Risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) among women with HPV-test in 1990-1992, a 30-year follow-up study.

BACKGROUND/OBJECTIVE: Having a 30-year follow-up of a cohort of women tested for HPV is a unique opportunity to further study long-term risk of CIN3+. The study objective was to compare HPV status at baseline with the risk of CIN3+ in the follow-up period of 30 years. METHODS: All women (n = 642) referred to the HPV outpatient clinic at the University Hospital of North Norway (UNN) in 1990-1992, with an HPV test at baseline, were included in a prospective cohort. HPV-testing was performed by two different HPV-DNA tests, and genotypes 6, 11, 16, 18, 31 and 33 were identified. High-risk (HR) HPV genotypes (16, 18, 31 and 33) were classified as HPV positive, whereas low-risk (LR) genotypes (6 and 11) in addition to absent HPV were classified as HPV negative. A single cohort in which women were classified for their HPV status underwent follow-up prospectively to the last time-point of observation of 30 years. RESULTS: During follow-up, 148 (148/642) cases of CIN3+ were detected, of whom 70.3% (104/148) were HPV positive and 29.7% (44/148) were HPV negative at baseline. The proportions of women who developed CIN3+ following a positive and a negative test were 46.6% (104/223) and 10.5% (44/419), respectively. Most cases of CIN3+ were seen shortly after the baseline HPV test, with 112 cases of CIN3+ diagnosed within the first year. In total, 48.6% (72/148) with HPV 16 and 57.6% (19/33) with HPV 33 developed CIN3+. Within the first year, CIN3+ was detected in 37.8% (56/148) with HPV 16, and 51.5% (17/33) with HPV 33. The long-term risk of CIN3+ was significantly lower than the short-term risk, and mainly associated with HPV 16. Overall, eight cases of cervical cancer were detected. Five were HPV positive, harboured HPV 16 at baseline and developed cervical cancer after 3, 4, 5, 11 and 24 years of follow-up. CONCLUSION AND CONSEQUENCES: HPV status at baseline is predictive for the subsequent risk of developing CIN3+. Women with a positive HPV test in 1990-1992 had a significantly higher risk of CIN3+ during 30 years of follow-up than those with a negative test. HPV 16 was associated with the greatest long-term risk of cervical cancer. All patients with a positive HPV test at baseline should be followed up until negative. TRIAL REGISTRATION: ISRCTN, ISRCTN10836802 . Registered 14 December 2020 - Retrospectively registered.

Prevalences of viremic hepatitis C and viremic hepatitis B in pregnant women in Northern Norway.

BACKGROUND/AIMS: No data exist for current infections of hepatitis C and hepatitis B virus in pregnant women in Northern Norway. The aim of this study was to determine the prevalences of viremic hepatitis C and hepatitis B of pregnant women in Northern Norway. A cross-sectional, multi-center study with participation of all hospitals and delivery rooms in this region was performed. METHODOLOGY: All pregnant women who consecutively underwent ultrasound screening in 17th - 19th weeks of pregnancy during the period between October 2003 and October 2004 were invited to participate in the study. On the day of ultrasonography venous blood samples were collected for analysis of serum for antibody to hepatitis C virus, hepatitis C virus ribonucleicacid, recombinant immunoblot assay, hepatitis B surface antigen, antibody to hepatitis B surface antigen and antibody to hepatitis B core antigen. RESULTS: Out of 4087 eligible pregnant women 1668 (41%) were included in the study. The prevalences of viremic hepatitis C (hepatitis C virus ribonucleicacid positive) and viremic hepatitis B (hepatitis B surface antigen positive) were 0.2% (95% CI 0.0 - 0.5) and 0.1% (95% CI 0.0 - 0.3) respectively. CONCLUSIONS: The prevalences of viremic hepatitis C and hepatitis B in pregnancy in Northern Norway were low.

