Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: A stepped wedge cluster randomised trial.

BACKGROUND: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. METHODS AND FINDINGS: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. CONCLUSIONS: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term. TRIAL REGISTRATION: The trial is registered with ISRCTN (41918550).

The impact of exclusion due to COVID-19 restrictions on partners' satisfaction with Swedish hospital postnatal ward care: A multi-methods approach.

BACKGROUND: To prevent the spread of SARS-CoV-2, hospitals around the world adopted protocols that, in varying ways, resulted in the exclusion of partners from hospital postnatal care wards. The objective of this study was to examine the effect this exclusion had on partners' satisfaction with postnatal care. METHODS: An online survey (the Swedish Pregnancy Panel) including free-text comments was conducted before and during the first wave of the COVID-19 pandemic; partners of pregnant women were recruited at an early ultrasound appointment and followed until 2 months after childbirth. Data were linked to the Swedish Pregnancy Register. RESULTS: The survey was completed by 524 partners of women who gave birth during the pandemic and 203 partners of women who gave birth before. Partners' satisfaction with hospital postnatal care dropped 29.8 percent (-0.94 OLS, 95% CI = -1.17 to -0.72). The drop was largest for partners of first-time mothers (-1.40 OLS, 95% CI = -1.69 to -1.11), but unrelated to clinical outcomes such as mode of birth and most social backgrounds, except higher income. The qualitative analysis showed that partners (1) felt excluded as partners and parents, (2) thought the strain on staff led to deficiencies in the care provided, and (3) perceived the decision about partner restrictions as illogical. CONCLUSIONS: The exclusion of partners from the hospital postnatal wards clearly impaired satisfaction with care, and partners of first-time mothers were particularly affected. Planning for future restrictions on partners from hospital wards should factor in these consequences.

Cervical excisional treatment increases the risk of intraamniotic infection in subsequent pregnancy complicated by preterm prelabor rupture of membranes.

BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia or very early stages of cervical cancer increases the risk of preterm prelabor rupture of membranes in subsequent pregnancies. The risk increases with the length of the excised cone. The subset of cases with preterm prelabor rupture of membranes and a history of cervical excisional treatment could also be at higher risk of intraamniotic infection/inflammation. However, there is a paucity of relevant information on this subject. OBJECTIVE: This study aimed to assess the differences in the rates of intraamniotic infection/inflammation and early-onset neonatal sepsis between singleton preterm prelabor rupture of membranes pregnancies without and with a history of cervical excisional treatment, and to investigate the association between these complications of preterm prelabor rupture of membranes and the excised cone length. STUDY DESIGN: This retrospective cohort study included 770 preterm prelabor rupture of membranes pregnancies in which transabdominal amniocentesis was performed as part of standard clinical management to assess the intraamniotic environment. The maternal and perinatal medical records of all included women were reviewed to obtain information on the absence or presence of history of cervical excisional treatment and neonatal outcomes. Women whose records contained any information on history of cervical excisional treatment were contacted by phone and in writing to inform them of the study and request permission to collect relevant information from their medical records. Women were divided into 4 subgroups according to the presence of microorganisms and/or their nucleic acids (through culturing and molecular biology methods) in amniotic fluid and/or intraamniotic inflammation (through amniotic fluid interleukin-6 concentration evaluation): intraamniotic infection (presence of both), sterile intraamniotic inflammation (intraamniotic inflammation alone), microbial invasion of the amniotic cavity without inflammation (presence of microorganisms and/or their nucleic acids in amniotic fluid alone), and negative amniotic fluid for infection/inflammation (absence of both). RESULTS: A history of cervical excisional treatment was found in 10% (76/765) of the women. Of these, 82% (62/76) had a history of only 1 treatment, and information on cone length was available for 97% (60/62) of them. Women with a history of cervical excisional treatment had higher rates of intraamniotic infection (with, 25% [19/76] vs without, 12% [85/689]; adjusted odds ratio, 2.5; adjusted P=.004), microbial invasion of the amniotic cavity without inflammation (with, 25% [19/76] vs without, 11% [74/689]; adjusted odds ratio, 3.1; adjusted P<.0001), and early-onset neonatal sepsis (with, 8% [11/76] vs without, 3% [23/689]; adjusted odds ratio, 2.9; adjusted P=.02) compared with those without such history. Quartiles of cone length (range: 3-32 mm) were used to categorize the women into 4 quartile subgroups (first: 3-8 mm; second: 9-12 mm; third: 13-17 mm; and fourth: 18-32 mm). Cone length of ≥18 mm was associated with higher rates of intraamniotic infection (with, 29% [5/15] vs without, 12% [85/689]; adjusted odds ratio, 3.0; adjusted P=.05), microbial invasion of the amniotic cavity without inflammation (with, 40% [6/15] vs without, 11% [74/689]; adjusted odds ratio, 6.1; adjusted P=.003), and early-onset neonatal sepsis (with, 20% [3/15] vs without, 3% [23/689]; adjusted odds ratio, 5.7; adjusted P=.02). CONCLUSION: History of cervical excisional treatment increases risks of intraamniotic infection, microbial invasion of the amniotic cavity without inflammation, and development of early-onset neonatal sepsis in a subsequent pregnancy complicated by preterm prelabor rupture of membranes.

