Early suppression policies protected pregnant women from COVID-19 in 2020: A population-based surveillance from the Nordic countries.

INTRODUCTION: The Coronavirus 2019 Disease (COVID-19) pandemic reached the Nordic countries in March 2020. Public health interventions to limit viral transmission varied across different countries both in timing and in magnitude. Interventions indicated by an Oxford Stringency Index ≥50 were implemented early (March 13-17, 2020) in Denmark, Finland, Norway and Iceland, and on March 26, 2020 in Sweden. The aim of the current study was to assess the incidence of COVID-19-related admissions of pregnant women in the Nordic countries in relation to the different national public health strategies during the first year of the pandemic. MATERIAL AND METHODS: This is a meta-analysis of population-based cohort studies in the five Nordic countries with national or regional surveillance in the Nordic Obstetric Surveillance System (NOSS) collaboration: national data from Denmark, Finland, Iceland and Norway, and regional data covering 31% of births in Sweden. The source population consisted of women giving birth in the included areas March 1-December 31, 2020. Pregnant women with a positive SARS-CoV-2 PCR test ≤14 days before hospital admission were included, and admissions were stratified as either COVID-19-related or non-COVID (other obstetric healthcare). Information about public health policies was retrieved retrospectively. RESULTS: In total, 392 382 maternities were considered. Of these, 600 women were diagnosed with SARS-CoV-2 infection and 137 (22.8%) were admitted for COVID-19 symptoms. The pooled incidence of COVID-19 admissions per 1000 maternities was 0.5 (95% confidence interval [CI] 0.2 to 1.2, I2 = 77.6, tau2 = 0.68, P = 0.0), ranging from no admissions in Iceland to 1.9 admissions in the Swedish regions. Interventions to restrict viral transmission were less stringent in Sweden than in the other Nordic countries. CONCLUSIONS: There was a clear variation in pregnant women's risk of COVID-19 admission across countries with similar healthcare systems but different public health interventions to limit viral transmission. The meta-analysis indicates that early suppression policies protected pregnant women from severe COVID-19 disease prior to the availability of individual protection with vaccines.

Risk Factors for Lichen Sclerosus: A Case-Control Study of 43,000 Finnish Women.

OBJECTIVES: Lichen sclerosus (LS) is an inflammatory skin disease probably arising from an interplay of genetics, local irritation, and autoimmune processes. We identified potential risk factors for the disease using data from nationwide Finnish registries. METHODS: We identified all women diagnosed with LS within specialized health care during 1998-2016 (n = 10,692) and selected 3 age-matched population control women for each case. We calculated odds ratios (ORs) for possible risk factors using conditional logistic regression. RESULTS: Dermatological autoimmune conditions were strongly associated with LS (OR = 15.1, 95% confidence interval [CI] = 13.6-16.7 for morphea; OR = 10.3, 95% CI = 5.02-19.0 for lichen planus; OR = 6.86, 95% CI = 5.65-8.33 for alopecia; OR = 2.20, 95% CI = 1.88-2.56 for vitiligo). A diagnosis of Crohn or celiac disease increased the odds of LS (OR = 1.80, 95% CI = 1.71-1.89; OR = 1.49, 95% CI = 1.28-1.73, respectively) as did urge and stress incontinence (OR = 1.79, 95% CI = 1.71-1.87; OR = 1.28, 95% CI = 1.22-1.35, respectively).The odds of LS were lower in women after a diagnosis of type 1 diabetes (OR = 0.43, 95% CI = 0.41-0.45), coronary artery disease (OR = 0.41, 95% CI = 0.38-0.43), and rheumatoid arthritis (OR = 0.38, 95% CI = 0.36-0.41).Parous women had higher odds of LS (OR = 1.11, 95% CI = 1.04-1.17) than nulliparous ones, but increasing number of births decreased the risk. Lichen sclerosus was not associated with socioeconomic status nor the urbanicity level of the place of residence. CONCLUSIONS: Certain autoimmune diseases and urinary incontinence were associated with LS.

Overtreatment rate after immediate local excision of suspected cervical intraepithelial neoplasia: A prospective cohort study.

