Reduction in popliteal lymph node graft-versus-host reactivity by homologous and heterologous pregnancy serum

The popliteal lymph node assay was used to investigate the effect of pregnancy on graft-versus-host reactivity (GvHR) of mouse spleen cells. After local injection of splenocytes from primiparous syngeneically pregnant (by BALB/cJ males) or allogeneically pregnant (by CBA/Ca males) mice no differences in lymph node weight gain were observed in F1 recipients (CBA/Ca x BALB/cJ) when compared to injections of cells from age-matched non-pregnant BALB/cJ mice. However, lymphocytes of pregnant BALB/cJ females which had previously been pregnant between 4 and 6 times by CBA/Ca males induced a significantly lower GvHR compared to cells of matched non-pregnant multiparous mice. These results suggested an inhibitory effect of gestation on cells possibly primed towards paternal antigens by multiple pregnancies. To test this hypothesis, virgin BALB/cJ mice were actively immunized with lymphocytes of male CBA/Ca mice. Before injection into F1 recipients, spleen cells of immunized animals were incubated for 1 h at 37 degrees C in heat-inactivated serum of primiparous pregnant or virgin non-pregnant mice. Pre-incubation in pregnancy serum had no effect on unprimed cells, but GvHR of cells derived from immunized donors was significantly depressed in female recipients. In male animals this effect was only irregularly observed. Inhibition of GvHR was also observed with serum from pregnant but not non-pregnant pigs. Depression of cellular immune response was observed as early as days 4-9 post-coitum (p.c.) with mouse serum and days 16-19 p.c. with pig serum. These results indicate that pregnancy serum contains factor(s) which modulates the GvHR of primed lymphocytes in both a species- and an antigen-non-specific manner while reactivity of naive spleen cells is not changed.     

Kinetics of lymphoproliferative responses of lymphocytes harvested from the uterine draining lymph nodes during pregnancy in rats

Paraaortic lymph node (PALN) cells were harvested from virgin and pregnant rats bearing syngeneic or allogeneic fetuses at all stages of pregnancy including the pre-implantation period. The specific and non-specific alloreactivity of these cells was analyzed in mixed lymphocyte reactivity (MLR) against mitomycin-C treated-paternal strain or unrelated cells. Mitogen stimulation of the cell utilized PHA, Con-A and PWM. Cells bearing T cell markers were labeled in an indirect assay using the monoclonal antibodies W3/25 and MRC OX 8. Specific alloreactivity is strongly suppressed in the pre-implantation and implantation stages of pregnancy. Specific and non-specific alloreactivities were enhanced at mid-pregnancy and normalized by the end of pregnancy. Reactivity to polyclonal mitogens is enhanced at mid-pregnancy, and the CD4+/CD8+ ratio is very low during all phases of pregnancy.     

Short-lived suppressor cell activity during normal human pregnancy

Short-lived suppressor cell (SLSC) activity was determined in normal pregnant women. This activity was significantly increased in all three trimesters of pregnancy and during the first week postpartum. When pregnant women were divided into primiparous and multiparous groups, no significant differences were found between the two groups in any of the periods studied. These results suggest that increased SLSC activity may play a role in the materno-fetal tolerance and that parity has no influence on this activity.     

Humoral immune activity in CBA/Ca mice during late pregnancy and the post-partum period

Syngeneically mated CBA/Ca mice were used to measure "spontaneous" immunoglobulin (Ig) secretion in the Peyer's patches (PP), spleen and the para-aortic lymph nodes (PALN), employing a protein A plaque assay, during the latter part of pregnancy and in the post-partum period. The lactating and non-lactating females were compared with respect to humoral immune activity (plaque-forming cells) and serum Ig levels (ELISA technique). The pregnancy-induced weight changes in some lymphoid organs and the elevation in the number of plaque-forming cells in spleen (IgG and IgM PFC), PALN (IgG and IgM PFC) and the PP (IgA PFC) lasted longer in the lactating than in the non-lactating mice (owing to hormonal differences). A very strong decrease in serum IgG was observed during pregnancy and after parturition IgG levels remained depressed longer in lactating than in non-lactating mice. Interest has been focused on IgA in the study and this has been discussed as well as the possible reasons for the increased turnover of maternal serum Ig (especially IgG).     

