Short-term variation of the fetal heart rate as a marker of intraamniotic infection in pregnancies with preterm prelabor rupture of membranes: a historical cohort study.

INTRODUCTION: Intraamniotic infection (IAI) and subsequent early-onset neonatal sepsis (EONS) are among the main complications associated with preterm prelabor rupture of membranes (PPROM). Currently used diagnostic tools have been shown to have poor diagnostic performance for IAI. This study aimed to investigate whether the exposure to IAI before delivery is associated with short-term variation of the fetal heart rate in pregnancies with PPROM. METHODS: Observational cohort study of 678 pregnancies with PPROM, delivering between 24 + 0 and 33 + 6 gestational weeks from 2012 to 2019 in five labor units in Stockholm County, Sweden. Electronic medical records were examined to obtain background and exposure data. For the exposure IAI, we used the later diagnosis of EONS in the offspring as a proxy. EONS is strongly associated to IAI and was considered a better proxy for IAI than the histological diagnosis of acute chorioamnionitis, since acute chorioamnionitis can be observed in the absence of both positive microbiology and biochemical markers for inflammation. Cardiotocography traces were analyzed by a computerized algorithm for short-term variation of the fetal heart rate, which was the main outcome measure. RESULTS: Twenty-seven pregnancies were categorized as having an IAI, based on the proxy diagnosis of EONS after birth. Fetuses exposed to IAI had significantly lower short-term variation values in the last cardiotocography trace before birth than fetuses who were not exposed (5.25 vs 6.62 ms; unadjusted difference: -1.37, p = 0.009). After adjustment for smoking and diabetes, this difference remained significant. IAI with a later positive blood culture in the neonate (n = 12) showed an even larger absolute difference in STV (-1.65; p = 0.034), with a relative decrease of 23.5%. CONCLUSION: In pregnancies with PPROM, fetuses exposed to IAI with EONS as a proxy have lower short-term variation of the fetal heart rate than fetuses who are not exposed. Short-term variation might be useful as adjunct surveillance in pregnancies with PPROM.

Incidence of stillbirth among women with different risk profiles in Stockholm 2001-2020: a repeated cross-sectional study.

INTRODUCTION: The incidence of stillbirth in Sweden has started to decline. However, some comparable high-income countries in Europe have an even lower incidence, indicating a potential for further reduction. The aim of our study was to investigate how the incidence of stillbirth for singleton pregnancies has changed over the past two decades in the Stockholm Region in different groups of women to detect the groups at highest risk. MATERIAL AND METHODS: This was a repeated cross-sectional study with data from the Stockholm Stillbirth Database and the Pregnancy Register including all cases of stillbirth in Stockholm in singleton pregnancies between 2001 and 2020, in total 1804 stillbirths. The time period was divided into four equal groups and the incidence of stillbirth was compared between the groups. RESULTS: The overall incidence of stillbirth in the Stockholm Region has decreased from 3.8/1000 births in 2001-2005 to 2.9/1000 births in 2016-2020 (P-value <0.001). In most of the groups studied, the incidence decreased, but among women originating from sub-Saharan Africa the incidence significantly rose from 7.9/1000 births in 2001-2005 to 10.1/1000 births in 2016-2020 (P-value 0.025). In this group, stillbirth occurred prematurely to a higher extent and the women were more likely to be multiparous. CONCLUSIONS: The incidence of stillbirth in the Stockholm Region has declined. However, among women originating from sub-Saharan Africa the incidence was significantly higher compared with women originating from other regions and it is still rising. More research is needed to understand why this group is at higher risk and how to monitor their pregnancies to decrease this risk.

Changes in perinatal management and outcomes of extremely preterm infants born below 26 weeks of gestation in a tertiary referral hospital in Sweden: Comparison between 2004-2007 and 2012-2016.

