Hungry in the womb: what are the consequences? Lessons from the Dutch famine

An increasing body of evidence suggests that poor nutrition at the very beginning of life – even before birth – leads to large and long term negative consequences for both mental and physical health. This paper reviews the evidence from studies on the Dutch famine, which investigated the effects of prenatal undernutrition on later health. The effects of famine appeared to depend on its timing during gestation, and the organs and tissues undergoing critical periods of development at that time. Early gestation appeared to be the most vulnerable period. People who were conceived during the famine were at increased risk of schizophrenia and depression, they had a more atherogenic plasma lipid profile, were more responsive to stress and had a doubled rate of coronary heart disease. Also, they performed worse on cognitive tasks which may be a sign of accelerated ageing. People exposed during any period of gestation had more type 2 diabetes. Future investigation will expand on the finding that the effects of prenatal famine exposure may reach down across generations, possibly through epigenetic mechanisms. Recent evidence suggests that similar effects of prenatal undernutrition are found in Africa, where many are undernourished. Hunger is a major problem worldwide with one in seven inhabitants of this planet suffering from lack of food. Adequately feeding women before and during pregnancy may be a promising strategy in preventing chronic diseases worldwide.     

Neurodevelopmental consequences of maternal distress: what do we really know?

Schuurmans C, Kurrasch DM. Neurodevelopmental consequences of maternal distress: what do we really know? A simple internet search of ‘maternal stress and pregnancy’ turns up hundreds of hits explaining that an adverse intrauterine environment can affect fetal development and potentially lead to various learning, behavioral, and mood disorders in childhood, as well as complex diseases such as obesity and cardiovascular conditions later in life. Indeed, a growing body of literature now links several intrauterine challenges, including maternal obesity and stress, with adverse developmental outcomes in the child. Over the past 5 years, nearly 5000 publications have explored the consequences of maternal distress on young offspring, a marked increase from the 475 published studies over a comparable period 20 years ago. Yet, despite this explosion of research and widespread warnings to pregnant mothers, we still lack a basic understanding of the pathophysiology linking adverse maternal health to the onset of disease in the child, especially regarding how prenatal and perinatal challenges might affect brain development. Recent studies have begun to explore the cellular basis of the abnormal brain cytoarchitecture associated with fetal exposure to intrauterine challenges. Here, our goal is to review the scientific evidence that maternal distress interferes with key neurodevelopmental steps, as an entry point toward mapping the pathophysiology of pre‐ and perinatal stress on the unborn child's brain.     

Severe asthma in adults: what are the important questions?

The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive re-evaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA. This report presents statements according to the literature defining SRA in order address the important questions. Phenotyping SRA will improve our understanding of mechanisms, natural history, and prognosis. Female gender, obesity, and smoking are associated with SRA. Atopy is less frequent in SRA, but occupational sensitizers are common inducers of new-onset SRA. Viruses contribute to severe exacerbations and can persist in the airways for long periods. Inflammatory cells are in the airways of the majority of patients with SRA and persist despite steroid therapy. The T(H)2 immune process alone is inadequate to explain SRA. Reduced responsiveness to corticosteroids is common, and epithelial cell and smooth muscle abnormalities are found, contributing to airway narrowing. Large and small airway wall thickening is observed, but parenchymal abnormalities may influence airway limitation. Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies.     

Are women in early pregnancy following the national pyramid recommendations?

Appropriate nutrition in pregnancy is fundamental for maternal and fetal health, and the long-term physiological wellbeing of the offspring. We aimed to determine whether a sample of pregnant women met the national guidelines for healthy eating during pregnancy, and to examine if compliance differs when analysed by Body Mass Index (BMI) category. Subjects completed a 24-hr dietary recall, and had their BMI calculated. The mean age was 27.8 years. The mean BMI was 25.1 kg/m2, with 32 (31.7%) subjects overweight and 14 (13.9%) obese based on BMI category. Although the majority of subjects thought that they had a healthy diet, less than half met the recommended guidelines for each individual food group with achievement of the dairy group being particularly low. Achievement of food group recommendations was not influenced by BMI category. Public health messages on healthy eating guidelines need to be clearly communicated to pregnant women.     

Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood-brain barrier?

