WHO recommendation on tetanus toxoid vaccination for pregnant women

Woman receiving an injection

WHO recommendation on tetanus toxoid vaccination for pregnant women

 

Recommendation

Tetanus toxoid vaccination is recommended for all pregnant women, depending on previous tetanus vaccination exposure, to prevent neonatal mortality fromtetanus.

(Recommended)

 

Publication history

First published: December 2016

Updated: No update planned

Assessed as up-to-date: December 2016

 

Remarks

  • This recommendation is consistent with recommendations from the 2006 WHO guideline on Maternal immunization against tetanus (1). The GDG endorses the 2006 guideline approach, which recommends the following.

– If a pregnant woman has not previously been vaccinated, or if her immunization status is unknown, she should receive two doses of a tetanus toxoid-containing vaccine (TT-CV) one month apart with the second dose given at least two weeks before delivery. Two doses protect against tetanus infection for 1–3 years in most people. A third dose is recommended six months after the second dose, which should extend protection to at least five years.

–– Two further doses for women who are first vaccinated against tetanus during pregnancy should be given after the third dose, in the two subsequent years or during two subsequent pregnancies.

–– If a woman has had 1–4 doses of a TT-CV in the past, she should receive one dose of a TT-CV during each subsequent pregnancy to a total of five doses (five doses protects throughout the childbearing years).

 

  • Tetanus vaccination and clean delivery practices are major components of the strategy to eradicate maternal and neonatal tetanus globally (2).
  • Effective surveillance is critical for identifying areas or populations at high risk of neonatal tetanus and for monitoring the impact of interventions.
  • A monitoring system should include an immunization register, personal vaccination cards and maternal health records, which should be held by the woman.
  • For effective implementation, ANC health-care providers need to be trained in tetanus vaccination and the vaccine, equipment and supplies (refrigerator, needles and syringes) need to be readily available at ANC services.
  • Policy-makers in low prevalence/high-income settings may choose not to include tetanus vaccination among ANC interventions if effective tetanus immunization programmes and good post-exposure prophylaxis exist outside of pregnancy.
  • ANC contacts should be used to verify the vaccination status of pregnant women, and administer any vaccines that are recommended in the national immunization schedule. ANC contacts are also opportunities to explain the importance of infant vaccination and communicate the infant/child vaccination schedule to pregnant women.
  • Further information can be found in the WHO guidance (1), available at: http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/immunization_tetanus.pdf and in WHO’s vaccine position papers, available at: http://www.who.int/immunization/documents/positionpapers/en

 

 

Background

Tetanus is an acute disease caused by an exotoxin produced by Clostridium tetani. Neonatal infection usually occurs through the exposure of the unhealed umbilical cord stump to tetanus spores, which are universally present in soil, and newborns need to have received maternal antibodies via the placenta to be protected at birth. Neonatal disease usually presents within the first two weeks of life and involves generalized rigidity and painful muscle spasms, which in the absence of medical treatment leads to death in most cases (3). Global vaccination programmes have reduced the global burden of neonatal tetanus deaths and continue to do so; estimates show a reduction from an estimated 146 000 in 2000 to 58 000 (CI: 20 000–276 000) in 2010 (4). However, because tetanus spores are ubiquitous in the environment, eradication is not biologically feasible and high immunization coverage remains essential (1).

 

Methods

The ANC recommendations are intended to inform the development of relevant health-care policies and clinical protocols. These recommendations were developed in accordance with the methods described in the WHO handbook for guideline development (5). In summary, the process included: identification of priority questions and outcomes, retrieval of evidence, assessment and synthesis of the evidence, formulation of recommendations, and planning for the implementation, dissemination, impact evaluation and updating of the guideline.

The quality of the scientific evidence underpinning the recommendations was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (6) and Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) (7) approaches, for quantitative and qualitative evidence, respectively. Up-to-date systematic reviews were used to prepare evidence profiles for priority questions. The DECIDE (Developing and Evaluating Communication Strategies to support Informed Decisions and Practice based on Evidence) (8) framework, an evidence-to-decision tool that includes intervention effects, values, resources, equity, acceptability and feasibility criteria, was used to guide the formulation and approval of recommendations by the Guideline Development Group (GDG) – an international group of experts assembled for the purpose of developing this guideline – at three Technical Consultations between October 2015 and March 2016.

To ensure that each recommendation is correctly understood and applied in practice, the context of all context-specific recommendations is clearly stated within each recommendation, and the contributing experts provided additional remarks where needed.

In accordance with WHO guideline development standards, these recommendations will be reviewed and updated following the identification of new evidence, with major reviews and updates at least every five years.

Further information on procedures for developing this recommendation are available here.

 

Recommendation question

For this recommendation, we aimed to answer the following question:

  • For pregnant women (P), does vaccination against tetanus (I) compared with no vaccination (C) reduce morbidity and improve outcomes (O)?

