Endocrine stress response in pregnancy and 12 weeks postpartum - Exploring risk factors for postpartum depression.

Pregnancy and the postpartum period are characterized by physiological alterations in cortisol and cortisone levels. In the present study, we sought to explore the risk factors for postpartum depression (PPD) and self-remitting postpartum adjustment disorder (AD) and whether cortisol/cortisone metabolism might have any bearing on them. Hair samples from 196 participants (mean age = 31.44, SD = 4.71) were collected at two time points (1-6 days after childbirth and 12 weeks postpartum) to determine the cumulative hair cortisol (HCC) and hair cortisone (HCNC) exposure in the third trimester and during the 12 weeks postpartum. Compared to the non-depressed group (ND, n = 141), more women in the AD (n = 28) and PPD (n = 27) groups had a personal or family history of depression and more stressful life events. Compared to ND and PPD, more women in the AD group had birth-related complications with their children being more often transferred to a pediatric ward. The factors associated with PPD were found to include being unmarried and having a lower household income, less support at home, more subjectively perceived stress after childbirth and lower maternal sensitivity. The natural decrease in HCC concentration from the third trimester to 12 weeks postpartum was significant only in the ND and AD groups, but not in PPD. In summary, prolonged subjectively perceived postpartum stress associated with living situations may contribute to the development of PPD while birth- and child-related complications are likely to trigger brief episodes of AD. Only in ND and AD, the pregnancy-related physiological changes in glucocorticoid levels return to the pre-pregnancy baseline after 12 weeks. Our observations point to the difference between the ND and PPD groups in glucocorticoid metabolism-related postpartum adjustment, which may be a factor in the development of PPD.

Cumulative cortisol exposure in the third trimester correlates with postpartum mothers' neural response to emotional interference.

Prolonged stress affects the central nervous system, rendering individuals vulnerable to a wide range of mental health disorders. 76 healthy postpartum mothers were studied by means of functional magnetic resonance imaging within 6 days of childbirth. The subjects were required to perform the emotional Stroop task involving happy and anxious word-face combinations. Hair samples were collected to determine cumulative hair cortisol concentration (HCC) in the third trimester. HCC was found to be negatively correlated with the recruitment of the dorsal anterior cingulate cortex (ACC) and the midcingulate cortex (MCC). In response to the emotional interference of only anxious target faces, a negative correlation was seen between HCC and the bilateral orbitofrontal cortex, extending to the rostral ACC and the MCC. Women with lower HCC recruited brain areas relevant to emotional cognitive control, indicating that lower HCC helps preserve conflict monitoring and resolution capacities and thus benefits mental health in pregnancy.

Prenatal and adult androgen activities in alcohol dependence.

OBJECTIVE: Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. METHOD: We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). RESULTS: The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). CONCLUSION: Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.

Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies.

OBJECTIVE: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies. METHODS: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations. RESULTS: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = - 0.47, ρ = - 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR. DISCUSSION: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the changes were most obvious in pregnancies complicated by IUGR and only minor changes were observed in pregnancies where patients had impaired liver function, our data suggests that placental rather than maternal hepatic function strongly determines lipid and steroid levels in pregnancy.

Strong hypoxia reduces leptin synthesis in purified primary human trophoblasts.

INTRODUCTION: Oxygen availability severely affects placental function. During placental hypoxia, stabilization of hypoxia inducible factors (HIFs) affects transcription, and leptin gene expression concomitantly increases in vivo and in vitro. However, a causal relationship is uncertain. METHODS: We investigated the effect of oxygen availability on HIF-1 alpha (HIF1A) and leptin regulation in primary human trophoblasts isolated from six normal term placentae cultured at 0.1%, 1%, 3%, and 8% oxygen for 6 h, 24 h and 48 h. Gene expressions of leptin (LEP), leptin receptors (LEPR), HIF1A, insulin receptor (INSR) and further genes relevant in hypoxia (VEGFA, EPO, NOS2) or apoptosis (BCL2, BAX, Tp53) were examined. Leptin, HIF1A, INSR, phospho-AKT/AKT (insulin receptor signaling), caspase 3 and cleaved caspase 3 (apoptosis) proteins were measured. RESULTS: A hypoxic reaction with stabilization of HIF1A protein as well as up-regulation of HIF1A and VEGFA gene expressions, but without any hint for apoptosis, was present at 0.1% and 1% oxygen. However, leptin protein concentration (cell supernatants) peaked at 8% oxygen (normoxia) and was significantly reduced at 0.1% oxygen. There was no significant correlation between leptin and HIF1A, neither on the gene nor on the protein level. DISCUSSION: Elevated leptin gene expression in hypoxic placentas may not originate from trophoblasts, but from other placental cells, or from interaction of trophoblasts with other cells. Not only fetal hyperleptinemia, but also fetal hypoleptinemia under hypoxic conditions is conceivable. Strategies to prevent leptin dysregulation during pregnancy should be elucidated to protect the offspring from fetal programming of leptin resistance and adiposity in later life.

