Pregnancy induces numerical and functional changes of CD4+CD25 high regulatory T cells in patients with rheumatoid arthritis

OBJECTIVE: In a prospective study we investigated whether numerical and functional changes of CD4+CD25(high) regulatory T cells (Treg) were associated with changes of disease activity observed during pregnancy and post partum in patients with rheumatoid arthritis (RA). METHODS: The frequency of CD4+CD25(high) T cells was determined by flow cytometry in 12 patients with RA and 14 healthy women during and after pregnancy. Fluorescence-activated cell sorting (FACS) was used to sort CD4+CD25(high) T cells and CD4+CD25- T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies alone or in co-culture to investigate proliferation and cytokine secretion. RESULTS: Frequencies of CD4+CD25(high) Treg were significantly higher in the third trimester compared to 8 weeks post partum in patients and controls. Numbers of CD4+CD25(high) Treg inversely correlated with disease activity in the third trimester and post partum. In co-culture experiments significantly higher amounts of IL10 and lowered levels of tumour necrosis factor (TNF)alpha and interferon (IFN)gamma were found in supernatants of the third trimester compared to postpartum samples. These findings were independent from health or disease in pregnancy, however postpartum TNFalpha and IFN gamma levels were higher in patients with disease flares. CONCLUSION: The amelioration of disease activity in the third trimester corresponded to the increased number of Treg that induced a pronounced anti-inflammatory cytokine milieu. The pregnancy related quantitative and qualitative changes of Treg suggest a beneficial effect of Treg on disease activity.

Antiretroviral treatment during pregnancy

OBJECTIVE: Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. METHODS: Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. FINDINGS: The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/microl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25-1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48-2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. CONCLUSION: Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

Anti-Müllerian hormone and inhibin B as predictors of pregnancy after treatment by in vitro fertilization/intracytoplasmic sperm injection

OBJECTIVE: To evaluate anti-Müllerian hormone (AMH) as a marker of reproductive outcome after IVF/intracytoplasmic sperm injection (ICSI). DESIGN: Longitudinal study. SETTING: University hospital. PATIENT(S): Two hundred seventy-six consecutive women undergoing IVF/ICSI. INTERVENTION(S): Ovarian stimulation, oocyte retrieval, IVF, ICSI, embryo transfer, AMH, and inhibin B determinations in serum and follicular fluid (FF). MAIN OUTCOME MEASURE(S): The AMH and inhibin B concentrations in 276 matched FF/serum pairs have been determined. Different outcome groups have been compared and set in relation to the oocyte count, morphological parameters, and steroid hormone levels. RESULT(S): The concentrations of AMH and inhibin B in both serum and FF were significantly higher in the group of women who became pregnant in the corresponding treatment cycle than in those who did not conceive. Positive correlations were observed between serum inhibin B concentrations and embryo morphology (r = 0.126, 95% confidence interval 0.026-0.284). Serum and FF AMH or inhibin B correlated positively with the oocyte count and negatively with the pretreatment cycle day 3 FSH level and the total administered gonadotropin dose. CONCLUSION(S): The AMH and inhibin B levels on the day of oocyte retrieval are correlated to reproductive outcome.

[Pregnancy in active acromegaly]

A 29-year-old woman with a long-lasting history of oligoamenorrhea, fell pregnant shortly after being diagnosed with acromegaly. LABORATORY TESTS AND IMAGING: A high IGF-1 concentration and an oral glucose tolerance test confirmed the diagnosis. Cranial magnetic resonance imaging demonstrated a macroadenoma of the pituitary with suprasellar extension and compression of the optic chiasm leading to incomplete hemianopsia.

A case of maternal herpes simplex virus encephalitis during late pregnancy

BACKGROUND: A pregnant 25-year-old woman at 32 weeks' gestation was admitted to an emergency unit after her husband had found her drowsy and with her tongue bitten. The day before admission, the patient had developed a fever of 39 degrees C, was suffering from headaches, was nauseated and had vomited. On admission, she had anterograde and retrograde amnesia, but no somatic neurological deficits were detected. INVESTIGATIONS: Routine laboratory testing, lumbar puncture, cerebrospinal fluid analysis, routine bacteriology, brain MRI, and polymerase chain reaction testing for neurotropic viruses including herpes simplex virus types 1 and 2. DIAGNOSIS: Maternal herpes simplex virus type 1 encephalitis. MANAGEMENT: Antiviral and anticonvulsive therapy, supportive treatment, and cesarean section.

