Induction of labour at 41 weeks of gestation versus expectant management and induction of labour at 42 weeks of gestation: A cost-effectiveness analysis.

OBJECTIVE: To assess the cost-effectiveness of induction of labour (IOL) at 41 weeks of gestation compared with expectant management until 42 weeks of gestation. DESIGN: A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. SETTING: Fourteen Swedish hospitals during 2016-2018. POPULATION: Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41 weeks of gestation to IOL or to expectant management and induction at 42 weeks of gestation. METHODS: Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. MAIN OUTCOME MEASURES: The cost per gained life year and per gained QALY. RESULTS: The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was €4108 in the IOL group (n = 1373) and €4037 in the expectant management group (n = 1373), with a mean difference of €71 (95% CI -€232 to €379). The ICER for IOL compared with expectant management was €545 per life year gained and €623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. CONCLUSIONS: Induction of labour at 41 weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42 weeks of gestation using standard threshold values for acceptable cost per life year/QALY. TWEETABLE ABSTRACT: Induction of labour at 41 weeks of gestation is cost-effective compared with expectant management until 42 weeks of gestation.

Effect of second-trimester sonographic cervical length on the risk of spontaneous preterm delivery in different risk groups: A prospective observational multicenter study.

INTRODUCTION: The aim of the study is to compare the effect of cervical length measured with transvaginal ultrasound in the second trimester on the risk of spontaneous preterm delivery (PTD) between different risk groups of asymptomatic women with a singleton pregnancy. MATERIAL AND METHODS: This is a pre-planned exploratory analysis of the CERVIX study, a prospective blinded multicenter diagnostic accuracy study. Asymptomatic women with a singleton pregnancy were consecutively recruited at their second-trimester routine ultrasound examination at seven Swedish ultrasound centers. Cervical length was measured with transvaginal ultrasound at 18-20 weeks (Cx1; n = 11 072) and 21-23 weeks (Cx2, optional; n = 6288). The effect of cervical length on the risk of spontaneous PTD and its discriminative ability was compared between women with: (i) previous spontaneous PTD, late miscarriage or cervical conization (high-risk group; n = 1045); (ii) nulliparae without risk factors (n = 5173); (iii) parae without risk factors (n = 4740). Women with previous indicated PTD were excluded (n = 114). Main outcome measures were: effect of cervical length on the risk of spontaneous PTD expressed as odds ratio per 5-mm decrease in cervical length with interaction analysis using logistic regression to test whether the effect differed between groups, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, number needed to screen to detect one spontaneous PTD. RESULTS: The effect of cervical length at Cx2 on the risk of spontaneous PTD <33 weeks was similar in all groups (odds ratios 2.26-2.58, interaction p value 0.91). The discriminative ability at Cx2 was superior to that at Cx1 and was similar in all groups (AUC 0.69-0.76). Cervical length ≤25 mm at Cx2 identified 57% of spontaneous preterm deliveries <33 weeks in the high-risk group with number needed to screen 161. The number needed to screen for groups (ii) and (iii) were 1018 and 843. CONCLUSIONS: The effect of cervical length at 21-23 weeks on the risk of spontaneous PTD <33 weeks is similar in high- and low-risk pregnancies. The differences in number needed to screen should be considered before implementing a screening program.

Women's childbirth experiences in the Swedish Post-term Induction Study (SWEPIS): a multicentre, randomised, controlled trial.