Off-label use of misoprostol for labor induction in Germany: a national survey.

OBJECTIVE: Misoprostol is safe and effective for labor induction in viable pregnancies. Little is known about the prevalence of off-label use of misoprostol, and the reasons for using or not using misoprostol for labor induction. As such, a national survey was conducted in Germany to assess reliable data about the use of misoprostol in clinical practice. STUDY DESIGN: A prospective study was performed in 2013 using a standardized survey questionnaire. All registered departments of obstetrics and gynecology in Germany were targeted. RESULTS: Out of 783 questionnaires, 542 (69%) were returned. Three hundred and fifty-five (66%) respondents reported that they use misoprostol for labor induction in viable term pregnancies, and 183 (34%) respondents reported that they never use misoprostol for this indication. The most common reasons given for using misoprostol in labor induction were: effectiveness (40%), good patient acceptance (35%), established/well proven in clinical practice (35%) and cost-effectiveness (32%). The most common reasons given for not using misoprostol were lack of licence (off-label use, 69%) and uncertainty of the legal situation (27%). CONCLUSION: Although misoprostol is not licensed in Germany for obstetric indications, the vast majority of respondents (66%) reported that they use misoprostol for labor induction. The main reasons for not using misoprostol for labor induction in Germany are legal concerns rather than lack of scientific evidence. Cost-effective medications with evidence-based effectiveness and safety should be supported by a clear statement from national medical societies.

[Hyperglycaemia and preterm infants: a chapter of its own]. / Hyperglykämie und Frühgeborene: Ein Kapitel für sich.

Antenatally, glucose maintenance takes place via transplacental transfer from mother to fetus. In the third trimester, the amount of glucose transported increases, while glycogen and fat stores are developed. After delivery a continuous and sufficient glucose supply for vital organs and brain is essential. In term infants hormonal and metabolic adaption is well-coordinated, involving adrenal gland, pancreas and liver. However, in preterm infants, mainly during first week of life, there is a high risk of abnormalities in glucose homeostasis. Due to limited glycogen and fat stores, hypoglycaemia may occur which is avoided by continuous glucose infusion. An underestimated risk is hyperglycaemia due to a combination of relative insulin deficiency and insulin resistance, associated with increased mortality and morbidity. Management of hyperglycaemia is one of the topics in neonatology and is still being discussed controversially. This review approaches different therapeutic strategies and gives an overview about the current recommendations in the literature.

Sonographic weight estimation in fetuses with breech presentation.

PURPOSE: To assess the accuracy of weight estimation (WE) in fetuses with breech presentation and to compare it directly with a control group of fetuses in vertex presentation. MATERIALS AND METHODS: In a retrospective cohort study, the accuracy of WE in fetuses with breech presentation (n = 244) was evaluated using eight sonographic models and was compared with a control group of fetuses in vertex presentation (n = 244). Each fetus underwent ultrasound examination with complete biometric parameters within 7 days before delivery. The accuracy of the different formulas was compared using means of percentage error (MPE), a measure that reflects systematic error; standard deviation values of MPEs, a measure for random error; medians of absolute percentage error (MAPE), which take both the systematic and random error into account and the percentage of fetal WEs falling within a 10 % range of the actual birth weight. RESULTS: Significantly lower (more negative) MPE values were found in the breech group with the Hadlock (AC, FL) formula, whereas no significant differences were seen with any of the other equations. When compared to zero, in the breech group, a significant systematic error was found with five formulas, while in the control group a significant systematic error was found with three equations. With regard to random error and MAPE, no significant differences were found between the two groups, irrespective of the formula applied. Generally, in both groups, formulas based on three or four biometric indices were more accurate in detecting fetal weight than formulas with only one or two parameters. CONCLUSIONS: Weight estimation in fetuses with breech presentation was as accurate as weight estimation in fetuses with vertex presentation. Using the currently available, well-established formulas should therefore also be appropriate for WE in fetuses with such malpresentations.

