Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Decreased plasma chemerin levels in women with gestational diabetes mellitus.

AIMS: To evaluate fasting and post-prandial serum chemerin levels in pregnant women with and without gestational diabetes, and again following delivery when normal glucose homeostasis is re-established. METHODS: Chemerin levels were measured in serum from nine women with gestational diabetes, and from eight age- and BMI-matched pregnant women with normal glucose tolerance during two meal tests: in the third trimester and 3-4 months post partum. All women with gestational diabetes re-established normal glucose tolerance after delivery. RESULTS: Meal intake did not affect serum chemerin levels. The group with gestational diabetes had lower mean serum chemerin levels during the third trimester compared with the group with normal glucose tolerance (28 ± 1.3 vs. 88 ± 3.5 ng/ml, P < 0.0001). In the group with normal glucose tolerance, mean serum chemerin levels decreased significantly post partum to 57 ± 2.8 ng/ml (P = 0.0001), but remained significantly (P = 0.0003) higher than post-partum levels in the group with gestational diabetes (31 ± 1.9 ng/ml), which did not differ significantly from third trimester levels (P = 0.31). CONCLUSIONS: Normal pregnancy is associated with increased circulating chemerin levels, which may act to reduce pregnancy-induced insulin resistance and prevent glucose intolerance. Women with gestational diabetes, however, have severely reduced chemerin levels that remain low after delivery, which may contribute to the insulin resistance, glucose intolerance and high type 2 diabetes risk associated with gestational diabetes.

Reduced postprandial GLP-1 responses in women with gestational diabetes mellitus.

AIM: We investigated postprandial glucagon-like peptide-1 (GLP-1) responses in pregnant women with and without gestational diabetes mellitus (GDM) and again following delivery when normal glucose tolerance (NGT) was re-established. METHODS: Eleven women with GDM [plasma glucose (PG) concentration at 120 min after a 75-g oral glucose tolerance test (OGTT): 10.0 ± 0.9 mM (mean ± SD); age: 31 ± 6 years; body mass index (BMI): 31.6 ± 6.4 kg/m(2) ; haemoglobin A1c (HbA1c): 5.6 ± 0.5%] and eight pregnant women with NGT (PG(120 min), OGTT : 5.7 ± 0.7 mM; age: 28 ± 3 years; BMI: 29.7 ± 5.4 kg/m(2) ; HbA1c: 5.4 ± 0.3%) were investigated with a 4-h liquid meal test during third trimester (TT) and 3-4 months postpartum (PP). All patients with GDM re-established NGT following delivery. RESULTS: Pregnancy was associated with low postprandial GLP-1 responses. Patients with GDM exhibited reduced postprandial GLP-1 responses compared to their PP levels [area under curve (AUC): 5.5 ± 1.3 vs. 8.4 ± 3.2 nM × min, p=0.005], but the difference among NGT women (7.3 ± 2.8 vs. 8.8 ± 2.0 nM × min, p=0.066) was not statistically significant. Pregnancy did not influence postprandial responses of the other incretin hormone glucose-dependent insulinotropic polypeptide (GIP) in any of the groups, but GDM patients were characterized by greater postprandial GIP responses during both TT and PP compared to NGT subjects. CONCLUSIONS: Pregnancy is associated with reduced postprandial GLP-1 responses (most pronounced in patients with GDM) that normalize after delivery. In contrast, postprandial GIP responses seem unaffected by pregnancy but is increased in GDM patients.

Bacterial vaginosis in a cohort of Danish pregnant women: prevalence and relationship with preterm delivery, low birthweight and perinatal infections.