OBJECTIVE: To compare childbirth experiences in women randomly assigned to either induction of labour at 41 weeks or to expectant management until 42 weeks, in the Swedish Post-term Induction Study. DESIGN: A register-based, multicentre, randomised, controlled, superiority trial. SETTING: Women were recruited at 14 hospitals in Sweden, 2016-2018. PARTICIPANTS: Women with an uncomplicated singleton pregnancy were recruited at 41 gestational weeks. INTERVENTIONS: The women were randomly assigned to induction of labour at 41 weeks (induction group, n=1381) or expectant management until 42 weeks (expectant management group, n=1379). OUTCOME MEASURES: As main outcome, women's childbirth experiences were measured using the Childbirth Experience Questionnaire version 2 (CEQ2), in 656 women, 3 months after the birth at three hospitals. As exploratory outcome, overall childbirth experience was measured in 1457 women using a Visual Analogue Scale (VAS 1-10) within 3 days after delivery at the remaining eleven hospitals. RESULTS: The total response rate was 77% (2113/2760). There were no significant differences in childbirth experience measured with CEQ2 between the groups (induction group, n=354; expectant management group, n=302) in the subscales: own capacity (2.8 vs 2.7, p=0.09), perceived safety (3.3 vs 3.2, p=0.06) and professional support (3.6 vs 3.5, p=0.38) or in the total CEQ2 score (3.3 vs 3.2, p=0.07), respectively. Women in the induction group scored higher in the subscale participation (3.6 vs 3.4, p=0.02), although with a small effect size (0.19). No significant difference was observed in overall childbirth experience according to VAS (8.0 (n=735) vs 8.1 (n=735), p=0.22). CONCLUSIONS: There were no differences in childbirth experience, according to CEQ2 or overall childbirth experience assessed with VAS, between women randomly assigned to induction of labour at 41 weeks or expectant management until 42 weeks. Overall, women rated their childbirth experiences high. TRIAL REGISTRATION NUMBER: ISRCTN26113652.

Second trimester cervical length measurements with transvaginal ultrasound: A prospective observational agreement and reliability study.

INTRODUCTION: Universal screening for preterm delivery by adding transvaginal ultrasound measurement of cervical length to routine second trimester ultrasound has been proposed. The aim is to estimate inter- and intraobserver agreement and reliability of second trimester transvaginal ultrasound measurements of cervical length performed by specially trained midwife sonographers. MATERIAL AND METHODS: This is a prospective reliability and agreement study performed in seven Swedish ultrasound centers. In total, 18 midwife sonographers specially trained to perform ultrasound measurements of cervical length and 286 women in the second trimester were included. In each center, two midwife sonographers measured cervical length a few minutes apart in the same woman, the number of women examined per examiner pair varying between 24 and 30 (LIVE study). Sixteen midwife sonographers measured cervical length twice ≥2 months apart on 93 video clips (CLIPS study). The main outcome measures were mean difference, limits of agreement, intraclass correlation coefficient, intra-individual standard deviation, repeatability, Cohen's kappa and Fleiss kappa. RESULTS: The limits of agreement and intraclass correlation coefficient of the best examiner pair in the LIVE study were -4.06 to 4.72 mm and 0.91, and those of the poorest were -11.11 to 11.39 mm and 0.31. In the CLIPS study, median (range) intra-individual standard deviation was 2.14 mm (1.40-3.46), repeatability 5.93 mm (3.88-9.58), intraclass correlation coefficient 0.84 (0.66-0.94). Median (range) interobserver agreement for cervical length ≤25 mm in the CLIPS study was 94.6% (84.9%-98.9%) and Cohen's kappa 0.56 (0.12-0.92), median (range) intraobserver agreement was 95.2% (87.1%-98.9%) and Cohen's kappa 0.68 (0.27-0.93). CONCLUSIONS: Agreement and reliability of cervical length measurements differed substantially between examiner pairs and examiners. If cervical length measurements are used to guide management there is potential for both over- and under-treatment. Uniform training and rigorous supervision and quality control are advised.

Safety of intravenous iron isomaltoside for iron deficiency and iron deficiency anemia in pregnancy.