Maternal human papillomavirus infection during pregnancy and preterm delivery: A mother-child cohort study in Norway and Sweden.

INTRODUCTION: Human papillomavirus (HPV) infection is common in women of reproductive age. Infection and inflammation are leading causes for preterm delivery (PTD), but the role of HPV infection in PTD and prelabor rupture of membranes (PROM) is unclear. We aimed to explore whether HPV infection during pregnancy in general, and high-risk-HPV (HR-HPV) infection specifically, increased the risk of PTD, preterm prelabor rupture of membranes (PPROM), PROM at term, and/or chorioamnionitis. MATERIAL AND METHODS: In pregnant women, who were participating in a prospective multicenter cohort study from a general population in Norway and Sweden (PreventADALL, ClinicalTrials.gov NCT02449850), HPV DNA was analyzed in available urine samples at mid-gestation (16-22 weeks) and at delivery, and in the placenta after delivery with Seegene Anyplex II HPV28 PCR assay. The risk of PTD, PPROM, PROM, and chorioamnionitis was analyzed using unadjusted and adjusted logistic regression analyses for any 28 HPV genotypes, including 12 HR-HPV genotypes, compared with HPV-negative women. Further, subgroups of HPV (low-risk/possibly HR-HPV, HR-HPV-non-16 and HR-HPV-16), persistence of HR-HPV from mid-gestation to delivery, HR-HPV-viral load, and presence of multiple HPV infections were analyzed for the obstetric outcomes. Samples for HPV analyses were available from 950 women with singleton pregnancies (mean age 32 years) at mid-gestation and in 753 also at delivery. RESULTS: At mid-gestation, 40% of women were positive for any HPV and 24% for HR-HPV. Of the 950 included women, 23 had PTD (2.4%), nine had PPROM (0.9%), and six had chorioamnionitis (0.6%). Of the term pregnancies, 25% involved PROM. The frequency of PTD was higher in HR-HPV-positive women (8/231, 3.5%) than in HPV-negative women (13/573, 2.3%) at mid-gestation, but the association was not statistically significant (odds ratio 1.55; 95% confidence interval 0.63-3.78). Neither any HPV nor subgroups of HPV at mid-gestation or delivery, nor persistence of HR-HPV was significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis. No HPV DNA was detected in placentas of women with PTD, PPROM or chorioamnionitis. CONCLUSIONS: HPV infection during pregnancy was not significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis among women from a general population with a low incidence of adverse obstetric outcomes.

