Am. J. Epidemiol.-1999-Li-608-11

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American Journal of Epidemiology

Copyright 1999 by The Johns Hopkins University School of Hygiene and Public Health

All rights reserved

Vol.149,

N o.

7

Printed in U.S.A.

A BRIEF ORIGINAL CONTRIBUTION

Maternal Placental Abnormality and the Risk of Sudden Infant Death

Syndrome

De-Kun Li and Soora Wi

To determine whether placental abnormality (placental abruption or placental previa) during pregnancy

predisposes an infant to a high risk of sudden infant death syndrome (SIDS), the authors conducted a

population-based case-control study using 1989-1 991 California linked birth and death certificate data. They

identified 2,107 SIDS cases, 96 of whom were diagnosed through autopsy. Ten controls were randomly

selected for each case from the same linked birth-death certificate data, matched to the case on year of birth.

Abo ut 1.4 of mothe rs of case s and 0.7 of mothers of controls had either placental abrup tion or placenta

previa during the index pregnancy. After adjustment for potential confounders, placental abnormality during

pregnancy was ass ociated with a twofold increase in the risk of SIDS in offspring (odds ratio = 2. 1, 95

confidence interval1.3-3.1 .The individual effects of placental abruption and placenta previa on the risk of SIDS

did not differ significantly. An impaired fetal development due to placental abnormality may predispose an infant

to a high risk of SIDS.

Am J Epidemiol 1999;

149:608-11.

abruptio, placentae; case-control studies; placenta praevia; sudden infant death

Although changing sleeping position has resulted in

a reduction of sudden infant death syndrome (SIDS) in

many countries (1-6), the etiology for abnormal fetal

development that predisposes infants to a high risk of

SIDS remains elusive. Among the potential risk factors

during pregnancy, intrauterine hypoxia has been

hypothesized to be an important etiologic factor.

However, few studies have examined this hypothesis

(7). Maternal smoking during pregnancy, which,

among other potential toxicities, could result in chron-

ic intrauterine hypoxia, has been associated with an

increased risk of SIDS in offspring (7, 8). Other con-

ditions that may potentially be related to intrauterine

hypoxia, such as placental abnormality, cord prolapse,

and preeclampsia/eclampsia, were much less studied

(9).

The placenta is vital for delivering oxygen and

nutrients to the fetus. An abnormal placental condition

such as placenta previa (implantation of

the

placenta in

Received for publication March 2, 1998, and accepted for publi-

cation August 5, 1998.

Abbreviation: SIDS, sudden infant death syndrome.

From the Division of Research, Kaiser Foundation Research

Institute, California Region, Kaiser Permanente Medical Care

Program, Oakland, CA.

Reprint requests to Dr. De-Kun Li, Division of Research, Kaiser

Foundat ion Research Inst i tute, Cal i forn ia Region, Kaiser

Permanente Medical Care Program, 3505 Broadway, Oakland, CA

94611.

the lower uterine segment) or placental abruption (pre-

mature separation of the normally implanted placenta

prior to birth) could result in an impaired delivery of

oxygen and nutrients to the fetus, thus leading to an

abnormal fetal development due to inadequate supply

of oxygen and essential nutrients (10-14). To examine

whether placental abnormality during pregnancy is

associated with an increased risk of SIDS in offspring,

we conducted a population-based case-control study

using the 1989-1991 California linked birth and death

certificate data.

MATERIALS AND METHODS

During the period of 1989-1991, 2,107 SIDS cases

with

International Classification of Diseases

Ninth

Revision, Clinical Modification, code 798.0 listed as

the underlying cause of death were identified from the

linked California birth and d eath certificate data. More

than 96 percent of the identified SIDS cases w ere diag-

nosed through autopsy. Controls were randomly

selected from infants who did not die from SIDS and

matched to cases on the year of birth with a 10/1 con-

trol/case ratio. The information on prenatal diagnoses

of placental abruption or placenta previa as well as

other conditions was listed under the category of

Com plications and P rocedures of Labor and

Delivery on the birth certificate. Any infant with a

60 8

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Placental Abnormality and the Risk of SIDS 60 9

diagnosis of maternal placental abruption or placenta

previa on the birth certificate was considered to have a

maternal placental abnormality during pregnancy. The

information on potential confounders that were avail-

able from the birth certificate data included maternal

age,

race/ethnicity, educational level, parity, prior mis-

carriage and preterm delivery, maternal sm oking, pres-

ence of preeclampsia/eclampsia, gestational age at ini-

tial prenatal visit during the index pregnancy, infant

low birth weight, sex, and year of birth. The informa-

tion on paternal age, race/ethnicity, and educational

level was also available for adjustment.