OBJECTIVE: The gold standard of cervical intraepithelial neoplasia (CIN) treatment is large loop excision of the transformation zone (LLETZ) after histopathological diagnosis from punch biopsies. In addition, treatment may be appropriate at initial colposcopy. Our objective was to study the applicability of immediate treatment strategy according to clinical parameters. METHODS: We conducted a prospective cohort study among patients referred to colposcopy at Helsinki University Hospital, Finland, between January 2014, and September 2018 (ISRCTN10933736). Patients treated with LLETZ, either after biopsies or immediately at initial colposcopy, were included. The main outcome measure was overtreatment (OT) rate defined as normal or low-grade histopathological findings in LLETZ specimen within both treatment groups. RESULTS: A total of 572 patients treated with LLETZ were included: 360 treated after biopsies and 212 treated immediately at initial colposcopy. When LLETZ was performed immediately after high-grade referral cytology and with colposcopic impression of high-grade disease, the overtreatment (OT) rate was 10.0% (95% CI 9.10 to 17.2), whereas when LLETZ was done after biopsy-confirmed high-grade lesions, the OT rate was 18.9% (95% CI 14.7 to 23.7), resulting in risk difference (RD) -8.91% (95% CI -16.0 to -1.82). Among HPV16/18 positive patients the OT rate was 8.22% (95% CI 3.08 to 17.0) for immediate treatment, resulting in RD of -10.7% (95% CI -18.3 to -3.04) compared to LLETZ after biopsies. CONCLUSIONS: Immediate LLETZ does not result in overtreatment when applied on selected cases, especially after high-grade referral cytology and when high-grade lesion is also colposcopically suspected.

Management of major obstetric hemorrhage prior to peripartum hysterectomy and outcomes across nine European countries.

INTRODUCTION: Peripartum hysterectomy is applied as a surgical intervention of last resort for major obstetric hemorrhage. It is performed in an emergency setting except for women with a strong suspicion of placenta accreta spectrum (PAS), where it may be anticipated before cesarean section. The aim of this study was to compare management strategies in the case of obstetric hemorrhage leading to hysterectomy, between nine European countries participating in the International Network of Obstetric Survey Systems (INOSS), and to describe pooled maternal and neonatal outcomes following peripartum hysterectomy. MATERIAL AND METHODS: We merged data from nine nationwide or multi-regional obstetric surveillance studies performed in Belgium, Denmark, Finland, France, Italy, the Netherlands, Slovakia, Sweden and the UK collected between 2004 and 2016. Hysterectomies performed from 22 gestational weeks up to 48 h postpartum due to obstetric hemorrhage were included. Stratifying women with and without PAS, procedures performed in the management of obstetric hemorrhage prior to hysterectomy between countries were counted and compared. Prevalence of maternal mortality, complications after hysterectomy and neonatal adverse events (stillbirth or neonatal mortality) were calculated. RESULTS: A total of 1302 women with peripartum hysterectomy were included. In women without PAS who had major obstetric hemorrhage leading to hysterectomy, uterotonics administration was lowest in Slovakia (48/73, 66%) and highest in Denmark (25/27, 93%), intrauterine balloon use was lowest in Slovakia (1/72, 1%) and highest in Denmark (11/27, 41%), and interventional radiology varied between 0/27 in Denmark and Slovakia to 11/59 (79%) in Belgium. In women with PAS, uterotonics administration was lowest in Finland (5/16, 31%) and highest in the UK (84/103, 82%), intrauterine balloon use varied between 0/14 in Belgium and Slovakia to 29/103 (28%) in the UK. Interventional radiology was lowest in Denmark (0/16) and highest in Finland (9/15, 60%). Maternal mortality occurred in 14/1226 (1%), the most common complications were hematologic (95/1202, 8%) and respiratory (81/1101, 7%). Adverse neonatal events were observed in 79/1259 (6%) births. CONCLUSIONS: Management of obstetric hemorrhage in women who eventually underwent peripartum hysterectomy varied greatly between these nine European countries. This potentially life-saving procedure is associated with substantial adverse maternal and neonatal outcome.

Methylation in Predicting Progression of Untreated High-grade Cervical Intraepithelial Neoplasia.