PURPOSE: To evaluate the efficacy and safety for mother and child of using intravenous iron isomaltoside (IV-IIM) during pregnancy. METHODS: Using an appointment register, we retrospectively identified all pregnant women who received a single dose of 1000 or 1500 mg IV-IIM in the maternity ward of Falu Hospital and subsequently gave birth between August 6, 2013 and July 31, 2018. Women who received IV-IIM (case group) were individually matched with pregnant women who did not receive IV-IIM (control group) by delivery date, maternal age (± 2 years), and parity. Adverse drug reactions (ADRs), demographic characteristics, hemoglobin and s-ferritin counts, pregnancy and delivery complications, and infant data (APGAR score, pH at umbilical artery, birthweight, birth length, intrauterine growth restriction and neonatal ward admission). Data were obtained from electronic patient charts. SPSS was used for descriptive statistics. RESULTS: During the 5-year period, 213 women each received a single administration of IV-IIM. Ten (4.7%) ADRs occurred during IV-IIM administration. All ADRs were mild hypersensitivity reactions, abated spontaneously within a few minutes, and did not recur on rechallenge. No association between IIM dose and ADR frequency was noted. Maternal and fetal outcomes, including hemoglobin counts at delivery and postpartum, were similar in the case and control groups. CONCLUSION: These results support the convenience, safety, and efficacy of a single high-dose (up to 1500 mg) infusion of IV-IIM for iron deficiency or iron deficiency anemia during pregnancy.

Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS): multicentre, open label, randomised, superiority trial.

OBJECTIVE: To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with a low risk pregnancy compared with expectant management and induction of labour at 42 weeks. DESIGN: Multicentre, open label, randomised controlled superiority trial. SETTING: 14 hospitals in Sweden, 2016-18. PARTICIPANTS: 2760 women with a low risk uncomplicated singleton pregnancy randomised (1:1) by the Swedish Pregnancy Register. 1381 women were assigned to the induction group and 1379 were assigned to the expectant management group. INTERVENTIONS: Induction of labour at 41 weeks and expectant management and induction of labour at 42 weeks. MAIN OUTCOME MEASURES: The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score less than 7 at five minutes, pH less than 7.00 or metabolic acidosis (pH <7.05 and base deficit >12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, or obstetric brachial plexus injury. Primary analysis was by intention to treat. RESULTS: The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group. The composite primary perinatal outcome did not differ between the groups: 2.4% (33/1381) in the induction group and 2.2% (31/1379) in the expectant management group (relative risk 1.06, 95% confidence interval 0.65 to 1.73; P=0.90). No perinatal deaths occurred in the induction group but six (five stillbirths and one early neonatal death) occurred in the expectant management group (P=0.03). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups. CONCLUSIONS: This study comparing induction of labour at 41 weeks with expectant management and induction at 42 weeks does not show any significant difference in the primary composite adverse perinatal outcome. However, a reduction of the secondary outcome perinatal mortality is observed without increasing adverse maternal outcomes. Although these results should be interpreted cautiously, induction of labour ought to be offered to women no later than at 41 weeks and could be one (of few) interventions that reduces the rate of stillbirths. TRIAL REGISTRATION: Current Controlled Trials ISRCTN26113652.

Maternal and fetal characteristics affect discrepancies between pregnancy-dating methods: a population-based cross-sectional register study.

INTRODUCTION: Gestational age is estimated by ultrasound using fetal size as a proxy for age, although variance in early growth affects reliability. The aim of this study was to identify characteristics associated with discrepancies between last menstrual period-based (EDD-LMP) and ultrasound-based (EDD-US) estimated delivery dates. MATERIAL AND METHODS: We identified all singleton births (n = 1 201 679) recorded in the Swedish Medical Birth Register in 1995-2010, to assess the association between maternal/fetal characteristics and large negative and large positive discrepancies (EDD-LMP earlier than EDD-US and 10th percentile in the discrepancy distribution vs. EDD-LMP later than EDD-US and 90th percentile). Analyses were adjusted for age, parity, height, body mass index, smoking, and employment status. RESULTS: Women with a body mass index >40 kg/m2 had the highest odds for large negative discrepancies (-9 to -20 days) [odds ratio (OR) 2.16, 95% CI 2.01-2.33]. Other factors associated with large negative discrepancies were: diabetes, young maternal age, multiparity, body mass index between 30 and 39.9 kg/m2 or <18.5 kg/m2 , a history of gestational diabetes, female fetus, shorter stature (<-1 SD), a history of preeclampsia, smoking or snuff use, and unemployment. Large positive discrepancies (+4 to +20 days) were associated with male fetus (OR 1.80, 95% CI 1.77-1.83), age ≥30 years, multiparity, not living with a partner, taller stature (>+1 SD), and unemployment. CONCLUSIONS: Several maternal and fetal characteristics were associated with discrepancies between dating methods. Systematic associations of discrepancies with maternal height, fetal sex, and partly obesity, may reflect an influence on the precision of the ultrasound estimate due to variance in early growth.