Effects of pseudopregnancy on immunoglobulin-secreting cells in mice

Pregnant mice characteristically show elevated numbers of immunoglobulin-secreting cells in their enlarged spleen and para-aortic lymph nodes. A comparative study of pseudopregnancy and syngeneic pregnancy in CBA/Ca mice was made to evaluate the role of maternal hormones in the induction of these changes. To induce pseudopregnancy, CBA/Ca female mice were mated with vasectomized males, the duration of pseudopregnancy induced in this way is 8-10 days. Serum progesterone levels were monitored periodically throughout pseudopregnancy using RIA technique. Changes were recorded in weight of the thymus, spleen and para-aortic lymph nodes, levels of serum IgG and IgM (ELISA-technique), and content of splenic IgG- and IgM-secreting cells (protein A plaque assay). Thymus involution was observed in pregnant and pseudopregnant mice. Patterns of change in the weight of the spleen and the para-aortic lymph nodes (PALN) were similar in pregnant and pseudopregnant mice until day 8. Ig-secretion in the spleen increased slightly day 5-8 in both pregnant and pseudopregnant mice, but to a lesser extent in the latter. No differences were observed in serum Ig levels between the two groups until day 8. A marked decrease in serum IgG levels and, to some extent, IgM levels between days 8 and 12 was observed in pregnant animals.     

Early increase in graft-versus-host reactivity during pregnancy in the mouse

Alloreactive T levels of para-aortic lymph nodes (PALN) and spleen were determined on different days of pregnancy in BALB/c females by local and systemic graft-versus-host (GvH) assays. A significant increase in GvH reactivity was registered early in both allogeneic and syngeneic matings, operating not only towards paternal but also towards third party strains. Immunoregulatory mechanisms in PALN also involved the appearance of progressive suppression during the first days of pregnancy. The possible role of non-specific early increases in T alloreactivity in triggering suppressor mechanisms and the nature of the immunogens responsible for the alterations in GvH reactivity are discussed.     

Body fat composition and weight changes during pregnancy and 6–8 months post-partum in primiparous and multiparous women

Objective:  To compare changes in maternal weight and body fat composition from early to late pregnancy and 6–8 months postnatally between primiparous and multiparous patients
Methods:  Maternal weight and body fat percentage were assessed in a cohort of low-risk uncomplicated women in a general antenatal clinic at 14–20 weeks gestation, after 36 weeks, and around six to eight months after delivery using a Tanita TBF 105 Fat Analyser. Maternal epidemiological and anthropometric data, as well as pregnancy characteristics and perinatal outcome, were derived from standard antenatal records after delivery. The cohort was stratified into primiparous and multiparous women for comparison.
Results:  In a cohort of 104 women, 55 (52.8%) were primiparous and 49 (47.1%) were multiparous. A relatively good overall correlation between body fat percentage gain and weight gain was observed (correlation coefficient 0.33) from early to late pregnancy. Primiparous women had higher weight gain (12 kg) and higher body fat gain (7.7%) during the pregnancy compared to multiparous women (10.8 kg and 6%, respectively), and they also retained more of the fat accumulated during pregnancy (1.92% vs – 0.44%, P  < 0.001) when assessed over six months after their delivery.
Conclusion:  The findings could represent more exaggerated physiological responses to the pregnant state in the primiparous woman as compared to multiparous women.     