BACKGROUND: There is no prognostic test to ascertain whether cervical intraepithelial neoplasias (CINs) regress or progress. The majority of CINs regress in young women, and treatments increase the risk of adverse pregnancy outcomes. We investigated the ability of a DNA methylation panel (the S5 classifier) to discriminate between outcomes among young women with untreated CIN grade 2 (CIN2). METHODS: Baseline pyrosequencing methylation and human papillomavirus (HPV) genotyping assays were performed on cervical cells from 149 women with CIN2 in a 2-year cohort study of active surveillance. RESULTS: Twenty-five lesions progressed to CIN grade 3 or worse, 88 regressed to less than CIN grade 1, and 36 persisted as CIN1/2. When cytology, HPV16/18 and HPV16/18/31/33 genotyping, and the S5 classifier were compared to outcomes, the S5 classifier was the strongest biomarker associated with regression vs progression. The S5 classifier alone or in combination with HPV16/18/31/33 genotyping also showed significantly increased sensitivity vs cytology when comparing regression vs persistence/progression. With both the S5 classifier and cytology set at a specificity of 38.6% (95% confidence interval [CI], 28.4-49.6), the sensitivity of the S5 classifier was significantly higher (83.6%; 95% CI, 71.9-91.8) than of cytology (62.3%; 95% CI, 49.0-74.4; P = 0.005). The highest area under the curve was 0.735 (95% CI, 0.621-0.849) in comparing regression vs progression with a combination of the S5 classifier and cytology, whereas HPV genotyping did not provide additional information. CONCLUSIONS: The S5 classifier shows high potential as a prognostic biomarker to identify progressive CIN2.

Incidence of Lichen Planus and Subsequent Mortality in Finnish Women.

The incidence pattern of lichen planus (LP) and LP-related mortality are unknown. The aim of this study was to assess these factors, based on Finnish nationwide registry data including 13,378 women with LP diagnosed during 1969 to 2012. The incidence rate for LP in 2003 to 2012 was 28 per 100,000 woman-years age-adjusted to the European Standard Population. Mortality was assessed using the standardized mortality ratio (SMR) with national mortality rates as the reference. All-cause mortality was increased (SMR 1.07, 95% confidence interval (95% CI) 1.02-1.11), with excess mortality from Hodgkin lymphoma (SMR 6.73, 95% CI 1.83-17.2), non-Hodgkin lymphoma (SMR 1.68, 95% CI 1.11-2.44), cancer of the oral cavity (SMR 10.5, 95% CI 5.99-17.0), cancer of the tongue (SMR 7.25, 95% CI 3.13-14.3), infections (SMR 1.78, 95% CI 1.14-2.64), respiratory diseases (SMR 1.31, 95% CI 1.07-1.57), and diseases of the digestive system (SMR 1.39, 95% CI 1.09-1.75). In conclusion, LP is a common disease and patients seem to have an impaired long-term prognosis.

Epidemiological analysis of peripartum hysterectomy across nine European countries.

INTRODUCTION: Peripartum hysterectomy is a surgical procedure performed for severe obstetric complications such as major obstetric hemorrhage. The prevalence of peripartum hysterectomy in high-resource settings is relatively low. Hence, international comparisons and studying indications and associations with mode of birth rely on the use of national obstetric survey data. Objectives were to calculate the prevalence and indications of peripartum hysterectomy and its association with national cesarean section rates and mode of birth in nine European countries. MATERIAL AND METHODS: We performed a descriptive, multinational, population-based study among women who underwent peripartum hysterectomy. Data were collected from national or multiregional databases from nine countries participating in the International Network of Obstetric Survey Systems. We included hysterectomies performed from 22 gestational weeks up to 48 hours postpartum for obstetric hemorrhage, as this was the most restrictive, overlapping case definition between all countries. Main outcomes were prevalence and indications of peripartum hysterectomy. Additionally, we compared prevalence of peripartum hysterectomy between women giving birth vaginally and by cesarean section, and between women giving birth with and without previous cesarean section. Finally, we calculated correlation between prevalence of peripartum hysterectomy and national cesarean section rates, as well as national rates of women giving birth after a previous cesarean section. RESULTS: A total of 1302 peripartum hysterectomies were performed in 2 498 013 births, leading to a prevalence of 5.2 per 10 000 births ranging from 2.6 in Denmark to 10.7 in Italy. Main indications were uterine atony (35.3%) and abnormally invasive placenta (34.8%). Relative risk of hysterectomy after cesarean section compared with vaginal birth was 9.1 (95% CI 8.0-10.4). Relative risk for hysterectomy for birth after previous cesarean section compared with birth without previous cesarean section was 10.6 (95% CI 9.4-12.1). A strong correlation was observed between national cesarean section rate and prevalence of peripartum hysterectomy (ρ = 0.67, P < .05). CONCLUSIONS: Prevalence of peripartum hysterectomy may vary considerably between high-income countries. Uterine atony and abnormally invasive placenta are the commonest indications for hysterectomy. Birth by cesarean section and birth after previous cesarean section are associated with nine-fold increased risk of peripartum hysterectomy.

