Emma Fransson

Pro-inflammatory and anti-inflammatory cytokines in human preterm and term cervical ripening

Cervical ripening is necessary for successful delivery. Since cytokines are believed to be involved in this process, the aim of this study was to investigate possible changes in the mRNA and protein expression of pro-inflammatory cytokines (interleukin (IL)-1alpha, IL-1beta, IL-12, IL-18) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) in the human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 59 women: 21 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. mRNA was analyzed with real-time RT-PCR and protein expression and/or secretion with immunohistochemistry and ELISA. There was an upregulation of mRNA for IL-10, IL-13, IL-1alpha and IL-1beta in the laboring groups, while mRNA for IL-12 and IL-18 was downregulated. IL-4 mRNA was detected more frequently, while IL-12 mRNA expression was lower, in the preterm labor group than in the term labor group. The protein levels of IL-4 and IL-12 were lower and IL-18 tended to be higher in the labor groups, while IL-10 protein levels were unaffected by labor. IL-4 protein levels were significantly higher in the preterm subgroup with bacterial infection than in the non-infected group. IL-10 had higher expression in squamous epithelium at preterm labor than at term. In conclusion, the major changes in pro-inflammatory and anti-inflammatory cytokine mRNA and protein expression in cervix occur during the labor process irrespective of the length of gestation. Our results indicate that dysregulation of anti-inflammatory cytokines in the human cervix could be involved in the pathogenesis of preterm labor.

Living in two homes-a Swedish national survey of wellbeing in 12 and 15 year olds with joint physical custody

BackgroundThe practice of joint physical custody, where children spend equal time in each parent’s home after they separate, is increasing in many countries. It is particularly common in Sweden, where this custody arrangement applies to 30 per cent of children with separated parents. The aim of this study was to examine children’s health-related quality of life after parental separation, by comparing children living with both parents in nuclear families to those living in joint physical custody and other forms of domestic arrangements.MethodsData from a national Swedish classroom study of 164,580 children aged 12 and 15-years-old were analysed by two-level linear regression modelling. Z-scores were used to equalise scales for ten dimensions of wellbeing from the KIDSCREEN-52 and the KIDSCREEN-10 Index and analysed for children in joint physical custody in comparison with children living in nuclear families and mostly or only with one parent.ResultsLiving in a nuclear family was positively associated with almost all aspects of wellbeing in comparison to children with separated parents. Children in joint physical custody experienced more positive outcomes, in terms of subjective wellbeing, family life and peer relations, than children living mostly or only with one parent. For the 12-year-olds, beta coefficients for moods and emotions ranged from −0.20 to −0.33 and peer relations from −0.11 to −0.20 for children in joint physical custody and living mostly or only with one parent. The corresponding estimates for the 15-year-olds varied from −0.08 to −0.28 and from −0.03 to −0.13 on these subscales. The 15-year-olds in joint physical custody were more likely than the 12-year-olds to report similar wellbeing levels on most outcomes to the children in nuclear families.ConclusionsChildren who spent equal time living with both parents after a separation reported better wellbeing than children in predominantly single parent care. This was particularly true for the 15-year-olds, while the reported wellbeing of 12-years-olds was less satisfactory. There is a need for further studies that can account for the pre and post separation context of individual families and the wellbeing of younger age groups in joint physical custody.

Antenatal Depressive Symptoms and Preterm Birth: A Prospective Study of a Swedish National Sample

BACKGROUND Preterm birth is the principal risk factor for neonatal morbidity and mortality. The objective of this study was to investigate the association between antenatal depressive symptoms and preterm birth. METHODS The study included a national sample of 2,904 pregnant women who were recruited at their first booked visit to antenatal clinics in Sweden. Data on depressive symptoms, and sociodemographic and reproductive background were collected by questionnaires. Depressive symptoms were assessed by the Edinburgh Postnatal Depression Scale (EPDS). The average length of gestation at the time for completion of the questionnaire was 16 weeks. Data on gestational length were extracted from the Swedish Medical Birth Register. Multiple logistic regression analyses were conducted to estimate the risk of preterm birth associated with antenatal depressive symptoms. RESULTS The presence of antenatal depressive symptoms above a cutoff score of 12 or higher on the EPDS increased the risk for preterm birth (OR: 1.56; 95% CI: 1.03-2.35). Being of age 35 years and over, being a primipara, and having experienced a previous miscarriage were also shown to be significant predictors in a multivariate model. CONCLUSION Pregnant women reporting antenatal depressive symptoms are at elevated risk of preterm birth.

