Cord blood erythropoietin in the presence and absence of labor in normal infants

To evaluate erythropoietin (Ep) levels in normal labor and cesarean section we studied the cord serum of 111 term pregnancies, divided into three groups: (i) those born by normal vaginal delivery (n = 69); (ii) those delivered vaginally from mothers who were smokers (n = 20); and (iii) those delivered by elective cesarean section (n = 22). The three groups did not differ in maternal age, gestational age, birthweight, infant sex and Apgar scores. No correlation was found between Ep and hematocrit in all three groups of normal terms studied. Although not statistically significant the lower mean Ep value observed in cesarean section compared with the values obtained from normal deliveries could suggest that the process of labor may be a cause of these differences.     

Does passive smoking in early pregnancy increase the risk of small-for-gestational-age infants?

OBJECTIVES: This study tested the hypothesis that women who deliver small-for-gestational-age infants are more often exposed to passive smoking at home or at work. METHODS: Among a 1-year cohort of nulliparous women in the city of Malm?, Sweden 872 (87.7%) women completed a questionnaire during their first prenatal visit. The study was carried out among women whose pregnancies resulted in a singleton live birth (n = 826), 6.7% of infants were classified as small for their gestational age. RESULTS: Passive smoking in early pregnancy was shown to double a woman's risk of delivering a small-for-gestational-age infant, independent of potential confounding factors such as age, height, weight, nationality, educational level, and the mother's own active smoking (odds ratio [OR] = 2.7). A stratified analysis indicated interactional effects of maternal smoking and passive smoking on relative small-for-gestational-age risk. CONCLUSIONS: Based on an attributable risk estimate, a considerable reduction in the incidence of small-for-gestational-age births could be reached if pregnant women were not exposed to passive smoking.     

Maternal serum human chorionic gonadotropin as a marker for the delivery of low-birth-weight infants in women with unexplained elevations in maternal serum alpha-fetoprotein

We wished to ascertain whether the measurement of maternal serum human chorionic gonadotropin (MShCG) in the serum of pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) would more precisely define those women at risk of adverse pregnancy outcomes. MShCG was measured in samples of serum obtained from women in the second trimester of pregnancy who had elevated MSAFP, normal Level II ultrasounds, and normal fetal karyotypes. Based on the characteristics of a receiver-operator curve for MShCG and birth weight, patients were divided into two groups and pregnancy outcomes were compared. Pregnant women with an unexplained elevation in MSAFP, who also had an abnormal MShCG (< or = 0.5 MoM > or = 2.5) were at significantly greater risk of delivering a low-birth-weight infant compared to women with a normal MShCG (43% and 15%, respectively; P = 0.013). They were also more likely to deliver a preterm infant (48% and 11.9%), respectively; P = 0.001). In the prediction of low birth weight, an abnormal MShCG had a sensitivity of 50%, a specificity of 81%, and a positive predictive value of 43%; in the detection of preterm delivery the values were 59%, 88%, and 48%, respectively. These findings suggest that in pregnant women with a second trimester unexplained elevation in MSAFP, abnormal MShCG levels may identify a group of women at high risk of preterm delivery or delivery of a low-birth-weight infant.     

Etiology and outcome of acute renal failure in elderly patients

OBJECTIVE: To test the usefulness of the fetal transverse cerebellar diameter/abdominal circumference (TCD/AC) ratio in predicting known small-for-gestational-age (SGA) infants. METHOD: The relationship between fetal TCD and AC throughout the second half of pregnancy was investigated in 635 well-dated, normal pregnancies and examined with regard to gestational age and infant birth weight percentiles. RESULTS: One hundred eighteen (19%) fetuses were excluded due to inadequate visualization of the fetal cerebellum. A strong correlation was noted between gestational age determined by the last menstrual period and both fetal TCD (r2 = 0.91338) and AC (r2 = 0.89361) in fetuses with birth weights between the 10th and 90th percentiles (n = 407; mean 14.4, S.D. 1.2). Although the TCD/AC ratio showed a poor correlation with gestational age (r2 = 0.15788), a slight increase was noted during gestation. A TCD/AC ratio greater than 15.5 was present in 80% of SGA infants when measurements were performed within 1 week of delivery. CONCLUSION: Fetal TCD/AC ratio as a gestational age-independent method could improve diagnostic sensitivity and specificity in the early detection of fetal growth abnormalities.     