Age-specific HPV type distribution in high-grade cervical disease in screened and unvaccinated women.

BACKGROUND AND AIM: Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination type-distribution helps to anticipate changes induced by mass vaccination and optimize screening. METHODS: We recruited 1279 women referred to colposcopy for abnormal cytology into a population-based study on HPV type distribution in diagnostic cervical samples (ISRCTN10933736). The HPV genotyping findings were grouped as: HPV16/18+, other hrHPV+ (HPV31/33/35/39/45/51/52/56/58/59/66/68), non-vaccine targeted hrHPV+ (HPV35/39/51/56/59/66/68), low-risk HPV, and HPV negative. We estimated the HPV group-specific prevalence rates according to diagnostic histopathological findings in the age groups of <30 (n = 339), 30-44.9 (n = 614), and ≥45 (n = 326). RESULTS: Altogether 503 cases with high grade squamous intraepithelial lesion or worse (HSIL+) were diagnosed. More than half, 285 (56.7%) of HSIL+ cases were associated with HPV16/18: 64.3% (101/157) in women <30 years (reference group), 58.4% (157/269) in women 30-44.9 years (risk ratio (RR) 0.91, 95% confidence interval (95% CI) 0.78-1.06), and 35.1% (27/77) in women ≥45 years of age (RR 0.55, 95% CI 0.39-0.75). Conversely, other hrHPV's were associated with 191 (38.0%) of HSIL+: 31.9% (50/157) in women <30, 36.8% (99/269) in women 30-44.9 years, 54.6% (42/77) and in women ≥45 (RR 1.71, 95% CI 1.26-2.33). The proportion of non-vaccine targeted hrHPV and HPV negative HSIL+ increased with advancing age. CONCLUSIONS: Pre-vaccination HPV type distribution in HSIL+ was distinctly polarised by age with HPV16/18 attributed disease being markedly more prevalent in women aged <30. In the older women the other hrHPV types, however, dominated suggesting a need for more age-dependent screening strategies.

Lessons learnt from anonymized review of cases of peripartum hysterectomy by international experts: A qualitative pilot study.

Severe obstetric complications are not extensively studied and individual cases are used too little and inappropriately in quality improvement activities, due to limited numbers and prioritization of quantitative research. Nordic and European experts performed a qualitative pilot study using anonymized cases of peripartum hysterectomy. It was feasible to anonymize narratives and we learned lessons in the form of themes for improved clinical care and future research. Therefore, we plan a Nordic anonymized review of the care of women who have undergone peripartum hysterectomy based on narratives. The qualitative outcomes of clinically relevant themes for quality improvement and research will add value to the quantitative analyses from the Nordic medical birth registries. In the longer term, we believe that qualitative audits should be an essential part of the process of continuing improvement in maternity care.

Cancer risk of Lichen planus: A cohort study of 13,100 women in Finland.

