Psychiatric disorders and changes in immune response in labor and postpartum.

Women may present with psychiatric disorders during pregnancy, normal labor, following delivery by caesarean section, or in the postpartum period. The accumulating evidence suggests that these disorders may be due to changes in immune responses. During pregnancy complications such as the prolongation of cervical ripening or descent, placental abruption, premature labor, and preeclampsia increase the risk of postpartum psychiatric disorders. Women may exhibit depression and postpartum psychosis following either normal birth or caesarean section. Since psychiatric disorders like schizophrenia, major depression, and bipolar disorder are associated with both alterations in the immune response and changes in immune cell subpopulations, in this study we have chosen to examine whether the psychiatric disorders in women during labor or postpartum also lead to aberrant immune responses.

Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome.

BACKGROUND: The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with antiphospholipid syndrome (APS) and seronegative APS (SNAPS). METHODS: One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus [SLE], 29 Sjogren's syndrome [SS], 30 ankylosing spondylitis [AS], 38 rheumatoid arthritis [RA]) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-ß2-glycoprotein I (anti-ß2GPI) antibodies were tested by ELISA. RESULTS: One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio [OR]=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (p<0.001). When both were positive, the OR for APS was 101.6. Notably, 91.95% (80/87) of LAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available. CONCLUSIONS: Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.

Inflammation and Epidural-Related Maternal Fever: Proposed Mechanisms.

Intrapartum fever is associated with excessive maternal interventions as well as higher neonatal morbidity. Epidural-related maternal fever (ERMF) contributes to the development of intrapartum fever. The mechanism(s) for ERMF has remained elusive. Here, we consider how inflammatory mechanisms may be modulated by local anesthetic agents and their relevance to ERMF. We also critically reappraise the clinical data with regard to emerging concepts that explain how anesthetic drug-induced metabolic dysfunction, with or without activation of the inflammasome, might trigger the release of nonpathogenic, inflammatory molecules (danger-associated molecular patterns) likely to underlie ERMF.

Anaphylaxis to cefazolin during labor secondary to prophylaxis for group B Streptococcus: a case report.

BACKGROUND: Anaphylaxis is an uncommon event during pregnancy, but if it does arise, it can lead to serious fetal consequences even if there are no serious long-term maternal complications. CASE: A parturient developed anaphylaxis in the labor unit shortly after intravenous cefazolin chemoprophylaxis had begun for perinatal group B streptococcal disease. Prompt treatment for anaphylaxis commenced, involving the administration of epinephrine and glucocorticoids, and an emergency cesarean section spared the mother serious morbidity, with a favorable perinatal outcome for the fetus. CONCLUSION: To the best of our knowledge, this case is the first reported one of anaphylaxis to cefazolin in pregnancy secondary to prophylaxis against for B Streptococcus. The case demonstrates that a life-threatening anaphylactic reaction can occur at any time during pregnancy and that all staff in a maternal unit should be familiar with the management of perinatal anaphylaxis.

Perinatal characteristics and obstetric complications as risk factors for asthma, allergy and eczema at the age of 6 years.

BACKGROUND: Considerable effort has been put into identifying early determinants for atopic disorders. Many studies have evaluated the role of fetal development and obstetric complications. However, the results are not unequivocal. STUDY OBJECTIVE: To assess the relationship between perinatal characteristics and obstetric complications, and the presence of reported current asthma, allergy and eczema at the age of 6 years in the framework of a previously conducted study. METHOD: Seven hundred families in the Netherlands with index children born in 1988-1990 were retrospectively selected. Data were extracted from the Municipal Health Service's records of health examinations of these children and their siblings. These examinations were carried out at the age of 6 years. The records contained data on reported atopic disorders and perinatal characteristics. RESULTS: Gestational age was inversely related to the risk of asthma (P for trend: 0.03). Children with low birth weight tended to have a lower risk of any allergy, albeit not significant (P=0.07). However, no link was found between neonatal head circumference and atopic disorders. The ratio of neonatal head circumference to birth weight was positively associated with the risk of atopic disorders, especially with the risk of asthma (odds ratio (OR)=1.87; 95% confidence interval (CI(95%))=[1.11, 3.15]). Vacuum extraction was a risk factor for allergy (OR=1.84, CI(95%)=[1.03, 3.28]), but not for asthma. Induced labour was positively associated with the risk of inhalant allergy (OR=2.22, CI(95%)=[1.09, 4.51]) and, to a lesser extent, asthma (OR=1.72, CI(95%)=[0.95, 3.10]). For caesarean section and forcipal extraction there were no such relationships. CONCLUSIONS: Prematurity is a risk factor for asthma reported at 6 years. A high ratio of head circumference to birth weight is a risk factor for any atopic disorder. Vacuum extraction was associated with a higher risk of allergy, and induced labour is a risk factor for inhalant allergy. All results should be viewed with the possibility of residual confounding.

