Influence of Birth Weight on Mortality From Infectious Diseases: A Case-Control Study

Study Influence of Birth Weight on Mortality From Infectious Diseases: A Case-Control http://pediatrics.aappublications.org/content/81/6/807 the World Wide Web at: The online version of

1988;81;807

Pediatrics

M Fuchs, L B Moreira, L P Gigante and F C Barros

C G Victora, P G Smith, J P Vaughan, L C Nobre, C Lombardi, A M B Teixeira, S.

Study Influence of Birth Weight on Mortality From Infectious Diseases: A Case-Control

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Influence of Birth Weight on Mortality From

c G Victora, MD, PhD, P G Smith, DSc, J P Vaughan, MD,

L. . Nobre, MD, C Lombardi, BSc, A.M.B Teixeira, MD,

S M Fuchs, MD, L B Moreira, MD, L P Gigante, MD, and

F C Barros, MD, PhD

ABSTRACT. The association between birth weight and

infant mortality from infectious diseases was

investi-gated in a population-based case-control study in two

urban areas in southern Brazil All deaths of children,

seven to 364 days of age, occurring in a year were

stud-ied and the parents of the 357 infants dying of an

in-fectious cause were interviewed, as were the parents of

two neighborhood control infants for each case Low

birth weight infants (<2,500 g) were found, after

a!-lowing for confounding factors, to be 2.3 (90%

confi-dence interval = 1.6 to 3.4) times more likely to die of

an infection than those ofhigher birth weight The odds

ratios were 2.0 (1.1 to 3.6) for deaths due to diarrhea,

1.9 (1.0 to 3.6) for respiratory infections, and 5.0 (1.3

to 18.6) for other infections These estimates ofthe risks

associated with low birth weight are considerably lower

than those from studies in developed countries

Pedi-atrics 1988;81:807-811; birth weight, infant mortality,

infectious disease, diarrhea, respiratory infection.

Low birth weight is associated with an

in-creased risk of infant mortality in both developed

and developing countries For the latter, however,

there is little information concerning the risks

as-sociated with low birth weight for specific causes

of death and, in a recent review of mortality due

to diarrhea, the authors1 reported that they were

unable to locate any studies concerning the effect

of birth weight

The lack of information is probably due to two

factors First, in many developing countries the

Received for publication May 26, 1987; accepted July 31, 1987.

Reprint requests to (C.G.V.) Department of Social Medicine,

Federal University of Pelotas, CP 464, 96100 PS, Brazil.

PEDIATRICS (ISSN 0031 4005) Copyright © 1988 by the

American Academy of Pediatrics.

proportion of babies delivered in hospitals is

small; therefore, birth weight data are not avail-able for a large proportion of infants Second, ob-taming reliable information about mortality is difficult and usually requires that a monitoring

system is set up Furthermore, it may then be nec-essary to consult medical records and interview

the parents of the deceased children to ascertain the probable cause of death

Whether low birth weight itself is a cause of

increased infant mortality may be difficult to

as-sess because there are several demographic,

so-cioeconomic, and environmental factors that may confound the association For example, infants from low-income families may have lower birth weights and also be more likely to die due to in-fectious diseases for reasons other than low birth weight.2 Failing to take into account such factors might lead to biased results

We have tried to overcome these difficulties by conducting a case-control study in a defined pop-ulation of urban children, where nearly all births occur in a hospital Extensive data were collected concerning factors that might confound the as-sociation between birth weight and infectious dis-ease mortality

The study was carried out in the metropolitan areas of Porto Alegre and Pelotas These cities have a total population of 2.5 million and are lo-cated in the state of Rio Grande do Sul, one of the most developed areas of Brazil The infant mor-tality rate in Pelotas is about 40/1,000,2 and ap-proximately 9% of the babies are of low birth

