ORIGINAL

Niger J Paed 2014; 41 (1):15 –21

Fatiregun AA

Oloko O

Breastfeeding and post-

immunisation fever amongst

infants receiving Diphtheria-

Pertussis-Tetanus vaccine at a

tertiary health institution in Ibadan,

Nigeria

DOI:http://dx.doi.org/10.4314/njp.v41i1,3

Accepted: 6th August 2013

Abstract Objective: To deter-

mine the incidence of fever after

vaccination with the first dose of

diphtheria-pertussis-tetanus

vaccination.

Results: Only 682 completed the

study. The overall rates of exclu-

sive and non-exclusive breastfeed-

ing were 48% and 52%, respec-

tively. Compared with the infants

who were non-exclusively breast-

fed, those who were breastfed ex-

clusively had a risk for fever of

0.675 (95% CI, 0.558-0.817). The

place of delivery and the highest

level of education were confound-

ers and effect modifiers of the as-

sociation between breastfeeding

and fever.

Fatiregun AA (

Oloko O

)

Department of Epidemiology /

Medical Statistics,

Faculty of Public Health,

College of Medicine,

University of Ibadan, Nigeria.

Email: akinfati@yahoo.com

Tel: +2348033720966

(

DPT) among exclusively breast-

fed and non-exclusively breastfed

infants in Ibadan, Nigeria.

Methods: A prospective study was

conducted on a cohort of 710 in-

fants who received first dose of

DPT vaccine at the Immunisation

Clinic of a tertiary health institu-

tion in Ibadan, between July and

October 2011. Based on the feed-

ing pattern in a 24-hour feeding

recall by mothers, infants were

classified into exclusive and non-

exclusive breastfeeding groups.

Each of the infant's mothers was

provided with a digital thermome-

ter and instructed on how to meas-

ure the temperature of her infant.

The information about the inci-

dence of fever was obtained by

telephone on the third day after

Conclusions: These findings sug-

gest that exclusive breastfeeding is

associated with a decreased inci-

dence of fever after immunisation.

Keywords: Exclusive breastfeed-

ing; Post-immunisation fever;

Diphtheria-pertussis-tetanus vacci-

nation; Nigeria

Introduction

immunisation, especially in infants and young children.

Although generally benign and self-limiting, fever is a

common concern for parents and health-care profession-

als fuelled by fears of febrile convulsions. It is estimated

that one of every four children develops fever following

Nigeria’s immunisation coverage for children is among

the lowest in the world. The percentage of children

fully immunised has only minimally increased from

1

4

1

4% in 2003 to 17% in 2008, with approximately 30%

the administration of the DPT vaccine. Fever after im-

of children 12-23 months of age having had no vaccina-

tions at all. Only 32% of children receive all three doses

of the diphtheria-pertussis-tetanus (DPT) vaccine and

only 47% of children receive the Bacillus-Calmette-

Guerin (BCG) vaccination. A study on maternal deter-

minants of complete child immunisation showed that

munisation may be caused by immunisation or may co-

incide temporally as an indication of underlying, usually

infectious, disease. The fever caused by immunisation is

triggered by immune and inflammatory res₄_-p₇onses to

vaccine components and is of short duration. Prophy-

laxis or therapeutic administration of analgesics

(acetaminophen or paracetamol) for fever following

immunisati₈o_,n₉has been shown to reduce vaccine immu-

nogenicity.

2

3

2.4% of children completed the immunisation sched-

3

ule. One of the reasons given by mothers for not vacci-

nating or completing the immunisation schedule is the

fear of side₂_,e₃ffects, which include fever following im-

munisation.

Breastfed infants have different immune responses to

diseases and some vaccines compared with infants who

5

Fever is a frequent systemic adverse event following

are not breastfed. Such responses might be attributable

1

6

to the several anti-inflammatory and imm_,₇unomodulatory

after immunisation) between the groups, with an abso-

lute precision of 10%, a 5% α leve₁₂l, a 20% β level, and

assuming a 10% loss to follow-up.