OBJECTIVE: To determine the prevalence of bacterial vaginosis (BV) in the second trimester of pregnancy in a Danish population using the Schmidt criteria and to examine whether BV was associated with subsequent preterm delivery, low birthweight or perinatal infections. DESIGN: Prospective cohort study. SETTING: Department of Obstetrics and Gynaecology at a University Hospital, Denmark. POPULATION: Three thousand five hundred and forty pregnant women aged 18 years or more. METHODS: A smear from the vagina was obtained from all women, air-dried and stored for subsequent diagnosis of BV. After rehydration with isotonic saline, the smear was examined in a phase-contrast microscope at 400x, and the numbers of lactobacilli morphotypes and small bacterial morphotypes were counted. A score for BV was calculated according to the method described by Schmidt. The outcome of pregnancy from 20 weeks of gestation was examined in the 3262 singleton pregnant women who were included in this study before 20 weeks of gestation. The relationship between BV and adverse outcome of pregnancy was examined by univariate and multivariate analyses. MAIN OUTCOME MEASURES: Prevalence of BV, preterm delivery (<37 weeks), low birthweight (<2500 g), preterm delivery of a low-birthweight infant and clinical chorioamnionitis. RESULTS: The prevalence of BV was 16%, and the rate of preterm delivery was 5.2% in the study population of 3262 singleton pregnant women who were included before 20 weeks of gestation. Mean birthweight was significantly lower in infants of women with BV than in infants of women without BV (3408 versus 3511 g, P < 0.01). Univariate analyses showed that BV was marginally associated with preterm delivery but significantly associated with low birthweight, preterm delivery of a low birthweight infant, indicated preterm delivery and clinical chorioamnionitis. Multivariate analyses, which adjusted for previous miscarriage, previous preterm delivery, previous conisation, smoking, gestational diabetes, fetal death and preterm premature rupture of membranes, showed that BV was significantly associated with low birthweight (OR 1.95, 95% CI 1.3-2.9), preterm delivery of a low-birthweight infant (OR 2.5, 95% CI 1.6-3.9), indicated preterm delivery (OR 2.4, 95% CI 1.4-4.1) and clinical chorioamnionitis (OR 2.7, 95% CI 1.4-5.1). CONCLUSIONS: The prevalence of BV determined using the Schmidt criteria in the early second trimester of pregnancy was similar to that found in similar studies. The presence of BV before 20 weeks of gestation was an independent risk factor for delivery of an infant with low birthweight, preterm delivery of a low-birthweight infant, indicated preterm delivery and clinical chorioamnionitis.

Perinatal complications in women with gestational diabetes mellitus.

BACKGROUND: The aim of the study was to examine the outcome of the pregnancy and neonatal period in 1) women with gestational diabetes mellitus and non-diabetic pregnant women, and 2) in women with early and late diagnosis of gestational diabetes mellitus. METHODS: Included were 327 women with gestational diabetes mellitus and 295 non-diabetic women, who were screened with a 75 g oral glucose tolerance test because of risk factors for gestational diabetes. Women with gestational diabetes mellitus were treated with low-caloric diet and insulin when appropriate, while women in the control group received routine antenatal care. RESULTS: Gestational age at delivery was significantly lower in the group with gestational diabetes mellitus, both when considering all deliveries (39.1+/-1.7 weeks versus 39.8+/-2.0 weeks, p<0.05) and only those with spontaneous onset of labor (38.8+/-2.0 weeks versus 40.0+/-1.6 weeks, p<0.05). The frequency of macrosomia was increased, although not statistically significant (8% vs. 2%, p=0.07), and the rate of admission to the neonatal ward was significantly increased (18% vs. 9%, p<0.05) in the group with gestational diabetes. Women with early diagnosis of gestational diabetes mellitus had a significantly increased need for insulin treatment during pregnancy (36% vs. 9% p<0.05) and a significantly higher occurrence of diabetes mellitus at follow-up from two months until three years postpartum. CONCLUSIONS: This study of women with gestational diabetes mellitus and non-diabetic pregnant women showed that gestational diabetes mellitus was associated with a significantly lower gestational age at delivery and an increased rate of admission to the neonatal ward. Women diagnosed with GDM before 20 weeks of gestation had an increased need for insulin treatment during pregnancy and a high risk of subsequent overt DM, compared with women diagnosed with GDM later in pregnancy.

Ampicillin-metronidazole treatment in idiopathic preterm labour: a randomised controlled multicentre trial.

OBJECTIVE: To determine whether treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour will prolong the gestation and reduce maternal and neonatal infectious morbidity. DESIGN: Randomised controlled double-blind trial. SETTING: Six obstetric departments in the Copenhagen area. POPULATION: One hundred and twelve women with singleton pregnancies, with threatened idiopathic preterm labour and intact amniotic membranes at 26 to 34 weeks of gestation. METHODS: Random allocation to eight days intravenous and oral treatment with ampicillin and metronidazole, or placebo. MAIN OUTCOME MEASURES: Number of days from admission to delivery, gestational age at delivery, rates of preterm delivery, low birthweight, maternal infections and neonatal infections. RESULTS: Treatment with ampicillin and metronidazole was associated with a significant prolongation of pregnancy (admission to delivery 47.5 days versus 27 days, P < 0.05), higher gestational age at delivery (37 weeks versus 34 weeks, P < 0.05), decreased incidence of preterm birth (42% versus 65%, P < 0.05), and lower rate of admission to neonatal intensive care unit (40% versus 63%, P < 0.05), when compared with placebo treatment. Antibiotic treatment had no significant effects on infectious morbidity. CONCLUSIONS: Treatment with ampicillin and metronidazole in women with threatened idiopathic preterm labour significantly prolonged the gestation, but had no effects on maternal and neonatal infectious morbidity.

