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.

Is obesity in pregnancy associated with signs of chronic fetal hypoxia?

INTRODUCTION: The prevalence of obesity in pregnancy is increasing worldwide. Maternal obesity increases risks of severe fetal and neonatal complications. The underlying pathophysiological mechanisms are unclear. One possible contributing factor could be chronic fetal hypoxia. The aim of this study was to compare placentas from women with and without obesity with respect to placental lesions, which could reflect compensatory mechanisms in response to chronic fetal hypoxia as well as lesions possibly leading to chronic fetal hypoxia. In addition, levels of erythropoietin in cord blood were compared between offspring of lean and obese women. MATERIAL AND METHODS: This cohort study included 180 women with uneventful, full-term, singleton pregnancies, out of which 91 lean women had a body mass index (BMI) of 18.5-24.9 kg/m2 and 89 women had obesity (BMI ≥30 kg/m2 ). Women were recruited at Södersjukhuset between 16 October 2018 and 2 December 2019. Placentas were investigated by two senior perinatal pathologists, who were blinded for maternal BMI. Cord blood was analyzed for levels of erythropoietin. RESULTS: Levels of erythropoietin in cord blood increased with maternal BMI (P = .01, ß = 0.97, 95% CI 0.27-1.68). There was no difference between placentas of obese and lean women in number of placental lesions reflecting chronic fetal hypoxia or in lesions that could possibly lead to chronic fetal hypoxia. CONCLUSIONS: This study of term and uneventful pregnancies demonstrated a positive association between maternal obesity and concentrations of erythropoietin in cord blood at birth. This finding supports the hypothesis of chronic fetal hypoxia as a risk factor for complications in the pregnancies of obese women. There were no differences in lesions associated with hypoxia between placentas of obese and lean women.

Prediction of large-for-gestational-age infants in pregnancies complicated by obesity: A population-based cohort study.

INTRODUCTION: Infants born large for gestational age (LGA) have increased risks of adverse perinatal outcomes. Maternal obesity, defined as body mass index (BMI) ≥30 kg/m2 , is one of the most prevalent risk factors for LGA and the proportion of pregnancies complicated by obesity is increasing. Early identification of women with BMI ≥30 kg/m2 at increased risk of giving birth to an LGA infant may open possibilities for prevention, aiming at decreasing the incidence of LGA. MATERIAL AND METHODS: A population-based cohort study using information from the first-trimester screening database, which was cross-linked with the Swedish Medical Birth Register. The database included 139 277 full-term singletons without fetal anomalies born between 2006 and 2015 to mothers without prepregnancy diabetes. Of these, 9.1% (n = 12 704) were infants of mothers with BMI ≥30 kg/m2 . For all women with BMI ≥30 kg/m2 , a prediction model for LGA to be used in early pregnancy was constructed based on information on biochemical markers and maternal characteristics. A similar model, as well as a prepregnancy prediction model, were constructed for parous women with BMI ≥30 kg/m2 . In parous women, data from the previous pregnancy were also used. Receiver operating characteristic curve and area under curve (AUC) were calculated. RESULTS: The predictive models for LGA in parous women with BMI ≥30 kg/m2 prepregnancy and in early pregnancy had AUCs of 0.80 (95% CI 0.78-0.82) and 0.81 (95% CI 0.79-0.82), respectively. For all women with BMI ≥30 kg/m2 , the prediction of LGA in early pregnancy had an AUC of 0.66 (95% CI 0.64-0.67). CONCLUSIONS: Performance of the prepregnancy and early pregnancy prediction models for LGA in parous women with BMI ≥30 kg/m2 was good. The predictive capacity was largely driven by previous child's birthweight. First-trimester measurements of fetal size did not improve the predictive capacity in parous women. Predictions of LGA in all women with BMI ≥30 kg/m2 in early pregnancy, without taking previous child's birthweight into account, remain difficult.

Comprehensive RNA sequencing of healthy human endometrium at two time points of the menstrual cycle.

Endometrial receptivity is crucial for implantation and establishment of a normal pregnancy. The shift from proliferative to receptive endometrium is still far from being understood. In this paper, we comprehensively present the transcriptome of the human endometrium by comparing endometrial biopsies from proliferative phase with consecutive biopsies 7-9 days after ovulation. The results show a clear difference in expression between the two time points using both total and small RNA sequencing. A total of 3,297 messenger RNAs (mRNAs), 516 long noncoding RNAs (lncRNAs), and 102 small noncoding RNAs were identified as statistically differentially expressed between the two time points. We show a thorough description of the change in mRNA between the two time points and display lncRNAs, small nucleolar RNAs, and small nuclear RNAs not previously reported in the healthy human endometrium. In conclusion, this paper reports in detail the shift in RNA expression from the proliferative to receptive endometrium.