The maternal and fetal levels of human chorionic gonadotropin, human placental lactogen and prolactin during the perinatal period (author's transl)

The levels of human chorionic gonadotropin (HCG), human placental lactogen (human choriosomatomamotropin HCS) and prolactin (PRL) were determined in the serum of 72 maternity patients and the serum of the newborn infants. The determinations were done with radioimmunologic tests (RIA). These three protein hormones were also determined in the amniotic fluid and in the maternal serum from 4-6 days prior to the delivery of the infant. The concentration of HCG or HCS in the serum of the newborn infants was a mean 0.43 or 0.37% of the level in the maternal serum. The concentration of PRL in the serum of the newborn was 118% and slightly higher than in the serum of the mothers. The concentration in the amniotic fluid was 1.5% for HCG, 5.8% for HCS, and 252% for PRL, compared to the corresponding levels in the maternal serum. The fact that the hormone concentrations in the amniotic fluid are significantly higher than in the serum of the newborn suggests excretion of the hormones from the fetal circulation via the fetal liver and the fetal kidney. The high levels of PRL in the maternal and the newborn serum may be caused by the high concentrations of estrogen or progesterone. Increased during the course of the pregnancy there was a significant sex linked difference in the level of HCG in the maternal serum correlated to the sex of the newborn infant.     

Necrosis of myometrial choriocarcinoma with fulminating sepsis complicating chemotherapy for trophoblastic tumor

OBJECTIVE: In normal pregnancy and pregnancies complicated by preeclampsia it has been demonstrated that there is increased activation of platelets and the clotting and fibrinolytic system. We measured plasma levels of thrombopoietin, a major regulator of platelet production in these conditions. STUDY DESIGN: We compared the thrombopoietin plasma levels of healthy term pregnant patients (n = 21) with those of healthy nonpregnant controls (n = 17), as well as patients with severe preeclampsia (n = 8) and the hemolysis, elevated liver enzymes, low platelets syndrome (n = 6). RESULTS: Thrombopoietin levels in normal pregnant patients and pregnancies complicated by the hemolysis, elevated liver enzymes, low platelets syndrome were statistically significantly higher than thrombopoietin levels in nonpregnant controls. Data were analyzed with the Kruskal-Wallis one-way analysis of variance by ranks. CONCLUSIONS: This study is the first to report thrombopoietin levels in pregnancy. Thrombopoietin levels are significantly greater in pregnant patients and in pregnancies complicated by the hemolysis, elevated liver enzymes, low platelets syndrome compared with nonpregnant controls.     

Maternal serum alpha-fetoprotein and dimeric inhibin A detect aneuploidies other than Down syndrome

OBJECTIVE: Our purpose was to determine whether the combination of maternal serum alpha-fetoprotein, free human chorionic gonadotropin-beta, dimeric inhibin A, and maternal age detects aneuploidies other than Down syndrome. STUDY DESIGN: We retrieved stored serum from pregnancies complicated by aneuploidies other than Down syndrome from 1988 to 1997 (n = 55, mean maternal age 35.2 +/- 5.6 years). Alpha-fetoprotein levels were obtained from our database, and free human chorionic gonadotropin-beta and dimeric inhibin A levels were measured in the thawed serum with use of commercial assays. Analyte values were used in both 3-analyte and 2-analyte multiple-marker screening tests; detection rates were determined at several different Down syndrome risk-positive cutoff values. RESULTS: In the 3-analyte test 58% (32/55) of all aneuploidies were detected with use of both the Down syndrome protocol at a screen-positive risk cutoff value of 1:300 (false-positive rate 17%) and a novel trisomy 18 screening algorithm. However, 67% (37/55) detection was obtained with use of the 2-analyte combination of alpha-fetoprotein and dimeric inhibin A, with both the Down syndrome protocol (screen positive cutoff value 1:300) and the trisomy 18 algorithm: 12 of 13 trisomy 18 (92%), 9 of 17 Turner's syndrome (53%), 10 of 17 other sex chromosome aneuploidies (59%), 1 of 1 trisomy 22 (100%), and 5 of 7 trisomy 13 (71%). CONCLUSIONS: The combination of maternal serum alpha-fetoprotein, dimeric inhibin A, and maternal age detects autosomal trisomies other than Down syndrome at a rate superior to that of the traditional analyte combination.     