6

factors that are present in breast milk. Epidemiologic

research has provided compelling evidence for the ef-

fects of human milk in decreasing infant m₁o₀_,r₁t₁ality and

morbidity from acute and chronic diseases.

In spite

Data collection

of the evidence supporting the importance of breastfeed-

ing during the first year of life, however, data on the

effect of breastfeeding on fever following immunisation

are limited. Indeed, only one study (known to the au-

thors) has evaluated the effect of breastfeeding on fever

following immunisation; it was reported that breastfed

infants are less likely to have a fever after₁im₂ munisation

compared with those that are not breastfed.

Mothers of infants were informed about the study and

written consent was obtained. Data on demographics,

telephone numbers, socio-economic characteristics, de-

livery history, infant feeding habits, and pre- and post-

immunisation health status of the infant were collected

using a semi-structured questionnaire. Infants were clas-

sified into exclusively breastfed (no other food or fluids

given) or non-exclusively breastfed (food and nutritive

foods added to breast milk or no breast milk at all) based

on their current feeding patterns using a 24-hour dietary

recall. Each of the mothers was provided with a standard

digital thermometer and a fever diary card, and was

taught how to measure and record the body temperature

of her baby on the evening of the vaccination and twice

a day for the next two days (once in the morning and

once in the evening before meals, and whenever fever

was suspected). The baseline temperature before vacci-

nation was taken by mothers and cross-checked by the

investigators before recording on the questionnaire. This

was done to ensure that mothers had acquired compe-

tency in handling and taking the temperature. One of the

authors, who was unaware of the feeding habits of the

infants, contacted all of the mothers by telephone on the

third day after vaccination. For every mother contacted,

information was obtained on how many times tempera-

ture had been recorded and the exact values in degrees

Centigrade. An infant was defined as having a fever

after im₁m₄ unisation if any oral temperature reading was

Fever associated with vaccinations is usually mild and

of short duration. Nevertheless, it would be useful to

know if there is a consistent association between breast-

feeding and post-immunisation fever in different races

and cultures. Such evidence can help promote breast-

feeding practices and improve infant vaccination across

the globe, especially in developing countries, including

Nigeria. This study was therefore conducted to deter-

mine the incidence of fever after immunisation among

exclusively breastfed and non-exclusively breastfed in-

fants who received the first dose of the DPT vaccination

at a tertiary health facility in Ibadan, Oyo State.

Methods

Study setting

The study was conducted in the Immunisation Clinic of

the Institute of Child Health of the College of Medicine,

0

which is located within the University College₃ Hospital

≥ 38 C.

1

(

UCH), a tertiary health institution in Ibadan. The Im-

munisation Clinic opens three times each week, on

Mondays and Wednesdays for infants from birth to 6

months of age and Thursdays for infants 9-11 months of

age, who are due to receive yellow fever and measles

Data analysis

Data were analysed using the statistical package for so-

cial sciences (SPSS) software (version 15.0). Descrip-

tive statistics were used to summarise variables and in-

ferential statistics using the chi-square test was used to

determine the association between categorical variables

including infant feeding habits categorised into exclu-

sively breastfed and partially breastfed infants and post-

immunisation fever. The incidence of post-immunisation

fever for the different levels of the variables was calcu-

lated and the relative risk (RR) with 95% confidence

intervals (CIs) was used as a measure of association.

Stratified analyses with adjusted RRs were used to de-

termine the role of socio-demographic and child-related

variables that were significant with both exclusive breast

-feeding and post-immunisation fevers as confounders

or effect modifiers in the relationship between exclusive

breastfeeding and post-immunisation fever. Ethical ap-

proval for the study was obtained from the joint Univer-

sity College Hospital and University of Ibadan Ethics

Committee.

3

according to the Nigerian immunisation schedule. On

average, 60 mothers and their infants are seen each day

the clinic is₁o₃pen, which usually opens at 9am and

closes at 4pm.

