Genetic variants in the genes of the sex steroid hormone metabolism and depressive symptoms during and after pregnancy.

PURPOSE: The aim of this study was to conduct an association analysis of depressive symptoms and polymorphisms in the ESR1, PGR, CYP19A1, and COMT genes in pregnant and postpartum women. METHODS: The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for assessment of maternal and fetal health. 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 pregnancy, visit 2 was shortly after birth, and visit 3 was 6-8 months after birth. Germline DNA and depression measurements from 361 pregnant women were available for analysis. Six single nucleotide polymorphisms (SNPs) in the above-mentioned genes were genotyped. After reconstruction of haplotypes for PGR (rs1042838 and rs10895068) and CYP19A1 (rs10046 and rs4646), a multifactorial linear mixed model was applied to the data to describe the association between haplotypes and depression values. The single SNPs for ESR1 (rs488133) and COMT (rs4680) were analyzed separately using linear mixed models analogously. RESULTS: The mean antepartum EPDS measurement was 5.1, the mean postpartal measurement after 48-72 h was 3.5, and the mean value 6-8 months postpartum was 4.2. The SNPs in PGR were reconstructed into three haplotypes. The most common haplotype was GG, with 63.43% of patients carrying two copies and 33.52% carrying one copy. For haplotype GA, the group of carriers of two copies (0.28%) was combined with the carriers of one copy (9.70%). Haplotype reconstruction using CYP19A1 SNPs resulted in three haplotypes. The most common haplotype was TC, with 25.48% of patients carrying two copies and 51.52% one copy. None of the haplotype blocks and neither of the two single SNPs showed any significant associations with EPDS values. CONCLUSIONS: The candidate haplotypes analyzed in PGR and CYP19A1 and single SNPs in ESR1 and COMT did not show any association with depression scores as assessed by EPDS in this cohort of healthy unselected pregnant women.

[Maternal Attachment Style and her Perinatal Wellbeing Influence Early Childhood Development]. / Der Bindungsstil der Mutter und ihr perinatales Wohlbefinden beeinflussen die frühkindliche Entwicklung.

An increasing number of children show signs of behavioral problems and dysregulation in early childhood. It is assumed that maternal depression and her attachment representations affect child development. This was investigated in a prospective study with 161 primiparae women. Via standardized questionnaires during the third trimester, 3 weeks, 6 months and 18 months postpartum, prenatal attachment of the mother to the unborn child, her general attachment style and postpartum depression as well as the child's dysregulation at 18 months were assessed. In the GLM, longer-lasting pre- and postpartum depressivity and insecure partnership attachment representation were associated with child dysregulation. Therefore, early detection of pre- and postpartum depression is important in order to support both the affected women and the children for better child development.

[Maternal depression and child development: A prospective analysis of consequences, risk and protective factors]. / Mütterliche Depressivität im kindlichen Entwicklungsverlauf: Eine prospektive Betrachtung von Auswirkungen, Risiko- und Schutzfaktoren.

Maternal depression and child development: A prospective analysis of consequences, risk and protective factors Abstract. Objective: Maternal stress, specifically maternal mental health problems, are considered risk factors for child development. The literature suggests that prenatal depressive symptoms as well as depressive symptoms are a widespread phenomenon during the further development of the child and have repeatedly been shown to have adverse effects on child mental health outcomes. The present study examined the longitudinal relationships between maternal depression (prenatal, postnatal, during childhood and adolescence) and child mental health from childhood to adolescence. Possible risk and protective factors were also considered. Method: N = 112 mothers were assessed for depressive symptoms via a questionnaire at four different timepoints (prenatal, T1; postnatal, T2; during childhood, T3; during adolescence, T4). Children's externalizing and internalizing symptoms (50.9 % girls) were assessed by their mothers both during childhood (M = 7.68, SD = 0.76 years) and during adolescence (M = 13.23, SD = 0.27 years). We evaluated the relationships between maternal depressive symptoms and children's externalizing/internalizing symptoms using multiple regression models and analyzed possible risk and protective factors using moderation analysis. Results: Externalizing/Internalizing symptoms were not directly associated with maternal depressive symptoms, while associations between such symptoms and maladaptive behavior were found in adolescents. The socioeconomic status of families showed a different risk profile for prenatal and postnatal depressive symptoms. The IQ of the children proved to be a risk factor for internalizing symptoms. Conclusions: Maternal depressive symptoms at any time during child development - in combination with further risk factors - have an impact on child mental health. The early identification of maternal symptoms followed by interventions to differentiate between prenatal and postnatal depression - especially in the context of socioeconomic status - are highly relevant for child development.