[Spontaneous intrauterine rupture of the umbilical cord is very uncommon but a serious condition]. / Intrauterin ruptur av navelsträng mycket ovanligt men allvarligt.

Spontaneous intrauterine rupture of the umbilical cord is an uncommon and dangerous complication during delivery. We describe a case of a 27-year-old woman with a normal pregnancy. When the membranes broke, the fetal heart sounds suddenly disappeared, and the vaginal bleeding was heavier than normal. An emergency caesarean section was executed and the examination of the placenta revealed a broken umbilical artery. The child was born with an Apgar score of 0,1,1 and a blood gas analysis from the umbilical vein showed pH 6.68 and Base Excess -24.3. Urgent treatment with heart massage, adrenaline, blood transfusion and tribonate was initiated and followed by therapeutic hypothermia. The child was discharged after 10 days with no pathological findings on a MRI examination of the brain. The 6 month follow-up showed a normal development. When a fetal bleeding is suspected, it is important to inform a neonatologist so that correct treatment can be started as early as possible.

Placental inflammation and overweight or obesity in term singleton stillbirths in Stockholm County 2002-2018; a case control study.

INTRODUCTION: Stillbirth is a severe pregnancy complication. Maternal obesity is one of the most important modifiable risk factors of stillbirth, yet the biological mechanisms behind this association remain unclear. The adipose tissue is an endocrine organ which, in persons with obesity, causes a hyperinflammatory state. The aim of this study was to investigate inflammation as a contributing mechanism to the risk of stillbirth in women with obesity and if there are possible signs of different BMI phenotypes with different risk. MATERIAL AND METHODS: This was a case control study based on all cases of term singleton stillbirth without major fetal malformation in Stockholm County between 2002-2018. Placentas have been examined according to a standardized protocol. Placental inflammatory lesions were compared both between placentas from pregnancies with live born and stillborn infants with different class of body mass index (BMI) as well as among women with stillborn and live born infants with different classes of BMI, respectively. RESULTS: All inflammatory placental lesions were more common in placentas from women with stillbirth compared to placentas from women with live born infants. Vasculitis, funisitis and chronic villitis as well as overall fetal and maternal inflammatory response were present with a significantly increased proportion with increasing BMI in placentas from women with term stillbirth however, there were no differences between placentas from women in different BMI classes with term live born infants. CONCLUSION: Both acute and chronic inflammatory placental lesions were more common in cases of stillbirth compared to pregnancies with live born infants. There were increased proportions of both acute and chronic placental inflammation (vasculitis, chronic villitis, funisitis and overall fetal and maternal inflammatory response) with increasing BMI among cases with term stillbirth, however no differences among controls with term live born infants.

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.

In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta.

Here, we present a method for in-depth human plasma proteome analysis based on high-resolution isoelectric focusing HiRIEF LC-MS/MS, demonstrating high proteome coverage, reproducibility and the potential for liquid biopsy protein profiling. By integrating genomic sequence information to the MS-based plasma proteome analysis, we enable detection of single amino acid variants and for the first time demonstrate transfer of multiple protein variants between mother and fetus across the placenta. We further show that our method has the ability to detect both low abundance tissue-annotated proteins and phosphorylated proteins in plasma, as well as quantitate differences in plasma proteomes between the mother and the newborn as well as changes related to pregnancy.

Single versus pairwise interpretation of cardiotochography, a comparative study from six Swedish delivery units.

OBJECTIVE: The aim of the study was to evaluate whether interpreting CTG pairwise brings about a higher level of correctly classified CTG recordings in a non-selected population of midwives and physicians. STUDY DESIGN: A comparative study. SETTING: Five delivery units in Stockholm and one delivery unit in Uppsala, with 1589, 3740, 3908, 4539, 6438, and 7331 deliveries in 2011, respectively. SUBJECTS: 536 midwives and physicians classified one randomly selected CTG recording individually followed by a pairwise classification. The pairs consisted of two midwives (119 pairs) or one midwife and one physician (149 pairs), a total of 268 pairs. MAIN OUTCOME MEASURE: The proportion of individually correctly classified CTG recordings versus the proportion of pairwise correctly classified CTG recordings. RESULTS: The proportion of individually correctly classified CTG's was 75% and the proportion of pairwise correctly classified CTG's was 80% (difference 5%, p = 0.12). CONCLUSIONS: There was no statistically significant difference when CTG's were classified pairwise compared to individual classifications. The proportion of individually correctly classified CTG's was high (75%). There were differences in the proportion of correctly classified CTG recordings between the delivery units, indicating potential areas of improvement.