Hypertensive diseases of pregnancy and parity

Chesley's classic long-term follow up study of eclamptic women clearly demonstrated the prognostic significance of parity in the differential diagnosis of various hypertensive diseases of pregnancy. Multiparous patients with eclampsia were different on long-term follow-up from primiparous eclamptic women. A logical conclusion from this observation is that multiparous and primiparous patient groups should be analyzed separately whenever hypertensive diseases of pregnancy are evaluated. This study is therefore an attempt to define the clinical profile of hypertension during pregnancy on the basis of parity alone. The prenatal and hospital records of 99 successive pregnant patients identified as hypertensive during a 1-year period at Mount Sinai Hospital Medical Center served as the study population. A group of 25 primiparous and 25 multiparous patients, all with uncomplicated pregnancies and normal deliveries in sequence during a 1-month period, served as normal nonhypertensive control groups. Various pregnancy parameters were statistically evaluated for study and control groups. Significant differences were found between hypertensive primiparous and multiparous patients in mean weight increase (p less than 0.05), gestational age at first increase in blood pressure (p less than 0.007), and time from first increase in blood pressure until delivery (p less than 0.008). The difference in birth weight was not significant between hypertensive groups. In contrast, among the control groups, multiparous patients had significantly larger offspring than primiparous patients (p less than 0.01). Weights of normal primiparous control women were almost identical to those of primiparous hypertensive women (3252.8 +/- 511.8 versus 3203.26 +/- 679.5 gm). Birth weights of offspring from multiparous hypertensive women, while not significantly different from those of primiparous hypertensive women, were significantly lower than those of multiparous control subjects (3093.94 +/- 898.7 versus 3593 +/- 305.6; p less than 0.01). No significant differences in a variety of laboratory findings, reflexes, edema, or mode of delivery were observed between the various groups. The clinical and laboratory presentation of hypertension in pregnancy may be similar between primiparous and multiparous patients. Nevertheless, clear differences do exist in both maternal presentation and impact of maternal disease on fetal growth and development. These differences strongly suggest a different pathophysiology as the underlying cause of hypertensive disease in primiparous and multiparous pregnant women.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reactivity to alloantigens and polyclonal mitogens and CD4+/CD8+ cell ratio shifts of cervical lymph node and spleen cells during pregnancy in rats

Cervical lymph node (CLN) cells and spleen cells were harvested from virgin and pregnant rats bearing syngeneic or allogeneic fetuses at all stages of pregnancy including the pre-implantation period. The specific and non-specific alloreactivity of these cells were analyzed in MLR against mitomycin-C treated paternal strain or unrelated cells. Mitogen stimulation of the cell cultures utilized PHA, Con-A and PWM. Cells bearing T cell markers were labeled in an indirect assay using the monoclonal antibodies W3/25 and MRC OX 8. Specific alloreactivity is enhanced at mid-pregnancy in both cell populations. Non-specific alloreactivity was suppressed in the cervical lymph node cells. Spleen cells demonstrated an increased non-specific alloreactivity and T polyclonal mitogen reactivity (PHA and Con-A) at mid-pregnancy. Reactivity to Con-A was depressed in the early phase and at the end of allogeneic pregnancy in the CLN. The CD4+/CD8+ ratio was very low during all phases of pregnancy.     

Thyroid function in pregnant women with pregnancy induced hypertension

OBJECTIVE: The aim of this study is to investigate thyroid's function in pregnant women with pregnancy induced hypertension. MATERIALS AND METHODS: 42 pregnant women with PIH diagnosed after 20 weeks of gestation (between 22-30 hbd) were hospitalized in Department of Obstetrics and Gynecology of Mother and Child Institute in Warsaw. This group consisted 20 multiparous and 22 primiparous. We measured thyroid hormone levels: TSH, fT4, fT3 and TBG. RESULTS: In 8 pregnant women (5 primiparous and 3 multiparous) thyroid function was normal (normal level of TSH, fT3, fT4) and middle blood pressure in term of beginning of the study was 155/100 mmHg. 34 pregnant women (19 primiparous and 15 multiparous) had abnormal thyroid function. 3 (1 primiparous and 2 multiparous) pregnant women of this group had subclinical hyperthyroidism (middle blood pressure in the beginning of the study was 155/105) and 31 (21 primiparous and 10 multiparous) had fT4 and fT3 levels lower then normal range with normal TBG levels. In this group only one patient TSH level was higher then 5 mlU/l, which allows to recognize overt hypothyroidism. In other cases the results indicate the subclinical hypothyroidism. The middle blood pressure was 140/95 mmHg. CONCLUSION: 1. Thyroid dysfunction in pregnant women was concluded in 78.2% of tested group. 2. Subclinical hypothyroidism was concluded the most frequent in the tested group. 3. The middle blood pressure at the term of beginning of the study was the lowest in pregnant women with hypothyroidism. 4. The thyroid function tests should be performed in all pregnant women with PIH.     