Suxamethonium apnoea terminated with commercial serumcholinesterase

The serum lipid values at different stages of pregnancy in twenty-six pregnany diabetic women attending a special antenatal clinic at the Department of Obstetrics and Gynecology, were compared with the corresponding values in four control series composed of non-diabetic pregnant women. Control series were studied at weeks 10, 22, 34 and after delivery, respectively. Serum triglycerides were higher in the diabetic women at week 10 (p less than 0.01), week 34 (p less than 0.05) and after delivery (p less than 0.05). Furthermore, in the diabetic women, infant birth weights were correlated (r=0.52, p=0.05) with maternal serum triglyceride values at week 31. Women with the highest serum triglyceride values (greater than 250 mg/100 ml) were delivered of infants with a higher birth weight (p less than 0.05) than those women with lower serum triglyceride values (less than 250 mg/100 ml). Intra-uterine deaths (n=4) were not related to maternal serum triglyceride values, but mean blood glucose values (during the whole pregnancy) were higher (p less than 0.001) in mothers with intra-uterine deaths. Elevated plasma free fatty acids (FFA) in the diabetic mother would be a possible cause for elevated serum triglycerides through increased liver triglyceride synthesis, while in the fetus an excess of plasma FFA (passing through the placental barrier) together with normal or elevated plasma insulin would be a likely explanation for increased triglyceride synthesis in adipose tissue and thereby of increased fat depots and body weight.     

Neuronal responses in monkey anterior putamen during operant bar-press behavior

OBJECTIVE: To determine whether computer assisted fetal heart rate analysis or the biophysical profile score can provide noninvasive prediction of fetal acidaemia. DESIGN: Cross sectional study. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital School of Medicine, London. SUBJECTS: Forty-one women with pregnancies complicated by diabetes mellitus. INTERVENTIONS: Fetal heart rate (FHR) monitoring with computer assisted analysis, biophysical profile score (BPS) and cordocentesis for measurement of umbilical venous blood glucose concentration and blood gases, up to 24 h before delivery at 27 to 39 weeks gestation. RESULTS: The mean umbilical venous blood pH was significantly lower than the normal mean for gestation, and was below the 5th centile in 18 pregnancies, including all six cases where the mother had nephropathy and hypertension. The mean pO2 was not significantly different from the normal mean for gestation. There were significant associations between fetal acidaemia and both the BPS (r = 0.46, P < 0.01) and FHR variation (r = 0.42, P < 0.01). However, of the 12 acidaemic fetuses of non-nephropathic mothers, nine had normal BPS and six had normal FHR variation. CONCLUSIONS: In pregnancies complicated by maternal diabetes mellitus, BPS and FHR variation are of limited value in the prediction of fetal blood pH.     

