The presence of maternal asthma during pregnancy suppresses the placental pro-inflammatory response to an immune challenge in vitro

The mechanisms that contribute to adverse outcomes for the neonate in pregnancies complicated by asthma may be mediated via changes in placental immune function. This study was designed to determine whether the presence of maternal asthma during pregnancy alters the placental pro-inflammatory immune response in vitro. A prospective cohort study of women with asthma (n = 22) and control (n = 11) subjects had placentae collected immediately after delivery. Placental explants were exposed to an immune challenge, lipopolysaccharide, in the presence and absence of cortisol in vitro. Cytokines, glucocorticoid receptor α (GR α) and p38 MAPK protein were measured. Placentae of control pregnancies had an increase in pro-inflammatory cytokine production over a 24 h period. Placentae from pregnancies complicated by maternal asthma had a reduced pro-inflammatory cytokine response to an immune challenge relative to the controls especially in relation to the production of interleukin (IL)-1β and TNFα regardless of fetal sex. Cortisol inhibition of placental cytokine production was dependent on timing of exposure, fetal sex and presence and absence of asthma. GRα and p38 MAPK protein expression did not appear to contribute to differences in response to endotoxin or cortisol. Maternal asthma during pregnancy induces a hyposensitive inflammatory state in the placenta which is regulated by cortisol in a sexually dimorphic manner.     

Review: Placental adaptations to the presence of maternal asthma during pregnancy

Asthma is a highly prevalent chronic medical condition affecting an estimated 12% of pregnant, women each year, with prevalence of asthma greatest (up to 16%) among the socially disadvantaged. Maternal asthma is associated with significant perinatal morbidity and mortality including preterm births, neonatal hospitalisations and low birthweight outcomes each year. We have identified that the placenta adapts to the presence of chronic, maternal asthma during pregnancy in a sex specific manner that may confer sex differences in fetal outcome. The male fetus was at greater risk of a poor outcome than a female fetus in the presence of maternal asthma and an acute inflammatory event such as an asthma exacerbation. This review will examine the role of sex specific differences in placental function on fetal growth and survival.     

妊娠期免疫系统的特点与妊娠合并自身免疫性疾病

妊娠是一个复杂的生理过程，其中免疫系统发生的一系列改变，是维持母体对胎儿这一"非己"成分的免疫耐受以及对外界刺激的正常应答。同时，在妊娠过程中某些自身免疫性疾病的发病率增加，或已经稳定的疾病在妊娠期间出现疾病活动或病情恶化，也与妊娠期间免疫系统的特殊变化密切相关。但其在妊娠期发生的确切机制尚不明确，本文通过复习文献对妊娠期免疫系统的变化特点及妊娠期合并自身免疫性疾病的免疫学基础进行讨论。     

The changes in the humoral immune system during pregnancy with diabetes

Gestational diabetes (GDM) is a carbohydrate intolerance of different severity with the onset during the pregnancy. GDM is a complication observed in 1-3% of pregnancies and has an important negative influence on foetal development. However most women with GDM do develop diabetes type 2, gestational diabetes could also be the beginning of a slow-progress towards the clinical onset of diabetes type 1. It is now possible, on the basis of the presence of antibodies directed against pancreatic autoantigens (ICA, GADA, IA-2A, IAA) to detect in the early stage of the autoimmune process leading to development of insulin-dependent diabetes (IDDM). In the present review we have summarised actual studies concerning the immune humoral alterations directed against pancreatic B cells in pregnant women with diabetes. We have also discussed the potential clinical implications of the presence of pancreatic autoantibodies in pregnant women with diabetes for the future risk of IDDM.     

Parvovirus B19 infection in pregnancy studied by maternal viral load and immune responses

OBJECTIVES: Facilitate risk assessment of vital complications in fetuses of pregnancies affected by acute parvovirus B19 (B19V) infection. DESIGN: Study of the natural course of maternal B19V infection in four cases, from early pregnancy on. SETTING: University Medical Center in the Netherlands. POPULATION: Pregnant mothers attending obstetric services. METHODS: Serial measurements of the maternal and fetal or neonatal viral load and antibody responses. MAIN OUTCOME MEASURES: Maternal and fetal/neonatal serum B19V viral DNA load and specific IgM and IgG antibodies in maternal serum. RESULTS: Peak viral load levels occurred within 1 week after maternal infection and peak IgM levels were observed 1 week after the peak viral load levels. Approximation of IgG and IgM ratios usually took place 4 weeks after infection. Vertical transmission occurred 1-3 weeks after maternal infection, suggesting that fetal infection occurs during the maternal peak viral load. CONCLUSIONS: Maternal B19V DNA load levels and IgM responses are useful to estimate the risk of parvovirus B19-associated fetal complications. The maternal peak viral load directly precedes the onset of fetal infection and may be used to indicate the stage of intrauterine B19V infection.     

