Socioeconomic status and depression during and after pregnancy in the Franconian Maternal Health Evaluation Studies (FRAMES).

PURPOSE: Depression during and after pregnancy can have a negative impact on women's quality of life and on the development of the newborn child. Interventions have been shown to have a positive influence on both mothers and children. Predictive factors for depressive symptoms might possibly be able to identify groups that are at high risk. The aim of this study was to investigate the value of socioeconomic factors in predicting depressive symptoms during and after pregnancy. METHODS: Depressiveness was measured using the German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) at three time-points, in a prospective cohort study (n = 1,100). Visit 1 (Q1) was at study entry in the third trimester of the pregnancy, visit 2 (Q2) was shortly after birth, and visit 3 (Q3) was 6-8 months after birth. Depression scores were associated with socioeconomic factors and time in linear mixed models. RESULTS: Parity status, education status, monthly income, residential property status, and partnership status, as well as interactions between them, were found to be predictive factors for EPDS scores. The strongest factor influencing depressive symptoms was partnership status. Women who did not have an intact partnership had EPDS scores that were on average four points higher than in women with a partner at all three study visits (P < 0.000001). CONCLUSIONS: Socioeconomic factors define subgroups that have different depression scores during and after pregnancy. Partnership status appears to be one of the most important influencing factors and could be useful for identifying women who should be offered an intervention to prevent possible negative effects on the mother or child.

Thromboprophylaxis following cesarean section - a nation-wide survey from Germany.

Objective: Our study aimed to assess current practice related to thromboprophylaxis following cesarean section (c.s.) among obstetricians in Germany taking account of the German and international guidelines.Study design: A nation-wide survey using a structured 22-item questionnaire was conducted in Germany. The questionnaire was sent to head of all registered departments of obstetrics and gynecology in Germany, followed by a single reminder followed 3 weeks after the first return deadline. The respondents' answers were related to the different levels of care (1-4) of German perinatal centers.Results: In total 726 obstetric departments were invited to participate. Questionnaires were returned by 389 (54%) of departments. Of the respondents 162 (41%) stated to undertake risk assessment for venous thromboembolism (VTE) using a structured checklist or interview. Compared to level 4 centers risk assessment was significantly more often performed by perinatal centers level 1 (47 versus 35%, p = .05). The majority of responding hospitals preferred universal heparin thromboprophylaxis following elective and emergency caesarean section, regardless of additional risk factors (n = 362; 93%). The "usual" prophylactic dose of heparin was given by the majority of hospitals (n = 280, 72%), while 98 (25%) hospitals used heparin doses adjusted to patients' body weight. In women at increased risk for VTE (e.g. previous VTE) there was a considerable variation in the recommended doses; 140 responding hospitals (36%) used 50-75% of the therapeutic heparin dose, 139 hospitals (36%) the "usual" prophylactic dose, and 97 hospitals (25%) preferred a therapeutic dose. In women at low risk for VTE 64% (n = 248) of hospitals recommended heparin thromboprophylaxis only during the hospital stay, 16% (n = 62) for at least 7 days after c.s., 4% (n = 15) for 10 days, 6% (n = 23) for 2-5 weeks, and 3% (n = 14) for 6 weeks postpartum. In women at increased risk level 1 centers prescribed heparin for VTE prophylaxis significantly more often for 6-8-week postpartum compared to level 4 centers (p = .02) whereas Level 4 centers used prophylactic heparin significantly more often <6 weeks (p = .01).Conclusion: Our survey reveals that the vast majority of hospitals (93%) used heparin prophylaxis after any c.s., irrespective of individual risk factors and the mode of c.s. (elective or emergency). This is in remarkable contrast to the recommendations from the German and other international guidelines. As well, we found a wide variation among respondents in dosing and duration of heparin related to the risk profile of VTE. This demonstrates, that there is little awareness and/or adherence to the German and other guideline recommendations which mirrors the inconsistencies between current guidelines. There is an urgent need to clarify optimal prophylaxis strategies after c.s. and the true magnitudes of benefits and harms associated with heparin prophylaxis by randomized controlled trials with sufficient statistical power.

Meconium indicators of maternal alcohol abuse during pregnancy and association with patient characteristics.

AIM: Identification of women with moderate alcohol abuse during pregnancy is difficult. We correlated self-reported alcohol consumption during pregnancy and patient characteristics with objective alcohol indicators measured in fetal meconium. METHODS: A total of 557 women singleton births and available psychological tests, obstetric data and meconium samples were included in statistical analysis. Alcohol metabolites (fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG)), were determined from meconium and correlated with patient characteristics. RESULTS: We found that 21.2% of the 557 participants admitted low-to-moderate alcohol consumption during pregnancy. Of the parameters analyzed from meconium, only EtG showed an association with alcohol history (P < 0.01). This association was inverse in cases with EtG value above 120 ng/g. These values indicate women with most severe alcohol consumption, who obviously denied having consumed alcohol during pregnancy. No other associations between socioeconomic or psychological characteristics and the drinking status (via meconium alcohol metabolites) could be found. CONCLUSION: Women who drink higher doses of ethanol during pregnancy, according to metabolite measures in meconium, might be less likely to admit alcohol consumption. No profile of socioeconomic or psychological characteristics of those women positively tested via meconium could be established.

