ABSTRACT
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.
Subject(s)
Cortisone , Depression, Postpartum , Adult , Female , Glucocorticoids , Humans , Hydrocortisone , Postpartum Period , Pregnancy , Risk FactorsABSTRACT
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.
Subject(s)
Hydrocortisone/metabolism , Mothers/psychology , Pregnancy Complications/metabolism , Pregnancy Trimester, Third/metabolism , Stress, Psychological/metabolism , Adult , Emotions/physiology , Facial Recognition , Female , Gyrus Cinguli/diagnostic imaging , Hair/metabolism , Humans , Magnetic Resonance Imaging , Postpartum Period/psychology , Prefrontal Cortex/diagnostic imaging , Pregnancy , Pregnancy Complications/psychology , Pregnancy Trimester, Third/psychology , Stress, Psychological/psychology , Stroop Test , Young AdultABSTRACT
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.
Subject(s)
Alcoholism/blood , Alcoholism/physiopathology , Androgens/metabolism , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Substance Withdrawal Syndrome/blood , Substance Withdrawal Syndrome/physiopathology , Adult , Alcohol Drinking/epidemiology , Alcoholism/epidemiology , Alcoholism/metabolism , Cross-Sectional Studies , Denmark/epidemiology , Dihydrotestosterone/blood , Female , Fingers/anatomy & histology , Humans , Longitudinal Studies , Male , Pregnancy , Prenatal Exposure Delayed Effects/epidemiology , Sex Factors , Smoking/epidemiology , Stress, Psychological/epidemiology , Testosterone/bloodABSTRACT
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 ρâ=â0.50, triglycerides ρâ=â0.57) and progesterone (ρâ=â0.49, ρâ=â0.53) and negatively with dehydroepiandrosterone (ρâ=â-â0.47, ρ = -â0.38). 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.
ABSTRACT
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.
Subject(s)
Gene Expression Regulation, Developmental , Leptin/metabolism , Placenta/metabolism , Trophoblasts/metabolism , Adult , Antigens, CD/chemistry , Antigens, CD/genetics , Antigens, CD/metabolism , Apoptosis , Blotting, Western , Cell Hypoxia , Cells, Cultured , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/chemistry , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Leptin/chemistry , Leptin/genetics , Placenta/cytology , Pregnancy , Pregnancy Trimester, Third , Protein Stability , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Receptor, Insulin/chemistry , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Receptors, Leptin/chemistry , Receptors, Leptin/genetics , Receptors, Leptin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Trophoblasts/cytologyABSTRACT
BACKGROUND: Commonly used heart valve prostheses have specific drawbacks and limitations. OBJECTIVES AND METHODS: Optimization of conventional methods and techniques for heart valve replacement by application of tissue engineering principles. RESULTS AND CONCLUSIONS: Recent studies have impressively shown that allogeneic decellularized matrices have the potential to overcome limitations of conventional prostheses and to provide all the characteristics of an ideal graft for heart valve replacement.
Subject(s)
Heart Valve Diseases/surgery , Heart Valves/surgery , Tissue Engineering/methods , Acellular Dermis , Heart Valve Prosthesis , Humans , Prosthesis FailureABSTRACT
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.
Subject(s)
Labor, Induced , Misoprostol/administration & dosage , Off-Label Use , Oxytocics , Female , Germany , Health Care Surveys , Humans , Off-Label Use/legislation & jurisprudence , Off-Label Use/statistics & numerical data , Pregnancy , Prospective Studies , Surveys and QuestionnairesABSTRACT
PURPOSE: Hypohidrotic ectodermal dysplasia, a potentially life-threatening heritable disorder, may be recognized already in utero by characteristic features such as oligodontia and mandibular hypoplasia. As therapeutic options and prognosis depend on the time point of diagnosis, early recognition was attempted during routine prenatal ultrasound examinations. SUBJECTS AND METHODS: Fetuses of nine pregnant women (one triplet and eight singleton pregnancies) with family histories of hypohidrotic ectodermal dysplasia were investigated by sonography between the 20th and 24th week of gestation. RESULTS: In 4 male and 2 female fetuses reduced amounts of tooth germs were detected, whereas 5 fetal subjects showed the normal amount. Three-dimensional ultrasound evaluation revealed mandibular hypoplasia in 5 of the 6 fetuses with oligodontia. Molecular genetic analysis and/or clinical findings after birth confirmed the prenatal sonographic diagnosis in each subject. CONCLUSION: In subjects with a family history of hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be established noninvasively by sonography in the second trimester of pregnancy. Early recognition of the disorder may help to prevent dangerous hyperthermic episodes in infancy and may allow timely therapeutic interventions.