Selective termination and elective reduction in twin pregnancies: 10 years experience at a single centre

Selective termination is employed in multifetal pregnancies, in the presence of an abnormal fetus, in order to improve the prognosis of the normal fetuses. The term elective reduction is used to describe reduction in twin pregnancies for maternal medical conditions, psychological, or socioeconomic reasons. The purpose of this study was to evaluate the factors that influence outcome in such pregnancies. Eighty-two twin pregnancies underwent selective termination (n = 59) or elective reduction (n = 23) over a 10-year period. Early procedures, performed < or = 14 weeks (n = 31), had a pregnancy loss of 9.7% and a mean procedure-to-loss interval of 4.1 +/- 2.8 weeks; mean birthweight was 3299 +/- 395 g in survivors, with a mean gestational age at delivery of 38.4 +/- 2.3 weeks. In comparison, procedures performed > 14 weeks (n = 51) had a pregnancy loss of 7.8%, with a procedure-to-loss interval of 1.2 +/- 0.6 weeks. Mean birthweight was 2577 +/- 999 g, with a mean gestational age at delivery of 35.7 +/- 5 weeks. In conclusion, outcomes were more favourable among patients who underwent a first trimester procedure. The slight increase in pregnancy loss may be attributed to a higher than expected rate of spontaneous abortions in the first trimester, as manifested by the higher procedure-to-loss interval after a first trimester procedure. These facts underscore the importance of early detection of fetal abnormalities in twin pregnancies by ultrasonography and chorionic villus sampling.     

Plasma trace element (Se, Zn, Cu) concentrations in maternal and umbilical cord blood in Poland. Relation with birth weight, gestational age, and parity

Selenium (Se), copper (Cu), and zinc (Zn) concentrations were determined in plasma of 64 mothers at delivery, 58 nonpregnant women, 64 neonates, and 12 infants, aged 2-12 mo. Se and Zn concentrations in mothers at delivery were significantly lower, and Cu higher than in nonpregnant women. Mean Se and Cu concentrations in newborns were statistically lower than those in mothers at delivery, and Zn and Cu concentrations in preterm infants (n = 13) were significantly higher than in fullterm infants (n = 51). Maternal parity had no significant influence on the distribution of plasma trace element levels. No significant differences were observed in Se and Zn levels in maternal and cord blood plasma according to birth weight, contrary to maternal Cu concentration. Significant correlations were found between maternal and cord blood Se content, and between maternal plasma Cu concentration and birth weight of neonates.     

Growth hormone-binding protein in normal and pathologic gestation: correlations with maternal diabetes and fetal growth

To date, measurements of GH-binding protein (GHBP) during human pregnancy have been carried out using assays susceptible to interference by the elevated levels of human placental GH typical of late gestation. We recruited a large cohort of pregnant women (n = 140) for serial measurements of GHBP and used the ligand immunofunctional assay for GHBP. For normal gravidas, GHBP levels fell throughout gestation. Mean levels were 1.07 nmol/L (SE = 0.18) in the first trimester, 0.90 nmol/L (SE = 0.08) at 18-20 weeks, 0.73 nmol/L (SE = 0.05) at 28-30 weeks, and 0.62 nmol/L (SE = 0.06) at 36-38 weeks. GHBP levels in the first trimester correlated significantly with maternal body mass index (r = 0.58; P < 0.01). GHBP levels in pregnancies complicated by noninsulin-dependent diabetes mellitus (NIDDM) were substantially elevated at all gestational ages. The mean value in the first quarter (2.29 nmol/L) was more than double the normal mean (P < 0.01). In contrast, patients with insulin-dependent diabetes mellitus (IDDM) showed reduced GHBP concentrations at 36-38 weeks. The correlation between body mass index and GHBP is consistent with a metabolic role for GHBP during pregnancy, as is the dramatic elevation in GHBP observed in cases of NIDDM. At 36 weeks gestation, GHBP was significantly elevated (P < 0.01) in those women whose neonates had low birth weight (< 10th percentile). In early gestation (< 14 weeks), GHBP tended to be higher in women whose fetuses were designated to be at risk of intrauterine growth retardation (1.39 nmol/L; n = 4; compared with 1.07 nmol/L in normals), but this did not reach statistical significance. Although both NIDDM and IDDM pregnancies are at risk of fetal macrosomia, their GHBP concentrations are markedly divergent. This paradox and the roles of glucose and insulin in the regulation of GHBP during gestation warrant further investigation.     