We investigated whether fetal cells can enter the maternal brain during pregnancy. Female wild-type C57BL/6 mice were crossed with transgenic Green Mice ubiquitously expressing enhanced green fluorescent protein (EGFP). Green Mouse fetal cells were found in the maternal brain. Quantitative real-time polymerase chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal cells were present in the maternal brain 4 weeks postpartum than on the day of parturition. After an excitotoxic lesion to the brain, more fetal cells were detected in the injured region. The presence of fetal cells in the maternal brain was also confirmed by quantitative real-time PCR for the sex-determining region of the Y chromosome. Four weeks postpartum, EGFP-positive Green Mouse fetal cells in the maternal brain were found to adopt locations, morphologies, and expression of immunocytochemical markers indicative of perivascular macrophage-, neuron-, astrocyte-, and oligodendrocyte-like cell types. Expression of morphological and immunocytochemical characteristics of neuron- and astrocyte-like cell types was confirmed on identification of fetal cells in maternal brain by Y chromosome fluorescence in situ hybridization. Although further studies are required to determine whether such engraftment of the maternal brain has any physiological or pathophysiological functional significance, fetomaternal microchimerism provides a novel model for the experimental investigation of the properties of fetal progenitor or stem cells in the brain without prior in vitro manipulation. Characterization of the properties of these cells that allow them to cross both the placental and blood-brain barriers and to target injured brain may improve selection procedures for isolation of progenitor or stem cells for brain repair by intravenous infusion.     

Are fetal cells in maternal plasma really there? We think they are

We describe a single centrifugation procedure that resulted in the recovery of fetal cells in maternal blood in 77% of normal male pregnancies and in 87.5% of aneuploid pregnancies. There was an average yield of one fetal cell/1,993 maternal cells in normal pregnancies, which increased to one in 994, in aneuploid pregnancies.     

Monitoring reproductive health in Europe: what are the best indicators?

The Reprostat Steering Committee asks for the best monitors of reproductive health. In many European countries, some deleterious agents have caused declines over the past half-century in both dizygotic (DZ) twinning rates and sperm counts. No strong evidence suggests that these declines have reversed, though they may have ceased in some countries. Here attention is only directed at potential secular changes in the proximate biological determinants of fertility (ovulation, coitus, semen quality, fertilization, spontaneous fetal loss and 'dead time'). The most comprehensive biological monitor of reproductive health is the 'natural' DZ twinning rate (viz the rate of DZ twinning in the absence of any medical intervention around the time of conception). At present, natural DZ twins are augmented by twins produced by new techniques. So efforts should be made to estimate the annual numbers of these iatrogenic twins in each European country. Then it would be possible to follow the movements of each national natural DZ twinning rate, and thus to continue monitoring a useful measure of reproductive health that has been available in most European countries for many years. Efforts should be made to assess the sperm quality of volunteer donors in each European country.     

Definitions matter: if maternal–fetal relationships are not attachment, what are they?

Since Cranley's conceptualization in 1981, which produced a useful measure to investigate the construct, maternal–fetal relationships have most often been referred to as maternal–fetal, antenatal or prenatal “attachment”. However, critical analysis of the literature suggests that this relationship is not an attachment relationship at all, as Bowlby and Ainsworth first defined it, but a multi-faceted construct guided instead by the caregiving system, the reciprocal partner to the attachment system, which evolved to provide care and protection.     

Uterine stem cells: what is the evidence?

The mucosal lining (endometrium) of the human uterus undergoes cyclical processes of regeneration, differentiation and shedding as part of the menstrual cycle. Endometrial regeneration also follows parturition, almost complete resection and in post-menopausal women taking estrogen replacement therapy. In non-menstruating species, there are cycles of endometrial growth and apoptosis rather than physical shedding. The concept that endometrial stem/progenitor cells are responsible for the remarkable regenerative capacity of endometrium was proposed many years ago. However, attempts to isolate, characterize and locate endometrial stem cells have only been undertaken in the last few years as experimental approaches to identify adult stem/progenitor cells in other tissues have been developed. Adult stem cells are defined by their functional properties rather than by marker expression. Evidence for the existence of adult stem/progenitor cells in human and mouse endometrium is now emerging because functional stem cell assays are being applied to uterine cells and tissues. These fundamental studies on endometrial stem/progenitor cells will provide new insights into the pathophysiology of various gynaecological disorders associated with abnormal endometrial proliferation, including endometrial cancer, endometrial hyperplasia, endometriosis and adenomyosis.     