The association between prenatal alcohol consumption and preschool child stress system disturbance.

BACKGROUND: Drinking alcohol during pregnancy is considered a risk factor for child development; however, child biomarkers of prenatal alcohol exposure have been rarely studied. We examined whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with child cortisol concentrations at primary school age. METHODS: For 137 children, prenatal alcohol exposure was operationalized by the meconium biomarker EtG and by maternal self-reports during pregnancy. Two EtG cut-offs (EtG ≥10 ng/g and EtG ≥112 ng/g) were applied. Cortisol concentrations were measured in saliva and hair samples. RESULTS: Children with EtG ≥10 ng/g showed significantly reduced hair cortisol concentrations (HCCs) (p = .050, ηp2  = 0.042). For children with EtG ≥112 ng/g, the cortisol awakening response (CAR) was significantly decreased (p = .025, ηp2  = 0.070). These effects were also present in correlational analyses with continuous EtG data, speaking for partly dose-dependent effects. Especially, within the EtG ≥112 ng/g group, the basal (CAR: rp  = -.642, p = .120) and cumulative (HCC: rp  = -.660, p = .107) cortisol parameters were associated with child emotional symptoms at medium effect size. CONCLUSIONS: The present study showed both the biological association of intrauterine alcohol exposure with the cortisol stress system, partly dose-dependent, and the functional association with emotional and behavioral symptoms.

Genetic variants in the glucocorticoid pathway genes and birth weight.

PURPOSE: The aim of this study was to examine associations between single nucleotide polymorphisms (SNPs) that tag genetic variation in the glucocorticoid pathways (particularly in maternal genes FKBP5, NR3C1, and CRHR1) and birth weight. METHODS: The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for the assessment of maternal and fetal health. Germline DNA was collected from 375 pregnant women. Nine SNPs in the above-mentioned genes were genotyped. After reconstruction of haplotypes for each gene, a linear regression model was applied to the data to describe the association between haplotypes and birth weight. RESULTS: Female sex in the newborn (compared to male) was associated with lower birth weight, whereas a later week of gestation, higher body mass index pre-pregnancy, and higher parity were associated with higher birth weight. No association with birthweight was shown for the haplotypes of the selected SNPs. CONCLUSIONS: In this cohort of healthy unselected pregnant women, the analyzed candidate haplotypes in FKBP5, NR3C1, and CRHR1 did not show any association with birth weight. This might be in line with several other studies that have found no influence of fetal polymorphisms in the glucocorticoid receptor gene or triggers of the maternal HPA axis such as stress and psychosocial problems on birth weight. However, the small sample size in this study and the lack of consideration of individual risk factors and levels of stress in this cohort needs to be taken into account when interpreting the results.

Reliability of prenatal detection of X-linked hypohidrotic ectodermal dysplasia by tooth germ sonography.