Maternal immunoregulation: interrelationship between alloreactive and anti-self plus conventional antigen T sets of cells

In a previous paper we reported early immunoregulatory mechanisms involving not only the appearance of progressive suppression but also significant increases in alloreactive T levels in paraaortic lymph nodes (PALN) and spleen, not only in allogeneic but also in syngeneic pregnancies. Taking into account the hypothesis of the superposition of the alloreactive and the anti-self plus conventional antigens T sets of cells, we investigated whether immunization with conventional antigens was able to alter alloreactive T levels. Weekly i.p. doses of rabbit red bloods cells (RRBC) in BALB/c mice resulted in a dose-dependent increase in spleen alloreactivity as determined by graft-versus-host (GvH) assays in strain combinations differing at H-2 level but not in those sharing the same H-2 with BALB/c. The increases could be significantly decreased by an anti-idiotype anti-RRBC serum. Pretreatment with i.p. weekly doses of sheep red blood cells (SRBC) before mating was able to induce dose-dependent fetal damage when the parents differed at the H-2 level. SRBC immunization in one of the uterine horns induced increases in PALN weight which were much higher in progesterone-pseudopregnant than in virgin mice; T alloreactivity was significantly increased in the draining PALN only in pseudopregnant females. These results favour the postulation of the superposition between the alloreactive and the anti-self plus conventional antigens T sets of cells and suggest a possible role for conventional fetal antigens (non H-2) in triggering immunoregulatory mechanisms operating in pregnancy.     

Pregnancy among obstetricians: a comparison of births before, during, and after residency

Questionnaires were sent to 1025 female board-certified obstetricians, and information was retrieved about pregnancy outcome. A total of 454 pregnancies, one third of which occurred during residency, were evaluated, and the relationship between pregnancy outcome and residency was assessed. Children of primiparous women who were delivered during or after residency had significantly lower mean birth weights than those who were delivered before residency (p less than 0.001 and p less than 0.005, respectively), whereas birth weights of infants born to multiparous women were not significantly different. The low birth weight rate (less than 2500 gm) was significantly increased during residency (p less than 0.002), and infants born during residency were 7.5 times more likely to be growth retarded than those born outside residency (p less than 0.002). The incidence of other pregnancy complications was not found to be increased during residency. Our data suggest a potentially negative impact of residency on the birth weights of infants born to female obstetricians in training.     

Levels of serum amyloid P-component associated with pregnancy and collagen-induced arthritis in DBA/1 (H-2q) mice

The levels of the acute-phase reactant serum amyloid P-component (SAP) were measured by quantitative rocket immunoelectrophoresis in pregnant and non-pregnant DBA/1 female mice with or without collagen-induced rheumatoid arthritis (CIA). Non-pregnant animals with CIA showed elevated SAP titres related to the severity of the disease. Pregnancy alone also caused increased SAP levels equivalent to those found in animals with established CIA but which were virgin. The clinical remission seen in arthritic animals during pregnancy was not associated with reductions in circulating SAP levels. Increasing parity, however, caused a lowering of SAP levels in animals with or without CIA compared to the primiparous individuals. Pregnancy causes a strain-dependent elevation of serum SAP which is not further elevated by CIA, thus limiting the usefulness of SAP measurements in assessment of disease progression or remission during gestation.     

