Transplacental Passage of Interleukins 4 and 13?

The mechanisms by which prenatal events affect development of adult disease are incompletely characterized. Based on findings in a murine model of maternal transmission of asthma risk, we sought to test the role of the pro-asthmatic cytokines interleukin IL-4 and -13. To assess transplacental passage of functional cytokines, we assayed phosphorylation of STAT-6, a marker of IL-4 and -13 signaling via heterodimeric receptor complexes which require an IL-4 receptor alpha subunit. IL-4 receptor alpha−/− females were mated to wild-type males, and pregnant females were injected with supraphysiologic doses of IL-4 or 13. One hour after injection, the receptor heterozygotic embryos were harvested and tissue nuclear proteins extracts assayed for phosphorylation of STAT-6 by Western blot. While direct injection of embryos produced a robust positive control, no phosphorylation was seen after maternal injection with either IL-4 or -13, indicating that neither crossed the placenta in detectable amounts. The data demonstrate a useful approach to assay for transplacental passage of functional maternal molecules, and indicate that molecules other than IL-4 and IL-13 may mediate transplacental effects in maternal transmission of asthma risk

Effect of Maternal HIV-1 Status and Antiretroviral Drugs on Haematological Profiles of South African Infants in Early Life

Maternal HIV-1 status and antiretroviral drug exposure may influence the haematological profiles of infants. We recruited infants from 118 uninfected control women and from 483 HIV-1 infected women who received no antiretroviral drugs (n=28), or received single-dose Nevirapine (sdNVP) (n=424) or triple-drug combination therapy (n=31) to reduce HIV-1 transmission. Blood was drawn from infants within 24 hours of delivery or 6-12 weeks post-delivery and full blood counts performed using a fully automated AcT-5-diff haematology analyser and reference controls. Exposed uninfected (EU; no NVP) differed from control infants only in having lower basophil counts and percentages. In all infant groups, leukocyte profiles showed characteristic quantitative changes with age in the first 6 weeks of life. HIV-1 infected infants displayed by 6 weeks elevations in white blood cells, lymphocyte, monocyte and basophil counts, and monocyte and basophil percentages, when compared to EU infants. At birth EU NVP-treated infants exhibited elevated monocyte percentages and counts and basophil counts that did not persist at 6 weeks. Interestingly, EU newborns of mothers with high CD4 counts (> 500 cells/μl) that had taken sdNVP had significantly elevated white blood cell, monocyte and basophil counts when compared to newborn infants of mothers with similar CD4 counts that had not taken sdNVP; this was not evident in infants of mothers with CD4 counts <200 cells/μl. These previously undescribed features may affect immune response capability in early life and clinical consequences of such changes need to be further investigated

Fetal programming of neuropsychiatric disorders by maternal pregnancy depression: a systematic mini review

BACKGROUND: Maternal depression complicates a large proportion of pregnancies. Current evidence shows numerous harmful effects on the offspring. Reviews, which include depression, concluded that stress has harmful effects on the offspring's outcomes neuro-cognitive development, temperament traits, and mental disorders. OBJECTIVE: This mini review of recent studies, sought to narrow the scope of exposure and identify studies specifically assessing prenatal depression and offspring neuropsychiatric outcomes. STUDY ELIGIBILITY CRITERIA: The review included longitudinal, cohort, cross-sectional, clinical, quasi-experimental, epidemiological, or intervention study designs published in English from 2014 to 2018. PARTICIPANTS: Study populations included mother-child dyads, mother-father-child triads, mother-alternative caregiver-child triads, and family studies utilizing sibling comparisons. METHODS: We searched PubMED and Web of Science. Study inclusion and data extraction were based on standardized templates. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Thirteen studies examining neuropsychiatric outcomes were included. We judged the evidence to be moderate to high quality. CONCLUSIONS: Our review supports that maternal prenatal depression is associated with neuropsychiatric adversities in children.Peer reviewe

Consensus protocols for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVES: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 to 26 weeks' gestation. Strong scientific evidence and uniform guidelines regarding the best clinical management of early (prior to 16 weeks and between 16 to 18 weeks) and late (after 26 weeks) TTTS are currently lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted to reach a consensus on the clinical management by an international panel of experts. Participants were chosen by their clinical expertise, affiliation, and relevant publications. A four-round Delphi survey was initiated. The questionnaires were sent using SurveyMonkey, an online survey platform, and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the following two rounds, participants were asked to grade each statement on a Likert scale (1-5) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of five without suggestions for change were accepted as the consensus. Statements with a median grade of below four were considered non-consensus and excluded from the Delphi. Statements with a median grade of four were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree on the statements, and statements with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 scholar clinicians met the inclusion criteria and were invited to participate. Fifty-three agreed to participate in the study. Of those, 75.4% completed all four rounds. Following four rounds, a consensus regarding optimal management of early as well as late TTTS was obtained. FLP can be offered as early as 15 weeks gestation for selected cases. Between 16- and 18-weeks gestation, management should be tailored according to Doppler severity. FLP can be considered up to 28 weeks of gestation. CONCLUSIONS: The Delphi method allowed the construction of a generally agreed upon treatment protocol for early and late TTTS. Nevertheless, this protocol can be modified at the discretion of the operators, and their experience and tailored to the specificity of each case. This should advance the quality of future studies, guide clinical practice, and improve patient care. This article is protected by copyright. All rights reserved

Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay

The maternal immune system may play a role in offspring neurodevelopment. We examined whether maternal autoimmune disease, asthma, and allergy were associated with child autism spectrum disorder (ASD) and developmental delay without autism (DD) using 560 ASD cases, 391 typically developing controls, and 168 DD cases from the CHildhood Autism Risk from Genetics and the Environment (CHARGE) study. Results from conditional logistic regression demonstrated few significant associations overall. Maternal autoimmune disease was significantly associated with a modest increase in odds of developmental disorders (combined ASD + DD; OR = 1.46, 95 % CI 1.01, 2.09) but not of ASD alone. Associations with certain allergens and onset periods were also suggested. These findings suggest maternal autoimmune disease may modestly influence childhood developmental disorders (ASD + DD)