A new formula for optimized weight estimation in extreme fetal macrosomia (≥ 4500 g).

PURPOSE: To develop and to evaluate a specific sonographic weight formula for fetuses with extreme macrosomia (≥ 4500 g). MATERIALS AND METHODS: A statistical estimation technique known as "gradient boosting with component-wise P-splines" was applied to a group of 174 fetuses with a birth weight (BW) ≥ 4500 g. Each fetus underwent an ultrasound examination with complete biometric parameters within 7 days of delivery. The exclusion criteria were multiple pregnancy, intrauterine death, and major structural or chromosomal anomalies. A new formula was derived using the obtained data and was then compared to currently available equations for estimating weight in the macrosomic fetus. RESULTS: The new formula is: log10 (EFW) = 3.6687781710 - 0.0003230278 × (BPD - 100.4080) - 0.0000843433 × (BPD - 100.4080)^2 + 0.0007281281 × (OFD - 120.6322) + 0.0000664323 × (OFD - 120.6322)^2 + 0.000000001794019 × exp(ATD - 120.1552) + 0.0005946974 × (APAD - 121.2069) - 0.0000210137 × (APAD - 121.2069)^2 - 0.000003318 × (APAD - 121.2069)^3, where EFW is the estimated fetal weight, BPD is the biparietal diameter, OFD is the occipitofrontal diameter, ATD is the abdominal transverse diameter, and APAD is the abdominal anteroposterior diameter. The new formula proved to be superior to other established equations, showing the lowest mean absolute percentage error (MAE 2.506), the smallest variance regarding the signed percentage error (SPE) (SD 3.376), and the best distribution of absolute percentage errors within prespecified error bounds. CONCLUSION: This new formula significantly improves weight estimation in fetuses with extreme macrosomia.

The association of prenatal attachment and perinatal factors with pre- and postpartum depression in first-time mothers.

PURPOSE: This prospective study investigated associations between prenatal attachment of adult first-time mothers to the unborn child, perinatal factors and levels of depression before and up to 18 months after delivery. METHOD: Primiparas (N = 161) without specific risk factors answered the following questionnaires during the last term of pregnancy (t1): Edinburgh Postnatal Depression Scale (EPDS), Maternal Antenatal Attachment Scale (MAAS), questionnaire on the schema of the unborn child, and a questionnaire about the pregnancy. Perinatal data were taken from the patients' files. The EPDS was answered 3 weeks (t2, N = 157), 6 months (t3, N = 159), and 18 months (t4, N = 132) postpartum. RESULTS: During pregnancy, 16.9 % of the women indicated mild depressive symptoms, and 7.5 %, medium to severe symptoms of depression. Mild symptoms of depression were found in 25.5 % at t2, 10.1 % at t3, and 12.2 % at t4; medium to severe symptoms were reported by 7.6, 1.9 and 5.6 %, respectively. Women with low control during delivery (emergency Caesarean) showed a tendency for higher levels (p = 0.067) of depression at t3 than women with elective Caesarean did. The quality of prenatal attachment to the unborn child correlated negatively with depressive symptoms at t1-t4. CONCLUSIONS: The closer the prenatal attachment of a mother to her unborn child, the less symptoms of depression she reports during the last term of pregnancy and postpartum. Therefore, promoting good mother-child attachment during pregnancy might influence the level of postpartum depression.

New sonographic method for fetuses with a large abdominal circumference improves fetal weight estimation.

PURPOSE: Birth weight (BW) is an important prognostic parameter for neonatal morbidity and mortality. Commonly used weight formulas lack accuracy, especially at the lower and upper end of the fetal weight range. Fetal abdominal circumference (AC) as part of most of the commonly used equations has the greatest impact on weight estimation. It has been shown that formulas specifically designed for a small fetal AC can improve weight estimation. The aim was to find out whether a new formula specifically designed for fetuses with a large AC may also improve weight determination. MATERIALS AND METHODS: The study included 830 singleton pregnancies. The inclusion criteria were ultrasound examination with complete biometric parameters and an AC ≥ 36.0 cm within 7 days of delivery, and an absence of structural or chromosomal malformations. Two "best-fit" formulas were derived by forward regression analysis. The accuracy of the new formulas was compared with commonly used weight equations using percentage error (PE), absolute percentage error (APE), limits of agreement (LOA) and cumulative distribution. RESULTS: New formula I had no systematic error while new formula II and the routine methods significantly overestimated fetal weight. The medians of the APE were the lowest among the new equations (5.77 and 7.25). The new formulas also demonstrated the narrowest LOA. Importantly, at all discrepancy levels (5 %, 10 %, 15 %, and 20 %), new formula I included significantly more cases than the commonly used methods. CONCLUSION: These specifically designed equations help to improve fetal weight estimation for fetuses with an AC ≥ 36.0 cm. For optimal weight estimation, we recommend using new formula I.