808 INFECTIOUS DISEASES AND MORTALITY

weight (ie, <2,500 g).3 Statistics for Porto Alegre

are likely to be similar

Between Dec 24, 1984, and Dec 23, 1985, all

hospitals, coroner services, health authorities,

and registries in the cities were visited weekly to

gather information about deaths occurring to

in-fants resident in the study areas This method has

been shown to ascertain the majority of such

deaths.2’4 Whenever an infectious disease was

mentioned as the underlying or associated cause

of death, or when the cause of death was

ill-de-fined or not stated, the parents or guardian of the

in-vestigate the underlying cause Of all potential

deaths, 96.5% were successfully located During

the home visit, the interviewer, a physician,

ques-tioned the parents regarding the signs and

symp-toms of the illness episode that preceded the

child’s death Further information was abstracted

from the hospital case notes, from health center

records, and from postmortem reports The

ques-tionnaires and forms completed were those used

in the Inter-American Investigation of Mortality

in Childhood.5 Two reviewers went through the

interview and clinical data independently to

as-sess the underlying causes of death If there was

any disagreement, a third reviewer (C.G.V.) made

the final decision The three reviewers were kept

unaware of the infant’s birth weight Causes of

death were classified according to the

Interna-tional Classification ofDiseases, 9th rev (lCD).6

The study was designed primarily to

investi-gate risk factors for post-perinatal infant

mortal-ity, and children dying before the eighth day of

life were excluded.7 In addition, infants at

in-creased risk of perinatal morbidity and mortality

or cerebral palsy) were also excluded, as were

those whose initial hospital stay exceeded 15 days

and those ofvery low birth weight (<1,500 g; 1.4%

of births) These criteria excluded 14% of infants

who might potentially die between seven and 364

days

For each case infant, two neighborhood control

infants were selected, the first being the nearest

neighbor seven to 364 days ofage and, the second,

the next child in the neighborhood seven days to

infants were expected to be younger than 6

months, this approach was designed to provide a

control group with a similar age distribution to

that of the case infants The same rigorous efforts

aimed at locating all babies were used to

inter-view all of the eligible control infants, including

repeated visits if necessary

Information regarding birth weight was

ob-tamed from hospital discharge cards (available for

61% of the infants) or by recall Birth weights were not recallable by 1.4% of the mothers In-formation was also collected about variables that may confound the association between birth weight and mortality These included the infant’s age and sex, birth order, birth intervals, family income, occupation and education of the parents, ethnic group, maternal age and smoking habits, housing, crowding, water and sanitation van-ables, antenatal cane, and type of delivery

Initial tabulations were conducted to assess which variables were associated both with birth weight among the control infants and with the risk of death Such variables were considered as potential confounders and were further analyzed through logistic regression for matched studies.8 Analyses were carried out independently for each

of the three groups of causes (diarrhea, respira-tory infections, and other infections) The infants’ age(coded0to2,2to4,4to6,6to9,and9to

11 months), family income (0 to 0.2, 0.2 to 0.4, 0.4

to 1.0, 1.0 + minimum wages per capita), and ma-ternal education (0, 1, 4, 6+ years) were adjusted

for in all analyses In addition, the following van-ables remained statistically significant in the con-ditional likelihood analysis: (1) deaths due to diar-rhea: availability of piped water (piped in house, piped to plot, other), maternal smoking (cigarettes per day), and preceding birth interval (first born,

0 to 24, 24 to 36, 36 + months); (2) deaths due to

respiratory infection: sex, maternal age (years)

and smoking, and birth order (0, 1, 2, 3 to 5, 5 +);

(3) deaths due to other infections: availability of piped water

The effect of birth weight was assessed after including these confounding factors in the logistic model One-sided tests of significance were used because it was expected that low birth weight would increase the risk of death

The study was of sufficient size to have a power

of 95% to detect as statistically significant at the 5% level (one-tailed test) a trebling of the risk of death among low birth weight infants, assuming that 9% of the control children would be of low birth weight For this purpose, 121 case infants would be necessary in each diagnostic group This number was achieved for deaths due to diarrhea and respiratory infections, but there were only 60 deaths due to other infections The power of the

study of other infections, was reduced, therefore,

to 73%

RESULTS

The 357 deaths due to infectious diseases were grouped into three categories: diarrhea (170 deaths, lCD 001_0096), respiratory infections

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(127 deaths, lCD 382, 460-466, 480-487, 519.8),

and other infections (60 deaths) The most

com-mon diagnoses in the latter group were

menin-gitis (12 deaths, lCD 320-322), skin infections

(ten deaths, lCD 682, 684), measles (eight deaths,

033), neonatal sepsis (six deaths, lCD 771.8), and

tuberculosis (5 deaths, lCD 010-018) The

distri-butions of case and control children by age, sex,

income and maternal education are shown in Table 1

The birth weight distributions ofcases and

con-trols are shown in Table 2 Weights were not

recorded for 11 case infants (eight with diarrhea, three with respiratory), and four control children

In the table and in subsequent analyses, these

in-fants have been assigned to the modal birth

weight category (3,000 to 3,499 g) Excluding such

TABLE 1. Distribution oflnfants According to Age, Sex, Family Income, and Maternal

Education

Control Infants 714)

Diarrhea (n = 170)

Respiratory Infections (n = 127)

Other Infections (n = 60) Age (mo)

Sex

Income*

Maternal education (yr)

* Monthly per capita inco me in minimum wages (1 minimum wage = US $50).