Study design

A prospective cohort study design was used to deter-

mine the incidence of post-immunisation fever 3 days

post-vaccination among exclusively breastfed and non-

exclusively breastfed infants who received the first dose

of the DPT vaccine. The study participants were mother-

infant pairs who came to the Immunisation Clinic be-

tween 1 July and 30 October 2011, and the infants re-

ceived the first dose of the DPT vaccine. Mother-infant

pairs were excluded if the infant had an acute febrile

illness in the 3 days preceding the vaccination, was the

product of a multiple birth, or had a birth weight < 2.5

kg, or the mother could not read or write. We estimated

that 358 infants in each feeding group (exclusive and

non exclusive breastfeeding) were required to detect a

statistically significant difference (31.0% rate of fever

1

7

Results

Table 1: Comparison of mothers and infants who completed

the study and those who were lost to follow-up on key

demographic and socio-economic characteristics

Seven hundred ten mother-infant pairs who attended the

clinic within the study period and met the eligibility

criteria consented to participate; however, only 682

completed the three day follow-up period. Of the 28

mother-infant pairs that were lost to follow-up, 24

dropped out because their telephone numbers were not

accessible and the remaining four were not included

because they did not collect and provide information on

the infants’ body temperatures. Table 1 shows the char-

acteristics of the mothers and infants who completed the

study and those who were lost to follow-up. The mother-

infant pairs who were lost to follow-up differed from the

remaining infants with respect to mother’s age

Characteristics

Completed

study

n = 682(%)

Lost to

follow-up

n = 28 (%)

P-value

Infant gender

Female

Male

Place of delivery

Home

359 (52.6)

323 (47.4)

12 (42.9)

16 (57.1)

0.312

0.06

61 (8.9)

4 (14.3)

Public health facility

Private health facility

158 (23.2)

463 (67.9)

11 (39.3)

13 (46.4)

Mode of delivery

Caesarean section

Vaginal delivery

Other children in the house-

hold

63 (9.2)

619 (90.8)

0 (0.0)

28 (100)

0.14*

0.001

465 (68.2)

217 (31.8)

11 (39.3)

17 (60.7)

Yes

(

p=0.006), parity (p<0.004), mother’s occupation

p<0.041), and the presence of other children within the

No

Mother’s parity

household (p< 0.001). Among mother-infant pairs that

completed the follow-up period, 332 (48.7%) mothers

exclusively breastfed the infants.

1

217 (31.8)

417 (61.1)

48 (7.0)

17 (60.7)

11 (39.3)

0 (0.0)

0.004

0.006

2-4

+

Age of mother in years

20

1-30

5

≤

2

22 (3.2)

330 (48.4)

2 (7.1)

21 (75.0)

5 (17.9)

The socio-demographic profile of the mother-infant

pairs and birth-related characteristics according to

breastfeeding practices are presented in Table 2. As indi-

cated, exclusive feeding practice was associated with the

mother’s level of education, marital status, and parity.

The place of delivery and delivery mode were also

shown to be significantly associated with the breastfeed-

ing pattern. Exclusive breastfeeding was observed in

Above 30

Mother’s marital status

Unmarried

Married

Religion

Christianity

Islam

Ethnic group

Yoruba

Others

Highest level of education

Primary

272 (39.9)

410 (60.1)

9 (32.1)

19 (67.9)

0.412

0.511

0.464

0.06

371 (54.4)

311 (45.6)

17 (60.7)

11 (39.3)

631 (92.5)

51 (7.5)

25 (89.3)

3 (5.6)

5

5.1% of the newborns delivered in public health facili-

ties compared to 48.2% and 36.1% delivered in private

health facilities and at home, respectively (p=0.039).

The majority of the mothers who exclusively breastfed

had normal vaginal deliveries (52.2%) compared to cae-

sarean deliveries (14.3%; p<0.0001).

155 (22.7)

237 (34.8)

290 (42.5)

7 (25.0)

15 (53.6)

6 (21.4)

Secondary

Tertiary

Current working status

Yes

No

Maternal occupation

Housewife

Trading

167 (24.5)

515 (75.5)

8 (28.6)

20 (71.4)

0.623

0.041

The incidence of post-immunisation fever among those

who completed the follow-up period was 274 (40.2%).