Genetic variants in the genes of the stress hormone signalling pathway and depressive symptoms during and after pregnancy.

PURPOSE: The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes of the stress hormone signaling pathway, specifically FKBP5, NR3C1, and CRHR1, are associated with depressive symptoms during and after pregnancy. METHODS: The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for the assessment of maternal and fetal health including the assessment of depressiveness. The German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) was completed at three time points in this prospective cohort study. Visit 1 was at study entry in the third trimester of the pregnancy, visit 2 was shortly after birth, and visit 3 was 6-8 months after birth. Germline DNA was collected from 361 pregnant women. Nine SNPs in the above mentioned genes were genotyped. After construction of haplotypes for each gene, a multifactorial linear mixed model was performed to analyse the depression values over time. RESULTS: EPDS values were within expected ranges and comparable to previously published studies. Neither did the depression scores differ for comparisons among haplotypes at fixed time points nor did the change over time differ among haplotypes for the examined genes. No haplotype showed significant associations with depressive symptoms severity during pregnancy or the postpartum period. CONCLUSION: The analysed candidate haplotypes in FKBP5, NR3C1, and CRHR1 did not show an association with depression scores as assessed by EPDS in this cohort of healthy unselected pregnant women.

Exenatide-induced reduction in energy intake is associated with increase in hypothalamic connectivity.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists such as exenatide are known to influence neural activity in the hypothalamus of animals and to reduce energy intake. In humans, however, significant weight loss has been observed in only a subgroup of patients. Why only some individuals respond with weight loss and others do not remains unclear. In this functional magnetic resonance imaging (fMRI) study, we investigated differences in hypothalamic connectivity between "responders" (reduction in energy intake after exenatide infusion) and "nonresponders." RESEARCH DESIGN AND METHODS: We performed a randomized, double-blinded, placebo-controlled, cross-over fMRI study with intravenous administration of exenatide in obese male volunteers. During brain scanning with continuous exenatide or placebo administration, participants rated food and nonfood images. After each scanning session, energy intake was measured using an ad libitum buffet. Functional hypothalamic connectivity was assessed by eigenvector centrality mapping, a measure of connectedness throughout the brain. RESULTS: Responders showed significantly higher connectedness of the hypothalamus, which was specific for the food pictures condition, in the exenatide condition compared with placebo. Nonresponders did not show any significant exenatide-induced changes in hypothalamic connectedness. CONCLUSIONS: Our results demonstrate a central hypothalamic effect of peripherally administered exenatide that occurred only in the group that showed an exenatide-dependent anorexigenic effect. These findings indicate that the hypothalamic response seems to be the crucial factor for the effect of exenatide on energy intake.

Factors influencing breast changes after pregnancy.

Pregnancy and breastfeeding are major factors reducing breast cancer (BC) risk. A potential mechanism for this effect might be changes in mammographic density, but other factors might be involved. The aim of this study was to investigate factors influencing changes in breast size and breast stiffness after pregnancy. Of a consecutive cohort of 5991 women who gave birth between 1996 and 1999, 559 replied to a questionnaire including questions about breast changes. The women completed their own assessments of changes in breast size and stiffness since their last pregnancy. Factors being investigated regarding their predictive value for these changes were: BMI before pregnancy, weight gain, age at first full-term pregnancy (FFTP), number of pregnancies, breastfeeding, and BMI of the children's fathers. A decrease in breast size was reported in 21.8% of the participants and an increase in 35.1%. With regard to the breast stiffness, 66.4% reported a decrease and only 5% reported an increase. Independent predictors for increased breast size were age at FFTP, increase in BMI since last pregnancy, BMI before pregnancy, and time since FFTP. Factors predictive of greater breast stiffness included age at FFTP, BMI before FFTP, time since FFTP, breastfeeding status, and number of pregnancies. Breast changes after pregnancy depend on several variables, which are described as BC-risk factors. Individual reaction of the female breast to a pregnancy leads to different outcomes with regard to breast size and stiffness. Further studies are needed to clarify whether these individual responses interact with the effect of pregnancy on the BC risk.

Vaccination with dendritic cells pulsed with hepatitis C pseudo particles induces specific immune responses in mice.

AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole "viral surface" induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. RESULTS: Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cells directed against HCV. Furthermore, T-cell responses confirmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. CONCLUSION: Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further.