OBJECTIVE: In X-linked hypohidrotic ectodermal dysplasia (XLHED), dysfunction of ectodysplasin A1 (EDA1) due to EDA mutations results in malformation of hair, teeth, and sweat glands. Hypohidrosis, which can cause life-threatening hyperthermia, is amenable to intrauterine therapy with recombinant EDA1. This study aimed at evaluating tooth germ sonography as a noninvasive means to identify affected fetuses in pregnant carrier women. METHODS: Sonography, performed at 10 study sites between gestational weeks 18 and 28, led to the diagnosis of XLHED if fewer than six tooth germs were detected in mandible or maxilla. The assessment was verified postnatally by EDA sequencing and/or clinical findings. Estimated fetal weights and postnatal weight gain of boys with XLHED were assessed using appropriate growth charts. RESULTS: In 19 of 38 sonographic examinations (23 male and 13 female fetuses), XLHED was detected prenatally. The prenatal diagnosis proved to be correct in 37 cases; one affected male fetus was missed. Specificity and positive predictive value were both 100%. Tooth counts obtained by clinical examination corresponded well with findings on panoramic radiographs. We observed no weight deficits of subjects with XLHED in utero but occasionally during infancy. CONCLUSION: Tooth germ sonography is highly specific and reliable in detecting XLHED prenatally.

Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children.

Epigenetic DNA modifications in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are discussed as a mechanism underlying the association between prenatal depression and altered child HPA activity. In a longitudinal study, DNA methylation changes related to prenatal depressive symptoms were investigated in 167 children aged 6 to 9 years. At six candidate genes, 126 cytosine-guanine dinucleotides were considered without correcting for multiple testing due to the exploratory nature of the study. Further associations with the basal child HPA activity were examined. Children exposed to prenatal depressive symptoms exhibited lower bedtime cortisol (p = .003, ηp2 = 0.07) and a steeper diurnal slope (p = .023, ηp2 = 0.06). For total cortisol release, prenatal exposure was related to lower cortisol release in boys, and higher release in girls. Furthermore, prenatal depressive symptoms were associated with altered methylation in the glucocorticoid receptor gene (NR3C1), the mineralocorticoid receptor gene (NR3C2), and the serotonin receptor gene (SLC6A4), with some sex-specific effects (p = .012-.040, ηp2 = 0.03-0.04). In boys, prenatal depressive symptoms predicted bedtime cortisol mediated by NR3C2 methylation, indirect effect = -0.07, 95% confidence interval [-0.16, -0.02]. Results indicate relations of prenatal depressive symptoms to both child basal HPA activity and DNA methylation, partially fitting a mediation model, with exposed boys and girls being affected differently.

Effects of prenatal alcohol consumption on cognitive development and ADHD-related behaviour in primary-school age: a multilevel study based on meconium ethyl glucuronide.

BACKGROUND: Alcohol intake during pregnancy is considered to be a risk factor for child development. Child biomarkers of intrauterine alcohol exposure have been rarely studied. We investigated whether a meconium alcohol metabolite (ethyl glucuronide, EtG) was associated with cognitive development, ADHD-related behaviour and neurophysiological markers of attention and executive control of children at primary-school age. METHODS: Mothers provided self-report on prenatal alcohol consumption during their 3rd trimester. Meconium samples were collected at birth. A total of 44 children with a meconium EtG above the detection limit (≥10 ng/g) and 44 nonexposed matched controls were compared. A second threshold (≥154 ng/g) was applied to study the dose effects. When children reached primary-school age, mothers rated ADHD-related behaviour, child cognitive development was measured using an IQ test battery, and event-related potentials were recorded during a cued go/nogo task. RESULTS: Children in both EtG-positive groups allocated fewer attentional resources than controls to the go/nogo task (reduced P3 component in go-trials). Children with a meconium EtG above 154 ng/g were also found to have an IQ that was six points lower than the other groups. Within the EtG ≥ 154 ng/g group, there was a positive correlation between EtG value and ADHD-related behaviour. These significant effects were not observed in relation to the maternal self-report data. CONCLUSIONS: Associations between EtG and cognitive deficits, attentional resource capacity and ADHD-related behaviour could be documented with effects that were partially dose-dependent. In addition to maternal self-reports, this biomarker of intrauterine alcohol exposure may be considered as a predictor of child development.

Cryopreservation of amniotic membrane with and without glycerol additive.