Is primiparity a risk factor for advanced maternal age pregnancies?

Objective: Currently, more women are delaying childbearing until their 40s.This study compared the pregnancy and maternal features, pregnancy and foetal outcomes between multiparous and primiparous patients. We compared the same factors between assisted reproductive technology (ART) and non-ART primiparous patients because of the high proportion of ART used in the primiparous patients.

Methods: The study retrospectively examined 1680 patients, 35 years of age and older, between March 2008 and February 2015.

Results: Comparing the features of these two groups, there was an increased incidence of employment and the use of ART in primiparous patients, while birthweight tended to be higher in the multiparous group. There were no significant differences in pregnancy complications other than hypertension disorders, such as pre-eclampsia and HELLP syndrome, which were significantly more frequent in primiparous patients. The rates of foetal growth retardation and perinatal death were significantly higher in primiparous women. Comparison of the data between ART and non-ART primiparous patients indicated that the ART group had a higher initial body mass index and a lower smoking rate. No significant differences in pregnancy complications or foetal outcome were observed between these two groups.

Conclusion: Primiparity is associated with increased pregnancy and foetal complications in advanced age pregnancies. However, the use of ART in this age group does not seem to be an additional risk factor.     

Maternal perception of lactogenesis time: a clinical report.

A study evaluating the time between delivery and the surge in milk production (lactogenesis time) determined whether lactogenesis time (LT) is affected by parity, factors in pregnancy and delivery, and especially cesarean section. Forty-six primiparous mothers and 81 multiparous mothers reported the time of sensation of milk production after delivery. The mean LT in the entire sample was 50 +/- 15 hours. The mean LT in 46 primiparous mothers was 59 +/- 14 hours, and in 81 multiparous mothers 45 +/- 12 hours (by student t test, p < 0.01). Mean LT did not decrease as parity increased in the multiparous mothers. By multivariate analysis, mean LT was 44 hours in multiparous mothers who delivered vaginally without medication, 11 hours longer if primiparous, 6 hours longer if delivery by cesarean section, and 13 hours longer if sedative or pain medication were given during labor.     

Altered mitogen- and alloantigen-induced lymphoproliferative responses in primary lymphoid organs of pregnant mice

The effect of syngeneic murine pregnancy on the response of lymphocytes from the primary lymphoid organs to mitogenic and alloantigenic stimulation was investigated. Thymocytes and bone marrow cells from gravid animals were found to exhibit elevated reactivity to T cell mitogens and allogeneic stimulator cells. In contrast, the LPS response of bone marrow cells from pregnant mice did not differ significantly from that of virgin animals. These findings indicate that the immune reactivity of T cells derived from the primary lymphoid organs is altered during syngeneic murine pregnancy. Pregnancy-induced modifications in T lymphocyte reactivity may contribute to the ability of the maternal immune system to recognize and react against fetal antigens.     

Pregnancy and miscarriage rates in 3978 donor insemination cycles: effect of age, parity and partner's infertility status on pregnancy outcome

The effects of age, parity and male infertility status on pregnancy outcome were studied in a cohort of 720 women receiving donor insemination (DI) treatment. Twenty-two percent of women failed to complete the treatment, leaving 562 women receiving 3202 cycles of DI for assessment. Of the 321 of pregnancies achieved, 57 (17.8%) ended in a miscarriage. After further DI treatments, 64.7% of mothers who had miscarried succeeded in giving birth. There was some evidence to indicate a trend of decreasing pregnancy rate with increasing maternal age, although this result was not significant (log rank trend statistics = 3.44, P > 0.05). The pregnancy rates of multiparous and primiparous women were significantly different, irrespective of their partner's infertility status (azoospermia: log rank statistics = 3.74, P less-than-or-eq, slant 0.05; oligozoospermia: log rank statistics = 4.71, P < 0.03). Furthermore, multiparous women were more likely to become pregnant than primiparous women (azoospermia: hazard ratio = 1.29; oligozoospermia: hazard ratio = 1.50). There was no significant association between miscarriage rate and maternal age (log rank trend statistics = 0.99, P > 0.05). The small number of older women (> 35 years) may confound this result. The mean (plus minus SD) sperm donor age was 23.6 years (plus minus 3.5 years). The implications of these observations are discussed.     