Subject(s)
Ectodermal Dysplasia 1, Anhidrotic/diagnostic imaging , Imaging, Three-Dimensional , Tooth Germ/diagnostic imaging , Ultrasonography, Prenatal , Anodontia/diagnostic imaging , Anodontia/embryology , Early Diagnosis , Ectodermal Dysplasia 1, Anhidrotic/genetics , Female , Humans , Infant, Newborn , Mandible/diagnostic imaging , Mandible/embryology , Micrognathism/diagnostic imaging , Micrognathism/embryology , Pregnancy , Pregnancy Trimester, Second , Prognosis , Sensitivity and SpecificityABSTRACT
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.
Subject(s)
Hyperglycemia/diagnosis , Hyperglycemia/drug therapy , Hypoglycemic Agents/administration & dosage , Infant, Premature , Insulin/administration & dosage , Intensive Care, Neonatal/methods , Humans , Hypoglycemic Agents/adverse effects , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/therapy , Insulin/adverse effectsABSTRACT
PURPOSE: To assess the diagnostic accuracy of a new automatic texture-based algorithm (ATBA) in ultrasound imaging of ovarian masses and to compare its performance to subjective assessment by examiners with different levels of ultrasound experience. MATERIALS AND METHODS: A total of 105 ultrasound images from three different groups of ovarian lesions (malignancies, functional cysts, and dermoid cysts) were evaluated using ATBA and by a total of 36 examiners with four different levels of experience (9 junior trainees, 8 senior trainees, 11 senior gynecologists, and 8 experts). Cohen's κ, Youden's indices, and the sensitivity and specificity of ATBA and of each observer were calculated for every subgroup of ovarian lesions. RESULTS: ATBA classified 78 of the 105 masses correctly (κ = 0.62) - results that were significantly better than those of the junior and senior trainees (p = 0.02 and p < 0.01), while differences from the group of level II examiners did not reach statistical significance (p = 0.27). The best diagnostic performance (κ = 0.70) was obtained by the group of expert level III ultrasonographers. The best classification rates overall, including both ATBA and subjective assessments, were achieved in the detection of functional cysts (Youden's indices from 0.73 to 0.85), while the poorest diagnostic performance was obtained for the classification of dermoid cysts (Youden's indices from 0.28 to 0.55). CONCLUSION: ATBA showed a significantly better diagnostic performance than observers with low or medium levels of experience, emphasizing its potential value for training purposes and in providing additional diagnostic assistance for inexperienced observers.
Subject(s)
Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Ovarian Neoplasms/diagnostic imaging , Ultrasonography/methods , Adolescent , Adult , Aged , Aged, 80 and over , Dermoid Cyst/diagnostic imaging , Dermoid Cyst/pathology , Dermoid Cyst/surgery , Diagnosis, Differential , Female , Humans , Middle Aged , Neoplasm Staging , Observer Variation , Ovarian Cysts/diagnostic imaging , Ovarian Cysts/pathology , Ovarian Cysts/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Ovary/diagnostic imaging , Ovary/pathology , Sensitivity and Specificity , Young AdultABSTRACT
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.
Subject(s)
Breech Presentation/diagnostic imaging , Fetal Weight , Ultrasonography, Prenatal , Anthropometry/methods , Birth Weight , Cohort Studies , Female , Gestational Age , Humans , Male , Pregnancy , Regression Analysis , Retrospective StudiesABSTRACT
PURPOSE: To develop and to evaluate a specific sonographic weight formula for fetuses with extreme macrosomia (≥â4500âg). 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) ≥â4500âg. 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.
Subject(s)
Fetal Macrosomia/diagnostic imaging , Fetal Weight/physiology , Adult , Birth Weight , Body Size/physiology , Diagnosis, Computer-Assisted , Female , Humans , Infant, Newborn , Maternal Age , Mathematical Computing , Pregnancy , Pregnancy Trimester, Third , Reference Values , Regression Analysis , Ultrasonography , Young AdultABSTRACT
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.
Subject(s)
Depression, Postpartum/epidemiology , Mother-Child Relations , Object Attachment , Adult , Cesarean Section/psychology , Female , Humans , Pregnancy , Pregnancy Trimester, Third , Prevalence , Prospective Studies , Psychiatric Status Rating Scales , Surveys and Questionnaires , Young AdultABSTRACT
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.
