Challenges in infant immunity: implications for responses to infection and vaccines.

The fetus and newborn face a complex set of immunological demands, including protection against infection, avoidance of harmful inflammatory immune responses that can lead to pre-term delivery, and balancing the transition from a sterile intra-uterine environment to a world that is rich in foreign antigens. These demands shape a distinct neonatal innate immune system that is biased against the production of pro-inflammatory cytokines. This bias renders newborns at risk of infection and impairs responses to many vaccines. This Review describes innate immunity in newborns and discusses how this knowledge might be used to prevent and treat infection in this vulnerable population.

Previous assessments have highlighted that less than a quarter of countries are on track to achieve Millennium Development Goal 4 (MDG 4), which calls for a two-thirds reduction in mortality in children younger than 5 years between 1990 and 2015. In view of policy initiatives and investments made since 2000, it is important to see if there is acceleration towards the MDG 4 target. We assessed levels and trends in child mortality for 187 countries from 1970 to 2010. We compiled a database of 16 174 measurements of mortality in children younger than 5 years for 187 countries from 1970 to 2009, by use of data from all available sources, including vital registration systems, summary birth histories in censuses and surveys, and complete birth histories. We used Gaussian process regression to generate estimates of the probability of death between birth and age 5 years. This is the first study that uses Gaussian process regression to estimate child mortality, and this technique has better out-of-sample predictive validity than do previous methods and captures uncertainty caused by sampling and non-sampling error across data types. Neonatal, postneonatal, and childhood mortality was estimated from mortality in children younger than 5 years by use of the 1760 measurements from vital registration systems and complete birth histories that contained specific information about neonatal and postneonatal mortality. Worldwide mortality in children younger than 5 years has dropped from 11.9 million deaths in 1990 to 7.7 million deaths in 2010, consisting of 3.1 million neonatal deaths, 2.3 million postneonatal deaths, and 2.3 million childhood deaths (deaths in children aged 1-4 years). 33.0% of deaths in children younger than 5 years occur in south Asia and 49.6% occur in sub-Saharan Africa, with less than 1% of deaths occurring in high-income countries. Across 21 regions of the world, rates of neonatal, postneonatal, and childhood mortality are declining. The global decline from 1990 to 2010 is 2.1% per year for neonatal mortality, 2.3% for postneonatal mortality, and 2.2% for childhood mortality. In 13 regions of the world, including all regions in sub-Saharan Africa, there is evidence of accelerating declines from 2000 to 2010 compared with 1990 to 2000. Within sub-Saharan Africa, rates of decline have increased by more than 1% in Angola, Botswana, Cameroon, Congo, Democratic Republic of the Congo, Kenya, Lesotho, Liberia, Rwanda, Senegal, Sierra Leone, Swaziland, and The Gambia. Robust measurement of mortality in children younger than 5 years shows that accelerating declines are occurring in several low-income countries. These positive developments deserve attention and might need enhanced policy attention and resources. Bill & Melinda Gates Foundation. Copyright 2010 Elsevier Ltd. All rights reserved.

As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregs that suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.