Pregnancy Outcomes in Women With a Prior Cervical Intraepithelial Neoplasia Grade 3 Diagnosis : A Nationwide Population-Based Cohort Study With Sibling Comparison Design.

BACKGROUND: Treatment of cervical intraepithelial neoplasia grade 3 (CIN 3) removes or destroys part of the cervix and might subsequently influence pregnancy outcomes. OBJECTIVE: To investigate pregnancy outcomes in women diagnosed with CIN 3. DESIGN: Population- and sibling-matched cohort study. SETTING: Sweden, 1973 to 2018. PARTICIPANTS: The general population comparison included 78 450 singletons born to women diagnosed with CIN 3 and 784 500 matched singletons born to women in the general population who had no CIN 3 diagnosis; the sibling comparison included 23 199 singletons born to women diagnosed with CIN 3 and 28 135 singletons born to their sisters without a CIN 3 diagnosis. MEASUREMENTS: Preterm birth, including spontaneous or iatrogenic preterm birth; infection-related outcomes, including chorioamnionitis and infant sepsis; and early neonatal death, defined as death during the first week after birth. RESULTS: Compared with the matched general population, women previously diagnosed with CIN 3 were more likely to have a preterm birth, especially extremely preterm (22 to 28 weeks; odds ratio [OR], 3.00 [95% CI, 2.69 to 3.34]) or spontaneous preterm (OR, 2.12 [CI, 2.05 to 2.20]); infection-related outcomes, including chorioamnionitis (OR, 3.23 [CI, 2.89 to 3.62]) and infant sepsis (OR, 1.72 [CI, 1.60 to 1.86]); or early neonatal death (OR, 1.83 [CI, 1.61 to 2.09]). Sibling comparison analyses rendered largely similar results. Over time, the risk difference attenuated for all outcomes and disappeared for early neonatal death. LIMITATION: Lack of data on CIN 3 treatment and spontaneous abortion. CONCLUSION: History of CIN 3 is associated with adverse pregnancy outcomes even after accounting for familial factors. Decreasing risk estimates over time suggest that adverse pregnancy outcomes among women diagnosed with CIN 3 may be minimized by improving treatment methods. PRIMARY FUNDING SOURCE: The Swedish Research Council, the Swedish Cancer Society, and the Swedish Research Council for Health, Working Life and Welfare.

Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden.

BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia (CIN) has been associated with increased risk of preterm delivery (PTD), although the underlying mechanism is as yet unclear. Studies on formalin-fixed excised tissue indicate that the risk increases with cone-length, but the magnitude of increase is uncertain, especially in case of minor excisions (≤10 mm), as well compared to women with untreated CIN during pregnancy. This study assesses the impact of cone-length at previous treatment for CIN as well as diagnosis of CIN during pregnancy on the risk of PTD. METHODS: A register-based cohort study in western Sweden linking cervical cytology, histology, and treatment data from the Swedish National Cervical Screening Registry to data on obstetric outcomes in singleton pregnancies 2008-2016 from the Swedish Medical Birth Registry. These groups were compared for PTD and other obstetric outcomes: (1) women with one excisional treatment (n=3250, including a subgroup (n=2408) with cone-length measured before fixation; (2) women with untreated CIN diagnosed during pregnancy (n=1380); and (3) women with normal cytology (n=42,398). Logistic regression analyses were adjusted for socioeconomic and health-related confounders. RESULTS: Treated women had increased risk of PTD (adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.21-2.12), spontaneous PTD (aOR 1.95, 95% CI 1.40-2.72) and preterm prelabor rupture of membranes (pPROM) (aOR 2.74, 95% CI 1.66-4.51) compared to the CIN during pregnancy group. ORs were similar when compared to the normal cytology group. Risks of these outcomes increased with cone-length. Mean cone-length was 9.1 mm. Cone-length ≤10 mm was associated with increased risk of PTD (aOR 1.41, 95% CI 1.02-1.94), spontaneous PTD (aOR 1.73, 95% CI 1.18-2.54), and pPROM (aOR 2.44, 95% CI 1.40-4.28), compared to the CIN during pregnancy group. The PTD risk was similar for cone-lengths 3-10 mm, thereafter increasing by 15% with each additional millimeter. CONCLUSIONS: This study suggests that all excisional treatment, including small cones, are associated with increased risk of PTD and pPROM. Risks increase further with cone-length. In women of reproductive age, clinicians should aim to remove all CIN but minimal healthy cervical tissue. Cone-length should be recorded at treatment, for future prenatal risk estimation.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.