Risk for girls can be adversely affected post-term due to underestimation of gestational age by ultrasound in the second trimester.

INTRODUCTION: Post-term pregnancies are associated with greater risks for mother and child. Accurate determination of gestational age is necessary for safe care. Female fetuses have been shown to be smaller than males at the time of second-trimester ultrasound (US) examination, leading to underestimation of their age and, potentially, greater impacts of perinatal complications in post-term girls than in post-term boys. The purpose of this study was to investigate the sex ratio of post-term births and differences in perinatal complications (stillbirth, low Apgar score, low birthweight, meconium aspiration and low umbilical artery pH) between post-term boys and girls according to dating method [second-trimester US and last menstrual period (LMP)]. MATERIAL AND METHODS: Data from gestational week ≥39 to delivery of 13 338 singleton pregnancies between 13 February 2006 and 15 January 2014, were collected from the Obstetrix(®) (Siemens Healthcare) medical records system in Dalarna County, Sweden. RESULTS: The neonatal male:female ratio increased with gestational age after week 40, as dated by US, reaching 1.69 in gestational week 42. This ratio remained 1 throughout gestation according to dating by the LMP. Post-term pregnancy increased the risks of meconium aspiration and low Apgar score, with no sex difference observed. CONCLUSIONS: US gestational dating indicated that more boys than girls were born post-term, whereas dating according to LMP revealed no sex difference. These results support the hypothesis that female fetuses are smaller than males, leading to underestimation of their gestational age, at the time of second-trimester US examination.

Pre-pregnancy restless legs syndrome (Willis-Ekbom Disease) is associated with perinatal depression.

OBJECTIVES: Both restless legs syndrome ([RLS], also known as Willis-Ekbom Disease [WED]) and depression are common during pregnancy. However, no prior studies have assessed if pregnant women with RLS have an elevated risk of depression during and/or after pregnancy. METHODS: 1,428 women who were pregnant in gestational week 16-17 were asked to participate in a longitudinal survey. They were followed by web-based questionnaires in gestational week 17 and 32, and 6 weeks after delivery. Data were also retrieved from prenatal and birth records. Two different sets of criteria were used to examine the prevalence of RLS in the cohort (International Restless Legs Syndrome Society Group standard criteria and the later developed CH-RLSQ11 questionnaire). The latter questionnaire attempts to exclude those with common "mimics" of RLS. RESULTS: Adjusted odds ratio for depression in gestational week 17, 32, and postpartum week 6 in relation to pre-pregnancy RLS onset and moderate to severe symptom severity were 4.74 (2.30 - 9.76), 3.67 (1.85 - 7.28), and 2.58 (1.28 - 5.21), respectively. No significant associations were seen in pregnant women with de novo RLS during pregnancy. When using the standard diagnostic RLS criteria and frequency of symptoms more than 2-3 days per week, the prevalence of RLS was 12.3%. With the CH-RLSQ11 questionnaire and the same threshold for frequency of symptoms the prevalence was 6.5%. CONCLUSION: Women with RLS onset before pregnancy with moderate or severe symptoms had an increased risk of both antenatal and postnatal depression. The self-reported prevalence of RLS during pregnancy is lower when a questionnaire dealing with "mimics" is used.