Humoral immune responses in murine pregnancy. I. Anti-paternal alloantibody levels in maternal serum

The kinetics and properties of anti-paternal alloantibody produced by female C57BL(H-2^b) mice in response to mating with CBA(H-2^k) males have been investigated using an immunobead adsorption assay. No alloantibody was ever detected in the first pregnancy or post-partum period. 72% of females exhibited a humoral response in their second pregnancy, detectable from day 16 or 17 post-coitum, and almost all females responded in their third pregnancy. Column chromatographic and immunoelectrophoretic analysis showed that the alloantibody was IgG. Although passive transfer experiments suggested similar stability characteristics to those of cytotoxic antibody induced by experimental hyperimmunization, the pregnancy-induced alloantibody did not exhibit complement-dependent cytotoxicity. The findings are discussed in relation to the nature of the immunogenic stimulus from the conceptus and the regulation and possible function of the humoral immune response in allogeneic pregnancy.     

Evidence for the role of the maternal immune system in balancing the sex ratio in mice

Two experiments have been conducted to verify the effect of maternal preimmunization to H-Y antigen on the secondary sex ratio in $\text{C57B}\text{1}\text{6}$ mice. In accord, with the theoretical model previously proposed, it was found that extensive immunization to H-Y antigen following splenectomy resulted in a significant increase in sex ratio (males/females) without affecting litter size. Litter size was also not correlated to sex ratio. The data from both experiments suggest that splenectomy alone or restimulation to H-Y antigen (after 30 days) both act to decrease sex ratio. It is concluded that the maternal immune system plays a limited, but significant, role in maintaining the normal sex ratio in mice.     

Alterations in the cellular component of the maternal immune system in a murine preterm delivery model

Abstract

Objective: Investigate changes in the cellular component of maternal immune system in a murine preterm delivery (PTD) model.

Methods: C57BL/6?J mice were mated and on day 14.5 after plugging either whole blood was harvested or Escherichia coli lipopolysaccharide (LPS) was intraperitoneally injected. PTD resulted within 24?h. Ten to twelve hours after LPS injection (initiation of labor), whole blood was harvested. Annexin-V, CD3, CD4, CD8, CD80 and CD86 were counted after running through flow cytometer with gating for mononuclear cells. Control group consisted of non-pregnant mice.

Results: Rate of apoptosis of monocytes and lymphocytes and expression of CD80⁺ and CD86⁺ was increased in non-pregnant mice after LPS injection (p?=?0.009, p?=?0.002, p?<?0.001 and p?=?0.005, respectively), but remained unaltered in pregnant mice. Expression of CD3⁺/4⁺ and CD3⁺/8⁺ on lymphocytes was increased after LPS injection in both pregnant (p?=?0.001, p?=?0.011, respectively) and non-pregnant mice (p?=?0.008, p?<?0.001, respectively).

Conclusions: Cellular component of maternal non-specific immune system is remain suppressed in pregnant mice, whereas specific immune responses of pregnant mice to infection are similar to these of non-pregnant mice.     

正常妊娠状态母体各器官系统功能代偿性改变

受到胎儿和胎盘的影响,妊娠期孕妇机体的解剖、生理及生化指标都会发生适应性的变化,一般从受孕开始,一直持续到整个妊娠期。分娩和哺乳期结束后,相应的变化会自然恢复至妊娠前状态,许多指标在非孕期会被认为是异常的。所以,了解这些变化对于产科医务人员非常重要。     

Potentiating maternal immune tolerance in pregnancy: A new challenging role for regulatory T cells

The maternal immune system needs to adapt to tolerate the semi-allogeneic conceptus. Since maternal allo-reactive lymphocytes are not fully depleted, other local/systemic mechanisms play a key role in altering the immune response. The Th1/Th2 cytokine balance is not essential for a pregnancy to be normal. The immune cells, CD4+CD25+Foxp3+, also known as regulatory T cells (Tregs), step in to regulate the allo-reactive Th1 cells. In this review we discuss the role of Tregs in foeto-maternal immune tolerance and in recurrent miscarriage as well as their potential use as a new target for infertility treatment. Animal and human experiments showed Treg cell number and/or function to be diminished in miscarriages. Murine miscarriage can be prevented by transferring Tregs from normal pregnant mice. Tregs at the maternal–fetal interface prevented fetal allo-rejection by creating a “tolerant” microenvironment characterised by the expression of IL-10, TGF-β and haem oxygenase isoform 1 (HO-1) rather than by lowering Th1 cytokines. Tregs increase placental HO-1. In turn, HO-1 may lead to up-regulation of TGF-β, IL-10 and CTLA-4. In vivo experiments showed Tregs sensitisation from paternal antigens to be essential for maternal–fetal tolerance. Tregs increase throughout pregnancy and diminish in late puerperium. Recent data also support the capacity of Tregs to block maternal effector T cells, thereby reducing the maternal–fetal pathological responses to paternal antigens. These findings also permit us to consider new strategies for improving pregnancy outcomes, i.e., anti-TNF blockers and granulocyte-colony stimulating factors as well as novel approaches to therapeutically exploiting Treg + cell memory.     

Cyanotic maternal heart disease in pregnancy

Cyanotic heart disease has major implications for maternal and fetal well-being during pregnancy. This article reports six patients with cyanotic congenital heart disease recently managed at our institutions. Although the maternal condition deteriorated to some extent during each pregnancy, it was the fetal condition that ultimately dictated delivery in each case.     