Noninvasive cerclage for the management of cervical incompetence: a prospective study.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a noninvasive cerclage pessary in the management of cervical incompetence. METHODS: This is a prospective cohort study of all pregnant women treated for cervical incompetence during a 4-year period. Women with known risk factors for preterm delivery had transvaginal ultrasonography every 2-3 weeks after 17-19 weeks of gestation. Those with progressive shortening of cervix diagnosed before 30 weeks were treated with a cerclage pessary when the cervical length was < or = 25 mm. The pessary was electively removed at 34-36 weeks. The course and outcome of pregnancy were recorded. RESULTS: Thirty-two women were treated with a cerclage pessary. There were nine twin and two triplet pregnancies. Fifteen (47%) had two or more risk factors for preterm delivery. The mean gestational age at cerclage was 23 (17-29) weeks, cervical length 17 (5-25) mm. Two women required delivery before the onset of labor due to severe intrauterine growth restriction and one due to HELLP syndrome. These were excluded from further analysis. In the remaining 29 women, the interval between cerclage and delivery was 10.4 (2-19) weeks, mean gestational age at delivery 34 (22-42) weeks, and birth weight 2,255 (410-4,045) g. Thirteen (45%) women delivered before 34 weeks. There were a total of 35 live-born infants and four intrapartum fetal deaths (all between 22 and 25 weeks gestation). All women complained of increased vaginal discharge, but no other significant complications were observed that could be attributed to the use of pessary. CONCLUSION: Cerclage pessary may be useful in the management of cervical incompetence. Whether it can be a noninvasive alternative to surgical cerclage merits further investigation.

Catheter-directed thrombolysis for the management of postpartum deep venous thrombosis.

BACKGROUND: Catheter-directed thrombolysis that removes the thrombus and restores patency of the veins appears to be a safe and effective management of acute deep venous thrombosis (DVT). It has been shown to reduce long-term postthrombotic morbidity and improve the quality of life. Pregnancy and the postpartum period are generally considered as contraindications for thrombolysis. However, catheter-directed thrombolytic therapy of DVT may reduce long-term sequelae in these young patients by restoring the patency of veins. The purpose of this pilot study was to evaluate the efficacy of catheter-directed thrombolysis in treating acute symptomatic postpartum DVT. METHODS: Patients enrolled had symptomatic acute DVT (<3 weeks duration) within 42 days of childbirth. Thrombolysis was performed using a recombinant human tissue plasminogen activator, alteplase 5 mg i.v. bolus, followed by an infusion at 0.01 mg/kg/h for the next 20-24 hr. Unfractionated heparin 5000 IU bolus followed by 300 IU/kg/24 hr was infused concomitantly into an arm vein. Fibrinogen and cephotest were obtained every 6 hr and maintained at >1 g/l and between 50 and 70 s, respectively, by adjusting heparin and alteplase infusion. Venography was repeated after 20-24 hr and angioplasty (+/- stenting) was performed if stenosis was present. In case of partial thrombolysis infusion was continued for a maximum of 96 hr. Lysis was considered complete if there was less than 5% residual luminal area narrowing. The treatment was considered successful if there was complete or partial resolution of lower extremity pain and edema, and recanalization of vein with less than 30% residual luminal area narrowing. Following thrombolytic therapy, patients were fitted with graduated compression stockings, and anticoagulated with oral warfarin for 1 year (or lifelong in case of stent implantation). RESULTS: Five women with postpartum DVT (four iliofemoral DVTs, and one renal and ovarian vein thrombosis on the left side) had catheter-directed thrombolysis. The treatment was successful in all four cases of iliofemoral DVT and symptom relief was achieved in all five cases. However, despite partial thrombolysis and restoration of some flow in the patient with renal and ovarian vein thrombosis, the renography performed 1 month later showed absent left kidney function. CONCLUSION: Where expertise exists, endovascular therapy consisting of catheter-directed thrombolysis with angioplasty and stenting in selected cases could be considered as a primary therapeutic procedure in patients with acute postpartum DVT.

Reference ranges for umbilical vein blood flow in the second half of pregnancy based on longitudinal data.

OBJECTIVES: To construct new reference ranges for serial measurements of umbilical vein (UV) blood flow. METHODS: Prospective longitudinal study of blood flow velocities and diameter of the UV measured at four-weekly intervals during 19 to 42 weeks' gestation in 130 low-risk singleton pregnancies. Regression models and multilevel modeling were used to construct the reference ranges. RESULTS: On the basis of 511 sets of longitudinal observations, we established new reference percentiles of UV diameter, blood flow velocities, volume flow, and blood flow normalized for fetal weight and abdominal circumference. They reflected some of the developmental patterns of previous cross-sectional studies, but with important differences, particularly near term. The UV blood flow showed a continuous increase until term, whereas the flow normalized per unit fetal weight, a corresponding reduction. Calculating the blood flow on the basis of intensity-weighted mean velocity or 0.5 of the maximum velocity gave almost interchangeable results for most fetuses. CONCLUSION: New reference ranges for UV blood flow based on longitudinal observations appear slightly different from cross-sectional studies, and should be more appropriate for serial evaluation of fetal circulation.

