = 1.46; p .05). Intervention during delivery was more common among older mothers than younger mothers and among primiparae than multiparae. On the other hand, perinatal outcomes of neonatal death and stillbirths were essentially the same for primiparae and multiparae (OR = 0.76 and 0.78; respectively). When the researchers controlled for race and parity, the odds of pregnancy-induced hypertension and diabetes increased for every 5-year increase in age (OR = 1.46 and 1.81, respectively). The same was true for induced labor (OR = 1.22), elective cesarean section (OR = 1.96), and instrumental delivery (OR = 1.48). The odds did not increase, however, for premature birth and low birth weight. Since Singapore has quality obstetric and neonatal care facilities, and the older mothers tend to be of a higher socioeconomic class than younger mothers, the increased risk of pregnancy complications does not adversely affect obstetric outcome.

Interrelationships of serum paraoxonase, serum lipids and apolipoproteins in normal pregnancy. A longitudinal study.

Serum paraoxonase (EC 3.1.1.2) may be implicated in the lipid metabolism. In order to substantiate this view we conducted a longitudinal study of interrelationships of serum paraxonase, lipids and apolipoproteins during pregnancy. Fasting serum levels of paraoxonase, serum lipids (total, HDL and LDL cholesterols, triglycerides) and apolipoproteins (AI, AII and B) were estimated in 91 pregnant women at 28 and 32 weeks of gestation and 6 weeks after delivery, and 40 nonpregnant women. Serum paraoxonase, total HDL and LDL cholesterol levels were significantly higher during pregnancy along with corresponding apolipoprotein (p < 0.001). The most striking increase was seen in serum triglycerides and paraoxonase levels (p < 0.001). Serum paraoxonase levels had a significant correlation with triglycerides (r: 0.45-0.60) and Apo-AII (r: 0.32-0.41) in both pregnant and nonpregnant states (p < 0.001). Moreover, both serum paraoxonase and triglyceride levels at 28 weeks of pregnancy were negatively correlated with birth weight (r: 0.3, p < 0.05), suggesting a possible role of paraoxonase in energy delivery for fetal development derived from maternal hypertriglyceridemia.

Premature childbirth: social and behavioural risks in Singapore.

The associations of social and behavioural factors on preterm birth in Singapore were studied using hospital maternity records of 20,723 consecutive singleton births between January 1986 and November 1991. The overall proportion of preterm births was 3.6%, the rates for the Chinese, Malay and Indian groups being 3.2%, 3.8% and 4.9% respectively. Teenage mothers were at a higher risk of preterm labour compared to women aged 20-29 years. The incidence of preterm labour decreased with increasing educational status. Preterm births were six times more likely in women who had no antenatal care. Women who had three or more previous births were at a higher risk, while those who had one or two previous births were at a lower risk compared to women who had none.

PIP: Maternity records for 19,772 singleton births from National University Hospital in Singapore between January 1986 and November 1991, provided data for chi=square analysis of the relationship between gestational age and sociodemographic factors. Multiple logistic regressions were generated to assess the joint effect of social and behavioral factors. The dependent variable was preterm or term labor. Preterm infants weighing less than 2500 gm constituted 3.6% of all births.

Evaluation of liver function and lipid metabolism following Norplant-2 rods removal.

The effect of Norplant-2 rods on liver function and lipid metabolism was evaluated in 100 Singaporean women. As with the Norplant six-capsule, the only change noted in liver function was that of a significantly elevated bilirubin, which was within the normal clinical range for the local population. As regards lipid metabolism, the mean values for total triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol seen at the end of five years of Norplant-2 rod use and six months postremoval were similar to the preinsertion mean. As a result, the HDL-cholesterol/total-cholesterol-HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratio remained fairly constant. This indicates that the use of Norplant-2 rods does not directly contribute to cardiovascular risk.

Evaluation of hemostatic function following Norplant-2 rods removal.

Women using the Norplant-2 rod system in Singapore have been shown to have a change in their hemostatic function. There is a decrease in vitamin K dependent factors II, VII and a tendency toward lowered fibrinolytic activity after use of Norplant-2 rods. There was also an increase in platelet number and accelerated-platelet aggregation. These changes are similar to those seen with the Norplant six-capsule system and it would appear that both systems do not activate the coagulation system or enhance a state of hypercoagulation. On removal of the Norplant-2 rods at the end of 5 years, the significant changes seen in hemoglobin function observed with Norplant-2 rod use remained.

Tramadol in labour pain in primiparous patients. A prospective comparative clinical trial.

The analgesic efficacy and safety of tramadol 50 mg, 100 mg and pethidine 75 mg, administered intramuscularly were compared in a randomized, double-blind clinical trial in 90 pregnant women with labour pain. Pain relief was measured by a 4-point verbal rating scale 10, 20, 30, 45 and 60 min after the administration of study drugs. The average total pain relief score within the first hour was 0.9 with tramadol 50 mg, 1.7 with tramadol 100 mg and 1.7 with pethidine 75 mg. In comparison to both tramadol doses the administration of pethidine was associated with a significantly higher frequency of adverse events and a significantly lower respiratory rate in the neonates. The results indicate that tramadol 100 mg is as effective as pethidine 75 mg but has a superior safety profile.