A version of this guideline for pregnant women, their partners and the public, called Routine antenatal care for healthy pregnant women. Understanding NICE guidance: information for pregnant women, their families and the public, is also available (reproduced as Appendix 1 in this version). It can be downloaded from the NICE website (www.nice.org.uk) or ordered from the NHS Response Line (087

Antenatal care : routine care for the healthy pregnant woman

Background
Allergic rhinitis is the most common of the allergic diseases. Despite improved understanding of the pathophysiology of allergic rhinitis and advances in its pharmacological treatment, its prevalence has increased worldwide. For patients whose symptoms remain uncontrolled despite medical treatment, allergen injection immunotherapy is advised. An allergen-based treatment may reduce symptoms, the need for medication and modify the natural course of this disease.

Objectives
To evaluate the efficacy and safety of subcutaneous specific allergen immunotherapy, compared with placebo, for reducing symptoms and medication requirements in seasonal allergic rhinitis patients.

Search methods
We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), Pre-MEDLINE, KOREAMED, INDMED, LILACS, PAKMEDINET, Scisearch, mRCT and the National Research Register. The date of the last search was February 2006.

Selection criteria
All studies identified by the searches were assessed to identify randomised controlled trials involving participants with symptoms of seasonal allergic rhinitis and proven allergen sensitivity, treated with subcutaneous allergen specific immunotherapy or corresponding placebo.

Data collection and analysis
Two independent authors identified all studies reporting double-blind, placebo controlled randomised trials of specific immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Two authors independently performed quality assessment of studies. Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.2.8. Analysis was performed using the Standardised Mean Difference (SMD) method and a random-effects model; P values < 0.05 were considered statistically significant. The primary outcome measures were symptom scores, medication use, quality of life and adverse events.

Main results
We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In total there were 2871 participants (1645 active, 1226 placebo), each receiving on average 18 injections. Duration of immunotherapy varied from three days to three years. Symptom score data from 15 trials were suitable for meta-analysis and showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97 to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33, p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14085 injections) of those on active treatment and in 0.01% (1 of 8278 injections) of the placebo group for treatment of adverse events. There were no fatalities.

Authors' conclusions
This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events.

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Allergen injection immunotherapy for seasonal allergic rhinitis

Publisher Summary This chapter describes the interaction of immune complexes (ICs) with complement and with the cells of the immune system. The effect of immune complexes depends to a great extent on their antigen–antibody ratio so that their influence, either stimulatory or suppressive, is itself modulated by quantitative aspects of the immune response. The development of numerous techniques for the detection and quantitation of immune complexes has stimulated clinically related research and expanded the list of diseases in which immune complexes appear to play an important role. An extension of this diagnostic technology is the ability to isolate immune complexes and, in turn, their antigenic component, thereby making it possible to identify the antigens involved in immune processes of a great many diseases, including those of unknown etiology. In vivo and in vitro experiments have clarified many factors involved in IC formation, removal, and localization as well as the mechanisms of IC-induced inflammatory reactions. An individual can make an immune response to a large number of exogenous and a smaller number of endogenous antigens. Depending upon the availability of antigen, the antibodies so produced form ICs, which for the most part serve the purpose of aiding the host in eliminating potential pathogens.

The Biology and Detection of Immune Complexes

Between 1973 and 1981, 61 cases of neonatal group B streptococcal early-onset disease occurred among 32,384 infants born at Michael Reese Hospital and Medical Center, Chicago. Forty-one (67%) of the 61 affected infants were bacteremic at birth, implying intrapartum acquisition of infection. No significant deviations from the overall attack rate of 1.9 per 1,000 live births were associated with maternal demographic factors, but increased attack rates were associated with birth weights of less than or equal to 2.5 kg (7.9 per 1,000), rupture of amniotic membranes greater than 18 hr before birth (7.6 per 1,000), and intrapartum fever (6.5 per 1,000). Forty-five (74%) of the 61 affected infants and 15 (94%) of the 16 with fatal outcome had one or more of these three perinatal risk factors. Based on an intrapartum vaginal carriage rate of 16.7% among parturients with perinatal risk factors, an attack rate of 45.5 per 1,000 was estimated for infants born to colonized "high-risk" parturients, a subgroup comprising approximately 3% of our obstetric population. These findings provide a compelling epidemiologic rationale for trials of selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease.

Selective intrapartum chemoprophylaxis of neonatal group b streptococcal early-onset disease. i. epidemiologic rationale