Periodic limb movements are associated with vasomotor symptoms.

STUDY OBJECTIVES: Periodic limb movements (PLMs) are characterized by involuntary movements of the lower extremity during sleep. The etiology of PLM has been suggested to involve the dopaminergic system which, in turn, can be modulated by estrogen. It is currently unknown whether PLMs are associated with the menopausal transition and/or concomitant vasomotor symptoms. The aim of the present study was to examine if objectively diagnosed PLMs (with and without arousals) are more common in postmenopausal women or in women with vasomotor symptoms. A secondary aim was to analyze the influence of PLMs on self-reported HRQoL. METHODS: A community-based sample of 348 women underwent full-night polysomnography. PLMs (index > 15) and associated arousals (PLM arousal index > 5) were evaluated according to AASM scoring rules. Health-related quality of life was measured using the SF-36 questionnaire. The occurrence of peri- and postmenopausal symptoms were evaluated by a questionnaire and plasma levels of follicle stimulating hormone (FSH) were measured. RESULTS: After adjusting for confounding factors, vasomotor symptoms remained a significant explanatory factor for the occurrence of PLMs (adj. OR 1.86, 95% CI 1.03-3.37). In women with PLM arousals, adjusted OR for vasomotor symptoms was 1.61, 95% CI 0.76-3.42. PLMs did not seem to affect HRQoL. CONCLUSION: We found that clinically significant PLMs, but not PLM with arousals, were more common among women with vasomotor symptoms, even after controlling for confounding factors. Menopausal status per se, as evidenced by FSH in the postmenopausal range, was not associated with PLMs.

When gender matters: restless legs syndrome. Report of the "RLS and woman" workshop endorsed by the European RLS Study Group.

Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

Health-related quality of life and restless legs syndrome among women in Sweden.

AIM: Restless legs syndrome (RLS) is a common neurological movement disorder with a female preponderance, an increasing prevalence with age and comorbidity. Previous studies on the relationship between health-related quality of life (HRQOL) and RLS are still sparse but knowledge is increasing. The aim of this study was to evaluate the unique impact of RLS on HRQOL in a population-based sample. METHODS: A random sample of 5000 women aged 25-64 years was selected from the general Swedish population. The women were sent diagnostic questions on RLS together with the Short Form 12 (SF-12) questionnaire for assessment of physical and mental HRQOL. The unique burden of RLS on HRQOL was analyzed by excluding RLS-positive women from four self-reported diagnostic groups (diabetes, depression, heart problems, muscle and joint pain) and by excluding subjects with these diagnoses from the group of RLS-positive women. RESULTS: Compared with mental SF-12 scores for the RLS-negative women in our population, mental HRQOL of the RLS sample in our study was lower in every age group but not significantly lower in the age group 35-44 years. Physical SF-12 scores for RLS-positive women were also below scores for RLS-negative women in every age group but significance was only found in women between 45 and 54 years. A unique burden of RLS on HRQOL remained after statistical adjustment for comorbidities. CONCLUSION: RLS-positive women had an impaired mental HRQOL compared to RLS-negative women in the studied population. The physical aspects of HRQOL were less affected among RLS-positive women. The impaired well-being among women with RLS further strengthens the importance of identifying women with this condition and evaluating their need for medication or other actions in order to improve their quality of life.

Sleep apnea and hormone replacement therapy: a pilot study and a literature review.

BACKGROUND: Sleep apnea syndrome (SAS) is a common condition and a risk factor of cardiovascular and cerebrovascular diseases. The purpose of this pilot study was to investigate the effect of a gestagen (trimegeston) and estradiol hormone combination on perimenopausal and postmenopausal women with SAS. METHODS: Four postmenopausal and one perimenopausal women were studied by polysomnography before and after treatment with hormone replacement therapy (HRT). RESULTS: The subjects had a mean reduction of the severity of their sleep apnea by 75% measured by apnea/hypopnea index. CONCLUSIONS: HRT might be an alternative in the treatment of SAS.