Kurdish pregnant women's feelings: A qualitative study

Objective

to gain a deeper understanding of how Kurdish pregnant women feel about their pregnancy.

Design

a qualitative study analysed by a grounded theory approach.

Setting

the study was conducted among women in the third trimester of their pregnancy in either their homes or the health-care centres in Sanandaj in the western part of Iran.

Participants

22 pregnant women were recruited and interviewed.

Findings

during pregnancy, women experienced a variety of feelings: ‘satisfied and happy’, ‘unpleasant’ and ‘ambivalent’.

Conclusions and implications for practice

it is important for midwives to ask pregnant women about their feelings concerning their current pregnancy, childbirth and future motherhood. If they express negative or ambivalent feelings, these should be discussed in greater detail and their causes identified. Special consideration should be given to primiparous women and multiparous women with negative experiences of previous pregnancies.     

Increased maternal T cell autoreactivity associated with syngeneic murine pregnancy

In this study T cells isolated from isopregnant and virgin CBA/J mice were examined for reactivity to self antigen(s) in vitro and in vivo. The autoproliferative capacity of maternal versus virgin T cells was tested in vitro using autologous mixed lymphocyte reactions (AMLR). The popliteal lymph node (PLN) assay was used to compare the ability of maternal versus virgin T lymphocytes to mediate syngeneic graft-versus-host (SGvH) reactions in vivo. Splenic T cells obtained from pregnant animals near term were found to be approximately 10-fold more reactive towards syngeneic virgin non-T stimulator cells in AMLR than splenic T lymphocytes from age-matched virgin animals. In addition, T cells isolated from the spleens of gravid CBA/J mice displayed a significantly enhanced capacity to mediate SGvH reactions in virgin CBA/J females as measured by regional lymph node enlargement. These findings indicate that syngeneic murine pregnancy is accompanied by an increase in autoreactive T cell activity.     

Fetal alloantigen is responsible for the expansion of the CD4(+)CD25(+) regulatory T cell pool during pregnancy

Increasing evidence suggests that CD4(+)CD25(+) regulatory T cells (Tregs) participate in the development of maternal tolerance to the fetus during pregnancy; however, the factors controlling the activities of Tregs are poorly understood. In the present study, CD4(+)CD25(+) Tregs were analyzed in syngeneically pregnant mice (BALB/cxBALB/c), allogeneically pregnant mice (BALB/cxC57), ovariectomized mice and pregnant women to investigate the influences of fetal alloantigens and pregnancy-related hormones on the activities of Tregs. It was demonstrated that the frequencies of CD4(+)CD25(+) Tregs increase more in allogeneically than in syngeneically pregnant mice, which contributes to a lowered alloreactivity against paternal antigens in allogeneically compared with syngeneically pregnant mice. The increased Tregs are most likely to be induced in peripheral lymphoid tissues, rather than develop in thymus. Allogeneically mated mice and humans share similar dynamic changes in Treg frequencies, markedly increasing during early pregnancy and progressively decreasing from mid-gestation onwards to return to non-pregnant levels at term. Induction of labor in humans appears to be associated with a decrease of CD4(+)CD25(high) Tregs and increase of CD4(+)CD25(low) T cells. Neither estrogen or progesterone alone, nor their combination, shows an impact on the frequencies of Tregs in ovariectomized mice. These results suggest that fetal alloantigen is responsible for the increase of Tregs during pregnancy, and the expansion of the Treg population is of importance for the allogeneic fetus to evade immune attack from the mother.