PURPOSE: Amniotic membrane (AM) is an essential tool in ocular surface reconstruction. In this study, we analyzed the differential effects of glycerol and straight storage at - 80 °C for up to 6 months on the structural, biological, and mechanical properties of amniotic membrane (AM). METHODS: Human placentae of 11 different subjects were analyzed. AMs were stored at - 80 °C, either with a 1:1 mixture of Dulbecco's modified Eagle medium and glycerol (glycerol) or without any medium or additives (straight). Histological image analysis, tensile strength, cell viability, and basic fibroblast growth factor (bFGF) secretion were evaluated at 0.5, 1, 3, and 6 months. RESULTS: Histologically, neither glycerol nor straight storage significantly altered the epithelial or stromal structure of the AM. However, the cell number of the stroma was significantly reduced during the freezing process, independently of the storage method (p = 0.05-0.001). Tensile strength and Young's modulus were not influenced by the storage method, but longer storage periods significantly increased the tensile strength of the AMs (p = 0.028). Cell viability was higher in glycerol rather than straight AM samples for up to 3 months of storage (p = 0.047-0.03). Secretion of bFGF at 3 months of storage was significantly higher in glycerol versus straight frozen AM samples (p = 0.04). DISCUSSION: Glycerol led to higher cell viability and higher bFGF secretion for up to 3 months of AM storage. However, no significant differences between the two methods were observed at 6 months of storage at - 80 °C.

Intrauterine Growth Restriction (IUGR) Induces Signs of Subclinical Atherosclerosis in 6-Year-Old Infants Despite Absence Of Excessive Growth.

Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants. Patients Data for 9 infants with IUGR defined by a birth weight<10th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available. Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT). Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ. Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.

Postnatal Mother-to-Infant Attachment in Subclinically Depressed Mothers: Dyads at Risk?

BACKGROUND: Dyadic interactions between children and depressed mothers have been characterized as less synchronous and with lower maternal sensitivity, fostering an inharmonious, insecure attachment relationship between mother and child. Thus, these children may experience enhanced early life stress and are at higher risk of disturbed socioemotional development. Recently, this association has also been found in women with mild depressive symptoms. However, potential confounding effects of mother's history of own rearing experiences or infant temperament on the link between depressive symptoms and postnatal mother-to-infant attachment have not yet been investigated. METHODS: Differences in mother-to-infant attachment (e.g. quality of attachment, absence of hostility, and pleasure in interaction) between mothers with and without symptoms of depression 6-8 months postpartum were analyzed in a low-risk community sample (n = 38, 19 per group). Depressive symptomatology was measured with the Beck Depression Inventory (BDI-II) and the Edinburgh Postnatal Depression Scale (EPDS). Depressed mothers indicated mild-to-moderate depressive symptomatology (mean BDI-II 11.26 ± 3.86) but did not fulfill criteria for a major depressive episode and, thus, were referred to as 'subclinically' depressed. Potential confounders, namely maternal history of own rearing experiences and infant temperament, were explored by multivariate AN(C)OVA. RESULTS: Primiparous mothers with subclinical depression differed significantly from healthy control mothers, i.e. showed poorer mother-to-infant attachment and higher infant-related hostility 6-8 months postpartum. As expected, infant temperament and mother's history of own rearing experiences were both associated with mother-to-infant attachment but did not explain the negative effects of subclinical depression on the mother-infant relationship. CONCLUSIONS: Given the high prevalence of maternal depression, the current findings give reason for increased concern for the developing mother-child relationship. Therefore, early interventions are needed that focus on the mother-child dyad and target not only clinically but also subclinically depressed mothers.

Differential effects of low birthweight and intrauterine growth restriction on umbilical cord blood insulin-like growth factor concentrations.