The association between Lichen planus (LP) and cancer has been under debate for decades. We studied the connection via population-based Finnish register data. All women with the diagnosis of LP (n = 13,100) were identified from the Finnish Hospital Discharge Registry from 1969-2012. These patients were linked with subsequent cancer diagnoses from the Finnish Cancer Registry until 2014. Standardized incidence ratios (SIRs) were counted for different cancers by dividing the observed numbers of cancers by expected numbers, which were based on national cancer incidence rates. In total, 1,520 women with LP were diagnosed with cancer (SIR 1.15, 95% confidence interval [CI] 1.09-1.20). LP was associated with an increased risk of cancer of lip (SIR 5.17, 95% CI 3.06-8.16), cancer of tongue (SIR 12.4, 95% CI 9.45-16.0), cancer of oral cavity (SIR 7.97, 95% CI 6.79-9.24), cancer of esophagus (SIR 1.95, 95% CI 1.17-3.04), cancer of larynx (SIR of 3.47, 95% CI 1.13-8.10) and cancer of vulva (SIR 1.99, 95% CI 1.18-3.13). The risk of cancer was not increased in other locations where LP manifests (pharynx and skin). Patients with diagnosed LP have an increased risk of developing cancer of lip, tongue, oral cavity, esophagus, larynx and vulva. These data are important when considering treatment and follow-up of patients with LP diagnosis.

Risk of preterm birth in women with cervical intraepithelial neoplasia grade one: a population-based cohort study.

INTRODUCTION: In this population-based register study our objective was to explore the association of cervical intraepithelial neoplasia, grade 1 and loop electrosurcigal excision procedure with preterm birth. MATERIAL AND METHODS: Our population consisted of 4759 women diagnosed with cervical intraepithelial neoplasia, grade 1 during 1997-2009 and their 3021 subsequent deliveries analyzed by loop electrosurcigal excision procedure and parity. Hospital Discharge Register was used to identify women diagnosed for cervical intraepithelial neoplasia, grade 1 and these data were linked with the Medical Birth Register data. We calculated odds ratios with 95% confidence intervals. RESULTS: Cervical intraepithelial neoplasia, grade 1 patients with loop electrosurcigal excision procedure had 54 (6.7%) subsequent preterm births and the corresponding figure among cervical intraepithelial neoplasia, grade 1 patients without loop electrosurcigal excision procedure was 116 (5.2%). This results in odds ratios 1.31 (95% confidence interval 0.94-1.83). We assessed the risk before and after diagnosis of cervical intraepithelial neoplasia, grade 1 both for patients with loop electrosurcigal excision procedure (odds ratios 1.47, 95% confidence interval 1.05-2.06) and without loop electrosurcigal excision procedure (odds ratios 0.90, 95% confidence interval 0.71-1.13). An increased risk for preterm birth after diagnosis of cervical intraepithelial neoplasia, grade 1 and loop electrosurcigal excision procedure was observed. We also compared both groups to the background population in the Medical Birth Register. For cervical intraepithelial neoplasia, grade 1 patients without loop electrosurcigal excision procedure the risk for preterm birth was not increased (odds ratios 0.95, 95% confidence interval 0.76-1.21) whereas for cervical intraepithelial neoplasia, grade 1 patients treated with loop electrosurcigal excision procedure the risk for preterm birth was increased (odds ratios 1.45, 95% confidence interval 1.02-1.92). CONCLUSIONS: Loop electrosurcigal excision procedure itself increases the risk for preterm birth. Cervical intraepithelial neoplasia, grade 1 as such does not increase the risk for preterm birth.

Lichen sclerosus and risk of cancer.

Malignant potential of lichen sclerosus (LS) has been suspected, but evidence is sparse. We used the population-based Finnish Cancer Registry data to further study this connection. We identified all women with the diagnosis of LS (n = 7,616) listed in the Finnish Hospital Discharge Registry from 1970 to 2012. The cohort was followed through the Finnish Cancer Registry for subsequent cancer diagnoses until 2014. Standardized incidence ratios (SIRs) were calculated for different cancers by dividing the observed numbers of cancers by expected ones. The expected numbers were based on national cancer incidence rates. During the follow-up period, we found 812 cancers among patients with LS (SIR: 1.13, 95% CI 1.05-1.21). LS was associated with an increased risk of vulvar (182 cases, SIR: 33.6, 95% CI 28.9-38.6) and vaginal cancer (4 cases, SIR: 3.69, 95% CI 1.01-9.44). The risk of cancers of the uterine cervix and lung was significantly decreased. LS is associated with an increased risk for vulvar and vaginal cancer. These data are important when designing the care of women diagnosed with LS.