Uro-genital microbial colonization and threatening preterm delivery.

OBJECTIVE: To examine whether there is a relationship between the uro-genital microbial colonization and threatening preterm delivery. STUDY DESIGN: The microflora in the urine and endocervix was studied in 43 women with preterm labor, 45 women with preterm premature rupture of the membranes (PPROM) and 80 normal pregnant women at 26-34 weeks of gestation. Amniotic fluid was examined in 20 of the patients with preterm labor. Data were analyzed by Fisher's exact test (two-tailed). RESULTS: The microflora in the urine was not significantly different in patients with preterm labor, PPROM and normal pregnant women. Compared with normal pregnant women, patients with preterm labor had significantly lower prevalences of corynebacteria (p < 0.05) and coagulase-negative staphylococci (p < 0.01) in the cervix, while patients with PPROM had significantly lower prevalences of lactobacilli (p < 0.05) and coagulase-negative staphylococci (p < 0.05) in the cervix. Positive amniotic fluid cultures were detected in three of the 20 patients with preterm labor who underwent transabdominal amniocentesis. Evidence of ascending colonization was found in two of these cases. CONCLUSIONS: The microbial colonization of the urine was not associated with threatening preterm delivery. Reduced prevalences of lactobacilli, corynebacteria and coagulase-negative staphylococci in the cervix were associated with threatening preterm delivery.

[Relation between cervical conization, microbial colonization and threatening preterm labor]. / Relationen mellem cervikal konisation, mikrobiel kolonisation i cervix og truende for tidlig fødsel.

UNLABELLED: The relationship between prior cervical conization, the cervical microbial colonization and threatening preterm delivery was investigated in 35 women with preterm premature rupture of the membranes (PPROM), 38 women with idiopathic preterm labor and 75 normal pregnant women at 26-34 weeks of gestation. Prior cervical conization occurred with a significantly higher frequency in PPROM patients than in patients with preterm labor (p < 0.01) and normal pregnant women (p < 0.001). The prevalence of lactobacilli was lower in patients with PPROM than in patients with preterm labor (p < 0.05) and control patients (p = 0.05)--and lower in patients with prior cervical conization than in patients without prior conization (p < 0.05). All other microorganisms occurred with the same frequencies in all groups. CONCLUSIONS: Prior conization was associated with PPROM. Women with prior conization and women with PPROM had a reduced prevalence of lactobacilli in the cervix. The "absence" of lactobacilli may indicate changes in the cervical microflora, which could be of importance for PPROM.

[Heterotopic pregnancy after in vitro fertilization]. / Heterotop graviditet efter in vitro fertilisering.

Until December 1991, 1171 pregnancies had been established in Denmark after in vitro fertilization and embryo transfer (IVF-ET). Thirteen of these pregnancies were heterotopic (1.1%). Three patients were asymptomatic, four patients presented with an acute abdomen, five had abdominal pain and only two patients had vaginal bleeding. In five cases the diagnosis of heterotopic pregnancy was made by ultrasound, while eight cases were diagnosed at the time of surgery. Eleven patients were treated in the first trimester, while two patients were treated at 23 and 38 weeks of gestation, respectively. In nine of the thirteen cases the intrauterine pregnancy resulted in term delivery. Heterotopic pregnancy occurred in 1% of pregnancies following IVF-ET. Abdominal pain was the predominant symptom, while vaginal bleeding was absent in the majority of women. In most cases removal of the ectopic gestation allowed the intrauterine pregnancy to proceed until term.

Heterotopic pregnancies after in-vitro fertilization and embryo transfer--a Danish survey.

Thirteen cases of heterotopic pregnancy were diagnosed among 1171 pregnancies established in Denmark after in-vitro fertilization and embryo transfer (IVF-ET). Thus the frequency of heterotopic pregnancy was 13/1171 or 1.1%. In five cases the diagnosis of heterotopic pregnancy was made by ultrasound at 6-9 weeks of gestation; three of these patients were asymptomatic, while two patients presented with abdominal pain and vaginal bleeding. All these patients had an unruptured ectopic pregnancy. Eight cases were diagnosed at the time of surgery; all these patients presented with abdominal pain. Only two of the 13 patients had vaginal bleeding. In nine of the 13 cases the intra-uterine pregnancy resulted in term delivery, while one pregnancy is ongoing. In pregnancies following IVF-ET, this diagnosis should particularly be considered in cases with abdominal pain; vaginal bleeding may be absent. Ultrasound examination may lead to early diagnosis even in asymptomatic cases. In most cases, removal of the ectopic gestation will allow the intrauterine pregnancy to proceed to term.