As shown in table 3, the incidence of post-immunisation

fever in infants was significantly less among those who

were exclusively breastfed (107/332, 32.2%) compared

to those who were not exclusively breastfed (167/350,

66 (9.7)

6 (21.4)

16 (57.1)

1 (3.6)

5 (17.9)

0 (0.0)

318 (46.6)

122 (17.9)

116 (17.0)

60 (8.8)

Artisan

Private sector employee

Public sector employee

Type of infant feeding

Exclusive breastfeeding

Non-exclusive breastfeeding

Fever among family member 3

days before immunisation

Yes

332 (48.7)

350 (51.3)

9 (32.1)

19 (67.9)

0.086

4

7.7%). Post-immunisation fever in infants was also

shown to be significantly associated with the place of

delivery of the infant, marital status, and the highest

level of education attained by the mother. Evaluating the

role these variables played in the relationship between

type of infant feeding and post-immunisation fever indi-

cated that place of delivery and level of education at-

tained by the mothers were both confounders and effect

modifiers (Table 4).

>0.99*

12 (1.8)

0 (0.0)

No

670 (98.2)

28 (100)

*

Fishers’ exact text

1

8

Table 2: Relationship between exclusive breastfeeding (EBF)

and maternal socio-demographic and birth-related characteris-

tics

Table 3: Mothers’ socio-demographic and birth-related

characteristics with the absolute and relative risks of post-

immunisation fever

Characteristics

EBF n=332 (%) Row total P-value

Characteristics

Risk of post-

immunisation

fever n (%)

Row Risk Ratio (95

total

Confidence Interval)

Infant gender

Female

Male

170

162

(47.4)

(50.2)

359

323

0.465

Infant gender

Female

Place of delivery

Home

146 (40.7)

128 (39.6)

359 1.03 (0.85-1.23)

22

(36.1)

61

0

.039

Public health facility

Private health facility

87

223

(55.1)

(48.2)

158

463

Male

Place of delivery

323

1

Mode of delivery

Caesarean section

Vaginal delivery

Other infants in the household

No

Yes

Parity

1

Home

Public health

facility

Private health

facility

Mode of delivery

32 (52.5)

40 (25.3)

61

1

9

323

(14.3)

(52.2)

63

619

<0.0001

0.580

158 0.48 (0.34-0.69)*

463 0.83 (0.64-1.08)

202 (43.6)

223

109

(48.0)

(50.2)

465

217

Caesarean section 25 (39.7)

63

1

95

223

14

(43.8)

(53.5)

(29.2)

217

417

48

Vaginal delivery 249 (40.2)

619 1.01 (0.74-1.40)

2

5

-4

+

0.001

Other infant in the household

No

Yes

Fever in family member in the 3 days before immunisation

Yes

No

Parity

1

Age of mother

20

1-30

179 (38.5)

95 (43.8)

465

217 1.14 (0.94-1.38)

1

≤

8

(36.4)

22

0

.188

2

153

171

(46.4)

(51.8)

330

Above 30

Marital status

Unmarried

Married

Religion

Christianity

Islam

Ethnic group

Yoruba

Others

Highest level of education attained by mother

7

(58.3)

12

670 0.68 (0.42-1.11)

1

267 (39.9)

112

220

(41.2) 272

(53.7) 410

0.0014

0.689

0.733

95 (43.8)

159 (38.1)

20 (41.7)

217 1.05 (0.73-1.52)

417 0.92 (0.64-1.31)

48

2

5

-4

+

1

178

154

(48.0) 371

(49.5) 311

Age of mother

20

1-30

≤

8 (36.4)

145 (43.9)

121 (36.7)

22

330 1.21 (0.69-2.13)

330 1.01 (0.57-1.78)

1

2

306

26

(48.5) 631

(51.0) 51

Above 30

Marital status

Unmarried

Married

Religion

Christianity

Islam

126 (46.3)

148 (36.1)

272

410 0.78 (0.65-0.93)*

1

Primary

66

(42.6) 155

0

.005

Secondary

Tertiary

104

162

(43.9) 237

(55.9) 290

139 (37.5)

