American Journal of Epidemiology

Copyright 2003 by the Johns Hopkins Bloomberg School of Public Health

All rights reserved

Vol. 158, No. 10

Printed in U.S.A.
DOI: 10.1093/aje/kwg226

Consanguinity and Apnea of Prematurity

Hala Tamim1, Mustafa Khogali2, Hind Beydoun3, Imad Melki4, Khalid Yunis5, and the National
Collaborative Perinatal Neonatal Network
1

Department of Epidemiology and Population Health, American University of Beirut, Beirut, Lebanon.
Department of Family Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
3 Social Statistics Section, United Nations Economic and Social Commission for Western Asia, Beirut, Lebanon.
4 Department of Pediatrics, Hotel Dieu de France Hospital, Beirut, Lebanon.
5 Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon.
2

Received for publication January 22, 2003; accepted for publication April 30, 2003.

apnea; consanguinity; infant, premature

Abbreviation: NCPNN, National Collaborative Perinatal Neonatal Network.

Consanguineous marriage is the union of individuals

having a common ancestor. This type of marriage has been
and still is a common cultural practice in Middle Eastern
countries, with cousin marriages being particularly frequent
among Muslim Arabs (14). In the above societies, it is
believed that consanguineous marriages would preserve
family dynamics and structure and provide social, economic,
and cultural benefits (5). Parental consanguinity is known to
increase the risk of autosomal recessive conditions through
the expression of recessive deleterious alleles, especially in
the offspring of first-degree cousins. It is a recognized risk
factor for several pediatric disorders including stillbirths and
perinatal mortality (6, 7), congenital birth defects, malformations, and mental retardation (811). In addition, consanguinity has been associated with congenital heart disease

(12), blood diseases (hemophilia, -thalassemia) (13), deafness, cystic fibrosis (14), chronic renal failure (15), and
neonatal diabetes mellitus (16).
Apnea of prematurity is a common problem in the neonatal
intensive care setting that affects premature infants (those
born before 37 weeks of gestation). It is defined as either the
cessation of breathing for longer than 20 seconds or that of
any duration if accompanied by cyanosis and sinus bradycardia (17, 18). Apnea of prematurity occurs in the absence
of an identifiable predisposing disease. Its incidence is
inversely correlated with gestational age and birth weight.
Apnea of prematurity has been linked to immaturity of the
respiratory and central nervous systems, whereby the central
respiratory center appears to have an altered response to
hypoxemia and hypercapnia (19). In addition to the above

Correspondence to Dr. Hala Tamim, Department of Epidemiology and Population Health, American University of Beirut, P.O. Box 11-236, Riad
El Solh, Beirut 1107 2020, Lebanon (e-mail: ht02@aub.edu.lb).

942

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Consanguinity, marriage between relatives, has been associated with perinatal mortality and morbidity. Apnea
of prematurity is defined as the cessation of breathing for longer than 20 seconds or that of any duration if
accompanied by cyanosis and sinus bradycardia, for infants born before 37 weeks of gestation. The objective of
the study was to examine the association between consanguinity and apnea of prematurity in Greater Beirut, an
area having a relatively high prevalence rate of consanguineous marriages. The study was cross-sectional.
Between September 1, 1998, and March 31, 2001, 21,723 newborn infants were admitted to the National
Collaborative Perinatal Neonatal Network in Greater Beirut, Lebanon. The inclusion criteria were infants less than
37 weeks of gestation who were admitted to the intensive care unit, with no congenital malformations, sepsis, or
neurologic disorders. Analysis was based on 597 infants of whom 66 had apnea of prematurity. With adjustment
for weeks and type of gestation, pregnancy complications, and Apgar score, the odds ratio of apnea of
prematurity for first-degree consanguineous parents as compared with other marriages was 2.9 (95% confidence
interval: 1.3, 6.4). In addition to the recognized etiologic factors for apnea of prematurity, this study suggests a
role played by genetic factors.

Consanguinity and Apnea of Prematurity 943

TABLE 1. Association between maternal demographic and pregnancy characteristics and apnea of
prematurity, National Collaborative Perinatal Neonatal Network, September 1998March 2001
Apnea of prematurity
Yes

No

No.

No.