Management of isoimmunization in the presence of multiple maternal antibodies

OBJECTIVE: Evaluation and management of patients with multiple maternal antibody isoimmunization is unclear. The presence of > or = 1 maternal antibody may suggest a worse scenario. The objective of this study was 2-fold: first, to determine whether the presence of multiple antibodies predicts a more severe course than single antibodies and second, to determine the utility of the Queenan curves/protocol in evaluating multiple-antibody isoimmunization. STUDY DESIGN: Amniotic fluid DeltaOD(450) measurements were obtained from the antenatal testing logbook and confirmed by chart review. Cases were categorized by antibody type and clinical outcomes obtained by chart review. RESULTS: Twenty-four pregnancies with isoimmunization and multiple maternal antibodies were identified; of these, 17 had 2 antibodies (anti-D and -C in 13; anti-D and -E in 1; anti-D and -Jka in 1; anti-c and -E in 1; and anti-c and -Jka in 1), and 7 had > 2 antibodies (anti-D, -C, and -E in 4; anti-D, -C, and -N in 1; anti-c, -E, and -FYA in 1; and anti-E, -K, -Fya, -S, and -C in 1). Eleven patients (46%) required at least 1 intrauterine fetal transfusion (mean initial fetal hematocrit, 15%; range, 4.9%-24%). In those not transfused, no DeltaOD(450) measurements occurred in the Queenan "fetal death risk" zone. Poorest outcomes (multiple transfusions/hydrops/fetal demise) were in patients with anti-D and anti-C, with or without anti-E. The absence of anti-D was associated with no need for fetal transfusions. The overall transfusion rate was significantly higher compared with a group of 57 isoimmunization patients with only anti-D (46% vs. 25%, P < or =.05). CONCLUSIONS: The presence of anti-D appears to be the most significant factor guiding the course of isoimmunization with multiple antibodies. The presence of another antibody with anti-D appears to significantly increase the need for intrauterine fetal transfusions. The Queenan protocol can successfully treat patients with multiple maternal red blood cell antibodies.     

Patterns of maternal weight gain in pregnancy

Summary. A retrospective study of 1145 pregnant women showed that trends in mean maternal weight gain from the time of booking until delivery were not linear. Statistically significant lower rates of maternal weight gain were seen before 16 weeks, after 36 weeks and between 28 and 32 weeks gestation (   P < 0.05  ). The mean maternal weight gain was 10.71 kg (SD 4.3) and the mean weekly weight gain was 0.38 kg (SD 0.16). A wide variation of maternal weight gain was seen in women with a normal outcome. The mean weight gain in heavy (>68 kg) and light (<55.4 kg) women was less than that in women whose weight was in the third quartile (60–68 kg,   P <0.05  ). The mean maternal weight gain was less in young (<20 years) women than in older women (>25 years;   P <0.05  ), less in parous than in primigravid women from week 37 onwards (   P <0.05  ), less in smokers than in non-smokers from 20 weeks onwards (   P <0.05  ), and greater in hypertensive women (BP> 140/90) than in normotensive women (   P <0.05  ) from week 24 onwards. The mean weight gain in women who had small for gestational age (SGA) infants was not significantly different from that in women who had infants that were of appropriate size for gestational age. After taking into account infant and placental weight using multiple regression analysis, the factors that were associated with statistically significant differences in average weekly weight gain were parity, body mass index, smoking habit and raised blood pressure. Only 9.6% of the variation in average weekly weight gain could be predicted using these variables. It is unlikely that the measurement of maternal weight gain would be useful in detecting women who will have SGA infants or will develop hypertension.     

Patterns of maternal weight gain in pregnancy

A retrospective study of 1145 pregnant women showed that trends in mean maternal weight gain from the time of booking until delivery were not linear. Statistically significant lower rates of maternal weight gain were seen before 16 weeks, after 36 weeks and between 28 and 32 weeks gestation (P less than 0.05). The mean maternal weight gain was 10.71 kg (SD 4.3) and the mean weekly weight gain was 0.38 kg (SD 0.16). A wide variation of maternal weight gain was seen in women with a normal outcome. The mean weight gain in heavy (greater than 68 kg) and light (less than 55.4 kg) women was less than that in women whose weight was in the third quartile (60-68 kg, P less than 0.05). The mean maternal weight gain was less in young (less than 20 years) women than in older women (greater than 25 years; P less than 0.05), less in parous than in primigravid women from week 37 onwards (P less than 0.05), less in smokers than in non-smokers from 20 weeks onwards (P less than 0.05), and greater in hypertensive women (BP less than 140/90) than in normotensive women (P less than 0.05) from week 24 onwards. The mean weight gain in women who had small for gestational age (SGA) infants was not significantly different from that in women who had infants that were of appropriate size for gestational age. After taking into account infant and placental weight using multiple regression analysis, the factors that were associated with statistically significant differences in average weekly weight gain were parity, body mass index, smoking habit and raised blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)