135 (43.4)

371 0.86 (0.72-1.04)

311

Current working status of mother

1

Working

82

250

(49.1) 167

(48.5) 515

0.90

Ethnic group

Yoruba

Others

Highest level of education attained by mother

Primary

Secondary

Tertiary

Current working status of mother

Not-working

Maternal occupation

Housewife

Trading

Artisan

Private sector employee 59

257 (40.7)

17 (33.3)

631 1.22 (0.82-1.82)

51

1

31

165

48

(47.0) 66

(51.9) 318

(39.3) 122

(50.9) 116

(48.3) 60

78 (50.3)

101 (42.6)

95 (32.8)

155

1

0.209

237 0.85 (0.69-1.05)

290 0.65 (0.52-0.82)*

Public sector employee 29

Working

74 (44.3)

200 (38.8)

167 1.14 (0.93-1.40)

Not-working

Maternal occupation

Housewife

Trading

Artisan

515

1

21 (31.8)

146 (45.9)

44 (36.1)

41 (35.3)

66

1

318 1.44 (0.99-2.10)

122 1.13 (0.74-1.73)

116 1.11 (0.72-1.71)

Private sector

employee

Public sector

employee

22 (36.7)

60

1.15 (0.71-1.87)

Type of infant feeding

Exclusive breast-

feeding

Non-exclusive

breastfeeding

107 (32.2)

167 (47.7)

332 0.68 (0.56-0.82)*

350

1

9

Table 4: Association between breastfeeding and fever strati-

fied by potential confounders

assessment of outcome, body temperatures were taken

by the mothers rather than by health professionals.

Although, the mothers were trained on how to measure

their infant’s temperature, provided with a standard digi-

tal thermometer, and were compliant with taking and

recording temperatures, it was not possible to exclude a

bias in the assessment of fever. The differences in char-

acteristics, such as mother’s age, parity, mother’s occu-

pation, and the presence of other children within the

household of those that were lost to follow-up and those

who completed the study, may indicate selection bias.

We ensure that only those mother-infant pairs in which

information was complete for both exposure and out-

come data were included in the analysis. Although infor-

mation about potential confounders was obtained, iden-

tified, and controlled for in the analysis, there is the pos-

sibility that our findings may have been influenced by

unknown confounders. Lastly, our study design could

not exclude fever following immunisation due to infec-

tive episodes.

Confounder

Breastfeed- Adjusted

ing pattern Relative risk

for fever

95% CI

Place of delivery

Home

Public health facility

Private health facility

Marital status of mother

Not married

Exclusive 0.647

Exclusive 0.925

Exclusive 0.663

0.365-1.144

0.542-1.581

0.533-0.824

Married

Exclusive 0.683

Exclusive 0.697

0.515-0.905

0.537-0.904

Highest level of education

attained by the mother

Primary

Secondary

Tertiary

Exclusive 0.544

Exclusive 0.944

Exclusive 0.608

0.373-0.792

0.701-1.271

0.434-0.850

Discussion

Several epidemiologic studies have demonstrated the

7, 10, 15-21

benefits of exclusive breastfeeding for the infant.

The role of exclusive breastfeeding in post-

immunisation fever in infancy is not fully understood.

The results of the current study indicated that exclusive

breastfeeding reduces the risk of post-immunisation fe-

ver in infants. We found that exclusively breastfed in-

fants were less likely to have fever following the first

dose of DPT vaccination compared with infants that

were not exclusively breastfed. However, the level of

education of mothers, and where the mothers delivered

the infants were both confounders and effect modifiers

in the relationship. While the reduction in risk of post-

immunisation fever was statistically significant if moth-

ers exclusively breastfed and reported having a tertiary

education, this reduction was not significant if mothers

exclusively breastfed and reported a primary or secon-

dary education. The significant reduction in risk of post-

immunisation fever was also found if mothers exclu-

sively breastfed and reported having delivered the new-

born at a private health facility. This finding was not the

case if the exclusively breastfed infant was delivered at

home or at a public health facility.