The relationship between prior cervical conization, cervical microbial colonization and preterm premature rupture of the membranes.

The occurrence of prior cervical conization and the cervical microbial colonization was investigated in 38 women with idiopathic preterm labor, 35 women with preterm premature rupture of the membranes (PPROM) and 75 normal pregnant women at 26-34 weeks of gestation. Data were analyzed by Fisher's exact test (two-tailed). The frequency of prior cervical conization was significantly higher in PPROM patients compared to normal pregnant women (P < 0.001) and to patients in preterm labor (P < 0.01). Lactobacilli occurred with a lower frequency in patients with PPROM compared to patients in preterm labor (P < 0.05) and control patients (P = 0.0543)-and with a lower frequency in patients with prior cervical conization (P < 0.05). All other microorganisms occurred with the same frequencies in all groups. The absence of lactobacilli may indicate changes in the cervical flora, which could increase the risk of PPROM. Prior cervical conization may impair the antimicrobial defense-mechanisms in the cervix, which could facilitate ascending microbial colonization. This may lead to a release of prostaglandins and proteolytic enzymes and subsequently preterm labor and rupture of the membranes.

[Idiopathic preterm delivery and subclinical genital infection]. / Idiopatisk praeterm fødsel og subklinisk genital infektion.

Investigations from abroad suggest that idiopathic preterm delivery may be due to ascent of microorganisms from the cervix. These may then colonize the decidua, foetal membranes and amniotic fluid and may thus precipitate preterm contractions or rupture of the membranes. In subclinical urogenital infections, antibiotic treatment appears, in some cases, to be capable of reducing the risk of preterm birth. In cases of treated premature delivery, antibiotic treatment may possibly prolong the pregnancy and prevent neonatal and puerperal infections. Further investigations are, however, recommended before introduction of routine antibiotic treatment in cases of threatened premature birth.

Maternal-fetal listeriosis: 2 case reports.

Two cases of maternal-fetal infection with Listeria monocytogenes are reported. Both women were admitted with influenza-like symptoms and preterm labor at 32 and 34 weeks of gestation, respectively. The infants were delivered within a few days of onset of maternal symptoms. One infant was seriously ill with meningitis and subsequently developed hydrocephalus. The other infant suffered from septicemia, but had no sequelae. It is recommended always to consider the diagnosis listeriosis in pregnant women with fever of unknown origin and preterm labor.

Group B streptococcal chorioamnionitis and neonatal septicemia following 8 days pivampicillin and metronidazol prophylaxis after premature rupture of membranes; a case report.

A case of preterm premature rupture of the membranes (PPROM) in the 31st week of gestation is reported. Initial cultures from the cervix and urine were without pathogenic microorganisms. After 8 days of prophylactic pivampicillin and metronidazol, culture from the cervix showed profuse growth of Group B Streptococci (GBS) and the patient developed symptoms of chorioamnionitis. Cesarean section was performed and the infant presented GBS-septicemia. In spite of continued treatment with pivampicillin, culture from the cervix on day 6 post partum still showed profuse growth of GBS. Prolonged prophylactic per oral administration of broad-spectrum antibiotics after PPROM may not always protect against infectious complications. Literature is reviewed, and it is discussed whether the applied regimen in some cases even may favour the occurrence of serious infections.

Ileal conduit urinary diversion--early and late complications.

110 adult patients with benign and malignant conditions subjected to an ileal conduit urinary diversion were followed from 1 to 8 years after the operation. 62 patients (59 with a malignant disease) died in the follow-up period. The patients were divided into 3 groups according to their primary diseases: (1) benign, (2) malignant without irradiation, and (3) malignant with irradiation. Early complication rates were 22% in group 1, 33% in group 2, and 29% in group 3. In addition, the complications were more serious in the group with malignant diseases. Late complication rates were 70% in group 1, 80% in group 2, and 54% in group 3, possibly due to a shorter time of observation in group 3. Renal function deteriorated in 18% of the patients but only 3% became uremic. When urinary diversion is inevitable we find this method acceptable, at least until the long-term results of newer methods are known.