National Rates of Uterine Rupture are not Associated with Rates of Previous Caesarean Delivery: Results from the Nordic Obstetric Surveillance Study.

BACKGROUND: Previous caesarean delivery and intended mode of delivery after caesarean are well-known individual risk factors for uterine rupture. We examined if different national rates of uterine rupture are associated with differences in national rates of previous caesarean delivery and intended mode of delivery after a previous caesarean delivery. METHODS: This study is an ecological study based on data from a retrospective cohort in the Nordic countries. Data on uterine rupture were collected prospectively in each country as part of the Nordic obstetric surveillance study and included 91% of all Nordic deliveries. Information on the comparison population was retrieved from the national medical birth registers. Incidence rate ratios by previous caesarean delivery and intended mode of delivery after caesarean were modelled using Poisson regression. RESULTS: The incidence of uterine rupture was 7.8/10 000 in Finland and 4.6/10 000 in Denmark. Rates of caesarean (21.3%) and previous caesarean deliveries (11.5%) were highest in Denmark, while the rate of intended vaginal delivery after caesarean was highest in Finland (72%). National rates of uterine rupture were not associated with the population rates of previous caesarean but increased by 35% per 1% increase in the population rate of intended vaginal delivery and in the subpopulation of women with previous caesarean delivery by 4% per 1% increase in the rate of intended vaginal delivery. CONCLUSION: National rates of uterine rupture were not associated with national rates of previous caesarean, but increased with rates of intended vaginal delivery after caesarean.

Mode of first delivery and severe maternal complications in the subsequent pregnancy.

INTRODUCTION: Severe obstetric complications increase with the number of previous cesarean deliveries. In the Nordic countries most women have two children. We present the risk of severe obstetric complications at the delivery following a first elective or emergency cesarean and the risk by intended mode of second delivery. MATERIAL AND METHODS: A two-year population-based data collection of severe maternal complications in women with two deliveries in the Nordic countries (n = 213 518). Denominators were retrieved from the national medical birth registers. RESULTS: Of 35 450 first cesarean deliveries (17%), 75% were emergency and 25% elective. Severe complications at second delivery were more frequent in women with a first cesarean than with a first vaginal delivery, and rates of abnormally invasive placenta, uterine rupture and severe postpartum hemorrhage were higher after a first elective than after a first emergency cesarean delivery [relative risk (RR) 4.1, 95% confidence intervals (CI) 2.0-8.1; RR 1.8, 95% CI 1.3-2.5; RR 2.3, 95% CI 1.5-3.5, respectively]. A first cesarean was associated with up to 97% of severe complications in the second pregnancy. Induction of labor was associated with an increased risk of uterine rupture and severe hemorrhage. CONCLUSION: Elective repeat cesarean can prevent complete uterine rupture at the second delivery, whereas the risk of severe obstetric hemorrhage, abnormally invasive placenta and peripartum hysterectomy is unchanged by the intended mode of second delivery in women with a first cesarean. Women with a first elective vs. an emergency cesarean have an increased risk of severe complications in the second pregnancy.

Pain Sensation During Colposcopy and Cervical Biopsy, With or Without Local Anesthesia: A Randomized Trial.

OBJECTIVE: The aim of the study was to determine whether an injection of a local anesthetic is more painful than a cervical punch biopsy without local anesthesia. MATERIALS AND METHODS: The study was a randomized controlled trial, conducted at the Helsinki University Central Hospital. It consisted of 204 women referred for colposcopic assessments. Half of them were randomized to receive local anesthesia before their cervical punch biopsies. After the injection of the local anesthetic, the cervical punch biopsy, and the endocervical curettage, the women scored their actual pain using a 10-cm visual analog scale (VAS).To measure the difference in VAS scores between two groups, a linear regression model was used. Binomial regression model was applied for comparing the probability of experiencing unbearable pain between the groups. Applying modeling approach allowed also for proper adjustment for other potential risk factors. RESULTS: The mean VAS score for the injection of the local anesthetic was 2.7, the VAS score for the cervical punch biopsy without local anesthesia was 3.5, and the difference was 0.8 (p = .017; 95% CI = 0.1-1.5). The mean VAS for the biopsy with local anesthesia was 0.8, which was significantly lower than the mean VAS for the biopsy without local anesthesia (difference = 2.7; p < .001; 95% CI = 2.2-3.3). The relative risk for experiencing moderate or severe pain (VAS ≥ 5) was 0.6 (p = .03; 95% CI = 0.3-0.9) for the injection of local anesthetic versus the biopsy without local anesthesia. CONCLUSIONS: Injection of a local anesthetic for colposcopy is less painful than biopsies without local anesthesia, and local anesthesia decreases the pain perceived.