66

11.1

531

88.9

Yes

11

16.7

45

8.5

No

55

83.3

486

91.5

Total

Odds
ratio

95% confidence
interval

2.16

1.06, 4.42

First-degree consanguinity

Mothers age (years)

<19

1.7

1.0

1934

43

71.7

357

72.4

1.66
1

0.19, 14.55

>34

16

26.7

131

26.6

1.01

0.55, 1.86

Mothers education
Illiterate or primary

11.5

65

13.9

1.16

0.44, 3.09

Intermediate or secondary

30

57.7

203

43.3

1.86

0.98, 3.51

Technical or university

16

30.8

201

42.9

Working

17.0

130

27.6

0.53

44

83.0

341

72.4

Smoker

10

20.0

96

20.1

0.99

Nonsmoker

40

80.0

382

79.9

16

35.6

148

38.1

4.4

33

8.5

0.56

0.12, 2.56

Skilled, unskilled, services

16

35.6

139

35.8

1.06

0.51, 2.21

Nonclassified, unemployed

11

24.4

68

17.5

1.49

0.66, 3.39

Moslem

44

77.2

370

79.1

0.89

0.46, 1.73

Christian or other

13

22.8

98

20.9

Single

31

47.7

299

60.6

Multiple

34

52.3

194

39.4

1.70

1.01, 2.84

Yes

36

54.5

221

41.6

1.68

1.01, 2.82

No

30

45.5

310

58.4

Male

34

51.5

272

52.9

0.95

Female

32

48.5

242

47.1

<1,000

7.6

20

3.8

6.61

2.09, 20.89

1,0001,249

7.6

1.7

14.69

4.22, 51.19

1,2501,499

16

24.2

55

10.4

7.69

3.39, 17.47

1,5001,749

17

25.8

65

12.3

6.92

3.09, 15.47

1,7501,999

12

18.2

88

16.7

3.61

1.54, 8.46

2,000

11

16.6

291

55.1

30

18

27.3

45

8.5

9.26

4.31, 19.89

3133

34

51.5

162

30.5

4.86

2.53, 9.31

3436

14

21.2

324

61.0

Not working

0.25, 1.13

Mothers smoking status

0.48, 2.06

Fathers occupation
Professional, managerial
Clerical, technical

Religion

Gestation

Complications during pregnancy

Gender
0.57, 1.58

Birth weight (g)

Gestational age (weeks)

5-minute Apgar score

<7

16.1

36

7.7

47

83.9

430

92.3

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2.29
1

1.04, 5.04

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Mothers work status

944 Tamim et al.

causes, neurologic stimulation of the primary muscles of

respiration, the diaphragm and the intercostals, may be inadequate, adding to the poor compliance of the chest wall in
premature infants (20).
The aim of this study was to examine the association
between consanguinity and apnea of prematurity among
infants born in Greater Beirut, Lebanon, a country with a
relatively high prevalence of consanguineous marriages.
MATERIALS AND METHODS

Odds
ratio

95% confidence
interval

2.89

1.30, 6.43

30

6.33

2.62, 15.31

3133

4.53

2.26, 9.08

3436

Variables

Model I: all infants

First-degree consanguinity
Gestational age (weeks)

Complications during pregnancy

1.37

0.75, 2.49

Multiple gestation

1.41

0.78, 2.55

5-minute Apgar score of <7

0.49

0.21, 1.18

1.91

0.61, 6.01

30

10.14

2.84, 36.21

3133

5.90

2.14, 16.27

3436

Model II: single gestations

First-degree consanguinity
Gestational age (weeks)

Complications during pregnancy

1.31

0.57, 3.01

5-minute Apgar score of <7

0.39

0.12, 1.29

4.41

1.38, 14.05

30

3.92

1.13, 13.60

3133

3.67

1.37, 9.79

3436

Model III: multiple gestations

First-degree consanguinity
Gestational age (weeks)

Complications during pregnancy

1.53

0.64, 3.67

5-minute Apgar score of <7

0.67

0.17, 2.69

RESULTS

Between September 1, 1998, and March 31, 2001, a total

of 21,723 consecutive newborn infants were delivered and
admitted to the NCPNN. The proportion of consanguineous
parents in the overall sample was 12.8 percent (6.7 percent
first-degree cousin marriages). The inclusion criteria
discussed in Materials and Methods were satisfied for 857
infants of the total of 21,723 infants, of whom 78 had apnea
of prematurity. The analysis was based on 597 infants with
complete information on consanguinity, 66 of whom had
apnea of prematurity.
Table 1 shows the association between each maternal
sociodemographic factor or pregnancy-related characteristic
and apnea of prematurity. Variables that were significant
risk factors for apnea of prematurity in the bivariate analysis
were first-degree consanguinity (odds ratio = 2.16, 95
percent confidence interval: 1.06, 4.42), multiple gestation
(odds ratio = 1.70, 95 percent confidence interval: 1.01,
2.84), presence of complications during pregnancy (odds
ratio = 1.68, 95 percent confidence interval: 1.01, 2.82), and
5-minute Apgar score of less than 7 (odds ratio = 2.29, 95
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Subjects for the present study were chosen from the