[Autoimmune hepatitis during pregnancy].

BACKGROUND: Autoimmune hepatitis is a rare chronic disease that mainly affects young women and may influence fertility and pregnancy in these patients. OBJECTIVES: To describe pregnancy and labor in a patient suffering from autoimmune hepatitis and to review the relevant literature. METHODS: Computerized literature research. RESULTS: The disease of 9 years' duration did not relapse during pregnancy under continuous treatment with steroids, cytotoxic drugs, ursodeoxycholic acid and vitamins. Pregnancy was uneventful and ended with preterm vaginal delivery at 35 weeks, of a 2299 gram healthy neonate. The patient did well during the postpartum period and 6 months thereafter. Since there is no single diagnostic test for the disease, the diagnosis is based on the combination of clinical, laboratory, and histopathological findings and by exclusion of other causes of hepatitis. CONCLUSIONS: There is paucity of data in the literature on pregnancy in these patients but the treatment protocols seem to be effective for the mother and safe for the fetus. Maternal and fetal complications rates appear to be currently lower than in the past. Given that relapse cannot be predicted, close surveillance during pregnancy is warranted.

[Hentaxan as an immunoregulator in purulent wounds in parturient women]. / Hentaksan iak imunorehuliator pry hniinykh ranakh u porodil'.

Hentaxan, a new silicon sorbent, is a complex drug preparation containing hentamycin sulfate and zinc-tryptophan, endowed with antioxidant and immunomodulating activities. We used it for treating suppurating wounds in those women in labour. As many as 65 parturient women were examined. The conclusion drawn from the obtained results is that the immunomodulating potential of hentaxan is not very high, for which reason we recommend that hentaxan be combined with laferon which effects the T-link of immunity. The proposed method is at present under study.

Prolonged gestation does not extend survival of uterine natural killer lymphocytes in mice deleted in the receptor for prostaglandin F2alpha.

During decidualization in mice and women, expansion of the Natural Killer (NK) cell lineage occurs within the uterus. In rodents, peak numbers of uterine (u)NK cells are reached at mid-gestation. The population then declines and residual cells are shed with the placenta. Decidualization, but not a fetus, is required to induce division and maturation of uNK cells. Mechanisms regulating the decline in uNK cells are unknown. To determine if the conceptus or its products have regulatory roles on uNK cell survival during normal gestation, a histological time course study was undertaken of implantation sites in mice ablated in the gene for the Prostaglandin F2alpha receptor (PGF2alphaR). These females experience normal gestation but fail to initiate labour and delivery. Their pregnancies extend a further 4-7 days before onset of maternal compromise. Large numbers of uNK cells were present in PGF2alphaR null mice by gestational day (gd) 10 and numbers had begun to decline at gd 14. By gd 18, very few uNK cells remained and no uNK cells were found at day 22 of extended gestation. Thus, the population history of uNK cells in PGF2alphaR null mice resembles that of uNK cells in normal mice, suggesting that the placenta, its products, the fetus and PGF2alpha are not factors that influence the rate of uNK cell decline in late gestation.

Control of neonatal group B streptococcal infection.

