References

Design

Study Population

Treatment

Outcomes

Results

Baltazar 1994

Case‐control study.

54 neonates admitted to hospital diagnosed with NT. 50
controls 1 to 4 months old admitted for causes other than NT.
Manila.

Immunisation with TT, considered immunised if received at least 2 doses of TT during pregnancy, otherwise not.

Incidence of immunisation: cases (1/54), controls (12/49).

Protective effect against NT if at least 2 doses of TT.

Chai 2004

Case‐control study.
Surveillance data after TT mass immunisation campaign carried out 1995 to 1996 in 320 out of 560 countries reaching about 23 million women aged 18 to 35 years, were also reported. Coverage with 2 doses of TT was estimate 10%. Surveillance data of 1996 to 2001 were analysed.

Cases: 60 children with NT (WHO case definition) reported by cards and hospital record in Bobai country (province of Guangxi, China) to the National Notifiable Disease Reporting System (NNDRS) from 1.1.97 to 30.4.98. Only children with accurate locating information were included. Controls: 60 infants born in the same village as the cases.

Mother of children were immunised with TT. No information about the number of administered doses is reported.

TT immunisation status of the mothers and other information (maternal: age, education level, annual income < 1000 Yuan; infant: gender, order of birth, home delivery; parental knowledge and attitude regarding NT) were assessed by means of a detailed questionnaire given to parents of both cases and controls. TT immunisation history was based only of mother's recall because they were not provided with vaccinal records. Mothers of 7 cases and 17 controls received previously TT.

Receiving of 1 or more of TT was significant protective against NT. Maternal age, education, family income, birth order, parental knowledge, were also significantly associated with NT.

Gupta 1998

Survey.

1688 pregnant women. India.

Immunisation with TT, considered immunised if received 2 doses of TT at least 4 weeks apart or a booster dose. Partially immunised, if received 1 dose of TT either during the current pregnancy or in the past 3 years.

Deaths from NT within 3 to 30 days of birth.

Immunisation during the antenatal period is highly protective against occurrence of NT.

Hlady 1992

Case‐control study.

Infants with clinically‐diagnosed tetanus. 3 controls. Bangladesh.

Immunisation with TT, 2 doses 4 weeks apart, with second dose administered at least 30 days before delivery.

Incidence of immunisation: cases (33/112), controls (122/336).

Immunisation failed to provide the expected high level of protection.

Yusuf 1991

Follow‐up survey.

Women aged 10 to 45 years. Indonesia.

Immunisation with TT, 1 or 2 doses.

Deaths from NT within 3 to 28 days of birth.

Immunisation caused an 85% reduction of NT.

Chongsuvivatwong 1993

Survey study.

Women aged 15 to 45 years. Thailand.

Immunisation with TT.

Cases of NT.

Immunisation caused a 8 to 10 times reduction of NT.

Rahman 1982a

Surveillance study.

Women from surveillance area. Bangladesh.

Immunised with TT at 6th, 7th, 8th month. Considered immunised if received 2 injections in 1974 or in the 1978 to 1979 programme.
Partially immunised, if received 1 injection in 1974 or 1978 to 1979.
Mixed immunised if received 1 or 2 doses in 1974 and again 1 or 2 doses in 1978 to 1979.

Deaths attributed to NT within 4 to 14 days after birth.

Full immunisation reduced neonatal mortality rates by about one half and mortality rates on days 4 to 14 by about 70%.

Koenig 1998

Survey.

Children between 1 to 14 years and non‐pregnant women at least 15 years. Bangladesh.

Immunised with cholera toxoid (1 or 2 0.5 mL doses) vs tetanus ‐ diphtheria toxoid (1 or 2 0.5 mL doses).

Deaths attributed to NT within 4 to 14 days after birth.

2 injections provided significant protection. Protection of 1 dose not significant.

Schofield 1961

Observational.

Pregnant women from 62 villages in New Guinea (Maprik, Wingei and Wosera areas). A retrospective "history‐taking survey" on children born from 1945 to the time of the study was also performed in the Maprik area.

3 doses of fluid formalinised TT (Commonwealth Serum Laboratories, Melbourne). The first dose was administered as early as possible in pregnancy, the second 6 weeks later and the third between 6 weeks and 6 months after the second.