Fetal weight estimation in extreme macrosomia (≥ 4,500 g): comparison of 10 formulas.

PURPOSE: The aim of this retrospective study was to compare the accuracy of 10 commonly used weight estimation formulas in a group of fetuses with extreme macrosomia ( ≥ 4 ,500 g). MATERIALS AND METHODS: Ten formulas were evaluated in a group of 174 fetuses with a birth weight (BW) ≥ 4 ,500 g. Each fetus underwent ultrasound examination with complete biometric parameters within 7 days of delivery. The accuracy of the different formulas for fetal weight estimation (EFW) was compared by mean percentage error (MPE), median of the absolute percentage error (MAPE), the "limits-of-agreement" method and the percentage of EFW falling within the 10 % range of the true birth weight. RESULTS: MPE showed the largest deviation from zero with the Schild formula (MPE - 15.43 %) and the Shepard formula (MPE + 6.08 %) and was closest to zero with the Hadlock II formula (MPE - 5.34 %). The MPE of all formulas showed significant bias when compared to zero. All tested formulas, except the Shepard and Shinozuka equations, significantly underestimated fetal weight. The lowest MAPE was found for the Merz formula (7.23 %). The Hadlock II formula obtained the highest percentage of EWF within the 10 % range of the true birth weight (66.1 %). CONCLUSION: Exact weight estimation in extreme macrosomia remains an unsolved problem, and can therefore only conditionally provide a sufficient basis for clinical decision processes.

New sonographic method for fetuses with small abdominal circumference improves fetal weight estimation.

PURPOSE: Accurate estimation of fetal weight is a valuable tool for determining further obstetric management. Commonly used weight formulas lack accuracy, even though some equations appear to be favorable within defined weight ranges. However, due to the fact that fetal weight is not known in advance, it is not always clear which formula is suitable. In most of the commonly used equations, the fetal abdominal circumference (AC) is not only included but also has the greatest impact on weight estimation. The aim of our study was to develop and evaluate a new formula specifically designed for a small fetal AC in order to improve weight estimation. MATERIALS AND METHODS: The study included 323 pregnancies. The inclusion criteria were singleton pregnancy, ultrasound examination with complete biometric parameters and an AC ≤ 29.0 cm within 7 days of delivery, and an absence of structural or chromosomal malformations. Two "best-fit" formulas were derived by forward regression analysis. Finally, the accuracy of the new formulas was compared to commonly used weight equations by using the percentage error, absolute percentage error (APE), limits of agreement (LOA) and cumulative distribution. RESULTS: Contrary to the routine methods, which significantly underestimated fetal weight, the new formulas did not have a systematic error. The medians of the APE were the lowest (7.13 and 7.16) when compared to other equations. Moreover, the new formulas demonstrated the narrowest LOA. At all discrepancy levels (5%, 10%, 15%, and 20%), the new formulas included significantly more cases than the commonly used methods. CONCLUSION: The specifically designed equations help to improve fetal weight estimation for fetuses with an AC ≤ 29.0 cm. For optimal weight estimation, we recommend using the new formula II.

[How does maternal alcohol consumption during pregnancy affect the development of attention deficit/hyperactivity syndrome in the child]. / Einfluss des mütterlichen Alkoholkonsums während der Schwangerschaft auf die Entwicklung von ADHS beim Kind.