National Collaborative Perinatal Neonatal Network
(NCPNN). The NCPNN, first initiated in September 1998, is
a voluntary collaboration of health professionals from 10
major tertiary care centers located in Greater Beirut,
Lebanon. The Network prospectively collects data on all
newborns delivered at the participating hospitals, with the
objective of establishing a model for a national, perinatalneonatal database. Information on the maternal and neonatal
characteristics is obtained from obstetric and nursery records
and through direct interviews with the mothers before
hospital discharge. The questionnaires are completed by
trained personnel and are subjected to continuous monitoring by the NCPNN team for quality control.
Inclusion criteria for the present study were as follows:
infants less than 37 weeks of gestation, admitted to the intensive care unit, and having no congenital malformations,
sepsis, neurologic disorders, or metabolic and electrolytic
disturbances such as hypoglycemia, hypocalcemia, or hypomagnesemia.
Consanguinity was categorized into two levels: firstdegree cousin marriages versus nonconsanguineous and
distantly related marriages. The neonatal characteristics
considered were type of gestation, gender, birth weight,
gestational age, and Apgar score, whereas the maternal characteristics considered were religion, age at delivery, education, work status, spouses occupation, cigarette smoking
during pregnancy, and pregnancy-related complications
including hypertension, diabetes, maternal bleeding, and
fetal distress. Birth weight, in grams, was measured upon
admission to the nursery. Gestational age was calculated in
completed weeks using all the data available in the prenatal
record, including the last menstrual period and ultrasonographic and physical examinations of the newborn infants.
To assess the relation between baseline characteristics and
apnea of prematurity, we calculated odds ratios and 95
percent confidence intervals. Variables significantly associated with apnea of prematurity were included in a logistic
regression model to determine the independent effect of
consanguinity on apnea of prematurity. In addition, the association between consanguinity and the different sociodemographic and health behavioral characteristics was examined
using a chi-square test statistic. Two-tailed p values were
calculated, and significance was set at 0.05. Statistical data
analyses were conducted using SPSS for Windows software
(21).

TABLE 2. Logistic regression analysis of the main predictors

of apnea of prematurity, National Collaborative Perinatal
Neonatal Network, September 1998March 2001

Consanguinity and Apnea of Prematurity 945

DISCUSSION

Consanguineous marriages have been recognized as a risk

factor for several pediatric disorders. Therefore, studying the
role of consanguinity in the pathogenesis of various neonatal
diseases is of importance. To our knowledge, this is the first
study that looked into the association between consanguinity
and apnea of prematurity. The results of the present study
reveal that there is a significantly higher proportion of firstdegree mating for infants with apnea of prematurity
compared with those with no apnea of prematurity. This
increased proportion may suggest an important role for
consanguinity in the causation of apnea of prematurity in our
study population. The calculated attributable risk was 7.3
percent (22).
In the population under study, parental consanguinity is
not a condition that would necessitate careful observation.
Therefore, no systematic inquiry is expected about consanguinity status on the part of nursery staff in the selected
hospitals. This lack of knowledge concerning the degree of
parental relation will tend to minimize any detection bias
related to the differential monitoring of children of consanguineous marriages versus their nonconsanguineous counterparts.
In Lebanon, a recent calculation of the prevalence of
consanguineous marriages is lacking. However, studies in
Beirut have shown that there has been a trend of decline in
the incidence of consanguineous marriages in general, from
37.4 percent before 1940 to 18 percent in 1983, with firstAm J Epidemiol 2003;158:942946

TABLE 3. Distribution of consanguinity among different

demographic, socioeconomic, and health characteristics of
parents, National Collaborative Perinatal Neonatal Network,
September 1998March 2001
First-degree consanguinity
Yes

p
value*

No

No.

No.

45

12.9

304

87.1

2.1

94

97.9

Religion
Moslem
Christian or other

0.002

Mothers age (years)

<19

16.7

83.3

1934

39

9.9

361

90.3

>34

15

10.2

132

89.9

0.85

Illiterate or primary

17

23.9

54

76.1

<0.001

Intermediate or
secondary

27

11.6

206

88.4

3.2

210

96.8

Mothers education

Technical or university
Mothers work status
Working

5.0

132

95

44

11.4

341

88.6

Smoker

15

14.2

91

85.8

Nonsmoker

36

8.5

386

91.5

0.080

Professional,
managerial

3.0

159

97.0

<0.001

Clerical, technical

25.7

26

74.3

Skilled, unskilled,
services

19

12.3

136

87.7

10.1

71

89.9

Yes

24

9.3

233

90.7

No

32

9.4

308

90.6

<1,000

12.0

22

88.0

1,0001,249

21.4

11

78.6

Not working

0.029

Mothers smoking status

Fathers occupation

Nonclassified,
unemployed
Complications during
pregnancy

0.98

Birth weight (g)