The efficacy of psychological interventions for infertile patients: a meta-analysis examining mental health and pregnancy rate

BACKGROUND: Psychological interventions for infertile patients seek to improve mental health and increase pregnancy rates. The aim of the present meta-analysis was to examine if psychological interventions improve mental health and pregnancy rate among infertile patients. Thus, controlled studies were pooled investigating psychological interventions following the introduction of assisted reproductive treatments (ART). METHODS: The databases of Medline, PsycINFO, PSYNDEX, Web of Science and the Cochrane Library were searched to identify relevant articles published between 1978 and 2007 (384 articles). Included were prospective intervention studies on infertile patients (women and men) receiving psychological interventions independent of actual medical treatment. The outcome measures were mental health and pregnancy rate. A total of 21 controlled studies were ultimately included in a meta-analysis comparing the efficacy of psychological interventions. Effect sizes (ES) were calculated for psychological measures and risk ratios (RR) for pregnancy rate. RESULTS: The findings from controlled studies indicated no significant effect for psychological interventions regarding mental health (depression: ES 0.02, 99% CI: -0.19, 0.24; anxiety: ES 0.16, 99% CI: -0.10, 0.42; mental distress: ES 0.08, 99% CI: -0.10, 0.51). Nevertheless, there was evidence for the positive impact of psychological interventions on pregnancy rates (RR 1.42, 99% CI: 1.02, 1.96). Concerning pregnancy rates, significant effects for psychological interventions were only found for couples not receiving ART. CONCLUSIONS: Despite the absence of clinical effects on mental health measures, psychological interventions were found to improve some patients' chances of becoming pregnant. Psychological interventions represent an attractive treatment option, in particular, for infertile patients who are not receiving medical treatment.

Does pregnancy have an impact on the subgingival microbiota?

BACKGROUND: We investigated clinical and subgingival microbiologic changes during pregnancy in 20 consecutive pregnant women > or =18 years not receiving dental care. METHODS: Bacterial samples from weeks 12, 28, and 36 of pregnancy and at 4 to 6 weeks postpartum were processed for 37 species by checkerboard DNA-DNA hybridization. Clinical periodontal data were collected at week 12 and at 4 to 6 weeks postpartum, and bleeding on probing (BOP) was recorded at sites sampled at the four time points. RESULTS: The mean BOP at week 12 and postpartum was 40.1% +/- 18.2% and 27.4% +/- 12.5%, respectively. The corresponding mean BOP at microbiologic test sites was 15% (week 12) and 21% (postpartum; not statistically significant). Total bacterial counts decreased between week 12 and postpartum (P <0.01). Increased bacterial counts over time were found for Neisseria mucosa (P <0.001). Lower counts (P <0.001) were found for Capnocytophaga ochracea, Capnocytophaga sputigena, Eubacterium saburreum, Fusobacterium nucleatum naviforme, Fusobacterium nucleatum polymorphum, Leptotrichia buccalis, Parvimonas micra (previously Peptostreptococcus micros or Micromonas micros), Prevotella intermedia, Prevotella melaninogenica, Staphylococcus aureus, Streptococcus anginosus, Streptococcus intermedius, Streptococcus mutans, Streptococcus oralis, Streptococcus sanguinis, Selenomonas noxia, and Veillonella parvula. No changes occurred between weeks 12 and 28 of pregnancy. Counts of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Tannerella forsythia (previously T. forsythensis), and Treponema denticola did not change. Counts of P. gingivalis and T. forsythia at week 12 were associated with gingivitis (P <0.001). CONCLUSIONS: Subgingival levels of bacteria associated with periodontitis did not change. P. gingivalis and T. forsythia counts were associated with BOP at week 12. A decrease was found in 17 of 37 species from week 12 to postpartum. Only counts of N. mucosa increased.

Pregnancy in patients with ankylosing spondylitis: do regulatory T cells play a role?