Creatine kinase isoenzymes in serum from cord blood and the blood of healthy full-term infants during the first three postnatal days

Isoenzymes of creatine kinase (ATP:creatine phosphotransferase; EC 2.7.3.2; CK) were measured by electrophoresis in serum from cord blood and skin-puncture blood taken from 45 healthy full-term infants during the first three postnatal days. Mean total CK activities (in U/L at 30 degrees C) were 185 in cord samples, 536 in samples taken between 5--8 h postnatally, 494 between 24--33 h, and 288 in the 72-100 h samples. Values for all three isoenzymes increased to a peak over this period, with the highest values generally being found in the samples taken 5--33 h after birth; the subsequent decline was most rapid for CK-BB. Serum CK isoenzymes in cord samples and those taken at 72--100 h in the 11 babies delivered by cesarian section did not differ significantly from those of babies delivered vaginally. However the postnatal increases in total CK, CK-MM, and CK-MB (but not in CK-BB) were significantly greater in those patients born by vaginal delivery. The reasons for the increases in CK isoenzymes after birth are not clear, but our results and reported studies on the ontogeny of CK suggest that CK-MB cannot be regarded as a "cardiac-specific" isoenzyme in the neonatal period.     

Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older

We analysed the results of oocyte donation to women of advanced reproductive age (> or = 45 years old) and followed their pregnancies through to delivery in order to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD; 47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy. Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old. Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized oestradiol and intramuscular progesterone. Following oocyte aspiration there were six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of 103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%, which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74 delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins, seven triplets, and two quadruplets. Two of the triplet and both of the quadruplet pregnancies underwent selective reduction to twins. Antenatal complications occurred in 28 women (37.8% of deliveries) and included preterm labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2), and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins 35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700-3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775 +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born) included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or neonatal deaths. We conclude that oocyte donation to women of advanced reproductive age is highly successful in establishing pregnancy. However, despite careful antenatal screening, obstetrical complications are common, often secondary to multiple gestation.     

Comparison of stature growth curves in children and adolescents

During the period 1988-1966, 737 pregnancies, in which the infant birth weight was > or = 4000 grams were studied. During the same period there were 11,631 newborns, and 6.3% of them were infants with a birth weight > or = 4000 grams. Normal vaginal delivery occurred in 583 cases (79.1%), vacuum extraction in 24 cases (3.3%) and caesarean section in 130 cases (17.6%). Regarding the caesarean section, 38 (29.2%) of them were elective and 92 (70.8%) were done in different periods of the labour. In these macrosomic babies perinatal death never occurred, but different pathological neonatal outcomes were observed and the majority of these were clavicle abruptions (39 cases: 5.3%). Maternal morbidity observed in the 607 (82.4%) cases with vaginal delivery is characterized by: 60 cases (9.8%) of vaginal and perineal tears, 4 cases (0.6%) of cervical tears, and 2 cases (0.3%) of pubic symphysis traumatic diastasis. Shoulder dystocia is the most likely outcome in fetal macrosomic delivery; for this reason we considered the diagnostic and therapeutic management of this obstetrical complication. Because the normal outcome of neonatal births actually encourages the preference for normal vaginal delivery, we concluded that mothers with macrosomic fetuses can safely be managed expectantly unless there is a high maternal and fetal risk.     

Food-borne outbreak of streptococcal pharyngitis in an Israeli Airforce Base

OBJECTIVE: To determine if maternal hematocrit and serum albumin can predict intrauterine growth retardation and/or preterm delivery. METHODS: Analyses were performed during each trimester of pregnancy to evaluate the predictive value of these two common laboratory parameters as predictors of intrauterine growth retardation and/or prematurity. RESULTS: 1468 women participated in the study. Intrauterine growth retardation occurred in 9.9% and preterm delivery in 6.1%. A significant inverse correlation between hematocrit and albumin and birth weight was found (r = -0.005, p = 0.04, and r = -0.07, p = 0.007, respectively), albumin being a stronger predictor as demonstrated by multiple regression. Low hematocrit at the third visit was associated with a longer pregnancy duration (r = -0.06, p = 0.02). Woman with higher serum albumin levels at the second visit, had a longer pregnancy duration, possibly reflecting a better nutritional status (r = 0.057, p = 0.03). To determine the predictive value of hematocrit and serum albumin, the prevalence of intrauterine growth retardation and premature delivery in the highest quartiles were compared with the lowest, and no significant differences were observed (p > 0.1). CONCLUSION: Maternal hematocrit and serum albumin concentration cannot be used as useful predictors of intrauterine growth retardation or preterm delivery.     