An odds ratio w ith its 95 percent confidence interval

was used to estimate the relative risk of SIDS associated

with prenatal placental abnormality. Logistic regres-

sion was used to obtain the estimates after adjustment

for potential confounders (15).

RESULTS

Table presents the characteristics of the study pop -

ulation. Compared with mothers of controls, mothers

of SIDS cases w ere more likely to be less than 18 years

old, to be black, to have had more prior live births and

more than two prior miscarriages, to have smoked, to

have had preeclampsia/eclampsia, or to have had inad-

equate prenatal care during the index pregnancy. In

addition, they were less likely to have any college ed u-

cation. SIDS cases were also more likely to have low

birth weight and to be male compared with controls.

After adjustment for maternal age, educational level,

parity, prenatal smoking, prenatal care, and infant sex,

maternal placental abnormality (placental abruption or

placenta previa) was associated with a twofold

increase in the risk of SIDS in offspring (table 2).

Further adjustment for other potential confounders

including birth year of infants, maternal race/ethnicity,

birth interval, a history of miscarriage, preterm deliv-

ery, preeclampsia/eclampsia during pregnancy, pater-

nal age, and infant with low birth weight did not mate-

rially change the estimate. The individual effects of

abruptio placenta and placenta previa on the risk of

SIDS do not seem to differ significantly (table 2).

DISCUSSION

Limitations of this study need to be kept in mind

when one interprets the findings. Because the study

was based on the birth certificate data, the recorded

diagnosis of placental abruption and placenta previa

may not be complete. Although no recent quality con-

trol data are available for the California birth certifi-

cate data, it is generally expected that the incidence of

placental abruption and placenta previa is around

1-1.5 percent (10). Therefore, the incidence of 0.7 per-

TABLE 1. Characteristics of the study population California

1996-1997

Factors

Maternal age (years)

35

Maternal education (years)

1 2

Maternal race

White

Black

Asian

Hispanic

Pacific Islander

American Indian

Other

Parity (no.)

1

2

3

>4

Prior miscarriage (no.)

0

1

2

>3

Prior preterm delivery

Yes

No

Prior baby with low birth weight

Yes

No

Prenatal smoking

Yes

No

Gestational age at initial

prenatal visit (months)

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610 LiandWi

underreporting had to be different between SIDS cases

and controls. Since the birth certificates were com-

pleted before the occurrence of SIDS, it is unlikely

that any differential recording was introduced because

of the SIDS status. In addition, because SIDS cases

had a relatively low socioeconomic status, a potential

differential recording bias, if it existed, would have

been more likely to result in underreporting of placen-

tal abnormality in the SIDS group than in the control

group, leading to attenuation of the observed associa-

tion between placental abnormality and SIDS risk.

Furthermore, when placental abnormality was rede-

fined to include excessive vaginal bleeding before

labor, the incidence of placental abnormality was

increased to 1 percent in the control group. How ever,

the risk of SIDS associated with the redefined placen-

tal abnormality remained elevated (odds ratio = 1.8, 95

percent confidence interval

1.2-2.6 .

The diagnosis of SIDS in the linked birth and death

certificate data should be reliable because more than

96 percent of cases were diagnosed through autopsy,

and all cases must be verified through a rigorous sys-

tem before the final diagnosis of SIDS could be

recorded on the California death certificate.

It is possible that some potential confounders such

as prenatal smoking exposure may be underreported

on the birth certificate, thus resulting in an incom-

plete control of the potential confounders. However,

any residual confounding, if it existed, was unlikely

to be strong enough to explain the observed twofold

increased risk of SIDS associated with placental

abruption or placenta previa during pregnancy, for

the current adjustment for those confounders,

though incomplete, resulted in essentially no change

between crude and adjusted odds ratios: 2.0 and 2.1,

respectively.