Group B beta-haemolytic streptococcus (GBS) is the leading cause of life-threatening perinatal infection in developed countries. As immunization of women is not yet available, selective intrapartum chemoprophylaxis appears to be the best current strategy for preventing disease. All pregnant women should be screened for GBS at 26 to 28 weeks gestation. During labour, all colonized women with risk factors for invasive GBS neonatal infection should be treated with intravenous penicillin or ampicillin. Risk factors include preterm labour, premature rupture of membranes, intrapartum fever, multiple births, prolonged rupture of membranes, maternal diabetes, previous sibling with invasive GBS disease, and maternal GBS bacteriuria. The latter two categories warrant chemoprophylaxis regardless of maternal colonization status.

IgG, IgM and IgA umbilical blood concentrations in normal singleton vaginal deliveries with stinking amniotic fluid or intrapartal maternal febrility > or = 38 degrees C or duration of delivery > 12 hours.

Total of 321 preterm/term newborns delivered in normal singleton vaginal deliveries was studied. Babies were divided into two groups. The first one includes 62 newborns with single, isolated clinical sign: stinking amniotic fluid or intrapartal maternal febrility > or = 38 degrees C or duration of delivery > 12 hours. The second one (control group) contained 259 newborns with no such a sign. In both groups the umbilical cord blood IgG, IgM and IgA concentration (g/L) were quantified by a radial immunodiffusion method. The obtained values were classified into the groups according to 500-grams-birth-weight-ranges. The differences of the mean IgG, IgM and IgA concentrations between the each 500-grams-birth-weight-range subgroup separately in both control and experimental group so as between the same subgroup of the control and experimental group were tested by the means of the Student's t-test. Obtained results did not express the significant differences in the mean IgG, IgM and IgA umbilical cord blood concentrations between the experimental and control group of the newborns.

[Lentivirus expression at the moment of lambing modifies the leukocyte number in the milk of multiparous ewes]. / L'expression des lentivirus au moment de l'agnelage modifie la formule leucocytaire du lait de brebis multipares.

Lambing in small ruminants is a time of high lentivirus expression; infected mononuclear phagocytes are frequent in colostrum and milk. We have studied mammary secretions in 5 multiparous ewes and shown that infected macrophages in milk are accompanied by an augmentation of leucocyte number. The lymphocyte CD8 subpopulation increased in size simultaneously with the onset of infected cell excretion. The udder infection by coagulase negative staphylococci did not modulate milk lymphocyte content. Although infected cell excretion was restricted to one half of the udder, virus-specific lesions were found in both udder halves. Milk leukocytes changes are a marker of infected macrophage presence; they do not control lentivirus spread.

Pathophysiology of the periparturient egg rise in sheep: the role of prolactin.

The involvement of prolactin in the periparturient rise in the faecal nematode egg count in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to adult immune ewes from three weeks before parturition to three weeks afterwards. Ten ewes were injected twice daily with 2-bromo-alpha-ergocryptine (bromocriptine), an antagonist of prolactin secretion, for two weeks starting two days after lambing while 10 ewes remained untreated. Bromocriptine treatment was initiated approximately two weeks pre partum in three other ewes. Plasma pepsinogen concentrations rose significantly by one week after the start of O circumcincta larval challenge in all the ewes but faecal egg counts remained negative until approximately one week post partum. Plasma prolactin concentration was reduced to a very low level in all bromocriptine treated ewes but this did not alter the dynamics of the periparturient rise in faecal egg counts. Neither cell-mediated nor humoral immunity of the ewes, as assessed by their sensitivity to BCG inoculation and by antibody titre raised against horse red blood cells, respectively, were impaired during the rise in faecal egg count, nor were these parameters altered by manipulation of plasma prolactin concentration. Lamb growth rate was not retarded by low plasma prolactin concentration in the bromocriptine treated ewes. These results are not consistent with the generally held hypothesis that elevated plasma prolactin concentration is directly associated with the periparturient rise.