INTRODUCTION: Perinatal management of extremely preterm births in Sweden has changed toward active care from 22-23 gestational weeks during the last decades. However, considerable regional differences exist. This study evaluates how one of the largest perinatal university centers has adapted to a more active care between 2004-2007 and 2012-2016 and if this has influenced infant survival. MATERIAL AND METHODS: In this historical cohort study, women admitted with at least one live fetus and delivered at 22-25 gestational weeks (stillbirths included) at Karolinska University Hospital Solna during April 1, 2004-March 31, 2007, and January 1, 2012-December 31, 2016, were compared regarding rates of obstetric and neonatal interventions, and infant mortality and morbidity. Maternal, pregnancy and infant data from 2004-2007 were obtained from the Extreme Preterm Infants in Sweden Study while data from 2012-2016 were extracted from medical journals and quality registers. The same definitions of interventions and diagnoses were used for both study periods. RESULTS: A total of 106 women with 118 infants during 2004-2007 and 213 women with 240 infants during 2012-2016 were included. Increases between the study periods were seen regarding cesarean delivery (overall rate 14% [17/118] during 2004-2007 vs. 45% [109/240] during 2012-2016), attendance of a neonatologist at birth (62% [73/118] vs. 85% [205/240]) and surfactant treatment at birth in liveborn infants (60% [45/75] vs. 74% [157/211]). Antepartum stillbirth rate decreased (13% [15/118] vs. 5% [12/240]) and the proportion of live births increased (80% [94/118] vs. 88% [211/240]) while 1-year survival (64% [60/94] vs. 67% [142/211]) and 1-year survival without major neonatal morbidity (21% [20/94] vs. 21% [44/211]) among liveborn infants did not change between the study periods. At 22 gestational weeks, interventions rates were still low during 2012-2016, most obvious regarding antenatal steroid treatment (23%), attendance of a neonatologist (51%), and intubation at birth (24%). CONCLUSIONS: Both obstetric and neonatal interventions at births below 26 gestational weeks increased between 2004-2007 and 2012-2016 in this single center study; however, at 22 gestational weeks they were still at a low level during 2012-2016. Despite more infants being born alive, 1-year survival did not increase between the study periods.

Stillbirth in term and late term gestations in Stockholm during a 20-year period, incidence and causes.

INTRODUCTION: The incidence of stillbirth has decreased marginally or remained stable during the past decades in high income countries. A recent report has shown Stockholm to have a lower incidence of stillbirth at term than other parts of Sweden. The risk of antepartum stillbirth increases in late term and postterm pregnancies which is one of the factors contributing to the current discussion regarding the optimal time of induction of labor due to postterm pregnancy. MATERIAL AND METHODS: This is a cohort study based on the Stockholm Stillbirth Database which contains all cases of stillbirth from 1998-2018 in Stockholm County. All cases were reviewed systematically and the cause of death was evaluated according to the Stockholm Stillbirth Classification. Stillbirths diagnosed between gestational week (GW) 37+0 and 40+6 n = 605 were compared to stillbirths diagnosed from GW 41+0 and onwards n = 157, according to the cause of stillbirth and pregnancy and maternal characteristics. The aim was to evaluate the incidence of stillbirth over time and the incidence of stillbirth diagnosed from GW 41+0. RESULTS: In Stockholm County the overall incidence of stillbirth has decreased from 4.6/1000 births during the period 1998-2004 to 3.4/1000 births during the period 2014-2018, p-value <0.001. When comparing the same time periods, the incidence of stillbirth diagnosed from GW 41+0 and onwards has decreased from 0.5/1000 births to 0.15/1000 births, p-value <0.001. Among women still pregnant at GW 41+0 the incidence of stillbirth has decreased from 1.8/ 1000 to 0.5/ 1000. When comparing stillbirths diagnosed at GW 37+0-40+6 with stillbirths diagnosed from GW 41+0 and onwards infection was a more common cause of stillbirth in the latter group. CONCLUSION: In Stockholm County there was a decreasing incidence of stillbirth overall and in stillbirths diagnosed from 41+0 weeks of gestation and onwards during the period 1998-2018. In stillbirths diagnosed from GW 41+0 and onwards infection was a more common cause of death compared to stillbirths diagnosed between GW 37+0 and 40+6.

Maternal obesity and stillbirth at term; placental pathology-A case control study.

OBJECTIVE: The aim was to explore the potential role of the placenta for the risk of stillbirth at term in pregnancies of obese women. METHODS: This was a case-control study comparing placental findings from term stillbirths with placental findings from live born infants. Cases were singleton term stillbirths to normal weight or obese women, identified in the Stockholm stillbirth database, n = 264 and n = 87, respectively. Controls were term singletons born alive to normal weight or obese women, delivered between 2002-2005 and between 2018-2019. Placentas were compared between women with stillborn and live-born infants, using logistic regression analyses. RESULTS: A long and hyper coiled cord, cord thrombosis and velamentous cord insertion were stronger risk factors for stillbirth in obese women compared to normal weight women. When these variables were adjusted for in the logistic regression analysis, also adjusted for potential confounders, the odds ratio for stillbirth in obese women decreased from 1.89 (CI 1.24-2.89) to 1.63 (CI 1.04-2.56). CONCLUSION: Approximately one fourth of the effect of obesity on the risk of stillbirth in term pregnancies is explained by umbilical cord associated pathology.

Reliability in cardiotocography interpretation - impact of extended on-site education in addition to web-based learning: an observational study.