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.

Challenges imposed by the COVID-19 pandemic on the Obstetrics and Gynecology residency program: a mixed-methods Swedish survey in the COPE Staff cohort study.

BACKGROUND: To outline how the training program and work situation of residents in Obstetrics and Gynecology (OB-GYN) was affected by the pandemic and to illuminate how residents experienced these changes. METHODS: As part of the COVID-19 in Pregnancy and Early Childhood Staff (COPE Staff) cohort study, between January and May 2021, all participating residents were invited to answer a 28-question online Resident Survey focusing on their specialist education, work situation and experiences during the COVID-19 pandemic. Descriptive statistics were given in percentages for categorical variables and means and standard deviations (SD) for continuous variables. Univariate comparative analyses were performed with the use of the Pearson's Chi-2-test for dichotomous data. The association between residents' worry about the quality and length of their specialist training, with extra clinical hours and transfer to other healthcare institutions were assessed by multivariate logistic regression. Free text responses were analyzed by content analysis. RESULTS: Of the 162 participating OB-GYN residents, 69% expressed concern that the pandemic would have a negative impact on their training. Ninety-five (95%) reported cancellation/postponement of educational activities, 70% performed fewer surgeries and 27% had been transferred to other healthcare institutions where about half reported having gained more general knowledge as a physician. Working extra clinical hours was reported by 69% (7.4 ± 5.3 hours per week) and 14% had considered changing their profession due to the pandemic. Senior residents, compared to junior residents, more often experienced cancelled/postponed clinical rotations (30% vs 15%, P=0.02) and reported performing fewer surgeries (P=0.02). The qualitative analysis highlighted the lack of surgical procedural training as a major concern for residents. CONCLUSION: The COVID-19 pandemic has strongly impacted the training program and work situation of OB-GYN residents in Sweden. Residents were concerned over the negative impact of the pandemic on their training program and senior residents reported more missed educational opportunities as compared to junior residents. Program directors, head of institutions and clinical supervisors can use the problem areas pinpointed by this study to support residents and compensate for missed educational opportunities. While hands-on-training and operating time cannot be compensated for, the authors hope that the findings of the study can help develop new strategies to minimize the negative impact of the current and future pandemics on resident education and work situation.

Associations of treated and untreated human papillomavirus infection with preterm delivery and neonatal mortality: A Swedish population-based study.