Randomised trial on treatment of vaginal intraepithelial neoplasia-Imiquimod, laser vaporisation and expectant management.

Vaginal intraepithelial neoplasia (VAIN) is associated with human papillomavirus (HPV) infection. The most common treatment modality is laser vaporisation, but recurrences are common. Imiquimod is an immune response modulator which is used for the treatment of external condylomas and other HPV-related genital neoplasias. The aim of the study was to evaluate the efficacy and tolerability of vaginally administered imiquimod in comparison with laser vaporisation and expectant management of high-grade VAIN. This proof of principle pilot study was a prospective 16-week randomised trial. We enrolled 30 patients with histologically confirmed VAIN 2 or 3 into three study arms: vaginally administered imiquimod, laser vaporisation and expectant management. Follow-up colposcopy visits included high-risk human papillomavirus (hrHPV) testing, cytology and punch biopsies. At baseline 77% (n = 20/26) of the patients were hrHPV positive. HPV clearance was significantly higher in the imiquimod arm (63%, n = 5/8) than in the laser arm (11%, n = 1/9) (p = 0.05) or in the expectant management arm (17%, n = 1/6) (p = 0.138). At baseline 25 patients (83%) had VAIN 2 and five (17%) had VAIN 3. None of the lesions progressed during the follow-up. Histological regression (≤VAIN 1) was observed in 80% (n = 8/10) of patients in the imiquimod arm, 100% (n = 10/10) of the laser arm (p = 0.474) and 67% (n = 6/9) of the expectant management arm (p = 0.628). Vaginal imiquimod appears to be as effective as laser treatment in high-grade VAIN.

Neonatal outcomes after the obstetric near-miss events uterine rupture, abnormally invasive placenta and emergency peripartum hysterectomy - prospective data from the 2009-2011 Finnish NOSS study.

INTRODUCTION: Neonatal outcomes after the maternal obstetric near-miss complications of uterine rupture, abnormally invasive placenta, and emergency peripartum hysterectomy were assessed. MATERIAL AND METHODS: This case-control study was conducted as part of the Nordic Obstetric Surveillance Study (NOSS). Data on 211 newborns from 197 deliveries in which an obstetric near-miss complication was involved, were collected prospectively from April 2009 to August 2011 from all Finnish delivery units via questionnaires. Missing cases were obtained from national health registers and confirmed by the clinics. Control populations consisted of all other children born during the same period of time in the Finnish Medical Birth Register (n = 147 551). RESULTS: The number of stillbirths in this cohort was high [n = 8, 3.8% vs. 0.3% among controls, odds ratio (OR) 12.5, 95% confidence interval (CI) 6.32-24.9]. In addition, there were two neonatal deaths. The majority of cases (n = 8, 80%) were connected to uterine rupture. The risk of severe birth asphyxia diagnosis was increased compared with controls (n = 17, 8.1% vs. 0.1%, OR 137, 95% CI 82.7-226). A low umbilical artery pH (<7.05) was also observed among these neonates (28.8% vs. 1.0%, OR 28.7, 95% CI 21.5-38.2). Post-term pregnancies were relatively common among the uterine rupture cases. Adverse neonatal outcomes in the AIP and emergency peripartum hysterectomy cases were associated with preterm deliveries. CONCLUSIONS: The prospective data collected from clinicians, combined with the information gathered from national health registers, provided valuable insights into rare maternal near-miss cases. These complications also predisposed stillbirth and neonatal death. In this study, 75% of fetal losses were associated with uterine rupture.

