The associations of parity and maternal age with small-for-gestational-age,preterm, and neonatal and infant mortality: a meta-analysis

Background

Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).

Methods

Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.

Results

Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.

Conclusions

Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.

Funding

Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

     

Oral fungal and bacterial infections in HIV-infected individuals: an overview in Africa

Oral opportunistic infections developing secondary to human immunodeficiency virus (HIV) infection have been reported from the early days of the epidemic and have been classified by both the EC-Clearinghouse and the World Health Organisation (WHO). Among the fungal infections, oral candidiasis, presenting in African HIV-infected patients has been sporadically documented. We review the literature with respect to candidal carriage, oral candidiasis prevalence and the predictive value of oral candidiasis for a diagnosis of underlying HIV disease in African HIV-infected patients. The use of oral candidiasis as a marker of disease progression, the species of yeasts isolated from the oral cavity in Africa and the resistance of the yeasts to antifungal agents and treatment regimens are discussed. Orofacial lesions as manifestations of the systemic mycoses are rarely seen in isolation and few cases are reported in the literature from Africa. In spite of the high incidence of noma, tuberculosis, chronic osteomyelitis and syphilis in Africa, surprisingly there have been very few reported cases of the oral manifestations of these diseases in HIV-positive individuals. Orofacial disease in HIV-infected patients is associated with marked morbidity, which is compounded by malnutrition. The authors indicate specific research areas, initially directed at the most effective management strategies, which would complete data in this important area.     

IL-10 has a protective role in experimental autoimmune uveoretinitis

The role of IL-10 in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein. IL-10-deficient mice were susceptible to EAU, indicating that pathogenesis can occur without presence of IL-10. Treatment of normal mice with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent EAU scores, and down-regulated antigen-specific production of tumor necrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4 further reduced disease, and resulted in emergence of antigen-specific IL-4 and IL-10 production, as well as in enhancement of the IgG1 antibody isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was able to inhibit the function of differentiated uveitogenic T cells in culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the course of EAU showed that while a Th1 pattern predominated early, IL-10 mRNA expression coincided with down-regulation of the Th1 response and resolution of EAU. Systemic neutralization of IL-10 during the expression phase of EAU resulted in elevated disease scores. Our results suggest that endogenous IL-10 limits expression of EAU and may play a role in the natural resolution of disease. The data further suggest that exogenous IL-10 may be useful in therapeutic control of autoimmune uveitis. While IL-10 by itself is sufficient to suppress Th1 effector development and function, a concomitant administration of IL-4 is required to shift the autoimmune response towards a non-pathogenic Th2 pathway.      

De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency

Objective  We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).
Design  Case study.
Setting  Tertiary referral obstetrics unit.
Sample  Pregnant woman attended the antenatal clinic.
Methods  Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures  Detection of chromosomal abnormality.
Results  Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions  This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.     

Modulation of spontaneous outgrowth of Epstein-Barr virus immortalized B-cell clones by granulocyte-macrophage colony-stimulating factor and interleukin-3

Spontaneous outgrowth of immortalized Epstein-Barr virus (EBV) infected B-cell clones will occur from cultures of peripheral blood mononuclear cells (PBMNCs) of some persons with a history of EBV infection. We determined that outgrowth of such clones may be reproducibly modulated by supplementation of cultures with the hematopoietic growth factors GM- CSF and interleukin-3 (IL-3). Continuous supplementation of cultures with GM-CSF facilitates emergence of immortalized B-cell clones, whereas supplementation with IL-3 completely prevents their emergence. The effect of GM-CSF may be direct, at least in part, as the proliferation of pure clones of EBV-transformed B lymphocytes was augmented in response to GM-CSF. An indirect mechanism appears to be responsible for the inhibition of transformed B-cell outgrowth in response to IL-3, as IL-3 had no inhibitory effect on proliferation of pure transformed B-cell clones and IL-3-mediated inhibition could be eliminated by antibody neutralization of gamma-interferon (gamma-IFN) or tumor necrosis factor-alpha (TNF-alpha) early in culture. The mechanisms of these effects deserve further study and may have clinical relevance to use of hematopoietic growth factors for support of bone marrow (BM) function in immunocompromised patients.     

Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells

A large number of biologic, technological, and clinical studies await the development of procedures that will allow totipotent hematopoietic stem cells to be expanded in vitro. Previous work has suggested that hematopoiesis can be reconstituted using transplants of cells from long- term marrow cultures. We have used retrovirus mediated gene transfer to demonstrate that marked totipotent hematopoietic stem cells are both maintained and can be amplified in such cultures, and then subsequently regenerate and sustain lympho-myeloid hematopoiesis in irradiated recipients. Marrow cells from 5-fluorouracil-treated male mice were infected with a recombinant virus carrying the neomycin resistence gene and seeded onto irradiated adherent layers of pre-established, long- term marrow cultures of female origin. At 4 weeks, cells from individual cultures were transplanted into single or multiple female recipients. Southern blot analysis of hematopoietic tissue 45 days posttransplantation showed retrovirally marked clones common to lymphoid and myeloid tissues in 14 of 23 mice examined. Strikingly, for 3 of 4 long-term cultures, multiple recipients of cells from a single flask showed marrow and thymus repopulation with the same unique retrovirally marked clone. These results establish the feasibility of retroviral-marking techniques to demonstrate the maintenance of totipotent lympho-myeloid stem cells for at least 4 weeks in the long- term marrow culture system and provide the first evidence of their proliferation in vitro. Therefore, such cultures may serve as a starting point for identifying factors that stimulate totipotent hematopoietic stem cell expansion.     

How much now to tell? Patients' attitudes to an information sheet prior to angiography and angioplasty

A prospectively controlled pilot study of 100 patients undergoing an invasive radiological procedure was undertaken to test patients' acceptance of risk disclosure and whether this increases anxiety and rate of procedure cancellation. Two sheets with differing amounts of information on adverse outcome were randomly allocated and patients provided a graded response to statements following the procedure. Eighty-one completed questionnaires were received (brief sheet n= 40; long sheet n= 41). There were 19 non-compliers with main causes either due to lack of interest or problems such as language difficulties, visual impairment and dementia. There were no significant differences between the two groups with respect to subjective anxiety caused by the information or risk of procedure cancellation. This preliminary work has shown that information sheets are well accepted and provide a simple, standardized format for risk disclosure.     

The use of drugs for the inhibition of prostaglandin or leukotriene synthesis from arachidonic acid is theoretically hazardous

It would appear that it has become almost common practice to regard arachidonic acid (AA) as the sole precursor of eicosanoids. The fact that both dihomogamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA) give rise to distinct families of eicosanoids is commonly almost completely ignored. Elevated tissue levels of AA eicosanoids have been found in and have been implicated in the etiology of a number of diseases. Drugs which selectively block AA mobilization or its eicosanoid metabolism have therefore been developed for therapeutic use in these conditions. The fact that such drugs will also simultaneously block the eicosanoid metabolism from DGLA as well as from EPA is also commonly ignored. It is suggested that the profoundly adverse side-effects displayed by some of these drugs, resulting in some instances in their withdrawal from use, could be the direct result of their concomitant action of interfering with the eicosanoid metabolism of DGLA and EPA. It is further suggested that, before the interactions between the eicosanoids derived from AA and those derived from DGLA and EPA are understood, the use of drugs for the manipulation of AA eicosanoid metabolism in isolation, could be hazardous. This implies that all such drugs currently in use are to be regarded as experimental and provisionally toxic in terms of their effects on the whole system of eicosanoid metabolism. Thus even drugs which have been passed by the FDA and similar Drug Control Councils require total re-evaluation especially in view of the fact that the non-steroidal anti-inflammatory drugs are often prescribed for chronic conditions which require therapy for several years.(ABSTRACT TRUNCATED AT 250 WORDS)