The findings from this study suggest that the placen-

tal problems during pregnancy may predispose an

infant to a higher risk of

SIDS.

The mechanism for this

observed association is not known at present. The pla-

centa provides a fetus with oxygen and essential n utri-

ents that are vital to normal fetal development.

Although the etiology of placenta previa is largely

unknown, it is believed that a need for increased pla-

cental surface area due to such factors as extensive

endometrial scarring is probably the driving force for

the formation of placenta previa (10). Therefore, pla-

centa previa not only results in the reduced supply of

oxygen and nutrients to the fetus due to decreased pla-

cental surface area, suboptimal uterine location, and

bleeding, but the presence of the condition also indi-

cates reduced uteroplacental oxygen and delivery of

nutrients (10). In the case of placental abruption, the

premature separation of the normally implanted pla-

centa will result in a decreased surface area for m aternal-

fetal blood exch ange, thus leading to a reduced supply

of oxygen and essential nutrients. It is obvious that

both placental abruption and placenta previa could

result in or indicate a reduced supply of oxygen and

essential nutrients to the fetus. Although placental

abruption may result in acute fetal hypoxia compared

with placenta previa which more likely leads to chronic

fetal hypoxia, the effect of fetal hypoxia on fetal devel-

opment, especially on the neurologic system, in terms

of duration and intensity is not well understood

(13,

16,

17). It is possible that both severe hypoxia for short

duration and chronic mild hypoxia can result in fetal

maldevelopment. Our separate analysis of the individ-

TABLE 2. Maternal placental abnormality and the risk of sudden infant death syndrome California

1996-1997

Factors

Placental abnormality^

Yes

No

Abruptio placenta

Yes

No

Placental previa

Yes

No

Cases

(n = 2,028)

No .

28

2,000

16

2,000

13

2,000

1.4

98.6

0.8

99.2

0.7

99.3

Controls

(n = 21,037)

No .

146

20,891

80

20,891

69

20,891

*

0.7

99.3

0.4

99.6

0.3

99.7

Odds

ratiof

2.1

1.9

2.3

95

confidence

interval

1.3-3.1

1.1-3.3

1.3-4.3

* Subjects with m issing data on the adjusted variables were excluded.

t Odd s ratio adjusted for m aternal age, educational level, parity, prenatal sm oking, prenatal care, and infant's

sex. Further ad justme nt for birth year of infant, materna l race, birth interval, a history of miscarriage, preterm deliv-

ery, preeclampsia during pregnancy, paternal age, and infant with low birth weight did not materially alter the esti-

mate.

XIncluding abruptio placenta and placental previa. One case and three controls had both conditions.

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Placental Abnormality and the Risk of SIDS 611

ual effects of placental abruption and placenta previa

on the risk ofSIDSdid not differ significantly (table 2).

Depending on the severity of the placental abnor-

malities, various damages to fetal development includ-

ing death may occur (12, 13 , 18, 19). Althoug h the

exact types of damages to live births by the placental

abnormalities during pregnancy are not well docu-

mented, the central nervous system is probably a

potential target because of the effect of fetal hypoxia

(13,

18). A defective cardiorespiratory con trol system

in the brainstem has been hypothesized to be involved

in the etiology of SIDS (20-25). Therefore, it is con-

ceivable that some of the neurologic damage could be

severe enough, though not detectable by autopsy, to

result in SIDS when extraneous risk factors such as

prone sleeping position are present. Although the inci-

dence of placental abruption and placenta previa is

low, understanding the association of placental abnor-

mality and the risk of SIDS may enhance our knowl-

edge of the role of the placenta in determining the risk

of SIDS as well as other adverse pregnancy outcomes.

ACKNOWLEDGMENTS

This study was supported in part by a grant from the

National Institute of Child Health and Human Development

(CRMC-94-01).

The authors thank the California Vital Statistics

Department for making the birth and death certificate data

available for research.

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