Emergency peripartum hysterectomy: results from the prospective Nordic Obstetric Surveillance Study (NOSS).

OBJECTIVE: To assess the prevalence and risk factors of emergency peripartum hysterectomy. DESIGN: Nordic collaborative study. POPULATION: 605 362 deliveries across the five Nordic countries. METHODS: We collected data prospectively from patients undergoing emergency peripartum hysterectomy within 7 days of delivery from medical birth registers and hospital discharge registers. Control populations consisted of all other women delivering on the same units during the same time period. MAIN OUTCOME MEASURES: Emergency peripartum hysterectomy rate. RESULTS: The total number of emergency peripartum hysterectomies reached 211, yielding an incidence rate of 3.5/10 000 (95% confidence interval 3.0-4.0) births. Finland had the highest prevalence (5.1) and Norway the lowest (2.9). Primary indications included an abnormally invasive placenta (n = 91, 43.1%), atonic bleeding (n = 69, 32.7%), uterine rupture (n = 31, 14.7%), other bleeding disorders (n = 12, 5.7%), and other indications (n = 8, 3.8%). The delivery mode was cesarean section in nearly 80% of cases. Previous cesarean section was reported in 45% of women. Both preterm and post-term birth increased the risk for emergency peripartum hysterectomy. The number of stillbirths was substantially high (70/1000), but the case fatality rate stood at 0.47% (one death, maternal mortality rate 0.17/100 000 deliveries). CONCLUSIONS: A combination of prospective data collected from clinicians and information gathered from register-based databases can yield valuable data, improving the registration accuracy for rare, near-miss cases. However, proper and uniform clinical guidelines for the use of well-defined international diagnostic codes are still needed.

The Nordic Obstetric Surveillance Study: a study of complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery.

OBJECTIVE: To assess the rates and characteristics of women with complete uterine rupture, abnormally invasive placenta, peripartum hysterectomy, and severe blood loss at delivery in the Nordic countries. DESIGN: Prospective, Nordic collaboration. SETTING: The Nordic Obstetric Surveillance Study (NOSS) collected cases of severe obstetric complications in the Nordic countries from April 2009 to August 2012. SAMPLE AND METHODS: Cases were reported by clinicians at the Nordic maternity units and retrieved from medical birth registers, hospital discharge registers, and transfusion databases by using International Classification of Diseases, 10th revision codes on diagnoses and the Nordic Medico-Statistical Committee Classification of Surgical Procedure codes. MAIN OUTCOME MEASURES: Rates of the studied complications and possible risk factors among parturients in the Nordic countries. RESULTS: The studied complications were reported in 1019 instances among 605 362 deliveries during the study period. The reported rate of severe blood loss at delivery was 11.6/10 000 deliveries, complete uterine rupture was 5.6/10 000 deliveries, abnormally invasive placenta was 4.6/10 000 deliveries, and peripartum hysterectomy was 3.5/10 000 deliveries. Of the women, 25% had two or more complications. Women with complications were more often >35 years old, overweight, with a higher parity, and a history of cesarean delivery compared with the total population. CONCLUSION: The studied obstetric complications are rare. Uniform definitions and valid reporting are essential for international comparisons. The main risk factors include previous cesarean section. The detailed information collected in the NOSS database provides a basis for epidemiologic studies, audits, and educational activities.

The Nordic medical birth registers--a potential goldmine for clinical research.

The Nordic medical birth registers have long been used for valuable clinical research. Their collection of data for more than four decades offers unusual possibilities for research across generations. At the same time, serum and blotting paper blood samples have been stored from most neonates. Two large cohorts (approximately 100 000 births) in Denmark and Norway have been described by questionnaires, interviews and collection of biological samples (blood, urine and milk teeth), as well as a systematic prospective follow-up of the offspring. National patient registers provide information on preceding, underlying and present health problems of the parents and their offspring. Researchers may, with permission from the national authorities, obtain access to individualized or anonymized data from the registers and tissue-banks. These data allow for multivariate analyses but their usefulness depends on knowledge of the specific registers and biological sample banks and on proper validation of the registers.