These benefits include an increase in immune responses,

fewer infections, a reduction in sudden infant death syn-

drome, less childhood obesity, fewer tendencies to de-

velop atopy and necrotizing enterocolitis, as well as

higher intelligence later in life. Pisacane et al. suggested

that breastfed infants are less likely to have fever after

immunisation compared with those who are not br₂east-

1

fed is similar to the finding from the present study. The

two studies, although similar in design, differ in cultural

and environmental settings, but demonstrated a consis-

tent association between breastfeeding and post-

immunisation fever. This has implications for policy and

advocacy for immunisation, especially in our environ-

ment. Exclusive breastfeeding could be promoted to

improve immunisation coverage because the risk of fe-

ver post-immunisation, which is one of the reasons for_,

2

not completing the immunisation schedule, is reduced.

3

Furthermore, the practice of prophylactic administra-

tion of analgesics (acetaminophen or paracetamol) be-

fore vaccination, with the antecedent risk of reducing

vaccine immunogenicity, could be discouraged if health

workers and household caregivers are_[a₈_,w₉_]a_.re of the safer

alternative of exclusive breastfeeding.

We recognise the limitations the design could have im-

posed on the findings of this study. First, misclassifica-

tion bias in the assessment of exposure and outcome is

possible. We relied on a 24-hour dietary recall method

to classify infants into exclusively or non-exclusively

breastfed infants. Although this method might minimise

recall bias because of the short duration of memory re-

call required, it may not accurately provide information

on feeding habits of infants during a long period prior to

the study. However, it is a method recommended by the

World Health Organization to measure current exclusive

breastfeeding rate, and it provided a basis for comparing

our results with a previous study which used the same

The mechanism by which exclusive breastfeeding re-

duces post-immunisation fever is not well understood;

however, the anti-inflammatory properties of human

1

2

milk or the act of nursing itself could be responsible.

The hypothesis that human milk is anti-inflammatory is

supported by studies documenting anti-inflammatory

effects in animal models and suppression of humoral

7

and cellular components of inflammation in vitro. It is

not clear whether or not this mechanism has topical ef-

fects within the digestive tract alone or whether or not

absorption of milk components results in systemic ef-

fects. Inflammation benefits the host as a defense

mechanism and precursor to immune responses. Inflam-

mation also contributes to the clinical manifestations of

illness. The biological effect of the anti-inflammatory

9

indicator. In addition, social desirability bias may be

introduced as a result of mothers wanting to impress the

investigators that they practiced exclusive breastfeeding,

which is the desirable practice based on ongoing health

education for nursing mothers in our environment. In the

2

0

character of breast milk may be to minimise clinical

symptoms withou₂t losing immune responsiveness for the

feeding for mothers and infants, the practice has the

potential of improving completion of the immunisation

schedule through a reduction in adverse events follow-

ing immunisation in our setting. In addition, further

studies with assessment of fever by healthcare workers

rather than the mothers and improved design are sug-

gested.

2

breastfed infant. It has also been observed that fever

could be due to poor feeding, which is common when

children are sick. As breastfed infants are less likely to

have poor feeding, the li₁k₂elihood of fever post-

immunisation is also reduced.

Author’s Contributions

AAF: conceived the study and draft

OO: Draft and analysis of data

Conflict of Interest: None

Funding: None

Conclusions

In conclusion, we showed that the incidence of fever

after the first dose of the DPT vaccination among exclu-

sively breastfed infants was lower compared with non-

exclusively breastfed infants. Although the association

was modified by level of education of mothers and the

sites where the infants were delivered, consistency in the

strength of association with a previous study conducted

in a different cultural setting was demonstrated. Health

care workers could promote exclusive breastfeeding as a

safer alternative to prophylactic administration of aceta-

minophen or paracetamol to prevent post-immunisation

fever. Apart from all the advantages of exclusive breast-

Acknowledgement

The authors gratefully acknowledge the support received

from staff of the immunisation clinic in accessing study

participants. We also appreciate the cooperation of all

mothers involved in the study.

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