INTRODUCTION: Previous studies have shown poor reproducibility in cardiotocography (CTG) interpretation. Studies evaluating the Swedish web-based CTG-education program have not proven to increase accurate CTG assessments. The aim of this study was to evaluate whether an extended education can improve inter- and intra-observer reliability in CTG interpretation. MATERIAL AND METHODS: Six obstetricians from two different departments interpreted 106 CTG tracings on two occasions. Both departments used a Swedish national web-based CTG education and test for training. One department had, in addition, an extended education program consisting of on-site lectures and oral examinations. Inter- and intra-observer agreements were calculated by simple or weighted kappa (κ) values for the five parameters assessed on CTG. RESULTS: In both departments inter-observer and intra-observer κ showed moderate to excellent agreement (ranges for κ 0.41-0.76 and 0.65-0.93, respectively). Obstetricians at the department with extended CTG education had better inter-observer reliability for variability and accelerations. This was also the case for intra-observer reliability with the addition of baseline frequency. Both inter- and intra-observer agreement increased from moderate to substantial in both departments when decelerations were dichotomized into harmless (including early and simple variable decelerations) or hypoxic (including late, severe variable, prolonged and combined decelerations) (κ 0.63-0.78) compared with the current sub-classification of decelerations (κ 0.42-0.65). CONCLUSIONS: Agreement in CTG interpretation was better than expected in both departments, especially when divided into harmless/hypoxic changes. Combination of different learning methods (web-based, on-site lectures and case discussion) might result in a better CTG interpretation agreement compared with web-based learning solely.

Causes of stillbirth at different gestational ages in singleton pregnancies.

OBJECTIVE: To compare causes of stillbirth in preterm and term pregnancies. DESIGN: Cohort study. SETTING: All delivery wards in Stockholm, 1998-2009. POPULATION: Stillbirths from singleton pregnancies of gestational age ≥22(+0) (n = 1089) extracted from a web-based database including all stillbirths in the major Stockholm area since 1998. METHODS: The parents of the stillborns were all offered an extensive standardized investigation. The causes of death were assigned in a perinatal audit using the Stockholm classification of stillbirth. Singleton stillbirths were divided into preterm (gestational week 22(+0) -36(+6) ) and term/post-term (gestational week ≥37(+0) ). The term/post-term group was subdivided into term (gestational week 37(+0) -40(+6) ) and post-term stillbirths (gestational week ≥41(+0) ). MAIN OUTCOME MEASURE: Causes of stillbirth at different gestational ages. RESULTS: A higher proportion of placental abruption and preeclampsia/hypertension was seen in preterm stillbirths compared with term/post-term stillbirths, which instead had a higher proportion of umbilical cord complications and infection. Infection was more common in post-term than term stillbirths (46.5 vs. 19.8%, p < 0.001). CONCLUSION: Increased knowledge of causes of stillbirth in different gestational ages may be valuable in developing strategies for prevention of fetal death. The high proportion of infection in post-term stillbirths could be clinically important and warrants further studies.

Chorioamnionitis without foetal inflammatory response is associated with stillbirth in early preterm pregnancies.

OBJECTIVE: The aim of this study was to compare placental findings from early preterm stillbirths with gestational week-matched liveborn infants. The main focus was to investigate the differences in the presence and distribution of inflammatory signs in the placentas of these two groups, especially referring to histological acute chorioamnionitis (CAM). METHODS: A case-control study of preterm stillbirths, between 22 and 32 weeks gestation, here referred to as early preterm, (cases, n = 112) and gestational week-matched liveborn infants (references, n = 166) in Stockholm. Relevant clinical data were collected from a web-based database (for cases) and delivery records (for references). Macroscopic and histological examinations of placentas were performed according to a structured protocol (placental weight relative to gestational age, accelerated villous maturation, infarction, intervillous thrombosis, foetal thrombosis, chronic villitis and CAM (polymorphonuclear leucocytes in the chorion/amnion), with and without foetal inflammatory responses (FIRs) (vasculitis in placental and/or cord vessels and funisitis). Statistical analyses were performed using a multivariable logistic regression. RESULTS: Small for gestational age (AOR: 2.13, CI: 1.26-3.62) and CAM without a FIR (AOR: 2.44, CI: 1.10-5.41) were associated with an elevated risk of preterm stillbirth. CONCLUSIONS: Histological acute CAM without a FIR is associated with a higher risk for stillbirth in early preterm pregnancies.

Both acute and chronic placental inflammation are overrepresented in term stillbirths: a case-control study.