OBJECTIVE: To investigate the numerical and functional changes of CD4+CD25(high) regulatory T (Treg) cells during pregnancy and postpartum in patients with ankylosing spondylitis (AS). METHODS: The frequency of CD4+CD25(high) T cells was determined by flow cytometry in 10 pregnant and 5 nonpregnant patients with AS as well as in 14 pregnant and 4 nonpregnant healthy controls. Pregnant individuals were investigated at the third trimester and 8 weeks postpartum. Treg cells and CD4+CD25- effector T (Teff) cells separated by fluorescence-activated cell sorting were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies, alone or in coculture, to investigate proliferation and cytokine secretion. RESULTS: The frequency of CD4+CD25(high) Treg cells was significantly higher during pregnancy than postpartum in both healthy control subjects and patients with AS. In contrast to Treg cells in healthy pregnant women, Treg cells in pregnant women with AS secreted only small amounts of interleukin-10 and showed lower suppression of tumor necrosis factor alpha and interferon-gamma secretion by CD4+CD25- Teff cells. At the postpartum time point, proinflammatory cytokine levels in the Treg/Teff cell cocultures and Teff cell monocultures were significantly higher in patients with AS than in healthy controls. CONCLUSION: Pregnancy influenced the expansion and cytokine secretion of Treg cells in both patients with AS and control subjects. However, the Treg cells of pregnant patients with AS failed to support an antiinflammatory cytokine milieu, thereby possibly contributing to the persistent disease activity of AS during pregnancy.

Management of early aggressive rheumatoid arthritis during pregnancy and lactation

This survey outlines the problems of drug therapy in women with early aggressive rheumatoid arthritis (RA) who desire children, are pregnant, or are lactating. Solutions for treatment that benefit the mother and do not harm the fetus or the breast-fed child are discussed. The most effective immunosuppressive drugs alone or in combination are contraindicated during pregnancy and, to a lesser degree, also during lactation. Judicious timing of therapy is therefore necessary, aiming at fast remission of symptoms with the most effective therapy and maintaining quiescent disease with drugs compatible with pregnancy or lactation.

High aldosterone-to-renin variants of CYP11B2 and pregnancy outcome

BACKGROUND: Increased aldosterone concentrations and volume expansion of normal pregnancies are hallmarks of normal pregnancies and blunted in pre-eclampsia. Accordingly, we hypothesized an active mineralocorticoid system to protect from pre-eclampsia. METHODS: In pregnant women (normotensive n = 44; pre-eclamptic n = 48), blood pressure, urinary tetrahydro-aldosterone excretion and activating polymorphisms (SF-1 site and intron 2) of the aldosterone synthase gene (CYP11B2) were determined; 185 non-pregnant normotensive individuals served as control. Amino acid-changing polymorphisms of the DNA- and agonist-binding regions of the mineralocorticoid receptor were evaluated by RT-PCR, SSCP and sequencing. RESULTS: Urinary tetrahydro-aldosterone excretion was reduced in pre-eclampsia as compared to normal pregnancy (P < 0.05). It inversely correlated with blood pressure (r = 0.99, P < 0.04). Homozygosity for activating CYP11B2 polymorphisms was preferably present in normotensive as compared to pre-eclamptic pregnancies, identified (intron 2, P = 0.005; SF-1 site, P = 0.016). Two mutant haplotypes decreased the risk of developing pre-eclampsia (RR 0.16; CI 0.05-0.54; P < 0.001). In contrast, intron 2 wild type predisposed to pre-eclampsia (P < 0.0015). No functional mineralocorticoid receptor mutant has been observed. CONCLUSIONS: High aldosterone availability is associated with lower maternal blood pressure. In line with this observation, gain-of-function variants of the CYP11B2 reduce the risk of developing pre-eclampsia. Mutants of the mineralocorticoid receptor cannot explain the frequent syndrome of pre-eclampsia.

Group B Streptococcus colonization in pregnancy: prevalence and prevention strategies of neonatal sepsis

Early onset neonatal sepsis due to Group B streptococci (GBS) is responsible for severe morbidity and mortality of newborns. While different preventive strategies to identify women at risk are being recommended, the optimal strategy depends on the incidence of GBS-sepsis and on the prevalence of anogenital GBS colonization. We therefore aimed to assess the Group B streptococci prevalence and its consequences on different prevention strategies. We analyzed 1316 pregnant women between March 2005 and September 2006 at our institution. The prevalence of GBS colonization was determined by selective cultures of anogenital smears. The presence of risk factors was analyzed. In addition, the direct costs of screening and intrapartum antibiotic prophylaxis were estimated for different preventive strategies. The prevalence of GBS colonization was 21%. Any maternal intrapartum risk factor was present in 37%. The direct costs of different prevention strategies have been estimated as follows: risk-based: 18,500 CHF/1000 live births, screening-based: 50,110 CHF/1000 live births, combined screening- and risk-based: 43,495/1000 live births. Strategies to prevent GBS-sepsis in newborn are necessary. With our colonization prevalence of 21%, and the intrapartum risk profile of women, the screening-based approach seems to be superior as compared to a risk-based approach.