BACKGROUND: Treatment of cervical intraepithelial neoplasia (CIN) is associated with an increased risk of preterm delivery (PTD) although the exact pathomechanism is not yet understood. Women with untreated CIN also seem to have an increased risk of PTD. It is unclear whether this is attributable to human papillomavirus (HPV) infection or other factors. We aimed to investigate whether HPV infection shortly before or during pregnancy, as well as previous treatment for CIN, is associated with an increased risk of PTD and other adverse obstetric and neonatal outcomes. METHODS AND FINDINGS: This was a retrospective population-based register study of women with singleton deliveries registered in the Swedish Medical Birth Register 1999-2016 (n = 1,044,023). The study population had a mean age of 30.2 years (SD 5.2) and a mean body mass index of 25.4 kg/m2 (SD 3.0), and 44% of the women were nulliparous before delivery. Study groups were defined based on cervical HPV tests, cytology, and histology, as registered in the Swedish National Cervical Screening Registry. Women with a history of exclusively normal cytology (n = 338,109) were compared to women with positive HPV tests (n = 2,550) or abnormal cytology (n = 11,727) within 6 months prior to conception or during the pregnancy, women treated for CIN3 before delivery (n = 23,185), and women with CIN2+ diagnosed after delivery (n = 33,760). Study groups were compared concerning obstetric and neonatal outcomes by logistic regression, and comparisons were adjusted for socioeconomic and health-related confounders. HPV infection was associated with PTD (adjusted odds ratio [aOR] 1.19, 95% CI 1.01-1.42, p = 0.042), preterm prelabor rupture of membranes (pPROM) (aOR 1.52, 95% CI 1.18-1.96, p < 0.001), prelabor rupture of membranes (PROM) (aOR 1.24, 95% CI 1.08-1.42, p = 0.002), and neonatal mortality (aOR 2.69, 95% CI 1.25-5.78, p = 0.011). Treatment for CIN was associated with PTD (aOR 1.85, 95% CI 1.76-1.95, p < 0.001), spontaneous PTD (aOR 2.06, 95% CI 1.95-2.17, p < 0.001), pPROM (aOR 2.36, 95% CI 2.19-2.54, p < 0.001), PROM (aOR 1.11, 95% CI 1.05-1.17, p < 0.001), intrauterine fetal death (aOR 1.35, 95% CI 1.05-1.72, p = 0.019), chorioamnionitis (aOR 2.75, 95% CI 2.33-3.23, p < 0.001), intrapartum fever (aOR 1.24, 95% CI 1.07-1.44, p = 0.003), neonatal sepsis (aOR 1.55, 95% CI 1.37-1.75, p < 0.001), and neonatal mortality (aOR 1.79, 95% CI 1.30-2.45, p < 0.001). Women with CIN2+ diagnosed within 3 years after delivery had increased PTD risk (aOR 1.18, 95% CI 1.10-1.27, p < 0.001). Limitations of the study include the retrospective design and the fact that because HPV test results only became available in 2007, abnormal cytology was used as a proxy for HPV infection. CONCLUSIONS: In this study, we found that HPV infection shortly before or during pregnancy was associated with PTD, pPROM, PROM, and neonatal mortality. Previous treatment for CIN was associated with even greater risks for PTD and pPROM and was also associated with PROM, neonatal mortality, and maternal and neonatal infectious complications.

Maternal caffeine intake during pregnancy and child neurodevelopment up to eight years of age-Results from the Norwegian Mother, Father and Child Cohort Study.

PURPOSE: Current knowledge of the effect of prenatal caffeine exposure on the child's neurodevelopment is contradictory. The current study aimed to study whether caffeine intake during pregnancy was associated with impaired child neurodevelopment up to 8 years of age. METHOD: A total of 64,189 full term pregnancies from the Norwegian Mother, Father and Child Cohort Study were included. A validated food-frequency questionnaire administered at gestational week 22 was used to obtain information on maternal caffeine intake from different sources. To assess child neurodevelopment (behaviour, temperament, motor development, language difficulties) validated scales were used to identify difficulties within each domain at 6, 18, 36 months as well as 5 and 8 years of age. Adjusted logistic regression models and mixed linear models were used to evaluate neurodevelopmental problems associated with maternal caffeine intake. RESULTS: Prenatal caffeine exposure was not associated with a persistently increased risk for behaviour, temperament, motor or language problems in children born at full-term. Results were consistent throughout all follow-ups and for different sources of caffeine intake. There was a minor trend towards an association between consumption of caffeinated soft drinks and high activity level, but this association was not driven by caffeine. CONCLUSION: Low to moderate caffeine consumption during pregnancy was not associated with any persistent adverse effects concerning the child's neurodevelopment up to 8 years of age. However, a few previous studies indicate an association between high caffeine consumption and negative neurodevelopment outcomes.