Besides genetic susceptibility, environmental factors and gene-environment interactions are of central interest in research on attention deficit/hyperactivity disorder in children. Focusing on maternal behaviour during pregnancy, prenatal maternal alcohol consumption is associated with behavioural disorders in children. In animal models, developmental disorders of brain structures as well as subsequent behavioural disorders - similar to findings in attention deficit disorder - were caused by prenatal alcohol exposure. These findings occur in small rodents (mice, rats) as well as in primates and can be caused by even moderate alcohol exposure. In foetal alcohol syndrome (FAS) and foetal alcohol spectrum disease (FASD) in humans, symptoms like hyperactivity, disruptive or impulsive behaviour along with reduced attention and slower reaction time are observed. These findings resemble the symptoms of ADHD. For that reason, children diagnosed with FAS/FASD are frequently diagnosed with ADHD in parallel. Even small amounts of alcohol during pregnancy are responsible for cognitive and behavioural impairments like a significantly decreased IQ. About 50 % of adult ADHD patients show alcohol abuse or dependency and/or other substance disorders. Due to this, a higher rate of prenatal exposition to psychoactive substances for children of mothers affected with ADHD seems probable. However, there are no sufficient data on ADHD and its association to substance abuse in pregnancy, which makes it difficult to quantify the impact of genetic and environmental causes for the development of childhood ADHD. So far, no link could be proven with a high level of evidence between moderate prenatal alcohol consumption and the development of childhood ADHD. It has to be recognised that all present studies are based on self-reported alcohol consumption. Data collected by this methodology are usually severely biased to an underestimation of alcohol abuse. Objective tests for alcohol abuse in pregnancy, such as the analysis of fatty acid ethyl esters or ethyl glucuronide in foetal feces after birth, show rates of alcohol consumption in pregnant women which are dramatically higher than reported. Therefore, studies investigating the association between prenatal alcohol exposure and ADHD should incorporate the analysis and validation of more objective methods, such as parameters for alcohol degradation.

The era of centers: the influence of establishing specialized centers on patients' choice of hospital.

PURPOSE: It is considered that establishing accredited specialized centers can serve as a marketing tool. This study investigated whether accredited specialized centers influence patients' choice of hospital. METHODS: A total of 2,389 patients was included in a questionnaire survey: 468 at the Department of Gynecology, 745 at the certified University Breast Center of Franconia, 1,000 at the University Perinatal Center of Franconia and 176 for whom classification details were lacking. RESULTS: Among the oncological patients, physicians in private practice played an important role in the choice of hospital (58.4 vs. 25.7%; P < 0.001; OR 4.058). Among obstetric patients, the primary factors were recommendations from family [odds ratio (OR) 0.495], friends (OR 0.218), and previous personal experience of the hospital (OR 0.695). For oncological patients, treatment quality (OR 2.693), availability of a center (OR 1.785), and certification (OR 3.939) were comparatively more important. For obstetric patients, friendliness (OR 0.409) and attractive accommodation (OR 0.153) were more important. CONCLUSIONS: Physicians are the most important source of recommendations for oncological patients. From the marketing point of view, intensive involvement of local private-practice physicians is necessary. The availability of certified perinatal centers does not currently play any part in patients' choice of hospital.

Disturbed Wnt Signalling due to a Mutation in CCDC88C Causes an Autosomal Recessive Non-Syndromic Hydrocephalus with Medial Diverticulum.

The etiology of non-syndromic hydrocephalus is poorly understood. Via positional cloning in a consanguineous family with autosomal recessive hydrocephalus we have now identified a homozygous splice site mutation in the CCDC88C gene as a novel cause of a complex hydrocephalic brain malformation. The only living patient showed normal psychomotor development at the age of 3 years and 3 months and her deceased aunt, who was assumed to suffer from the same condition, had mild mental retardation. The mutation in the affected patients, a homozygous substitution in the donor splice site of intron 29, resulted in a shorter transcript due to exclusion of exon 29 and loss of functional protein, as shown by Western blotting (p.S1591HfsX7). In normal human tissue panels, we found CCDC88C ubiquitously expressed, but most prominently in the fetal brain, especially in pons and cerebellum, while expression in the adult brain appeared to be restricted to cortex and medulla oblongata. CCDC88C encodes DAPLE (HkRP2), a Hook-related protein with a binding domain for the central Wnt signalling pathway protein Dishevelled. Targeted quantitative RT-PCR and expression profiling of 84 genes from the Wnt signalling pathway in peripheral blood from the index patient and her healthy mother revealed increased mRNA levels of CCDC88C indicating transcriptional upregulation. Due to loss of CCDC88C function ß-catenin (CTNNB1) and the downstream target LEF1 showed increased mRNA levels in the patient, but many genes from the Wnt pathway and transcriptional target genes showed reduced expression, which might be explained by a complex negative feedback loop. We have thus identified a further essential component of the Wnt signalling pathway in human brain development.