Subject(s)
Fetal Weight/physiology , Ultrasonography, Prenatal/methods , Waist Circumference/physiology , Adolescent , Adult , Birth Weight/physiology , Data Interpretation, Statistical , Female , Humans , Infant, Newborn , Middle Aged , Predictive Value of Tests , Pregnancy , Reproducibility of Results , Ultrasonography, Prenatal/statistics & numerical data , Young AdultABSTRACT
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.
Subject(s)
Fetal Macrosomia/diagnostic imaging , Fetal Weight/physiology , Image Interpretation, Computer-Assisted/methods , Ultrasonography, Prenatal/methods , Waist Circumference/physiology , Adolescent , Adult , Birth Weight/physiology , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Male , Middle Aged , Pregnancy , Regression Analysis , Sensitivity and Specificity , Young AdultABSTRACT
In families with clustering of breast and ovarian cancer, molecular testing of the major susceptibility genes BRCA1/2 helps to identify patients with disease mutations and healthy persons at high risk who can participate in targeted intervention programs. We investigated 5559 families from the German Consortium for Hereditary Breast and Ovarian Cancer included between 1997 and 2008 and treated under clinical routine conditions. In each family an index patient/person had been screened for deleterious mutations in BRCA1/2. Healthy relatives agreed to predictive testing in 888 of 1520 BRCA1/2 mutation-positive families (58%). Of 2646 eligible unaffected first-degree relatives 1143 decided to be tested (43%). In 325 families with BRCA1/2-positive index patients one related BC/OC patient was tested and 39 (12.0%; 95% confidence interval: 8.7-16.0%) discrepant cases found. A second related individual was screened in 163 of 3388 (4.9%) families with BRCA1/2-negative index patient and in eight families a BRCA1/2 mutation was found. In BRCA1/2 mutation-positive families, BC/OC patients lacking the familial mutation have to be expected at a rather high rate. In families with BRCA1/2-negative index patient we recommend a second screening if another patient with a high probability of carrying a BRCA1/2 mutation is available.
Subject(s)
BRCA2 Protein/genetics , Genetic Testing , Ubiquitin-Protein Ligases/genetics , Adult , Aged , Breast Neoplasms/genetics , Female , Genetic Predisposition to Disease , Germany , Humans , Middle Aged , Mutation , Ovarian Neoplasms/genetics , Pedigree , Phenotype , Risk FactorsABSTRACT
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 (â≥â4â,500âg). MATERIALS AND METHODS: Ten formulas were evaluated in a group of 174 fetuses with a birth weight (BW) ≥â4â,500âg. 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 10â% range of the true birth weight. RESULTS: MPE showed the largest deviation from zero with the Schild formula (MPE -â15.43â%) and the Shepard formula (MPE +â6.08â%) and was closest to zero with the Hadlock II formula (MPE -â5.34â%). 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 (7.23â%). The Hadlock II formula obtained the highest percentage of EWF within the 10â% range of the true birth weight (66.1â%). CONCLUSION: Exact weight estimation in extreme macrosomia remains an unsolved problem, and can therefore only conditionally provide a sufficient basis for clinical decision processes.
Subject(s)
Birth Weight , Body Weights and Measures/statistics & numerical data , Fetal Weight/physiology , Mathematical Computing , Ultrasonography, Prenatal/methods , Ultrasonography, Prenatal/statistics & numerical data , Adult , Body Height/physiology , Body Mass Index , Cephalometry/statistics & numerical data , Cross-Sectional Studies , Female , Gestational Age , Humans , Infant, Newborn , Male , Predictive Value of Tests , Pregnancy , Regression Analysis , Retrospective Studies , Young AdultABSTRACT
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.
Subject(s)
Alcohol Drinking/adverse effects , Attention Deficit Disorder with Hyperactivity/etiology , Pregnancy/physiology , Adult , Alcohol Drinking/epidemiology , Attention Deficit Disorder with Hyperactivity/epidemiology , Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/physiopathology , Central Nervous System Depressants/adverse effects , Child , Ethanol/adverse effects , Female , Gene-Environment Interaction , Humans , Infant, Newborn , Substance-Related Disorders/complicationsABSTRACT
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.
Subject(s)
Choice Behavior , Hospitals, Special , Marketing of Health Services , Female , Health Care Surveys , Humans , Obstetrics and Gynecology Department, Hospital , Oncology Service, Hospital , Surveys and QuestionnairesABSTRACT
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.