OBJECTIVE: Alterations in the growth hormone-insulin-like growth factor (IGF) axis have been considered as a causal factor for intrauterine growth restriction (IUGR) and for the increased risk of metabolic disease in later life. We compared members of the IGF axis in umbilical cord blood between IUGR neonates, small for gestational age without foetal restriction (SGA) and appropriate for gestational age (AGA) neonates. DESIGN: Prospective controlled multicenter study. PATIENTS: Sixteen ultrasound-proven IUGR, 8 SGA and 40 AGA neonates. MEASUREMENTS: Concentrations of total IGF-I and total IGF-II by immunoassays, bioactive IGF by cell-based bioassay and IGFBP-I in mixed venous and arterial umbilical cord blood samples at birth. Auxological parameters at birth. RESULTS: IGF-I concentrations in IUGR [17·7 µg/l (CI 13·8;21·6)] were clearly below those in AGA [48·3 µg/l (CI 43·7;52·9)] and SGA neonates [36·0 µg/l (CI 26·6;45·4)]. IGF-II levels were significantly reduced in IUGR [201·4 µg/l (CI 190·2;212·6)] compared to AGA neonates [231·2 µg/l (CI 220·6;241·9)]. A trend for lower IGF-II concentrations was observed in IUGR when compared to SGA neonates [232·0 µg/l (CI 207·2;256·8)]. These differences could not be explained by confounding. For IGFBP-1, a trend towards higher values in IUGR was observed. CONCLUSIONS: Low IGF-I cord blood concentrations in hypotrophic neonates after IUGR might not only result from low birthweight per se, but also reflect prenatal placental environment. Alterations of the IGF axis could be in the causal pathway of IUGR and thus constitute a potential surrogate marker for IUGR in the assessment of foetal programming.

Feedback signals in myelodysplastic syndromes: increased self-renewal of the malignant clone suppresses normal hematopoiesis.

Myelodysplastic syndromes (MDS) are triggered by an aberrant hematopoietic stem cell (HSC). It is, however, unclear how this clone interferes with physiologic blood formation. In this study, we followed the hypothesis that the MDS clone impinges on feedback signals for self-renewal and differentiation and thereby suppresses normal hematopoiesis. Based on the theory that the MDS clone affects feedback signals for self-renewal and differentiation and hence suppresses normal hematopoiesis, we have developed a mathematical model to simulate different modifications in MDS-initiating cells and systemic feedback signals during disease development. These simulations revealed that the disease initiating cells must have higher self-renewal rates than normal HSCs to outcompete normal hematopoiesis. We assumed that self-renewal is the default pathway of stem and progenitor cells which is down-regulated by an increasing number of primitive cells in the bone marrow niche--including the premature MDS cells. Furthermore, the proliferative signal is up-regulated by cytopenia. Overall, our model is compatible with clinically observed MDS development, even though a single mutation scenario is unlikely for real disease progression which is usually associated with complex clonal hierarchy. For experimental validation of systemic feedback signals, we analyzed the impact of MDS patient derived serum on hematopoietic progenitor cells in vitro: in fact, MDS serum slightly increased proliferation, whereas maintenance of primitive phenotype was reduced. However, MDS serum did not significantly affect colony forming unit (CFU) frequencies indicating that regulation of self-renewal may involve local signals from the niche. Taken together, we suggest that initial mutations in MDS particularly favor aberrant high self-renewal rates. Accumulation of primitive MDS cells in the bone marrow then interferes with feedback signals for normal hematopoiesis--which then results in cytopenia.

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.

Regulation of the human endogenous retroviral Syncytin-1 and cell-cell fusion by the nuclear hormone receptors PPARγ/RXRα in placentogenesis.