TABLE 2. Odds Ratios

by Groups of Causes

for Infectious Diseases Mortality Accordi ng to Birth Weight,

Cause of Death and Birth Wt (g)

Odds Ratio (90% Confidence Interval) No of Infants

Adjusted for Age Adjusted for Age

and Confounders*

Diarrhea

<2,500 3.4 (1.9-6.2) 2.2 (1.1-4.5) 31 25

2,500-2,999 1.7 (1.0-2.7) 1.2 (0.6-2.1) 45 90

3,000-3,499 1.2 (0.8-1.9) 1.1 (0.6-1.8) 61 136

Respiratory infections

<2,500 2.6 (1.3-5.2) 3.3 (1.5-7.5) 22 24

2,500-2,999 2.0 (1.1-3.7) 2.3 (1.1-4.8) 41 65

Other infections

<2,500 8.6 (2.4-30.4) 12.8 (2.6-62.6) 9 3

2,500-2,999 2.7 (1.2-6.0) 4.5 (1.6-12.4) 21 27

3,000-3,499 1.5 (0.7-3.4) 1.9 (0.7-5.1) 19 54

*The following confounding variables were included in the logistic model, in addition

to age, family income, and maternal education: for diarrhea, birth interval, availability

of piped water, and maternal smoking; for respiratory infections, sex, maternal age

and smoking, and birth order; for other infections, availability of piped water

20

10

2

S

infants from the analyses did not affect the

find-ings For each of the three causes of death

con-sidered, the odds ratios for mortality increased

monotonically as birth weight decreased, and in

each case the trend was statistically significant

Controlling for confounding variables resulted in

some changes to the risk estimates but did not

alter the main findings After such adjustment,

infants weighing less than 2,500 g at birth were

found to be 2.2, 3.3, and 12.8 times more likely to

die due to diarrhea, respiratory infections, and

other infectious diseases, respectively, than those

weighing more than 3,500 g

The risks associated with different birth

weights were examined in smaller intervals by

pooling deaths due to all types of infection

(Fig-ure) The risk ofdeath did not vary much for

chil-dren weighing more than 3,000 g at birth It

in-creased slightly for children weighing 2,500 to

at about twice the risk, and those 1,500 to 2,000

g were at nine times the risk ofchildren more than

3,000 g

Compared with infants who weighed 2,500 g or

more at birth, low birth weight infants were 2.0

times (90% confidence interval 1.1 to 4.4) more

likely to die of diarrhea, 1.9 times (1.0 to 3.6) as

times (1.3 to 18.6) as likely to die of other

infec-tions For all infections, the odds ratio for low

birth weight babies was 2.3 (1.6 to 3.4) We tested

for interactions of the effects on mortality of age

Odds

Ratio

0.5

1500- 2000- 2500- 3000- 3500- 4000+

BIRTHWEIGHT (grams)

Figure. Odds ratios and 90% confidence intervals for

mortality due to infectious diseases according to birth

weight (adjusted for age, sex, family income, birth

in-terval, birth order, availability of piped water,

mater-nal education, age, and smoking), Rio Grande do Sul,

Brazil.

and birth weight and socioeconomic status and birth weight There was no evidence that the rela-tive magnitude of the effect of birth weight on infectious diseases mortality changed during the

first year of life, and there was no evidence that

the effects varied according to socioeconomic group

DISCUSSION

In this study, low birth weight was found to be associated with an increased risk of death due to infectious diseases, and the association persisted after allowing for confounding variables The

risks associated with low birth weight seemed to

be larger for deaths from other infections than for diarrhea or respiratory infections, but the confi-dence intervals on the estimated relative risks were wide The risks were considerably lower than would have been expected from previous studies of postneonatal mortality from all causes,

weight infants.’

The choice ofneighbors as controls ensured that the control group was of broadly similar socioeco-nomic status to that of the case group Further-more, by adjusting for several confounding van-ables in the analyses, we endeavored to separate out the effects of birth weight which otherwise would have been confused with effects due to other factors In general we would expect this method

of design and analysis to result in lower (and bet-ten) risk estimates than those derived from in-vestigations in which such procedures were not followed, as is the case for previous studies We

had previously shown that birth weight is one of the determinants of the duration of breast-feeding.9

Our risk estimates are likely to have been biased toward unity by our exclusion of very low birth weight infants and those infants with sig-nificant risk of peninatal morbidity or congenital malformations It is unlikely that this will have biased the findings seriously For example, if one

half of the excluded babies were of low birth weight, the risk estimates associated with low birth weight would have increased by 35% had they been included in the study If two thirds of those excluded had a low birth weight, the in-crease would be of about 50% On the other hand, excluding some of these high-risk babies was also

a strategy for the control of confounding For ex-ample, an infant with a major malformation would be more likely to have a low birth weight and also more likely to die due to an infectious