Differences in gene expression dependent on sampling site in placental tissue of fetuses with intrauterine growth restriction.

OBJECTIVE: The human placenta as part of the feto-placental unit may influence fetal endocrine systems and may therefore represent a very important link between intrauterine growth restriction (IUGR) and metabolic disorders in later life. We aimed to analyze the effect of sample origin on gene expression of placental factors potentially involved in fetal programming in IUGR versus appropriate for gestational age growth (AGA) to standardize sample collection procedure for a multicenter approach. DESIGN: Placental gene expression of insulin-like growth factor-binding protein (IGFBP)-1, prolactin, corticotropin releasing hormone (CRH) and leptin was measured and compared between proximal, intermediate and peripheral region of the placenta in 22 IUGR (proven by anomalous placental Doppler velocimetry) and 19 AGA neonates. RESULTS: Whereas no difference in gene expression was seen in the proximal portion, in the intermediate placental region mRNA expression of IGFBP-1 (p = 0.01), prolactin (p = 0.04), CRH (p = 0.01) and leptin (p = 0.04) was increased in IUGR samples compared to controls. At the placental periphery, gene expression of these placental transcripts showed a higher expression level in IUGR placentas without statistical significance, except for leptin (p = 0.03). CONCLUSION: Placental sampling site seems to be relevant for detecting differences in gene expression between IUGR and AGA neonates.

[Pre-, peri- and postpartal depression]. / Prä-, peri- und postpartale Depressivität.

INTRODUCTION: Postpartal affective disorders are with a prevalence between 8 % and 15 % highly frequent maternal diseases after childbirth. An undetected and untreated postpartum depression causes a wide range of negative consequences such as risk of a chronic manifestation of a major depression, social retreat, limitations in the bonding behavior, and behavioral disorders of the child. Therefore, an early detection of pregnant women at risk is warranted. METHODS: Within a prospective study (FRAMES: Franconian Maternal Health Evaluation Studies), 1,100 pregnant women were interviewed with standardized questionnaires at three points of time: Prepartal (U1): from the 30 (th) week of pregnancy onwards, 48 - 72 hours (U2) postpartum (pp) und 6 - 8 months pp (U3). 554 women were included in the substudy Blue FRAMES, where an additional telephone interview at the 10 (th) day pp was conducted with a focus on symptoms relating to Baby Blues such as mood instability, irritability and concentration deficits. The Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale For Depression (HAMD) were used for quantification of depressivity at each point of time. RESULTS: EPDS values differed significantly (Friedman Test; chi (2) = 110.8; df = 2, p < 0,001) between the different examination points (Wilcoxon Test; U1 - U2: Z = -11.0; p < 0.001; U1 - U3: Z = -6.6; p < 0.001; U2 - U3: Z = -4,5; p < 0,001). Regarding EPDS values, higher values were observed prepartum (U1). After a decrease after two to three days postpartum (U2), values increased again. However, EPDS values six months postpartum (U3) were still lower than prepartum (U1). DISCUSSION: The observed EPDS values postpartum are comparable to results of other studies. The higher EPDS values prepartum have a good predictive value. There is a great need and possibility for improved prevention of postpartal disorders, when appropriately addressed in the prepartum period.

Polymorphisms in estrogen metabolism and estrogen pathway genes and the risk of miscarriage.

PURPOSE: This study investigated genetic variations in the estrogen pathway and their association with miscarriages. METHODS: A total of 483 patients were recruited from a comprehensive control group for case-control studies. Three variants of the CYP19A1 gene (rs10046, rs4646 and rs700519) and one variant each of the estrogen (ESR1) and progesterone (PGR) receptor genes (rs3020314 and rs1042838) were investigated using polymorphism genotyping. The chi-squared test and one-way analysis of variation (ANOVA) were used for statistical analysis. RESULTS: For rs10046 (CYP19A1), the C/C genotype was associated with a greater frequency of miscarriages (P = 0.017). The other genotypes were not found to be associated with recurrent miscarriage. CONCLUSIONS: This is the first study that has identified a single-nucleotide polymorphism in the aromatase gene that suggests a significant association between genotypes and miscarriage. As aromatase is an essential enzyme in the estrogen pathway, it may be speculated that variations in the aromatase gene in some way give rise to different conditions in the endocrine environment that can lead to impaired fertility.

Weight estimation by three-dimensional ultrasound imaging in the small fetus.

OBJECTIVES: To improve birth weight estimation in fetuses weighing