Pregnancy outcome after loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia.

OBJECTIVE: Previous studies have shown conflicting results on the outcome of pregnancy following loop electrosurgical excision procedure (LEEP). The purpose of this study was to evaluate whether LEEP affects the outcome of pregnancy after 20 weeks' gestation. METHODS: This is a matched cohort study of all women who had a LEEP for a biopsy-confirmed cervical intraepithelial neoplasia (CIN) in between December 1995 and December 2000 and subsequently delivered (after 20 weeks' gestation) at the University Hospital of Northern Norway. Women who had an ectopic pregnancy or an abortion (spontaneous or induced) following LEEP were excluded from analysis. Two controls matched for the date of delivery, age, parity, previous obstetric history and smoking habit were identified for each case using routinely entered data from the birth register. The main outcome measures were the duration of pregnancy and birth weight. Other variables recorded included the grade of cervical dysplasia, size of the electrosurgical loop, age, parity, pregnancy complications, mode of delivery, and perinatal outcome. RESULTS: Of a total of 428 women of reproductive age who had LEEP performed during the study period, 89 had a pregnancy after the procedure. Ten women were excluded (three ectopic pregnancies, two induced abortions and five spontaneous abortions) from the study. Data from 79 women whose pregnancies progressed beyond 20 weeks and 158 matched controls were analysed. The mean age at the time of LEEP was 27 (range 19-36) years. The histological diagnosis was normal in 3 (3.8%), CIN1 in 5 (6.3%), CIN2 in 18 (22.8%), and CIN3 in 53 (67.1%) of the cases. Overall, mean gestation at delivery (38.3 vs. 39.1 weeks), mean birth weight (3,412 vs. 3,563 g), prevalence of preterm birth (11.4% vs. 10.8%) and low birth weight (10.1 vs. 5.1%) were not significantly different among the cases and controls. But when a relatively large loop (25 mm) had been used, the risk of preterm delivery (odds ratio 4.0) and low birth weight (odds ratio 14.0) was significantly higher than in controls. Pregnancy complications occurred more frequently (20 vs. 7%; p=0.006) among the cases than the controls. CONCLUSION: LEEP in women with CIN did not significantly increase the risk of low birth weight or preterm birth in subsequent pregnancy in comparison to their controls, except when the size of electrosurgical loop was relatively large. However, the prevalence of pregnancy complications was significantly higher after LEEP.

Reference ranges for serial measurements of umbilical artery Doppler indices in the second half of pregnancy.

OBJECTIVE: The purpose of this study was to construct new reference ranges for serial measurements of commonly used umbilical artery Doppler indices (pulsatility index, resistance index, and systolic:diastolic ratio). STUDY DESIGN: This was a prospective longitudinal study of the umbilical artery Doppler indices that were obtained serially at the free-loop of umbilical cord at 4-week intervals at 19 to 42 weeks of gestation in 130 low-risk singleton pregnancies. A total of 513 observations were used to construct the reference ranges with the use of multilevel modeling. RESULTS: Longitudinally established percentiles of Doppler indices from the present study show a continuous reduction throughout the second half of pregnancy without any plateau or increase near term, as reported previously. There was a significant negative association between Doppler indices and placental weight and neonatal birth weight, but not with gender. The intraobserver coefficients of variation for the umbilical artery pulsatility index, resistance index, and systolic:diastolic ratio were 10.5%, 6.8 %, and 13.0 %, respectively. CONCLUSION: New reference ranges for umbilical artery Doppler indices that are based on longitudinal observations appear to be slightly different from cross-sectional studies and are more appropriate for serial evaluation of fetal hemodynamics.

[Postpartum hemorrhage--prophylaxis and treatment in Norway]. / Blødning post partum--profylakse og behandling i Norge.

BACKGROUND: Routine oxytocic prophylaxis is known to significantly reduce the risk of severe postpartum haemorrhage (> 1,000 ml) and need for blood transfusion after delivery. To what extent this evidence is implemented in clinical practice in Norway is not known. MATERIAL AND METHODS: A telephone questionnaire survey was carried out in September 2001 to evaluate the routine clinical practice for prevention and treatment of postpartum haemorrhage in Norwegian delivery units. RESULTS: Data were available for 55 out of 57 institutions with a delivery unit. Routine third stage prophylaxis with 5-10 IU oxytocin was practiced in 47% of delivery units. Intravenous oxytocin infusion was used primarily in all the delivery units for the treatment of established primary postpartum haemorrhage. 74% of units used methylergometrine, 21% misoprostol as the second-line treatment. INTERPRETATION: Despite evidence for the use of oxytocics for the prevention of postpartum haemorrhage, less than half of delivery units in Norway practice routine prophylaxis in the third stage of labour. Norwegian women may benefit if all maternity care providers implement evidence-based practice.