Objective To identify and to establish the prevalence of ORs factors associated with increased risk for early-onset group B streptococcal (EOGBS) infection in neonates. streptococcal (EOGBS) infection in neonates. Study design Literature review and reanalysis of published data. Results Risk factors for EOGBS infection include group B streptococcal (GBS)-positive vaginal culture at delivery (OR: 204), GBS-positive rectovaginal culture at 28 (OR: 9.64) or 36 weeks gestation (OR: 26. 7), vaginal Strep B OIA test positive at delivery (OR: 15.4), birth weight 18 hours (OR: 7.28), intrapartum fever >37.5 degrees C (OR: 4.05), intrapartum fever, PROM, or prematurity (OR: 9.74), intrapartum fever or PROM at term (OR: 11.5), chorioamnionitis (OR: 6.43). Chorioamnionitis is reported in most (88%) cases in which neonatal infection occurred despite intrapartum maternal antibiotic therapy. ORs could not be estimated for maternal GBS bacteriuria during pregnancy, with preterm premature rupture of membranes, or with a sibling or twin with invasive GBS disease, but these findings seem to be associated with a very high risk. Multiple gestation is not an independent risk factor for GBS infection. Conclusions h Mothers with GBS bacteriuria during pregnancy, with another child with GBS disease, or with chorioamnionitis should receive empirical intrapartum antibiotic treatment. Their infants should have complete diagnostic evaluations and receive empirical treatment until infection is excluded by observation and negative cultures because of their particularly high risk for EOGBS infection. Either screening with cultures at 28 weeks gestation or identification of clinical risk factors, ie, PROM, intrapartum fever, or prematurity, may identify parturients whose infants include 65% of those with EOGBS infection. Intrapartum screening using the Strep B OIA rapid test identifies more at-risk infants (75%) than any other method. These risk identifiers may permit judicious selection of patients for prophylactic interventions.

https://pediatrics.aappublications.org/content/pediatrics/103/6/e77.full.pdf

Risk Factors for Early-onset Group B Streptococcal Sepsis: Estimation of Odds Ratios by Critical Literature Review

Group B beta-hemolytic streptococcus: randomized controlled treatment study at term.

Patients with allergic rhinitis receiving maintenance inhalant immunotherapy and two control groups were studied for evidence of circulating immune complexes. The first control group contained patients with allergic rhinitis who had never received immunotherapy. The second control group contained normal volunteers. Patients in the treatment group had no proteinuria. When compared with the control group, the treatment group had no statistically significant differences in incidence of Clq binding immune complexes, cryoglobulinemia, rheumatoid factor, or complement depletion. This initial study suggests that maintenance immunotherapy does not result in an increase of circulating immune complexes.

https://www.jacionline.org/article/0091-6749(78)90209-9/pdf

A laboratory evaluation of immune complexes in patients on inhalant immunotherapy.

Forty patients with various types of myeloproliferative disorders were evaluated immunologically. Serum immunoglobulin levels were within the normal range in most patients and no monoclonal gammopathies were detected. Serum C'3 levels were decreased in 19 of 40 (48%) patients. The response of peripheral blood lymphocytes to phytohemagglutinin was decreased in 26 of 40 (65%) and to pokeweed mitogen in 18 of 28 (64%) patients studied. Lymphocytes from patients with polycythemia vera were least affected. Unstimulated lymphocytes from some patients demonstrated markedly increased thymidine uptake activity. Despite the diminished mitogenic response, only 2 of 33 patients (6%) were anergic by intradermal skin testing. There was no association between depressed lymphocyte response and recent chemotherapy except in chronic myelogenous leukemia where 6 of 8 patients were receiving cytotoxic therapy when studied. These observations suggest that most of our patients with myeloproliferative disorders have abnormal cellular responses in vitro, but that delayed hypersensitivity and humoral responses are minimally affected.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197807%2942%3A1%3C149%3A%3AAID-CNCR2820420125%3E3.0.CO%3B2-I

Immunologic dysfunction in the myeloproliferative disorders.

The use of incubators in the care and support of premature babies has received attention since Martin Cooney, a student of Pierre Budin, began showing premature infants in incubators at the 1896 Berlin Exposition. 1 As early as 1907, Budin 2 observed increased survival in low birth weight infants if they were kept warm. This effect of the thermal environment was not fully appreciated until Silverman and co-workers 3-5 demonstrated increased survival in warmer environments in a series of studies first published in 1958. Since the first edition of Standards and Recommendations for Hospital Care of Newborn Infants , 6 the use of incubators has been suggested for thermal support and isolation. In 1969, Du and Oliver 7 demonstrated the effectiveness of a radiant warmer in protecting against the cold stress of the delivery room. The increased access to the infant during resuscitation has led to increased use of radiant warmers

https://jamanetwork.com/journals/peds/articlepdf/508698/archpedi_133_8_022.pdf

Radiant Warmers vs Incubators for Neonatal Care

The response to preseasonal immunotherapy with aqueous grass extract, timothy antigen D, or water-soluble timothy (WST) in alginate was compared in patients sensitive to grass pollen. Injections of antigen D in alginate produced little evidence of clinical or immunologic response. Treatment with aqueous grass extract or WST in alginate, on the other hand, significantly reduced the seasonal rise in grass-specific IgE. Aqueous extract therapy was also associated with a decline in leukocyte sensitivity during the pollen season, while WST treatment produced the greatest rise in hemagglutinating antibodies.

https://www.jacionline.org/article/0091-6749(76)90062-2/pdf

George L. Brown

Papers

Group B beta-hemolytic streptococcus: randomized controlled treatment study at term.

A laboratory evaluation of immune complexes in patients on inhalant immunotherapy.

Immunologic dysfunction in the myeloproliferative disorders.

Radiant Warmers vs Incubators for Neonatal Care

Clinical and immunological studies of timothy antigen D immunotherapy