BackgroundThere is a growing body of epidemiologic literature reporting associations between atmospheric pollutants and reproductive outcomes, particularly birth weight and gestational duration.ObjectivesThe objectives of our international workshop were to discuss the current evidence, to identify the strengths and weaknesses of published epidemiologic studies, and to suggest future directions for research.DiscussionParticipants identified promising exposure assessment tools, including exposure models with fine spatial and temporal resolution that take into account time–activity patterns. More knowledge on factors correlated with exposure to air pollution, such as other environmental pollutants with similar temporal variations, and assessment of nutritional factors possibly influencing birth outcomes would help evaluate importance of residual confounding. Participants proposed a list of points to report in future publications on this topic to facilitate research syntheses. Nested case–control studies analyzed using two-phase statistical techniques and development of cohorts with extensive information on pregnancy behaviors and biological samples are promising study designs. Issues related to the identification of critical exposure windows and potential biological mechanisms through which air pollutants may lead to intrauterine growth restriction and premature birth were reviewed.ConclusionsTo make progress, this research field needs input from toxicology, exposure assessment, and clinical research, especially to aid in the identification and exposure assessment of feto-toxic agents in ambient air, in the development of early markers of adverse reproductive outcomes, and of relevant biological pathways. In particular, additional research using animal models would help better delineate the biological mechanisms underpinning the associations reported in human studies.

The phenomenon of pregnancy can be compromised by a number of complications, such as threatened abortion, recurrent spontaneous miscarriage, preeclampsia, and preterm delivery. Research conducted during the last decade has opened up the possibility that cellular immune effectors may underlie such pregnancy complications. Particularly interesting are the effects of pro-inflammatory and anti-inflammatory cytokines on the conceptus and thus on the success or failure of pregnancy. This review focuses on the association between cytokines and the different complications of pregnancy as well as on the possible pathways of the effector function of cytokines in pregnancy loss. This review also goes on to discuss the redirection of the cytokine profile towards one that is more conducive to pregnancy. Among the most promising agents for the modulation of the Th1/Th2 balance are progestogens such as progesterone and dydrogesterone. Recently published studies lead us to propose that a therapeutic approach worth pursuing would be to assess the individual cytokine profiles of women with pregnancy complications and then to adjust individual therapy using the most effective progestogen.

Maternal exposure to tobacco smoke in early pregnancy, as measured by serum cotinine concentrations at 20-24 weeks of gestation, adversely affects fetal BPD. Preventive measures need to be undertaken to encourage pregnant women to stop smoking and avoid passive exposure to tobacco smoke from the very beginning of pregnancy.

The acceptance of paternally-derived alloantigens during pregnancy and escape from host immunosurveillance by cancer are based on similar immunological mechanisms. Among them both natural and peripherally-induced T CD4+ CD25+ Foxp3+ and Tr1 regulatory cells (Tregs) play important role. Interactions of Tregs with other immunocytes including dendritic cells, mechanisms of Tregs recruitment and their suppressive properties in cancer and pregnancy have been presented in this paper. Despite the fact that mechanisms of Treg regulation are still in progress, there is a hope for use of Tregs-related immunotherapy in clinical practice, and the first attempts of such management have already been described. However, more information about the function of Tregs cells is needed to provide safe treatment devoid of potential side-effects. Resolving the secrets of Tregs cells will probably offer new options of cancer treatment and will help to improve the management of pregnancy failure.

These data suggest that by inducing PIBF production, dydrogesterone might improve pregnancy success rates in threatened aborters.

These changes in the Treg cell subpopulation in the decidua would seem to be related to a brief activation of the maternal immune system as labor begins and lack of analogical changes in the subpopulation of decidual suppressive B7-H4+ macrophages that enable the restriction of this same activation as labor progresses.

Progesterone (P) has been widely used in an attempt to prevent threatened miscarriage, recurrent miscarriage and pre-term labour. Successful pregnancy depends on maternal tolerance of the fetal "semi-allograft". Along with its endocrine effects, P also acts as an "immunosteroid", by controlling the bias towards a pregnancy protective immune milieu. A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2 dominant cytokine production mediates the immunological effects of progesterone. Progesterone plays a role in uterine homing of NK cells and up-regulates HLA-G gene expression, the ligand for various NK inhibitory receptors. At high concentrations, progesterone is a potent inducer of Th2-type cytokines as well as of LIF and M-CSF production by T cells. The possible mechanisms by which progesterone contributes to the maintenance of early and late pregnancy are discussed.

No abstract