1,2501,499

7.0

66

93.0

1,5001,749

10

12.2

72

87.8

1,7501,999

10

10.0

90

90.0

2,000

25

8.3

277

91.7

30

10

15.8

53

84.2

3133

19

9.7

177

90.3

3436

27

7.9

311

92.1

<7

15.6

38

84.4

40

8.4

437

91.6

0.51

Gestational age (weeks)

0.14

5-minute Apgar score

* p value of the chi-square test statistic.

Row percent.

0.11

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percent confidence interval: 1.04, 5.04). A decrease in birth

weight or gestational age increased significantly the odds of
having apnea of prematurity (p < 0.05).
Table 2 shows the results of the logistic regression model
with the dependent variable being apnea of prematurity. The
variables significant with apnea of prematurity in the
bivariate analysis (consanguinity, weeks of gestation,
maternal complications during pregnancy, type of gestation,
and 5-minute Apgar score) were included in the model as
independent variables. Birth weight was not included in the
model because of its correlation with gestational age
(Pearsons correlation coefficient = 0.6). With adjustment
for all of the variables, the odds of having apnea of prematurity among first-cousin marriages were 2.9 times higher than
those for the other marriages (95 percent confidence interval:
1.3, 6.4). With stratification by single versus multiple gestation, the odds ratio for the association between consanguinity and apnea of prematurity increased from 1.91 (95
percent confidence interval: 0.61, 6.01) among single births
to 4.41 (95 percent confidence interval: 1.38, 14.05) among
multiple gestations.
Table 3 shows the relation of first-degree consanguinity
with parental sociodemographic and pregnancy-related characteristics. First-degree consanguinity was significantly
higher (p = 0.002) among Moslems compared with Christians (13 percent vs. 2 percent, respectively). Moreover, it
was strongly and inversely associated (p < 0.05) with
maternal education and was significantly more prevalent
among nonworking mothers as well as among fathers
holding technical or clerical jobs.

946 Tamim et al.

ACKNOWLEDGMENTS

The authors acknowledge the following NCPNN investigators and institutions (in alphabetical order): Dr. Alia Aaraj
(Rassoul Aazam Hospital), Dr. Mona Alameh (Sahel
General Hospital), Dr. Philip Chedid (Lebanese University),
Dr. Imad Chokr (Middle East Hospital), Dr. Mohammad
Itani (Najjar Hospital), Dr. Mustafa Khogali (American
University of Beirut), Dr. Imad Melki (Hotel Dieu de France
Hospital), Dr. Fadlallah Nassif (St. Charles Hospital), Dr.
Yolla Nassif (St. Georges Hospital), Dr. Mariam Rajab
(Makassed General Hospital), Dr. Hala Tamim (American
University of Beirut), Dr. Gerard Wakim (Rizk Hospital),
and Dr. Khalid Yunis (American University of Beirut
Medical Center).

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cousin marriages constituting 6070 percent of all consanguineous marriages (4, 23, 24). Based on the NCPNN data
from September 1998 to March 2001, the overall proportion
of consanguineous marriages was 12.8 percent, with 6.7
percent being first-cousin marriages. This estimate is relatively lower than the rates reported for Egypt (2950
percent) (25), Turkey (2025 percent) (26), Jordan (32
percent) (27), Kuwait (54 percent) (28), and the United Arab
Emirates (51 percent) (29).
The results of the study show an uneven distribution of
first-cousin consanguineous marriages compared with
several factors including religion and social status (4, 27,
29). Consistent with other studies, this study shows that
Muslims had a significantly higher first-cousin consanguinity rate when compared with Christians (4). Moreover,
in this study, maternal education and paternal occupation
were negatively correlated with consanguineous mating, a
finding that is consistent with previously reported associations between paternal education and occupational and
social status and consanguineous mating (5, 24).
Consanguinity is known to concentrate autosomal recessive genes in the offspring, but the contribution of these
genes to apnea of prematurity has not been studied before.
Our study suggests a role played by the genetic factors in our
study population, in addition to the already recognized etiologic factors for apnea. In conclusion, there is an urgent need
to inform the public properly about the anticipated deleterious effects of inbreeding in societies where intermarriage is
widely practiced. Furthermore, more etiologic studies that
look into the association of consanguinity and apnea of
prematurity are needed to support this finding and clarify the
significance of such an association.