Franziska Voigt

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.

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.

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 patients 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 patients 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.

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.

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.

Sonographic weight estimation in fetuses with congenital diaphragmatic hernia.

PURPOSE To determine the accuracy of sonographic weight estimation (WE) for fetuses with congenital diaphragmatic hernia (CDH), and to assess whether certain sonographic models perform better than others in cases of CDH. MATERIAL AND METHODS In a retrospective, multicenter cohort study, the accuracy of WE in fetuses with CDH (n = 172) was evaluated using eight sonographic models and was compared with a control group of fetuses without malformations (n = 172). Each fetus underwent ultrasound examination with complete biometric parameters within 7 days of delivery. The accuracy of the different formulas was compared using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. RESULTS Fetuses with CDH had a significantly lower abdominal circumference (AC) in comparison with the control group (293.6 vs. 312.0 mm, p < 0.001). All of the formulas tested in fetuses with CDH, except for the Siemer equation (the only model that does not incorporate any abdominal measurements), showed significantly lower (more negative) MPEs, larger MAPEs, and smaller proportions of estimates within 10 % of actual birth weight in comparison with the control group.  CONCLUSION The accuracy of sonographic WE in fetuses with CDH is significantly poorer than in fetuses without malformations, principally because of a larger systematic error due to artificially small AC measurements. The development of new, specific models derived from fetuses with CDH could improve the accuracy of WE for infants with this condition.

Analyse der Schwangerschaftsabbrüche der Jahre 1998–2010 am Universitäts-Perinatalzentrum Franken

franziska.voigt@uk-erlangen.de Einleitung: Die absolute Zahl der Schwangerschaftsabbruche (SSA) ist in den letzen Jahren gesunken. Die Abbruchsziffer (SSA pro 1000 Geborene) dagegen gestiegen. Die Zahl der Abbruche aus medizinischer Indikation ist mit knapp 3% in den letzten Jahren stabil geblieben. In der vorgestellten Untersuchung werden die Schwangerschaftsabbruche aus medizinischer Indikation am Universitats-Perinatalzentrum Franken (UPF) auf Art und Haufigkeit der zu Grunde liegenden Pathologie untersucht und die Ubereinstimmung zwischen pranataler Diagnostik und postpartalem Obduktionsergebnis analysiert sowie das Vorgehen von der Diagnose bis zur postpartalen Betreuung dargestellt. Methode: Retrospektive Analyse der Schwangerschaftsabbruche aus medizinischer Indikation am UPF uber einen Zwolfjahreszeitraum (1998–2010), unterteilt in SSA 23 SSW. Ergebnisse: In den Jahren 1998–2010 sind am UPF insgesamt 391 SSA aus medizinischer Indikation vorgenommen worden. 10% fanden vor der 12. SSW, 77% zwischen der 13–23. SSW und 12% der SSA fanden nach der 24. SSW statt. Die sonographische Diagnose stimmte in >99% mit der Ergebnissen der Obduktion uberein. Bei 4% wurden im Rahmen der Obduktion zusatzliche (die Prognose des Kindes nicht verandernden) Fehlbildungen gefunden, die im Ultraschall nicht dokumentiert waren. Schlussfolgerung/Summary: Die sonographische pranatale Diagnostik stimmt mit den postmortem gefunden Auffalligkeiten gut uberein. Trotz verbesserter Ultraschalldiagnostik konnte ein Shift hin zu Abbruchen in fruheren Schwangerschaftswochen nicht festgestellt werde. Das gesetzeskonforme, patientenorientierte Vorgehen beim Wunsch zum Schwangerschaftsabbruch ist die Grundlage einer guten Patientenversorgung in der fur die Paare schwierigen Lebenssituation.

Gestationsdiabetes mellitus – Aktuelle Diagnostik und Therapie

Der Gestationsdiabetes (GDM) ist eine Glukosetoleranzstorung, die erstmals in der Schwangerschaft diagnostiziert wird. Es ist eine der haufigsten Schwangerschaftskomplikation mit moglichen schwerwiegenden Akut- und Langzeitfolgen fur Mutter und Kind. Der aktuelle Stand zu Diagnostik und Therapie wird im Folgenden beschrieben.