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disease, the malformation being the cause of both

outcomes

collected, and nearly 40% of the information was

based on recall We have shown previously,

how-ever, that even 1 year after delivery mothers were

able to recall the birth weight oftheir infants with

good The likely effect of recall and

measurement errors would be to lead to an

un-derestimate of the true relative risks It should be

noted, however, that most of the previous work

reporting higher relative risks for infant

mortal-ity due to low birth weight has been based on data

that were also collected routinely

The impact oflow birth weight might be erased

quickly if these infants grew faster than those

born with an adequate weight However, in an

earlier cohort study in the same population, we

have shown that this is not the case.” Low birth

weight infants tended to put on less weight during

the first year, although the differences were no

longer significant after adjustment for family

income

We believe, therefore, that the effect of low

birth weight on infectious diseases mortality in

the population we studied is not as marked as that

reported for overall infant or postneonatal

mor-tality in developed countries This is due to the

fact that, when compared with similar infants

from developed countries, the relative risks of

mortality in developing countries are higher for

infants born with an appropriate weight than for

those with a low birth weight.2 This is in

agree-ment with our previous finding of an interaction

between birth weight and socioeconomic status on

infant mortality due to all causes, with the

nela-tive risks associated with low birth weight being

higher for high-income than for low-income

in-fants, deaths among the former being due most

often to noninfectious causes.2

Based on the odds ratios presented, it is possible

to calculate the proportion of deaths that may be

attributed to a low birth weight (assuming a

causal association) These are 8% for diarrhea, 7%

for respiratory infections, 26% for other

infec-tions, and 10% for all infections Thus, if our risk

estimates are correct, low birth weight is associ-ated with a small proportion ofdeaths due to diar-rhea and respiratory infections and for about one fourth of those due to other infections These find-ings suggest that estimates ofthe possible impact

of improving birth weight on mortality rates in the developing world or, at least in southern Bra-zil, may be less than has been estimated, based

on data from developed countries

ACKNOWLEDGMENTS

The study was funded by the International

Devel-opment Research Center of Canada

REFERENCES

1 Ashworth A, Feachem RG: Strategies for the control of diarrhoeal diseases: The prevention of low birthweight.

2 Victora CG, Barros FC, Vaughan JP, et a!: Birthweight

and infant mortality: A study of 5914 Brazilian children.

mt J Epidemiol 1987;16:239-245

3 Barros FC, Victora CG, Vaughan JP, et a!: Bajo peso a! nacer en el municipio de Pelotas, Brasil: Factores de riesgo. Bol ofSanit Partam 1987;102:541-553

4 Victora CG, Vaughan JP, Barros FC: Seasonality of infant

death due to diarrhoea! and respiratory diseases in

south-em Brazil 1974-78. Pan Am Health Organ Bull

1985;19:29-39

5 PufFer RR, Serrano CV: Patterns ofMortality in Childhood,

scientific publication No 262 Washington, Pan American Health Organization, 1975

6 World Health Organization: International Statistical Clas-sification ofDiseases, Injuries and Causes ofDeath, rev 9.

7 Victora CG, Smith PG, Vaughan JP, et a!: Evidence for a strong protective effect of breastfeeding against infant deaths from infectious diseases in Brazil. Lancet

1987;2:319-322

8 Storer B, Wacholder S, Breslow NE: Maximum likelihood fitting of general risk models to stratfied data. Appl Stat

1983;32:172-181

9 Barros FC, Victora CG, Vaughan JP, et a!: Birth weight

and the duration of breast-feeding: Are the beneficial ef-fects of breast-feeding being overestimated? Pediatrics

1986;78:656-661

10 Victora CG, Barros FC, Martines JC, et al: As maes lem-bram o peso ao nascer de seus filhos? Rev Saude Publica

Sao Paulo 1985;19:195-200

11 Victora CG, Barros FC, Vaughan JP, et a!: Birthweight, socio-economic status and growth of Brazilian infants.

Ann Hum Biol 1987;14:49-57

1988;81;807

Pediatrics

M Fuchs, L B Moreira, L P Gigante and F C Barros

C G Victora, P G Smith, J P Vaughan, L C Nobre, C Lombardi, A M B Teixeira, S.

Study Influence of Birth Weight on Mortality From Infectious Diseases: A Case-Control

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Copyright © 1988 by the American Academy of Pediatrics All rights reserved Print ISSN: 0031-4005 American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007 has been published continuously since 1948 PEDIATRICS is owned, published, and trademarked by the PEDIATRICS is the official journal of the American Academy of Pediatrics A monthly publication, it

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