An interrater reliability study on the Gothenburg obstetric triage system- a new obstetric triage system.

BACKGROUND: Triage, identifying patients with critical and time-sensitive disorders, is an integrated process in general emergency medicine. Obstetric triage is more specialised, requiring assessment of both woman, fetus and labour status. Failure to identify severely ill obstetric patients has repeatedly led to maternal morbidity and mortality. Reliable triage systems, adapted to obstetric patients as well as local conditions, are thus essential. The study aims to assess the interrater reliability (IRR) of the Gothenburg Obstetric Triage System (GOTS). METHODS: Midwives (n = 6) and registered nurses with no experience in managing obstetric patients (n = 7), assessed 30 paper cases based on actual real-life cases, using the GOTS. Furthermore, a reference group consisting of two midwives and two obstetricians, with extensive experience in obstetric care, determined the correct triage level in order to enable analysis of over- and undertriage. IRR was assessed, both with percentage of absolute agreement and with intra-class correlation coefficients (ICC) with 95% confidence intervals (CI). RESULTS: A total of 388 assessments were performed, comprising all five levels of acuity in the GOTS. Absolute agreement was found in 69.6% of the assessments. The overall IRR was good, with a Kappa value of 0.78 (0.69-0.87, 95% CI) for final triage level. Comparison with reference group assessments established that over- and undertriage had occurred in 9% and 21% of the cases, respectively. The main reasons for undertriage were "not acknowledging abnormal vital sign parameters" and "limitations in study design". CONCLUSION: The GOTS is a reliable tool for triaging obstetric patients. It enables a standardized triage process unrelated to the assessors' level of experience in assessing and managing obstetric patients and is applicable for triaging obstetric patients presenting for emergency care at obstetric or emergency units.

Postpartum septic symphysitis, a rare condition with possible long-term consequences: a cohort study with long-term follow-up.

BACKGROUND: Postpartum septic symphysitis (PPSS) is defined as acute onset of severe pain around the symphysis, restricted movement, fever, and elevated inflammatory parameters. It is a rare but serious condition requiring urgent diagnosis and treatment. The aim of this study was to describe the incidence, symptoms, diagnosis, treatment, and long-term follow-up of PPSS. METHODS: This follow-up study included 19 out of 21 women diagnosed with PPSS from 1989 to 2017 at one tertiary care hospital in Sweden. Clinical data were retrieved from hospital records and compared to those retrieved from a regional registry. Women completed a postal questionnaire, and those who reported lumbopelvic pain (LPP) were offered a clinical examination. RESULTS: 1) PPSS was diagnosed after a normal postpartum period of 24 to 50 h by blood tests (n = 19/19), ultrasonography (n = 9 /19), computer tomography (n = 8/19) or magnetic resonance imaging (n = 16/19) Treatment included aspiration of symphyseal abscesses, i.v. antibiotics and different physiotherapeutic interventions. Women with PPSS more frequently were primiparous (n = 14/19, p = 0.001), had an instrumental delivery (n = 14/19, p = 0.003), longer time of active labour (p = 0.01) and second stage of labour (p = 0.001) than women in the regional registry. 2) Ten out of 19 (52%) women reported LPP at follow-up. These women more often suffered impaired function related to LPP (Pelvic Girdle Questionnaire, 27 versus 0, p < 0.0001), a poorer health-related quality of life (EuroQol-5 dimensions p = 0.001 and EuroQol-visual analogue scale, 65 mm versus 84 mm, p = 0.022) and higher levels of anxiety and depression (Hospital Anxiety Depression Scale (HADS) HADS-Anxiety, 7 versus 2, p = 0.010; and HADS-Depression, 1 versus 0, p = 0.028) than women with no pain. 3). Of the eight women who were clinically assessed, one had lumbar pain and seven had pelvic girdle pain (PGP). CONCLUSIONS: In the largest cohort of patients with PPSS to date, primiparas and women with instrumental vaginal delivery were overrepresented, indicating that first and complicated deliveries might be risk factors. Approximately half of the women reported PGP at follow-up, with considerable consequences affecting health-related quality of life and function decades after delivery. Prospective multicentre studies are needed to establish risk factors, long-term consequences, and adequate treatment for this rare pregnancy complication.