The 5-HTTLPR polymorphism modulates the influence on environmental stressors on peripartum depression symptoms.

BACKGROUND: Maternal depression during the peripartum period has an incidence of about 13%. Individuals with specific genetic predispositions are more vulnerable to stressful life events suggesting that exploration of gene-environmental pathways might facilitate the identification of risk factors for peripartum depression. The aim of this study was to evaluate the influence of stressful life events in combination with the serotonin transporter gene 5-HTTLPR polymorphism on peripartum depressive symptoms. METHODS: In a non-psychiatric cohort of 419 Caucasians, the severity of depression was assessed prospectively during pregnancy (3rd trimester) and the postpartum period (2-3 days and 6-8 months) using the Edinburgh Postnatal Depression Scale. Satisfaction with the partner and exposure to negative life events were evaluated using self-report questionnaires and the genotype of the 5-HTTLPR was assessed. Repeated measures generalized linear models were used to investigate the gene-environment interaction on depressive symptoms across late pregnancy and the postpartum period. RESULTS: The 5-HTTLPR S-allele carrier status predicted late postpartum depressive symptom severity only in the presence of negative life events. This interaction was not observed for depressive symptoms during the 3rd trimester or the early postpartum. In addition, S-allele carrier status increased the negative effects of dissatisfaction with the current partner on depressive symptoms in the late postpartum period. CONCLUSIONS: In this non-psychiatric cohort, the 5-HTTLPR interacts with both lifetime and current stressors to influence depressive symptoms in the late post partum period. These findings could have clinical implications by allowing identification of women at higher risk for developing postpartum depressive symptoms.

Genetic variants in the tryptophan hydroxylase 2 gene (TPH2) and depression during and after pregnancy.

BACKGROUND: A number of studies indicate that altered serotonergic transmission may be a risk factor for depression in the peripartum period. The aim of this study was to investigate whether genetic polymorphisms in the TPH2 gene, the gene product of which is the rate-limiting enzyme in the biosynthesis of serotonin in the central nervous system, are associated with depressive symptoms in pregnancy and the postpartum period. METHODS: In a cohort of 361 Caucasians, the severity of depression was assessed prospectively during pregnancy (third trimester) and the postpartum period (2-3 days and 6-8 months) using the Edinburgh Postnatal Depression Scale (EPDS). Tagging single nucleotide polymorphisms (SNPs) in TPH2 and SNPs that are known to be of functional relevance were genotyped. For each haplotype block or SNP, a multifactorial linear mixed model was performed to analyse the EPDS values over time. RESULTS: The haplotype block in the promoter region of TPH2 showed significant associations with depression values during pregnancy and 6-8 months afterwards. Additionally, a haplotype block in intron 8 had an influence on depression values during pregnancy, but not after birth. There was a significant interaction between time and haplotypes and the severity of depression. The effect of TPH2 haplotypes on EPDS values was strongest during pregnancy and 6 months after birth, with a low depression rating in the first few days after delivery for all women. CONCLUSIONS: In this cohort, TPH2 haplotypes known to be of functional relevance were found to be associated with different EPDS values during and after pregnancy. These haplotypes were associated with depressive symptoms both before and after delivery and were thus not specific for postpartum-onset depression. This underlines the relevance of these functional polymorphisms for depression in general and the importance of longitudinal assessments in research on postpartum depression.

Treatment of heterotopic cervical pregnancies.

OBJECTIVE: To describe a rare case of a heterotopic pregnancy with a gestational sac in the cervix and one in the uterine cavity, managed successfully with subsequent delivery of a healthy newborn. DESIGN: Case report and review of the literature. SETTING: Tertiary university hospital. PATIENT(S): A woman with heterotopic twin gestation after stimulation treatment at 9 weeks gestation. Transvaginal ultrasound scan revealed two gestational sacs containing two viable fetuses: one sac inside the uterine cavity and the other sac in the uterine cervix. INTERVENTION(S): Selective termination of the cervical pregnancy by curettage under sonographic guidance in combination with cervical cerclage. MAIN OUTCOME MEASURE(S): Intrauterine pregnancy preservation; maternal morbidity and mortality. RESULT(S): The termination of the cervical pregnancy was performed successfully without intraprocedural or postprocedural complications with preservation of the patient's fertility. The intrauterine pregnancy progressed uneventfully through 39½ weeks with delivery of a healthy newborn. CONCLUSION(S): Combined intrauterine and cervical pregnancy is a remote but possible event, particularly after assisted reproductive technology procedures with a high rate of maternal morbidity. Other factors such as concomitant intrauterine pregnancy and the patient's infertility history generally would be secondary concerns. In this case, we were able to terminate the cervical pregnancy selectively, while preserving the intrauterine one, allowing this couple to have a healthy newborn.