 

Evidence summary

The evidence on the effects of TT vaccination was derived from a Cochrane review that assessed the effect of tetanus vaccination in women of reproductive age or pregnant women to prevent neonatal tetanus (9). Two RCTs contributed data: one was conducted in Colombia between 1961 and 1965 and compared a tetanus vaccine (aluminium phosphate adsorbed tetanus toxoid [10LF]; 3 doses) with an influenza vaccine (1618 women, 1182 neonates); the other was conducted in the USA and compared a combined vaccine (tetanus/diphtheria/ acellular pertussis [Tdap]; 1 dose) with saline placebo in 48 pregnant women between 30 and 32 weeks of gestation. Due to the relative paucity of RCT data, additional evidence on effects is also considered in the “Additional considerations” section.

Maternal outcomes

Low-certainty evidence suggests that local sideeffects, such as pain, were more common with the Tdap vaccination than placebo (48 women; RR: 3.94, 95% CI: 1.41–11.01). There is no evidence on other maternal outcomes.

Fetal and neonatal outcomes

Low-certainty evidence from the Colombian trial suggests that there may be fewer neonatal tetanus cases among neonates whose mothers receive TT vaccination than among those who do not (1182 neonates; RR: 0.20, 95% CI: 0.10–0.40). Moderate-certainty evidence suggests that two or more doses of TT probably reduce neonatal mortality from any cause (1 trial, 688 neonates; RR: 0.31, 95% CI: 0.17–0.55). Further low-certainty evidence suggests that neonatal mortality from tetanus may be reduced among neonates whose mothers receive at least two TT doses (1 trial, 688 neonates; RR: 0.02, 95% CI: 0.00–0.30), but not among neonates whose mothers receive only one dose (1 trial, 494 neonates; RR: 0.57, 95% CI: 0.26–1.24). Congenital anomalies and other ANC guideline outcomes were not reported in the trials.

 

Additional considerations

A systematic review that pooled data from the Colombian trial with that of a large cohort study of antenatal TT vaccination from India found moderate-certainty evidence to support a large effect (94% reduction) on neonatal tetanus deaths in favour of TT vaccination with at least two doses in pregnant women and women of childbearing age (2 trials, 2146 neonates; RR: 0.06, 95% CI: 0.02–0.20) (10).

TT vaccination has been widely used over 40 years, leading to a substantial decrease in neonatal tetanus and an increase in neonatal survival, with no sign of possible harm to pregnant women or their fetuses (11). The WHO strategy for eliminating maternal and neonatal tetanus includes immunization of pregnant women, supplementary immunization activities in selected high-risk areas, promotion of clean deliveries and clean cord practices, and reliable neonatal tetanus surveillance (1).

Resources

The cost of three doses of TT vaccine has been estimated at around US$ 3 per woman (12), although lower costs in vaccination programmes have been reported (13). The need for cold-chain equipment and staff training may add to costs.

Equity

Most deaths from neonatal tetanus occur in countries with low coverage of facility-based births, ANC and tetanus vaccination (10). In addition, in LMICs, ANC coverage and infant mortality is often unequal between the most- and least-educated, urban and rural, and richest and poorest populations (14). Therefore, increasing tetanus immunity in LMICs and among disadvantaged populations could help to address inequalities.

Acceptability

Qualitative evidence indicates that most women view ANC as a source of knowledge, information and medical safety, and generally appreciate the interventions and advice they are offered. However, engagement may be limited if vaccinations are not explained properly or when women feel their beliefs, traditions and social support mechanisms are overlooked or ignored by health-care professionals (high confidence in the evidence) (15). Lack of engagement may be compounded if services are delivered in a hurried, inflexible, didactic manner (high confidence in the evidence).

Feasibility

Antenatal services provide a convenient opportunity for vaccinating pregnant women, particularly in settings without effective childhood immunization programmes.  Qualitative evidence indicates that if there are additional costs associated with vaccination (including transport costs and loss of earnings), uptake may be limited (high confidence in the evidence) (15). In addition, ANC providers in many LMIC settings feel that a lack of resources, both in terms of the availability of vaccines and the lack of suitably trained staff, may limit implementation (high confidence in the evidence) (16).

