Fetal thymus size in human pregnancies reveals inverse association with regulatory T cell frequencies in cord blood.

OBJECTIVE: To determine fetal thymus growth and its relationship with fetal weight and cord blood T-regulatory cells in a prospective study. Assessment of fetal immune organs by ultrasound could provide a screening approach to identify fetuses at risk of impaired postnatal immunity. STUDY DESIGN AND OUTCOME MEASURES: Thymus size was measured with four ultrasound techniques. The approaches with lowest coefficient of variation (thymus transverse diameter, 3 vessel edge) were used to longitudinally assess fetal and thymus growth in 137 cases at four time points between a gestational age (GA) of 13 and 37 weeks. Cord blood at birth was analyzed by flow-cytometry to evaluate the frequency of regulatory T (Treg) cells. RESULTS AND CONCLUSION: Fetal thymus growth is significantly correlated with fetal weight (GA 23-25 weeks r=0.40, p<0.01; GA 28-30 weeks r=0.21, p=0.04, GA 35-37 weeks r=0.56, p<0.01). We observed an inverse correlation between fetal thymus size at GA 23-25 weeks and cord blood Treg cells (r=0.37, p=0.01). Thymus growth occurs in a linear fashion throughout pregnancy and can be reliably measured using ultrasound. Our findings of an inverse correlation between thymus growth and Treg cells in cord blood suggests a link between fetal growth, thymus development and immune-status at birth.

Babies Galore; or recent findings and future perspectives of pregnancy cohorts with a focus on immunity.

Population-based pregnancy cohorts recruiting women before or at the moment of childbirth allow a longitudinal follow-up on children's health later in life. Important findings arising from pregnancy cohorts are discussed in the present review. These insights have led to revised guidelines on how to minimize disease risks in children, e.g., in the context of chronic immune diseases including allergies and asthma. Moreover, insights from pregnancy cohorts also unveiled a collateral effect of pregnancy on maternal immunity, mirrored by an ameliorated course of certain autoimmune diseases, but also an increased risk of infection with influenza A virus. Future pregnancy cohort studies are still required to close gaps in knowledge on how parameters involved in the developmental origin of health or poor immunity observed in children later in life are operational. We discuss here features that should be covered by future pregnancy cohort studies. Expected insights from such studies will then lay the foundation for biomarker discovery and offer opportunities for interventions to ameliorate adverse immune responses in humans.

Prenatal adverse life events increase the risk for atopic diseases in children, which is enhanced in the absence of a maternal atopic predisposition.

BACKGROUND: There is evidence to suggest an association between prenatal maternal stress and the development of asthma or other atopic diseases in offspring. Yet, insights on the lasting effect of multiple, common prenatal stressors are rare, and the effects of prenatal timing are poorly understood. Further, it remains elusive if prenatal life events modify the risk for atopic diseases in the context of a parental predisposition to atopy. OBJECTIVE: We tested whether women's experiences of common, adverse life events during the first or second half of pregnancy predicted the risk of developing atopic diseases in their children and whether a reported parental atopic disease moderated this association. METHODS: We calculated the odds of a child developing asthma, eczema, and/or allergic rhinitis at ages 6 or 14 years, depending on maternal prenatal exposure to negative life events in a sample of 1587 children from the Western Australian Pregnancy Cohort (Raine) Study by using multivariable logistic regression. RESULTS: We observed that the likelihood of asthma and eczema at age 14 years was significantly increased in children of mothers who had experienced adverse life events during the second half of gestation (1 life event: adjusted odds ratio for asthma, 2.08 [95% CI, 1.22-3.54]). A stronger increase in the odds to develop asthma upon prenatal life events was present in children of mothers without asthma compared with mothers with asthma. CONCLUSIONS: Maternal adverse life events during the second half of gestation are linked to an increased risk for the development of atopic disorders, asthma, and eczema, in the case of asthma, particularly in the absence of a maternal asthma.

Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only.