Cytotrophoblast (CT) cell fusion into a syncytiotrophoblast is obligatory for placentation and mediated by the human endogenous retrovirus (HERV)-W envelope gene Syncytin-1. Abnormal placentation is associated with preeclampsia (PE), HELLP and intrauterine growth restriction (IUGR). In placentogenesis, the MAP-kinase p38α regulates PPARγ/RXRα signaling and target genes, like leptin, resistin, ABCG2, and hCG. The aim of this study was to analyze PPARγ/RXRα signaling and target gene regulation using primary CT cultures, the trophoblastic cell line BeWo and placental tissues from patients with normal and abnormal placentation. CT from four different human control placentae and BeWo cells demonstrated that Syncytin-1, other signaling members and CT cell fusions were regulated with PPARγ/RXRα activators troglitazone and 9-cis retinoic acid, via protein kinase A and p38α inhibition. Significant discordant regulations between CTs and BeWo were found. Two PPARγ/RXRα-response-elements from upstream regulatory elements and the 5'LTR of HERV-W were confirmed with DNA-protein binding assays using nuclear extracts and recombinant PPARγ/RXRα proteins. These promoter elements were validated with luciferase assays in the presence of PPARγ/RXRα modulators. Furthermore, troglitazone or 9-cis retinoic acid treatment of siRNA-PPARγ and siRNA-RXRα transfected BeWo cells proved the requirement of these proteins for Syncytin-1 regulation. Thirty primary abnormal placentae from PE, HELLP and IUGR patients compared to 10 controls showed significant deregulation of leptin RNA and protein, p38α, phospho-p38α, PPARγ, ABCG2, INSL4 and Syncytin-1. Our study characterized PPARγ/RXRα signaling in human CT and cell fusions identifying Syncytin-1 as a new target gene. Based on these results, a disturbed PPARγ/RXRα pathway could contribute to pathological human pregnancies.

Fresh and cryopreserved amniotic membrane secrete the trefoil factor family peptide 3 that is well known to promote wound healing.

Amniotic membrane (AM) is often used for the treatment of ocular surface ulcerations and other corneal defects. Trefoil factor family (TFF) peptide 3 is produced by conjunctival goblet cells, participates in tear film physiology and has also been shown to be involved in ocular surface restitution after corneal injury. In the present study, we questioned whether AM also might be a source of TFF3 and if yes whether the secretion rate of TFF3 is changed by proinflammatory cytokines or by cryoconservation of AM. By means of RT-PCR, the mRNA expression of all three known TFF peptides could be detected in AM. Immunohistochemistry on paraffin-embedded sections localized TFF3 protein and also TFF2 in AM cells and Western blot analysis revealed TFF3 protein in AM. Stimulation experiments with proinflammatory cytokines and subsequent TFF3 ELISA measurements revealed that the secretion rate of fresh or cryoconserved AM was not significantly changed. The results indicate that TFF peptides are produced by AM. TFF3 may contribute to ocular surface wound healing after AM transplantation, but its production by AM is not further inducible by proinflammatory stimuli. Cryopreservation has no effect on the secretion rate of TFF3 supporting the use of cryopreserved AM for transplantation.

Sex-specific differences in the concentration of tubular parameters in the amniotic fluid of second trimester fetuses.

OBJECTIVE: Renal dysplasia and obstructive uropathy are more common in males and are associated with an increased tubular loss of electrolytes. We aimed to compare the midtrimester concentration of tubular parameters in the prenatal period between healthy male and female fetuses. METHODS: Amniotic fluid was collected at 16 weeks of gestation at the time of genetic amniocentesis. The concentration of sodium, chloride, potassium, calcium, phosphate, magnesium, α1-microglobulin, creatinine and urea was determined in the amniotic fluid of 92 male and 108 female fetuses. RESULTS: The concentration of sodium, chloride and calcium was not significantly higher in male than in female fetuses. In contrast, the concentration of potassium (p=0.01), phosphate (p=0.04), magnesium (p=0.04) and α1-microglobulin (p=0.04) was significantly increased in the amniotic fluid of male fetuses. The concentration of electrolytes correlated to the concentration of creatinine, urea and α1-microglobulin. CONCLUSION: The concentration of specific tubular parameters in the amniotic fluid was higher in male compared with female fetuses. Whether this might point to sex-specific differences in tubular function in second trimester fetuses or reflect glomerular filtration or other interfering factors remains speculative.

Subjective assessment of ovarian masses using pattern recognition: the impact of experience on diagnostic performance and interobserver variability.

