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      Tetanus toxoid immunization to reduce mortality from neonatal tetanus

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          Abstract

          Background Neonatal tetanus remains an important and preventable cause of neonatal mortality globally. Large reductions in neonatal tetanus deaths have been reported following major increases in the coverage of tetanus toxoid immunization, yet the level of evidence for the mortality effect of tetanus toxoid immunization is surprisingly weak with only two trials considered in a Cochrane review.

          Objective To review the evidence for and estimate the effect on neonatal tetanus mortality of immunization with tetanus toxoid of pregnant women, or women of childbearing age.

          Methods We conducted a systematic review of multiple databases. Standardized abstraction forms were used. Individual study quality and the overall quality of evidence were assessed using an adaptation of the GRADE approach. Meta-analyses were performed.

          Results Only one randomised controlled trial (RCT) and one well-controlled cohort study were identified, which met inclusion criteria for meta-analysis. Immunization of pregnant women or women of childbearing age with at least two doses of tetanus toxoid is estimated to reduce mortality from neonatal tetanus by 94% [95% confidence interval (CI) 80–98%]. Additionally, another RCT with a case definition based on day of death, 3 case–control studies and 1 before-and-after study gave consistent results. Based on the consistency of the mortality data, the very large effect size and that the data are all from low/middle-income countries, the overall quality of the evidence was judged to be moderate.

          Conclusion This review uses a standard approach to provide a transparent estimate of the high impact of tetanus toxoid immunization on neonatal tetanus.

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          Most cited references43

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          Estimating the causes of 4 million neonatal deaths in the year 2000.

          Information on cause-of-death is lacking for 98% of the world's 4 million neonatal deaths that occur in countries with inadequate vital registration (VR). Our aim was to estimate, by country for the year 2000, the distribution of neonatal deaths across programme-relevant causes including: asphyxia, preterm birth, congenital abnormalities, sepsis/pneumonia, neonatal tetanus, diarrhoea, and 'other'. Two sources of neonatal cause-of-death data were examined: VR datasets for countries with high coverage (>90%), and published and unpublished studies identified through systematic searches. Multinomial regression was used to model the distribution of neonatal deaths. A VR-based model was used to estimate the distribution of causes of death for 37 low-mortality countries without national data. A study-based model was applied to obtain estimates for 111 high-mortality countries. Uncertainty estimates were derived using the jackknife approach. Data from 44 countries with VR (96 797 neonatal deaths) and from 56 studies (29 countries, 13 685 neonatal deaths) met inclusion criteria. The distribution of reported causes of death varied substantially between countries and across studies. Based on 193 countries, the major causes of neonatal death globally were estimated to be infections (sepsis/pneumonia, tetanus, and diarrhoea, 35%), preterm birth (28%), and asphyxia (23%). Regional variation is important. Substantial uncertainty surrounds these estimates. This exercise highlights the lack of reliable cause-of-death data in the settings in which most neonatal deaths occur. Complex statistical models are not a panacea. Representative data with comparable case definitions and consistent hierarchical cause-of-death attribution are required.
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            Placental antibody transfer: influence of maternal HIV infection and placental malaria.

            To determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer. One hundred and eighty materno-neonatal pairs from a Malawian population were assessed. Cord and maternal serum samples were tested for total serum IgG antibody titres using nephelometry, and for specific IgG antibody titres to Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme linked immunosorbent assay (ELISA). Multiple regression analyses showed that placental malaria was associated with a decrease in placental IgG antibody transfer to S pneumoniae and measles to 82% and 81%, respectively. Maternal HIV infection was associated with a reduction in IgG antibody transfer to S pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S pneumoniae and measles IgG antibody transfer reduction to 86% and 87%, respectively. No effect was seen with tetanus toxoid antibody transfer. The combined influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia seems to be linked to the low transplacental antibody transfer observed in the Malawian population.
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              Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection.

              Transplacental transfer of specific IgG antibodies was studied in 46 pairs of human immunodeficiency virus type 1 (HIV-1)-seropositive women and their neonates and in 53 pairs of healthy HIV-seronegative mothers and their newborns. Neonatal and maternal sera were assessed by nephelometry for total levels of serum IgG and by ELISA for IgG antibodies to herpes simplex virus (HSV), varicella-zoster virus (VZV), measles virus, tetanus toxoid, streptolysin O, and Streptococcus pneumoniae capsular antigens. Placental transfer of IgG antibodies to VZV, tetanus toxoid, measles, streptolysin O, and S. pneumoniae was decreased by maternal HIV infection. Maternal levels of total IgG had an independent effect on transfer of antibodies to HSV, VZV, measles, and S. pneumoniae. Neonatal antibody levels to tetanus toxoid, measles, and S. pneumoniae were significantly lower in the HIV group. Both maternal hypergammaglobulinemia and maternal HIV infection may contribute to these low antibody levels at birth and thus lead to early infection in this high-risk population.
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                Author and article information

                Journal
                Int J Epidemiol
                ije
                intjepid
                International Journal of Epidemiology
                Oxford University Press
                0300-5771
                1464-3685
                April 2010
                23 March 2010
                23 March 2010
                : 39
                : suppl_1 , Development and use of the Lives Saved Tool (LiST): A model to estimate the impact of scaling up proven interventions on maternal, neonatal and child mortality
                : i102-i109
                Affiliations
                1London School of Hygiene and Tropical Medicine, London, UK, 2Saving Newborn Lives/Save the Children-USA, Cape Town, South Africa, 3Health Systems Strengthening Unit, Medical Research Council, Cape Town, South Africa, 4UNICEF, Health Section, New York, USA and 5WHO, Department of Immunisation, Vaccines and Biologicals, Geneva, Switzerland.
                Author notes
                Corresponding author. Simon Cousens, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK. E-mail: simon.cousens@ 123456lshtm.ac.uk
                Article
                dyq027
                10.1093/ije/dyq027
                2845866
                20348112
                666295ca-5927-4188-966e-daf44f80c3d5
                Published by Oxford University Press on behalf of the International Epidemiological Association. © The Author 2010; all rights reserved.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Articles

                Public health
                neonatal mortality,neonatal tetanus,newborn care,tetanus toxoid,immunization
                Public health
                neonatal mortality, neonatal tetanus, newborn care, tetanus toxoid, immunization

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