Observational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n = 409 families), women were recruited between the 4th and 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airway disease in children between 3 and 5 years of age, multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergic rhinitis) in daughters (adjusted OR 0.92; 95% confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95% CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal progesterone during pregnancy-which can result from high stress perception-increase the risk for allergic airway diseases in females but not in males. Key messages: Lower maternal progesterone during pregnancy increases the risk for allergic airway disease only in female offspring. Prenatal progesterone supplementation ameliorates airway hyperreactivity in prenatally stressed murine offspring.

Sex-specific effect of first-trimester maternal progesterone on birthweight.

STUDY QUESTION: Are maternal progesterone levels in early pregnancy associated with fetal birthweight? SUMMARY ANSWER: Low levels of first-trimester maternal progesterone are significantly associated with a reduction in birthweight in girls, but not boys. WHAT IS ALREADY KNOWN: Progesterone in the third trimester of pregnancy has previously been related to birthweight in humans. STUDY DESIGN, SIZE, DURATION: Pregnant women between gestational weeks 4 and 12 were recruited by 99 obstetricians in private practice and enrolled in a prospective cohort study. A follow-up took place at birth. Women younger than 18 years, who had undergone fertility treatments or were diagnosed with infectious diseases, were excluded from the study. A subgroup of 906 participants in whom progesterone had been measured was then selected retrospectively based on the following criteria: no miscarriages, elective abortions or pregnancy complications, infections or multiple births. Data from the follow-up were available for 623 women, who were included in the analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was coordinated at the Charité University Medicine in Berlin, Germany. Anthropometric, medical and psychosocial information were collected and serum progesterone and estradiol levels were measured in women during the first trimester of pregnancy, followed by the documentation of the pregnancy outcome at birth. Univariable and multivariable regression analyses were performed to identify maternal markers, among them progesterone, affecting birthweight and to determine environmental and maternal factors that are associated with maternal progesterone levels during pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the multivariable regression model, each increase in maternal progesterone by 1 ng/ml during the first trimester increased girls' birthweight by 10.17 g (95% CI: 2.03-18.31 g). If the mother carried a boy, maternal smoking and perceived worries during early pregnancy predicted a reduced birthweight, irrespective of progesterone levels. Maternal body mass index over 25 and maternal age <21 years significantly correlated with the reduced levels of progesterone. Correlations between environmental challenges and maternal progesterone did not reach levels of significance. Since the analyses were exploratory, the likelihood that results may be due to chance is increased. LIMITATIONS, REASONS FOR CAUTION: Due to the exploratory nature of the analyses, results need to be independently confirmed in a larger sample. Furthermore, our findings pertain to pregnant women without pregnancy complications or fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: Maternal progesterone during early pregnancy is an indicator of subsequent fetal development in female children. Future studies should confirm this relationship and determine whether maternal progesterone is a useful tool in predicting pregnancies at risk resulting in the birth of a girl with low birthweight. Detailed identification of environmental factors modulating maternal progesterone levels should be addressed in future studies. STUDY FUNDING/POTENTIAL COMPETING INTERESTS: Financial support was provided by the Alexander von Humboldt Foundation, Excellence Initiative of the Hamburg Foundation for Research and the Association for Prevention and Information for Allergy and Asthma (Pina e.V.). The authors have no conflict of interest.

Validation of the Symptom Checklist SCL-27 in psychiatric patients: Psychometric testing of a multidimensional short form.

Abstract SCL-90-R, a multidimensional assessment instrument for mental health status, is among the most widely used instruments for the evaluation of therapies and quality management in mental institutions. With 90 items it is rather long and has a high redundancy as can be seen in its highly correlated scales. Thus many short versions have been constructed, among them the SCL-27, which was devised as a screening tool. It has 27 items, retains six of the nine SCL-90 dimensions and has shown a good factor structure. So far it has only been validated in non-psychiatric samples. The aim of this study is to determine validity and other psychometric qualities of the SCL-27, compared to the SCL-90-R within a group of 449 psychiatric patients. The study found a large concordance between the symptom scales of the SCL-27 and the corresponding scales of the SCL-90-R. The SCL-27 further showed good reliability and a sensitivity to change comparable to that of the 90-item version. A confirmatory factor analysis yields an acceptable factor validity which is better than that of the long version. This study concludes that the SCL-27 is suitable as a short assessment instrument for psychological health in psychiatric patients.