High-mobility group box protein 1 and its signalling receptors in human preterm and term cervix

The objective of this study was to identify possible changes in mRNA and protein expression of high-mobility group box protein 1 (HMGB1) and its suggested receptors - receptor for advanced glycation end-products (RAGE) and Toll-like receptor 2 (TLR2) and TLR4 - in human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 58 women: 20 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. Real-time RT-PCR was used to quantify mRNA expression, and immunohistochemistry and ELISA for protein analysis. HMGB1, RAGE, TLR2 and TLR4 proteins were localized and their mRNA expression was detected in the cervix. There was more extranuclear HMGB1 in the cervical epithelium and stroma in preterm and term labor compared to the term not in labor. TLR2 mRNA expression was upregulated 5-fold in term labor and 3-fold in preterm labor compared to term not in labor and non-pregnant controls. There was lower expression of TLR2 and TLR4 mRNAs in preterm labor compared to term. Lower mRNA expression of HMGB1 was found in the subgroup with preterm premature rupture of membranes than in the rest of the preterm group, where levels were significantly higher than in term labor. In conclusion, extranuclear expression of HMGB1 during labor suggests a possible role of HMGB1 during the process of cervical ripening. Changes in expression of mRNAs encoding HMGB1, TLR2 and TLR4 in preterm labor suggest differences in the mechanism of cervical ripening at preterm and term delivery.

Mental health in Swedish children living in joint physical custody and their parents' life satisfaction: A cross‐sectional study

This study compared the psychological symptoms of 129 children in joint physical custody with children in single care and nuclear families, using a nationally representative 2011 survey of 1,297 Swedish children aged between four and 18 years. The outcome measure was the Strengths and Difficulties Questionnaire (SDQ) and its association with three dimensions of parental life satisfaction was investigated. Linear regression analyses showed higher SDQ-scores for children in joint physical custody (B = 1.4, p < 0.001) and single care (B = 2.2, p < 0.001) than in nuclear families, after adjustment for socio-demographic variables. The estimates decreased to 1.1 and 1.3, respectively, after being adjusted for parental life satisfaction ( p < 0.01). Our findings confirm previous research that showed lower symptom scores for children in nuclear families than children in single care and joint physical custody. Parental life satisfaction should be investigated further as a possible explanation of differences in symptom load between children in different living arrangements.

Fifty moves a year: is there an association between joint physical custody and psychosomatic problems in children?

Background In many Western countries, an increasing number of children with separated parents have joint physical custody, that is, live equally much in their parents respective homes. In Sweden, joint physical custody is particularly common and concerns between 30% and 40% of the children with separated parents. It has been hypothesised that the frequent moves and lack of stability in parenting may be stressful for these children. Methods We used data from a national classroom survey of all sixth and ninth grade students in Sweden (N=147839) to investigate the association between childrens psychosomatic problems and living arrangements. Children in joint physical custody were compared with those living only or mostly with one parent and in nuclear families. We conducted sex-specific linear regression analyses for z-transformed sum scores of psychosomatic problems and adjusted for age, country of origin as well as childrens satisfaction with material resources and relationships to parents. Clustering by school was accounted for by using a two-level random intercept model. Results Children in joint physical custody suffered from less psychosomatic problems than those living mostly or only with one parent but reported more symptoms than those in nuclear families. Satisfaction with their material resources and parent–child relationships was associated with childrens psychosomatic health but could not explain the differences between children in the different living arrangements. Conclusions Children with non-cohabitant parents experience more psychosomatic problems than those in nuclear families. Those in joint physical custody do however report better psychosomatic health than children living mostly or only with one parent. Longitudinal studies with information on family factors before and after the separation are needed to inform policy of childrens postseparation living arrangements.

Negative Emotions and Cytokines in Maternal and Cord Serum at Preterm Birth

Problem  This study investigates whether affectivity differs between mothers delivering preterm and term and whether maternal and umbilical cord serum cytokines differ between these groups. Further, whether there are associations between mothers’ emotions and maternal and cord cytokines at preterm and term birth.