Objectively measured tobacco exposure during pregnancy: neonatal effects and relation to maternal smoking

OBJECTIVES: To measure quantitatively and objectively the maternal and fetal tobacco exposure during pregnancy and its neonatal effects. DESIGN: Tobacco exposure was assessed from maternal serum samples, obtained during the first half of pregnancy and from umbilical serum samples obtained at delivery, by measuring the concentration of nicotine metabolite, cotinine. Data on the respective pregnancies and neonates were collected from the Finnish Medical Birth Registry. SETTING: Finland. SUBJECTS: One thousand two hundred and thirty-seven pregnancies and newborns, representing all pregnancies resulting in a liveborn infant during one week in one country. MAIN OUTCOME MEASURES: Gestational age, birthweight and crown-heel length of newborns. RESULTS: Cotinine (> 6 micrograms/l) was detected in either maternal or umbilical serum in 300 pregnancies, and these mothers and newborns were classified as exposed. Important differences occurred between measured exposure and reported smoking behaviour. Of the exposed mothers, 38% were nonsmokers and 3.4% of the nonexposed mothers were smokers. Tobacco exposure was associated with shorter gestational age, reduced birthweight and shorter crown-heel length of the newborns. After correction for parity, gender, and gestational age, the exposed newborns were on average 188 g (95% confidence interval (CI) 123-253 g) lighter and 10 mm (95% CI 7-13 mm) shorter than the nonexposed newborns. One micrograms/ml of cotinine in maternal serum resulted in a mean decrease of 1.29 g (95% CI 0.55-2.02 g) in birthweight and in a mean decrease of 0.059 mm (95% CI 0.035-0.083 mm) in birth length. Maternal cotinine concentrations better explained the neonatal findings than the reported smoking habits. CONCLUSIONS: There is a quantitative dose and effect relation between tobacco exposure and a decrease in the gestational age at birth and size of the neonate. The smoking habit reported by mothers themselves is not an accurate measure of fetal tobacco exposure.     

Bicarbonate binding to the water-oxidizing complex in the photosystem II. A Fourier transform infrared spectroscopy study

OBJECTIVE: To investigate the association between a low unconjugated estriol (uE3) in the second trimester and adverse pregnancy outcomes. METHODS: Three hundred nine women who underwent second-trimester maternal serum alpha-fetoprotein (AFP)-hCG-uE3 screening were divided into two groups: those with uE3 at most 0.75 multiples of the median (MoM) (n = 81) and those with uE3 exceeding 0.75 MoM (n = 228). Entry criteria included: hCG below 2 MoM, AFP below 2 MoM, age less than 35 years at delivery, complete prenatal records, and completed delivery. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for a variety of adverse pregnancy outcomes. RESULTS: After adjusting for smoking and hCG, women with uE3 at or below 0.75 MoM were found to have significantly higher odds of developing fetal growth restriction, low amniotic fluid index (AFI), and small for gestational age (SGA) with ORs (and 95% CIs) of 6.73 (2.55, 17.74), 3.85 (1.53, 9.68), and 2.89 (1.27, 6.57), respectively, for each of the outcomes. CONCLUSION: Low uE3 in the second trimester appears to be associated with fetal growth restriction, low AFI, and SGA, and the risk seems to be independent of risk for adverse infant outcome associated with elevated AFP or hCG.     

The alpha beta versus gamma delta T-cell lineage choice

OBJECTIVE: To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term. MATERIALS AND METHODS: Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM). RESULTS: All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg. CONCLUSION: The MTD was calculated to be at 200 microg carbetocin.