 

Further information and considerations related to this recommendation can be found in the WHO guidelines, available at:

http://apps.who.int/iris/bitstream/10665/250796/8/9789241549912-websupplement-eng.pdf?ua=1

 

Implementation considerations

  • The successful introduction of evidence-based policies related to antenatal care into national programmes and health care services depends on well-planned and participatory consensus-driven processes of adaptation and implementation. These processes may include the development or revision of national guidelines or protocols based on this recommendation.
  • The recommendation should be adapted into locally-appropriate documents and tools that are able to meet the specific needs of each country and health service. Modifications to the recommendation, where necessary, should be justified in an explicit and transparent manner.
  • An enabling environment should be created for the use of this recommendation, including changes in the behaviour of health care practitioners to enable the use of evidence-based practices.
  • Local professional societies may play important roles in this process and an all-inclusive and participatory process should be encouraged.
  • Antenatal care models with a minimum of eight contacts are recommended to reduce perinatal mortality and improve women’s experience of care. Taking this as a foundation, the GDG reviewed how ANC should be delivered in terms of both the timing and content of each of the ANC contacts, and arrived at a new model – the 2016 WHO ANC model – which replaces the previous four-visit focused ANC (FANC) model. For the purpose of developing this new ANC model, the ANC recommendations were mapped to the eight contacts based on the evidence supporting each recommendation and the optimal timing of delivery of the recommended interventions to achieve maximal impact.

 

Research implications

The GDG did not identify any priority question related to this recommendation.

 

 

Related links

WHO recommendations on antenatal care for a positive pregnancy experience

(2016) - full document and evidence tables

Managing Complications in Pregnancy and Childbirth: A guide for midwives and doctors

Pregnancy, Childbirth, Postpartum and Newborn Care: A guide for essential practice

WHO Programmes: Sexual and Reproductive health

WHO Health topics: Maternal Health

WHO Health topics: Immunization

 

 

References

  1. Maternal immunization against tetanus: integrated management of pregnancy and childbirth (IMPAC). Standards for maternal and neonatal care 1.1. Geneva: Department of Making Pregnancy Safer, World Health Organization; 2006 (http://www.who.int/reproductivehealth/ publications/maternal_perinatal_health/ immunization_tetanus.pdf, accessed 28 September 2016).
  2. Thwaites CL, Loan HT. Eradication of tetanus. Br Med Bull. 2015;116(1):69–77. doi:10.1093/bmb/ ldv044.
  3. Blencowe H, Lawn J, Vandelaer J, Roper M, Cousens S. Tetanus toxoid immunization to reduce mortality from neonatal tetanus. Int J Epidemiol. 2010;39(Suppl 1):i102–i109.
  4. Lui L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE et al. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet. 2012;379:2151–61.
  5. WHO handbook for guideline development, 2nd edition. Geneva: World Health Organization; 2014 (http://www.who.int/kms/handbook_2nd_ ed.pdf, accessed 6 October 2016).
  6. GRADE [website]. The GRADE Working Group; 2016 (http://gradeworkinggroup.org/, accessed 27 October 2016).
  7. GRADE-CERQual [website]. The GRADECERQual Project Group; 2016 (https://cerqual. org/, accessed 27 October 2016).
  8. The DECIDE Project; 2016 (http://www.decide-collaboration.eu/, accessed 27 October 2016).
  9. Demicheli V, Barale A, Rivetti A. Vaccines for women for preventing neonatal tetanus. Cochrane Database Syst Rev. 2015;(7):CD002959
  10. Blencowe H, Lawn J, Vandelaer J, Roper M, Cousens S. Tetanus toxoid immunization to reduce mortality from neonatal tetanus. Int J Epidemiol. 2010;39(Suppl 1):i102-i109
  11. Statement on tetanus toxoid vaccine. Geneva: World Health Organization; 2014 (http://www. who.int/immunization/statement_on_tetanus_ toxoid_vaccine.pdf, accessed 25 June 2016).
  12. Wolfson LJ, Gasse F, Lee-Martin S-P, Lydon P, Magan A, Tibouti A et al. Estimating the costs of achieving the WHO–UNICEF Global Immunization Vision and Strategy, 2006–2015. Bull World Health Organ. 2008;86(1):27–39.
  13. Mvundura M, Kien VD, Nga NT, Robertson J, Cuong NV, Tung HT et al. How much does it cost to get a dose of vaccine to the service delivery location? Empirical evidence from Vietnam’s Expanded Program on Immunization. Vaccine. 2014;32:834–8.
  14. . State of inequality: reproductive, maternal, newborn and child health. Geneva: World Health Organization; 2015 (http://www.who.int/gho/ health_equity/report_2015/en/, accessed 29 September 2016)
  15. Downe S, Finlayson K, Tunçalp Ö, Gülmezoglu AM. Factors that influence the use of routine antenatal services by pregnant women: a qualitative evidence synthesis. Cochrane Database Syst Rev. 2016;(10):CD012392
  16. Downe S, Finlayson K, Tunçalp Ö, Gülmezoglu AM. Factors that influence the provision of good quality routine antenatal care services by health staff: a qualitative evidence synthesis. Cochrane Database Syst Rev. 2016

 

Citation: WHO Reproductive Health Library. WHO recommendation on tetanus toxoid vaccination for pregnant women. (December 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.