[The pathogenesis of generalized suppurative-septic complications in patients with eclampsia and massive blood loss of obstetrical origin]. / Patogenez generalizovannykh gnoino-septicheskikh oslozhnenii u bol'nykh s éklampsiei i massivnoi krovopoterei akusherskogo geneza.

Changes in immune status, central hemodynamics, oxygen regimen and endogenous intoxication indexes have been compared in patients with eclampsia combined with blood loss and in patients with isolated blood loss. It has been established that severe septic processes were 1.5 times and lethality was 4 times more frequent in the first group of patients than in patients with isolated blood loss. Generalized septic processes accompany marked secondary immune defects. The main reasons for the immune system damage are circulatory hypoxia and severe endogenous intoxication.

Infection and labor. III. Interleukin-1: a signal for the onset of parturition.

The regulatory signals responsible for the increased biosynthesis of prostaglandins during parturition have not been established. Because interleukin-1 is capable of stimulating prostaglandin production by intrauterine tissues and is an inflammatory mediator, we propose that interleukin-1 may act as a signal for the onset of human labor in the setting of intrauterine infection. The purpose of these studies was to determine interleukin-1 activity in amniotic fluid and to establish its relationship with the onset of term and preterm labor. Amniotic fluid from 182 patients was assayed for interleukin-1 activity. Cell-associated interleukin-1 activity was detected in fluid obtained in the third trimester but not in fluid obtained in the second trimester of pregnancy, suggesting a maturational event in interleukin-1 production. The factor responsible for interleukin-1 activity had biochemical characteristics of interleukin-1 alpha (estimated molecular weight of 14 kilodaltons, isoelectric point = 4.9), and its activity was blocked with an anti-interleukin-1 alpha antisera. Women in spontaneous labor at term were likely to have fluid phase interleukin-1 activity in amniotic fluid than women who were not in labor at term. Preterm labor in the setting of intraamniotic infections was associated with significant interleukin-1 activity in amniotic fluid. This bioactivity was predominantly attributable to interleukin-1 beta. A strong correlation between interleukin-1 and amniotic fluid concentrations of prostaglandin E2 and prostaglandin F2 alpha was found in women in preterm labor. These findings support the hypothesis that interleukin-1 may play a role in the initiation of preterm labor associated with intraamniotic infection.

[Changes in specific and nonspecific immune reactivity in women with a complicated obstetrico-gynecologic status]. / Promiana na spetsifichnata i nespetsifichnata imunna reaktivnost pri zheni s uslozhnen akushero-ginekologichen status.

The immunologic status of some groups of women from the obstetric practice was, studied by using some routine immunologic tests. BT test and C-reactive protein were used in parturients with complicated puerperium. Pregnant women with preserved amniotic sac at tenth lunar month were investigated as well as pregnant women with declared labour activity and ruptured amniotic sac and women with normal pos-partial period and parturients with inflammatory process (complicated puerperium). It was established a statistically significant lowering of active and total T-rosette forming cells and increased level of immunoglobulin G in women with declared labour activity and ruptured amniotic sac. There were lowered values of active T-lymphocytes in parturients with inflammatory complications. The performed studies on these women showed that the usage of BT test and determination of C-reactive protein were indicative methods presenting clear picture of the instant state of the infected organism.

Peripheral lymphocyte subpopulations changes during labor.

Peripheral circulating E-rosette-forming cells subpopulations (high affinity and low affinity E--RFC) were studied in pregnant women. In prelabor the high affinity/low affinity E--RFC ratio was found to decrease as compared with the controls by the decrease of the high affinity E--RFC (mean +/- SD, 33.4 +/- 15.9%, p less than 0.01) and the increase of the low affinity E--RFC percentage (mean +/- SD, 37.0 +/- 11.8%, p less than 0.001). As compared with prelabor the low affinity E--RFC subpopulation decreased during normal labor (mean +/- SD, 14.1 +/- 6.2%, p less than 0.001) and not in abnormal labor. These changes might be implicated in the final "fetal allograft rejection" and are probably due to some serum factors in pregnancy.