Immune cells and molecules in pregnancy: friends or foes to the fetus?

Considering allograft rejection as a basic feature of the immune system, the mammalian pregnancy is an immunological paradox where the semi-allogeneic fetus is not rejected. How are the demands of pregnancy solved in the context of maternal immunity? Medawar’s original proposal of maternal immune inertness during pregnancy should be revised to active materno-placental tolerance. Multiple mechanisms are involved in peripheral and local tolerance induction that prevents fetal rejection while maintaining competent immune surveillance and protection. The goal of this review is to discuss the major cellular and molecular components of the immune system that control and promote fetal survival.     

Satisfaction with pregnancy loss aftercare: are women getting what they want?

While there is increasing recognition that early miscarriage represents a significant loss experience that often provokes depression and anxiety, women’s dissatisfaction with some aspects of care received from healthcare professionals following a pregnancy loss and the potentially negative consequences of this are often less recognized. This review examines available literature to identify what comprises “treatment as usual,” how satisfied women are with the typical services they receive from healthcare personnel, and whether these services are consistent with women’s self-identified needs. Results are reviewed according to four major themes—patient satisfaction with: attitudes of healthcare providers, provision of information, interventions provided, and follow-up care. In general, women and families who have experienced a miscarriage report low levels of satisfaction in the presence of perceived negative attitudes from healthcare providers, insufficient provision of information, and inadequate follow-up care that did not focus on emotional well-being. Higher levels of satisfaction are reported among women whose providers were emotionally attuned to the magnitude of the loss, provided information, and involved women in treatment decisions when possible. Limitations of current research are reviewed and directions for future research, training, and practice are briefly discussed.     

Antidepressant use in pregnancy: are we closer to consensus?

Archives of Women's Mental Health - We specify and summarize significant data from recent large studies in a tool with which to aim at consensus on the question of whether and how...     

Modifications of pancreatic diffusion MRI by tissue characteristics: what are we weighting for?

Diffusion‐weighted imaging holds the potential to improve the diagnosis and biological characterization of pancreatic disease, and in particular pancreatic cancer, which exhibits decreased values of the apparent diffusion coefficient (ADC). Yet, variable and overlapping ADC values have been reported for the healthy and the pathological pancreas, including for cancer and other benign conditions. This controversy reflects the complexity of probing the water‐diffusion process in the pancreas, which is dependent upon multiple biological factors within this organ's unique physiological environment. In recent years, extensive studies have investigated the correlation between tissue properties including cellularity, vascularity, fibrosis, secretion and microstructure and pancreatic diffusivity. Understanding how the various physiological and pathological features and the underlying functional processes affect the diffusion measurement may serve to optimize the method for improved diagnostic gain. Therefore, the aim of the present review article is to elucidate the relationship between pancreatic tissue characteristics and diffusion MRI measurement.     

Geriatric depression and vascular diseases: what are the links?

BACKGROUND: The term "vascular depression" has been proposed to describe a subset of depressive disorders that occurs in old age as a consequence of cerebrovascular disease. However, depression has been shown to result from other cardiovascular diseases such as coronary heart diseases, as well as to precipitate, worsen or precede vascular diseases. Depression also increases the likelihood of the incidence of vascular risk factors such as diabetes. AIMS: To review clinical and epidemiological evidence linking geriatric depression and vascular diseases, and to discuss the potential mechanisms that could underlie this association. METHOD: Systematic review of the literature of the last 5 years through Medline database search. RESULTS: Papers report the following potential ways of association: (1) there is a direct influence of vascular disease, in particular, arteriosclerosis, on the incidence of depression; (2) depressive disorders have a direct impact on the cardiovascular system; (3) depression and vascular disease share either a common pathophysiological process or genetic determinants. DISCUSSION: Depression can be understood as the direct consequence of brain damage in neurodegenerative disorders such as Parkinson's or Huntington's diseases. Similarly, vascular depression is mostly considered to be the consequence of microvascular lesions on prefrontal and subcortical regions. However, this functional neuroanatomical model offers no explanation for cases where depression has been shown to precede vascular diseases. Since cardiovascular diseases develop in a context of acquired environmental factors together with genetically determined disease, it may be postulated that geriatric depression could both result from brain lesions of vascular origin and also share some pathogenic or genetic determinants.