Cases of NT observed in children born from mothers who received different number of doses of TT during pregnancy.
Not immunised: 8/86.
Once immunised: 8/74.
Twice immunised: 8/234.
3 times immunised: 1/175.
From the history‐taking survey it results that during the examination period 184 deaths due to NT occurred out of 3017 live births.

3 doses of formalinised TT administered during pregnancy afforded substantial protection against NT. Immunisation with only 2 doses provided also a significant protection level. No reactions to the vaccine were noticed.

References

Study design

Study population

Intervention

Safety outcomes

Results

MacLennan 1965

2 studies are reported in this paper:
a) 1 cluster‐RCT evaluating reactogenicity and side‐effects;
b) 1 RCT assessing safety only, with a 24‐weeks' follow‐up.

Both studies were performed in New Guinea on indigenous populations.
a) Pregnant women belonging to the Abelam tribe (n = 179).
b) Non‐pregnant women from the Maprik area (n = 999).

a) TT prepared by Parke Davis & co with different adjuvants and administered in different doses (Drakeol, 1 dose vs H ‐ 24, 1 dose vs AlPO4, 2 doses vs none, 3 doses) or TT prepared by the Commonwealth Serum Laboratories without adjuvant, 3 doses.
b) TT prepared by Parke Davis & co with Drakeol (A, 1 dose) vs H ‐ 24 (B, 1 dose) vs AlPO4 (C, 2 doses).

a) Swelling (severe or no tender).
b) Abscess (A = 103 /327; B = 96/332; C = 2/340 at the 14th week after immunisation).
c) Fever between 37.8 to 38.3 °C.
d) Swelling.

Although oil‐adjuvated preparations provide longer persistence of antitoxin and require to be administered only once, they caused frequently severe side‐effects. The Al‐adjuvated preparations, administered in 2 doses, appeared to be the best way at the time of the study to prevent the occurrence of NNT.

Silveira 1995

Case‐control study.

Cases (n = 34,293): newborn with congenital malformation. The 10 most frequent in South America were considered.
Controls (n = 34,777): non‐malformed babies of the same sex, born in the same hospital immediately after the malformed ones.
Data were obtained from examination of 1282,403 neonates in 173 hospitals in 105 cities across 9 different countries in South America.

Immunisation of the mothers with TT during pregnancy.

Cleft lip, pes equinovarus, postaxial polydactyly, hip subluxation, hemangioma, periauricular tag, fistula auris, pigmented naevus, other skin defects, multiple malformed.

No association for each of the examined factors was found.

Salama 2009

RCT.

Healthy pregnant Egyptian women at about 20 weeks of gestational age (n = 122).

Participants were randomised to :

a) 0.5 mL of TT (TT, 5Lf, n = 62).

b) 0.5 mL of combined tetanus and reduced diphtheria (Td, 5 Lf of each toxoids, n = 60).

First dose at 20 to 26 weeks of pregnancy, 2nd and 3rd administered respectively 8 and 4 weeks apart.

Systemic (fever, malaise, headache,
or body aches) and local reactions at the site of
injection (pain, redness, swelling) within 3 days after each immunisation.

Pain at the site of injection was complained more frequently in Td group after both first (P < 0.01) and second (P < 0.04) dose.

Shakib 2013

Retrospective Cohort study

‐ Exposed cohort: 138 women aged between 12 and 45 years with documented Tdap immunisation during pregnancy. They were identified among the 162,448 pregnancies occurred within the Intermountain Healthcare facilities (Salt Lake, Utah) between May 2005 and August 2009.

‐ Not exposed cohort: 552 randomly selected women from the same population (without documented vaccination during pregnancy).

In the exposed cohort Tdap immunisation occurred more frequently within 1st (63%), than during 2nd (17%) and 3rd (20%) pregnancy trimester. Immunisation with Tdap occurred mainly as prophylactic measure in consequence of wound, trauma or routine health supervision.

Spontaneous or elective abortion

Stillbirth

Preterm delivery (<37 weeks)

Gestational age

Birth weight

Congenital anomalies

Incidence of spontaneous or elective abortion was no greater in Tdap cases than in controls.

No significant differences in preterm delivery, gestational age, or birth weight between groups.

Frequence of ICD‐9‐CM codes diagnosis for congenital anomalies reported among children born to Tdap exposed women do not differ significantly from that observed among born to not Tdap exposed women.