PURPOSE: To compare diagnostic performance and interobserver variability in a group of 36 examiners, with four different levels of experience. METHODS: Nine junior trainees, eight level I senior trainees, 11 level II senior gynecologists, and eight level III expert sonologists classified 105 ultrasound images of adnexal masses into three subgroups of ovarian lesions (malignancies, functional cysts, and dermoid cysts). RESULTS: The level III sonologists obtained the best diagnostic results together with the lowest interobserver variability (κ = 0.70, SD = 0.04). They achieved significantly better results in comparison with the junior trainees and also the senior trainees (κ = 0.51, SD = 0.12, p < 0.001; and κ = 0.51, SD = 0.09, p < 0.001). Differences between level III sonologists and the group of level II observers did not reach statistical significance (κ = 0.65, SD = 0.09, p = 0.70). There were no significant differences between senior and junior trainees (p = 1.0) and both groups achieved a significantly poorer diagnostic performance in comparison with the level II observers (p < 0.01 and p < 0.01). For all observers, the largest differences were seen for classifying malignancies, the best results for classifying functional cysts, and the poorest for evaluating dermoid cysts. CONCLUSIONS: Diagnostic performance of pattern recognition significantly improves with an increasing level of experience, emphasizing the importance of standardized ultrasound training programs with supervision by experts.

Delivery mode and the course of pre- and postpartum depression.

PURPOSE: To compare depressiveness scores, both during and after pregnancy, with the delivery mode (DM). METHODS: In a longitudinal, prospective study, standardized questionnaires for the Edinburgh Postnatal Depression Scale were presented to 1,100 women and used to assess the presence and severity of depressiveness at three time points: prenatal, from the 30th gestational week (Q1); 48-72 h postnatal (Q2); and 6-8 months postnatal (Q3). The patients were divided into four groups relative to DM: spontaneous delivery, primary cesarean section (CS), secondary CS, and assisted vaginal delivery. The final number of participating women with both delivery mode and depression information for all three time points was 753. RESULTS: There was a significant difference of the mean EPDS values between the spontaneous delivery and primary CS groups (P=0.04) at Q1 (5.1 vs. 6.3). None of the other comparisons was significant. Significant differences relative to DM were seen at Q2 (P<0.0001), but there were no significant differences between the patient groups at Q3 (P=0.54). CONCLUSIONS: DM only showed coherence with the extent of depression briefly during the peripartal period. A relationship was found between depressiveness during pregnancy and DM, with higher depressiveness scores in the group of patients undergoing primary CS. This should be taken into account when patients requesting an elective cesarean section are being counseled.

Intrauterine growth restriction (IUGR) is associated with increased leptin synthesis and binding capability in neonates.

OBJECTIVE: Animal studies suggest pathological foetal programming of hypothalamic circuits regulating food intake in the setting of leptin deficiency and intrauterine growth restriction (IUGR). We aimed to compare placental leptin synthesis and leptin-binding capability in venous cord blood between IUGR newborns and neonates born appropriate for gestational age (AGA). DESIGN: Prospective controlled multicentre study. PATIENTS: Twenty-one ultrasound-proven IUGR and 33 AGA neonates. MEASUREMENTS: The concentration of leptin and soluble leptin receptor (sOB-R) in venous cord blood at birth was determined. Moreover, placental gene and protein expression of leptin and placental mRNA expression of functional and total leptin receptor isoforms were measured. RESULTS: Whereas log-leptin concentration in venous cord blood did not differ between IUGR and AGA newborns, the concentration of log-sOB-R was elevated in IUGR neonates (p(confounder adjusted)=0·009). Placental leptin protein synthesis as well as leptin mRNA was significantly higher in IUGR than in AGA infants (log-transformed, relative gene expression, p(confounder adjusted)=0·004). Analysis of gene expression of functional and total leptin receptor isoforms did not show any difference between both groups. CONCLUSIONS: Leptin-binding capability in venous cord blood is increased in IUGR newborns. Thus, via foetal programming, reduced biologically active leptin levels might contribute to a perturbed regulation of appetite.