Efficacy and safety of oral misoprostol vs transvaginal balloon catheter for labor induction: An observational study within the SWEdish Postterm Induction Study (SWEPIS).

INTRODUCTION: Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41+0 to 42+0 to 1 weeks of gestation. MATERIAL AND METHODS: In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score. RESULTS: Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] vs 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31-1.89]; maternal composite 2.3% [17/744] vs 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58-4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3-6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups. CONCLUSIONS: Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.

Glycemic, maternal and neonatal outcomes in women with type 1 diabetes using continuous glucose monitoring during pregnancy - Pump vs multiple daily injections, a secondary analysis of an observational cohort study.

INTRODUCTION: Continuous glucose monitoring (CGM) provides detailed information about glucose level fluctuations over time. The method is increasingly being used in pregnant women with type 1 diabetes. However, only one previous study compared CGM results related to pregnancy outcomes in women using insulin pumps with those administering multiple daily injections (MDI). We performed a secondary analysis of CGM metrics from an observational cohort of pregnant women with type 1 diabetes and compared insulin pump and MDI therapies in relation to maternal and neonatal outcomes. MATERIAL AND METHODS: The study included 185 pregnant Swedish women with type 1 diabetes undergoing CGM throughout pregnancy. Women were divided according to insulin administration mode, ie MDI (n = 131) or pump (n = 54). A total of 91 women used real-time CGM and 94 women used intermittently viewed CGM. Maternal demographics and maternal and neonatal outcome data were collected from medical records. CGM data were analyzed according to predefined glycemic indices: mean glucose; standard deviation; percentage of time within, below and above glucose target range; mean amplitude of glycemic excursion; high and low glucose indices; and coefficient variation in percent. Associations between insulin administration mode and CGM data, on the one hand, and maternal and neonatal outcomes, on the other, were analyzed with analysis of covariance and logistic regression, respectively, adjusted for confounders. RESULTS: There were no differences in maternal characteristics or glycemic indices between the MDI and pump groups, except for a longer duration of type 1 diabetes and higher frequencies of microangiopathy and real-time CGM among pump users. Despite improvement with each trimester, glucose levels remained suboptimal throughout pregnancy in both groups. There were no differences between the MDI and pump groups concerning the respective associations with any of the outcomes. The frequency of large for gestational age was high in both groups (MDI 49% vs pump 63%) and did not differ significantly. CONCLUSIONS: Pregnant women with type 1 diabetes did not differ in glycemic control or pregnancy outcome, related to MDI or pump administration of insulin. Glycemic control remained suboptimal throughout pregnancy, regardless of insulin administration mode.

Preterm birth and risk for language delays before school entry: A sibling-control study.

We investigated whether children born preterm are at risk for language delay using a sibling-control design in the Norwegian Mother and Child Cohort Study (MoBa), conducted by the Norwegian Institute of Public Health. Participants included 26,769 siblings born between gestational weeks 23 and 42. Language delay was assessed when the children were 1.5, 3, and 5 years old. To adjust for familial risk factors, comparisons were conducted between preterm and full-term siblings. Pregnancy-specific risk factors were controlled for by means of observed variables. Findings showed that preterm children born before week 37 had increased risk for language delays at 1.5 years. At 3 and 5 years, only children born before week 34 had increased risk for language delay. Children born weeks 29-33 and before week 29 had increased risk for language delay at 1.5 years (RR = 4.51, 95% CI [3.45, 5.88]; RR = 10.32, 95% CI [6.7, 15.80]), 3 years (RR = 1.50, 95% CI [1.02, 2.21]; RR = 2.78, 95% CI [1.09, 7.07]), and 5 years (RR = 1.63, 95% CI [1.06, 2.51]; RR = 2.98, 95% CI [0.87, 10.26]), respectively. In conclusion, children born preterm are at risk for language delays, with familial confounders only explaining a moderate share of the association. This suggests a cause-effect relationship between early preterm birth and risk for language delay in preschool children.