Psychological complaints among children in joint physical custody and other family types : Considering parental factors

Aims: Increasing proportions of Scandinavian children and children in other Western countries live in joint physical custody, moving between parents’ homes when parents live apart. Children and parents in non-intact families are at risk of worse mental health. The potential influence of parental ill-health on child well-being in the context of differing living arrangements has not been studied thoroughly. This study investigates the psychological complaints of children in joint physical custody in comparison to children in sole parental care and nuclear families, while controlling for socioeconomic differences and parental ill-health. Methods: Data were obtained from Statistics Sweden’s yearly Survey of Living Conditions 2007–2011 and child supplements with children 10–18 years, living in households of adult participants. Children in joint physical custody (n=391) were compared with children in sole parental care (n=654) and children in nuclear families (n=3,639), using a scale of psychological complaints as the outcome measure. Results: Multiple regression modelling showed that children in joint physical custody did not report higher levels of psychological complaints than those in nuclear families, while children in sole parental care reported elevated levels of complaints compared with those in joint physical custody. Adding socioeconomic variables and parental ill-health only marginally attenuated the coefficients for the living arrangement groups. Low parental education and parental worry/anxiety were however associated with higher levels of psychological complaints. Conclusions: Psychological complaints were lower among adolescents in joint physical custody than in adolescents in sole parental care. The difference was not explained by parental ill-health or socioeconomic variables.

Inflammatory markers in late pregnancy in association with postpartum depression—A nested case-control study

Recent studies indicate that the immune system adaptation during pregnancy could play a significant role in the pathophysiology of perinatal depression. The aim of this study was to investigate if inflammation markers in a late pregnancy plasma sample can predict the presence of depressive symptoms at eight weeks postpartum. Blood samples from 291 pregnant women (median and IQR for days to delivery, 13 and 7-23days respectively) comprising 63 individuals with postpartum depressive symptoms, as assessed by the Edinburgh postnatal depression scale (EPDS≥12) and/or the Mini International Neuropsychiatric Interview (M.I.N.I.) and 228 controls were analyzed with an inflammation protein panel using multiplex proximity extension assay technology, comprising of 92 inflammation-associated markers. A summary inflammation variable was also calculated. Logistic regression, LASSO and Elastic net analyses were implemented. Forty markers were lower in late pregnancy among women with depressive symptoms postpartum. The difference remained statistically significant for STAM-BP (or otherwise AMSH), AXIN-1, ADA, ST1A1 and IL-10, after Bonferroni correction. The summary inflammation variable was ranked as the second best variable, following personal history of depression, in predicting depressive symptoms postpartum. The protein-level findings for STAM-BP and ST1A1 were validated in relation to methylation status of loci in the respective genes in a different population, using openly available data. This explorative approach revealed differences in late pregnancy levels of inflammation markers between women presenting with depressive symptoms postpartum and controls, previously not described in the literature. Despite the fact that the results do not support the use of a single inflammation marker in late pregnancy for assessing risk of postpartum depression, the use of STAM-BP or the novel notion of a summary inflammation variable developed in this work might be used in combination with other biological markers in the future.

Exploring salivary cortisol and recurrent pain in mid-adolescents living in two homes

BackgroundEach year, around 50.000 children in Sweden experience a separation between their parents. Joint physical custody (JPC), where the child alternates homes between the parents for about equal amount of time, has become a common living arrangement after parental separation. Children in two homes could benefit from everyday contact with both parents and access to both parents’ financial resources. However, children could experience stress from being constantly moving and potentially exposed to parental conflicts. Still, studies on JPC and biological functioning related to stress, are lacking. The aim of this study was to investigate how living arrangements (intact family/JPC) relate to HPA-axis activity and recurrent pain in mid-adolescents.MethodsMid-adolescents (106 girls and 51 boys) provided demographic details, self-reports of recurrent pain (headache, stomachache, neck/shoulder and back pain) and salivary samples. Salivary cortisol samples were collected: 1) immediately at awakening, 2) +30 minutes, 3) +60 minutes, and 4) at 8 p.m. The cortisol awakening response (CAR) was computed using an established formula. Additionally, the diurnal decline between the waking and 8 p.m. samples was computed.ResultsHierarchical multiple regressions showed that living arrangements (intact family/JPC) was not associated with morning cortisol (CAR), the diurnal cortisol decline or with recurrent pain. However, sex was a significant predictor of both cortisol measures and recurrent pain with girls exhibiting a higher cortisol awakening response and a greater diurnal decline value as well as reporting more recurrent pain than did boys.ConclusionsLiving arrangements were not associated with HPA-axis activity or recurrent pain in this group of well-functioning mid-adolescents. Although this study is the first to investigate how living arrangements relate to HPA-axis functioning and additional studies are needed, the tentative findings suggest that these mid-adolescents have adapted to their living arrangements and that other factors play a more pertinent role for HPA-functioning and subjective health.