OBJECTIVE: To elucidate differences in the frequency and severity of acute chorioamnionitis (CAM) and chronic villitis in placentas from stillborns compared with liveborns at term and to evaluate other risk factors and placental findings. DESIGN: Case-control study. SETTING: All delivery wards in major Stockholm area. Population or Sample. Placentas from stillborn/case (n = 126) and liveborn/control (n = 273) neonates were prospectively collected between 2002 and 2005. METHODS: CAM was assessed on a three-grade scale based on the presence and distribution of polymorphonuclear leucocytes in the chorion/amnion. The presence of vasculitis and funisitis was recorded separately. Chronic villitis was diagnosed by the presence of mononuclear cells in the villous stroma. Relevant clinical data were collected from a specially constructed, web-based database. The statistic analyses were performed using multivariable logistic regression. RESULTS: CAM (especially severe, AOR: 7.39 CI: 3.05-17.95), villous immaturity (AOR: 7.17 CI: 2.66-19.33), villitis (<1 % AOR: 4.31 CI: 1.16-15.98; ≥ 1 %, AOR: 3.87 CI: 1.38-10.83), SGA (AOR: 7.52 CI: 3.06-18.48), and BMI >24.9 (AOR: 2.06 CI: 1.21-3.51) were all connected to an elevated risk of term stillbirth. CONCLUSIONS: We found that CAM, chronic villitis, villous immaturity, SGA, and maternal overweight, but not vasculitis or funisitis are independently associated with risk for stillbirth at term.

Stillbirth classification--developing an international consensus for research: executive summary of a National Institute of Child Health and Human Development workshop.

Stillbirth is a major obstetric complication, with 3.2 million stillbirths worldwide and 26,000 stillbirths in the United States every year. The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop from October 22-24, 2007, to review the pathophysiology of conditions underlying stillbirth to define causes of death. The optimal classification system would identify the pathophysiologic entity initiating the chain of events that irreversibly led to death. Because the integrity of the classification is based on available pathologic, clinical, and diagnostic data, experts emphasized that a complete stillbirth workup should be performed. Experts developed evidence-based characteristics of maternal, fetal, and placental conditions to attribute a condition as a cause of stillbirth. These conditions include infection, maternal medical conditions, antiphospholipid syndrome, heritable thrombophilias, red cell alloimmunization, platelet alloimmunization, congenital malformations, chromosomal abnormalities including confined placental mosaicism, fetomaternal hemorrhage, placental and umbilical cord abnormalities including vasa previa and placental abruption, complications of multifetal gestation, and uterine complications. In all cases, owing to lack of sufficient knowledge about disease states and normal development, there will be a degree of uncertainty regarding whether a specific condition was indeed the cause of death.

[Researchers show growing interest in antenatal mortality. Increased understanding of intrauterine fetal death may reduce the number of cases in the long run]. / Växande forskarintresse kring antenatal mortalitet. Okad kunskap om intrauterin fosterdöd kan på sikt minska antalet fall.

The incidence of intrauterine fetal death (from the 28th gestational week) is reported to be 3.6/1000 births in Sweden. Continuous improvements in perinatal care have resulted in a dramatic decrease in early neonatal mortality during the last few decades, but no comparable reduction of antenatal mortality has been observed. A better knowledge of the etiology of stillbirth is imperative to achieve a further decrease in the perinatal mortality rate. Advanced maternal age, smoking during pregnancy, maternal overweight/obesity and low socioeconomic class has been demonstrated to increase the risk for stillbirth. Several studies have been published concerning specific causes of intrauterine fetal death. Abruption of the placenta, some infectious disorders, fetal chromosomal aberration/malformation and maternal disease such as diabetes are some of the conditions that are associated to stillbirth. In order to arrive at a potential cause, a number of investigations have been recommended in the diagnostic evaluation of IUFD.

Diagnostic evaluation of intrauterine fetal deaths in Stockholm 1998-99.

BACKGROUND: To evaluate the diagnostic methods and to elucidate the etiology of intrauterine fetal death. MATERIAL AND METHODS: A prospective study was conducted on all intrauterine fetal deaths occurring in Stockholm County in 1998-99. During a 24-month period, 188 cases of intrauterine fetal death with gestational ages of > or = 22 weeks were investigated in accordance with structured test protocol. All information from antenatal and delivery records as well as all test results were entered in to an Internet-based database for continuous evaluation. RESULTS: A presumptive explanation to the stillbirth was established in 91% of the cases. The most common factors associated with intrauterine fetal death could be identified as infections (24%), placental insufficiency/intrauterine growth restriction (22%), placental abruption (19%), intercurrent maternal conditions (12%), congenital malformations (10%), and umbilical cord complications (9%). CONCLUSIONS: A relevant test protocol in cases of intrauterine fetal death reduces the number of unexplained cases to a minimum. An Internet-based register on test results of fetal deaths may enable a continuous evaluation of the diagnostic tools and etiologic factors in an ever-changing panorama. The results from the present study can serve as a base for a case-control study in Sweden.