Role of routine ultrasonography in monitoring the outcome of medical abortion in a clinical setting.

BACKGROUND: Clinical methods generally used to evaluate the completeness of medical abortion are not accurate. There are no published reports evaluating the role of routine ultrasonography in monitoring the outcome of medical abortion. The purpose of this study was to investigate whether routine transvaginal ultrasonography (TVS) at the follow-up visit after medical abortion can accurately identify women who will require surgical intervention. DESIGN: Retrospective review of medical records and charts of all women undergoing medical abortion in the first trimester of pregnancy between January 1999 and December 2001. METHODS: Medical abortion was performed using oral mifepristone and a vaginal prostaglandin analog before 63 days gestation. All women had an initial TVS to confirm intrauterine pregnancy and gestational age, and another TVS at the follow-up visit 2-3 weeks later to assess the completeness of abortion. Surgical evacuation of the uterus was allowed as indicated on clinical grounds but not on the basis of ultrasound findings only. RESULTS: A total of 690 women consented to medical abortion during the study period. Eleven of these women were excluded from the study for various reasons. Of the remaining 679 cases, 95% (645/679) had a documented follow-up at the hospital. The pregnancy termination rate among these women was 99.2% (640/645) and TVS identified all five cases of continuing pregnancy at the follow-up. A total of 66 (10.2%) patients had complications. The uterine cavity was empty on TVS at the follow-up visit in 84.8% (547/645) of cases and only 3.1% (17/547) of them required surgical aspiration/curettage due to excessive or prolonged vaginal bleeding. In the remaining 15.2% (98/645) the uterine cavity was not empty, and 43.9% (43/98) of them had a curettage. The risk of requiring a surgical intervention was significantly higher [odds ratio (OR) 24.4; 95% confidence interval (95% CI) 14.9-39.7] when the uterine cavity was not demonstrated to be empty at the follow-up visit 2-3 weeks after medical abortion. However, 59.1% (55/93) of women did not require surgical intervention despite ultrasound evidence of thick endometrial echo-complex. CONCLUSION: Routine TVS 2-3 weeks after medical abortion appears to be an efficient means of accurately identifying the cases of ongoing pregnancy and diagnosing a complete abortion. Although TVS could be used as an adjunct to clinical examination to diagnose an incomplete expulsion, it does not accurately differentiate those women who require surgical intervention from those who do not.

Major congenital heart disease in Northern Norway: shortcomings of pre- and postnatal diagnosis.

BACKGROUND: Congenital heart disease (CHD) is a significant cause of perinatal mortality and morbidity worldwide. Prenatal detection rate of CHD remains low in most European countries and a substantial proportion of infants with serious heart disease are diagnosed only after discharge from hospital after birth. Earlier recognition of treatable abnormalities may improve the perinatal outcome. The purpose of this study was to evaluate the incidence, pre- and postnatal diagnosis and outcome of major CHD in two northern-most counties of Norway. MATERIALS AND METHODS: All cases of major CHD were identified by reviewing the records of all fetal and neonatal echocardiographies and all perinatal autopsies performed during the study period. Data were obtained on maternal age, associated risk factors, time of diagnosis, type of CHD and outcome. RESULTS: Ninety-one fetal and 52 neonatal echocardiographies and 77 perinatal autopsies were performed during the 2-year study period. There was a total of 5658 births during this period. Twenty-five cases of major CHD were identified. Six of them were diagnosed prenatally, 18 after birth, and one additional case was identified from the perinatal autopsy register. The incidence of major CHD in Northern Norway was 4.4 per 1000 births. The prenatal detection rate was 24% (6/25). In 39% (7/18) of cases diagnosed postnatally the diagnosis was made following a second admission after the baby has been initially discharged from hospital after birth. The mortality among liveborn infants with major CHD was 17.4% (4/23). CONCLUSION: Despite almost universal prenatal ultrasound screening and at least one neonatal examination before discharge, the diagnosis of major CHD is made after a relevant delay in a substantial proportion of cases.