Pregnant under the pressure of a pandemic: a large-scale longitudinal survey before and during the COVID-19 outbreak.

BACKGROUND: One of the groups that is most vulnerable to the COVID-19 pandemic is pregnant women. They cannot choose to refrain from care; they and their children are at risk of severe complications related to the virus; and they lose comfort and support as clinics prohibit their partners and as societal restrictions demand isolation from friends and relatives. It is urgent to study how this group is faring during the pandemic and we focus here on their health-related worries. METHODS: A longitudinal survey at a Swedish hospital starting 6 months before (16 September 2019) and continuing during the COVID-19 outbreak (until 25 August 2020). A total of 6941 pregnant women and partners of diverse social backgrounds were recruited. Ninety-six percent of birth-giving women in the city take early ultrasounds where recruitment took place. Sixty-two percent of the women with an appointment and fifty-one percent of all partners gave consent to participate. RESULTS: Pregnant women experienced dramatically increased worries for their own health, as well as for their partner's and their child's health in the beginning of the pandemic. The worries remained at higher than usual levels throughout the pandemic. Similar, but less dramatic changes were seen among partners. CONCLUSIONS: There is a need for heightened awareness of pregnant women's and partners' health-related worries as a consequence of the COVID-19 pandemic. Related feelings, such as anxiety, have been linked to adverse pregnancy outcome and might have long-term effects. The healthcare system needs to prepare for follow-up visits with these families.

Improving assessment of acute obstetric patients - introducing a Swedish obstetric triage system.

BACKGROUND: Failure to identify severely ill obstetric patients seeking acute care, and hence delaying treatment, can lead to maternal morbidity and mortality. Triage is the prioritization of patients seeking emergency care, based on clinical decision-making tools assessing medical urgency. While triage has been applied in general emergency medicine for 30 years, there are only a few obstetric triage systems (OTS) and obstetric triage has hitherto been unknown in Sweden. Obstetric triage is more complex than general triage since both mother and fetus require assessment, and pregnancy-related physiological changes must be taken into account. This paper aims to describe the development and an initial evaluation of the first OTS in Sweden. METHODS: A multidisciplinary team surveyed reasons to seek acute obstetric care and the current patient flow at the largest obstetric unit in Scandinavia, Sahlgrenska University Hospital, Gothenburg, Sweden, with about 10,000 deliveries/year. A semi-structured literature review on obstetric triage was undertaken. Based on the survey and the literature review the first Swedish OTS was developed and implemented. Patient satisfaction was followed by electronical questionnaires. Initial validity evaluation was performed, defined by the system's ability to identify patients with need for hospital admission, stratified by acuity level. RESULTS: The Gothenburg Obstetrical Triage System (GOTS) addresses the patient to one of five acuity levels based on both vital signs and 14 chief complaint algorithms. It entails recommendations for initial procedures of care as well as an acuity form for documentation. Initial evaluation of the system indicates good correlation between need for admission and acuity level. The implementation has provided the staff with an improved medical overview of the patients and patient flow and enabled the unit to monitor emergency care in a structured way. Implementation came along with increased patient and staff satisfaction. CONCLUSION: The GOTS is the first OTS developed in and for Sweden and implementation has improved management of obstetric patients seeking acute care. Patients are now prioritized according to level of acuity and the time to assessment and treatment of severely ill patients can be structurally evaluated. Both patients and staff express improved satisfaction with obstetric triage.

Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes.

Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy. Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. Results: Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.