Göran Berg

Prevalence of depressive symptoms in late pregnancy and postpartum.

Background. Postnatal depression refers to a non‐psychotic depressive episode that begins in or extends into the postpartum period. The aims of this study were to examine the prevalence of depressive symptoms in a pregnant and later postnatal population, to determine the natural course of these symptoms and whether there is an association between antenatal and postnatal depressive symptomatology.

Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype.

Background Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known. Methodology/Principal Findings Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications. Conclusions/Significance The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.

Obstetric, somatic, and demographic risk factors for postpartum depressive symptoms ☆

OBJECTIVE To identify and test the predictive power of potential independent risk factors of postpartum depressive symptoms during pregnancy and the perinatal period. METHODS We conducted a case‐control study where 132 women with postpartum depressive symptoms were selected as an index group and 264 women without depressive symptoms as a control group. Data related to sociodemographic status, medical, gynecologic, and obstetric history, pregnancy, and perinatal events were collected from standardized medical records. RESULTS The strongest risk factors for postpartum depressive symptoms were sick leave during pregnancy and a high number of visits to the antenatal care clinic. Complications during pregnancy, such as hyperemesis, premature contractions, and psychiatric disorder were more common in the postpartum depressed group of women. No association was found between parity, sociodemographic data, or mode of delivery and postpartum depressive symptoms. CONCLUSION Women at risk for postpartum depression can be identified during pregnancy. The strongest risk factors, sick leave during pregnancy and many visits to the antenatal care clinic, are not etiologic and might be of either behavioral or biologic origin. The possibilities of genetic vulnerability and hormonal changes warrant further investigation to reach a more thorough understanding.

Immunology of preeclampsia

Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (Mϕ), one of the major leukocyte populations at the fetal–maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual Mϕ with an in vitro Mϕ differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) Mϕ markers expressed on human decidual Mϕ (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual Mϕ polarization. M-CSF/IL-10–stimulated and decidual Mϕ also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-γ–stimulated Mϕ produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 Mϕ-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual Mϕ, confirming that M-CSF/IL-10–induced Mϕ are closely related to decidual Mϕ. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual Mϕ with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy.

FOXP3+ Regulatory T Cells and T Helper 1, T Helper 2, and T Helper 17 Cells in Human Early Pregnancy Decidua

In pregnancy, the decidua is infiltrated by leukocytes promoting fetal development without causing immunological rejection. Murine regulatory T (Treg) cells are known to be important immune regulators at this site. The aim of the study was to characterize the phenotype and origin of Treg cells and determine the quantitative relationship between Treg, T-helper type 1 (TH1), TH2, and TH17 cells in first-trimester human decidua. Blood and decidual CD4+ T cells from 18 healthy first-trimester pregnant women were analyzed for expression of Treg-cell markers (CD25, FOXP3, CD127, CTLA4, and human leukocyte antigen-DR [HLA-DR]), chemokine receptors (CCR4, CCR6, and CXCR3), and the proliferation antigen MKI67 by six-color flow cytometry. Treg cells were significantly enriched in decidua and displayed a more homogenous suppressive phenotype with more frequent expression of FOXP3, HLA-DR, and CTLA4 than in blood. More decidual Treg cells expressed MKI67, possibly explaining their enrichment at the fetal-maternal interface. Using chemokine receptor expression profiles of CCR4, CCR6, and CXCR3 as markers for TH1, TH2, and TH17 cells, we showed that TH17 cells were nearly absent in decidua, whereas TH2-cell frequencies were similar in blood and decidua. CCR6+ TH1 cells, reported to secrete high levels of interferon gamma (IFNG), were fewer, whereas the moderately IFNG-secreting CCR6− TH1 cells were more frequent in decidua compared with blood. Our results point toward local expansion of Treg cells and low occurrence of TH17 cells. Furthermore, local, moderate TH1 activity seems to be a part of normal early pregnancy, consistent with a mild inflammatory environment controlled by Treg cells.

Climacteric symptoms among women aged 60–62 in Linköping, Sweden, in 1986

By means of a simple postal questionnaire, all women aged 60, 61 and 62 (n = 2015) living in the community of Linköping, Sweden, were screened for vasomotor symptoms and local vaginal complaints. After one reminder, answers were received from 73% of the women. At the time of the survey (April 1986) all the women were post-menopausal, the median period since menopause being 11 yr. Slightly over one in four of the women (27%) were suffering from sweating and hot flushes. Ten percent (10%) of the women who were more than 15 yr post-menopausal still had moderate to severe climacteric symptoms. Vasomotor symptoms were significantly more common among oophorectomized women than among those whose ovaries were intact. Local vaginal symptoms were positively correlated with urinary problems, repeated urinary tract infections and a high risk of disturbance of sexual activity. It was concluded that climacteric symptoms often persist for more than 15 yr after the menopause.

Obstetric anal sphincter injury ten years after: subjective and objective long term effects

Objective  To establish the long term effects of obstetric anal sphincter rupture.

β-Adrenergic receptors in human myometrium during pregnancy: Changes in the number of receptors after β-mimetic treatment☆

Abstract The concentration of available β-adrenoceptors has been studied in the myometrium of women treated with terbutaline for premature uterine contractions and in an untreated control group. Myometrial strips were taken at cesarean section from the lower uterine segment and the uterine fundus. The concentration of β-adrenoceptors was determined with a radioligand binding assay. In untreated women we found no difference in the concentration of β-adrenoceptors in the uterine fundus compared to that in the lower uterine segment. The cyclic adenosine monophosphate production after β-adrenoceptor agonist stimulation in vitro was equal in both locations. In the terbutaline-treated women, the binding site concentrations in both the fundus and lower uterine segment were lower compared to those in the control group. The decrease was most pronounced in the fundus where receptor concentration was only half that found in the control group. The results suggest that treatment with β-mimetics causes a desensitization in the β-adrenoceptor system of human myometrium during pregnancy. This desensitization may partly explain the limited duration of the relaxant effect of β-mimetics often seen in the treatment of preterm labor

Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood : Implications for suppressor macrophages in decidua

Problem:  Local immune modulation has been shown to be of considerable importance for the maintenance of successful pregnancy. We have previously reported the secretion of interferon‐γ (IFN‐γ), interleukin‐4 (IL‐4) and IL‐10 in human decidua from early normal pregnancy. The aim of this study was to investigate the cellular source of cytokine secretion in the decidua, and compare this to secretion patterns in peripheral blood.