Maternal and Child Health Journal

, Volume 14, Issue 2, pp 283–289

Consanguinity and Adverse Pregnancy Outcomes: The North of Jordan Experience

Authors

    • Department of Obstetrics and GynecologyJordan University of Science and Technology
  • Yousef S. Khader
    • Department of Community Medicine and Public HealthJordan University of Science and Technology
  • Zouhair O. Amarin
    • Department of Obstetrics and GynecologyJordan University of Science and Technology
  • Mohammad Kassawneh
    • Department of PediatricsJordan University of Science and Technology
  • Mousa Al Omari
    • Department of Community Medicine and Public HealthJordan University of Science and Technology
Article

DOI: 10.1007/s10995-008-0426-1

Cite this article as:
Obeidat, B.R., Khader, Y.S., Amarin, Z.O. et al. Matern Child Health J (2010) 14: 283. doi:10.1007/s10995-008-0426-1
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Abstract

This cross-sectional study was carried out to assess the association between consanguineous marriages and adverse pregnancy outcome in the north of Jordan. Women delivered in four major hospitals in the north of Jordan between April 2007 and May 2007 were included in the study. Non-Jordanian women and women with multiple pregnancies were excluded. Mothers answered a pilot-tested structured questionnaire administered by trained personnel in the maternity ward. Data regarding pregnancy outcomes were obtained from the patients’ individual records. A total of 3,269 women with a mean age of 27.2 (SD 6.6) years were included. About 49% of women had consanguineous marriages. Consanguineous marriages were significantly associated with low birth weight delivery (13.9% vs. 10.1%), preterm delivery (19.9% vs. 12.3%), and births with congenital anomalies (4.1% vs. 0.8%) compared with non-consanguineous marriages. In the multivariate analysis, consanguinity was significantly associated with preterm delivery (OR = 1.5, 95% CI 1.2, 1.9), and congenital malformations (OR = 6.5, 95% CI 2.8, 15.3). In conclusions, this study supports the association between consanguinity and some adverse pregnancy outcomes.

Keywords

ConsanguinityPregnancyStillbirthPreterm delivery

Introduction

About one-fifth of the human population around the world lives in communities with a preference for consanguineous marriage and at least 8.5% of children have consanguineous parents [1]. Consanguineous marriage refers to union of individuals having a common ancestor or marriage between a man and woman related by blood [2, 3]. The most common form of consanguineous union contracted is between first cousins [4]. Such marriages have been a common feature of Arab and some Muslim countries for thousands of years [5]. The distribution and percentage of consanguinity among these countries are different. In Jordan, consanguineous marriages are widespread and comprise one third to one half of all marriages, with first cousin marriage rates in the range of 20–30% [6, 7].

Marriage between relatives has been associated with adverse child health outcomes [8]. Parental consanguinity increases the autosomal recessive conditions through the expression of recessive deleterious alleles, especially in the offspring of first degree cousins [913]. Many of these marriages have been associated with increased risk of adverse perinatal outcomes including stillbirths [1416], low birth weight (LBW) [8, 17], preterm delivery [18], apnea of prematurity [3], abortion [19], infant and child mortality [2023], congenital birth defects and malformations [24]. The literature consistently shows an increased risk of congenital anomalies associated with consanguineous marriages. However, there is a mixed effect on other adverse pregnancy outcomes. Most of these reports have small sample size, lack enough power and are inconsistent in the definition of the cases.

The objective of this study was to assess the association between consanguineous marriages and adverse pregnancy outcomes including stillbirths, low birth weight, preterm deliveries, and congenital malformations in the north of Jordan.

Methods

Participants

This cross-sectional study was carried out at the main four hospitals in the north of Jordan, namely Princess Bade’ah hospital, Jarash hospital, Al-Eman hospital, and Al-Ramtha hospital. Women who delivered in these hospitals between the 1st of April 2007 and 31st of May 2007 were included in the study. The sample size was calculated using a level of significance of 0.05 and power of 80%. The expected incidence of any congenital anomalies of 2% was used in sample size calculation. The estimated sample size using the null hypothesis value of 3% was 2,042. A larger sample was intended to increase the power of the study and to detect a very small incidence of adverse pregnancy outcomes. All participants agreed to participate and gave informed consent at the time of data collection. Jordanian women, defined by their surnames and their national identity numbers (recorded on medical charts), were included in this study to create a homogenous sample. Non-Jordanian women and women with multiple pregnancies were excluded. An ethical approval was obtained from the Institutional Review Board.

Data Collection

Within 24 h of delivery, mothers answered a pilot-tested structured questionnaire administered by trained personnel on the maternity ward. The questionnaire consisted of 70 questions concerning mother’s age, education, employment, total family income, residency in rural or urban areas, active and passive smoking during pregnancy, blood group, consanguinity with the partner, coffee and tea consumption, history of preterm birth delivery, low birth weight delivery, pre-eclampsia, caesarian delivery, planning for and acceptance of pregnancy, self-reported emotional status during pregnancy, regular use of medication, history of urinary tract infections or candidal vaginosis during pregnancy, inter-pregnancy interval, parity, gravidity, number of prenatal care visits, onset of prenatal care, and previous miscarriages. Information regarding family history of preterm birth and LBW was documented using yes or no responses.

Additional information was extracted from the records including chronic illnesses, medical complications during pregnancy including diabetes (pre-existing and gestational), hypertension, and anemia. Prepregnancy height (cm) and weight (Kg) were self- reported and documented on the records. Several studies have reported that recalled pre-pregnancy weight reflects actual weight in women [25, 26]. Women’s weight prior to the delivery was obtained from the records. Information on pregnancy complications, pregnancy and neonatal outcomes was collected by the nurses and midwives who took care of delivery and neonatal care. Birth weight, outcome of pregnancy (live or stillbirth), gender and gestational age at birth were obtained from obstetric records.

Definition of Variables

Consanguinity refers to a marriage between a man and woman related by blood, and is divided into first cousins, second cousins or distant relatives. Maternal prepregnancy body mass index was calculated as weight (kg) divided by height (m2). Age was defined as the age of mother in completed years at the time of delivery. Estimated gestational age was calculated as the interval between the date of delivery and the date of recalled last normal menstrual period. When there were uncertainties about patients’ menstrual history, gestational age was determined using their first trimester ultrasound scan results, and if the two were not in correspondence, gestational age was determined by the results of the ultrasound. Parity was categorized as: no previous pregnancies, one or two previous pregnancies, and three or more previous pregnancies.

Birth outcomes of interest in this study were spontaneous preterm delivery (live infant delivered at <37 weeks’ gestation with no medical indication) and LBW (live infant delivered at >37 weeks’ gestation and weighting <2500 g at birth). Stillbirth was defined as delivery of a baby after 24 weeks of gestation with no signs of life. Congenital malformations included any minor or major abnormality in structure or function of any organ, and were confirmed by the attending neonatologists and the appropriate investigations if needed. The mode of delivery was recorded as spontaneous, instrumental or caesarean section. The admission rate to the neonatal intensive care unit (NICU) was recorded as infants requiring more than 24 h surveillance.

Methods of Analysis

The Statistical Package for Social Sciences software (SPSS, version 15) was used for data processing and data analysis. Participants’ socio-demographic and obstetric characteristics were described using frequency distribution. Chi-square test was used to compare percentages of women with adverse pregnancy outcomes according to socio-demographic and obstetric variables. Crude and adjusted odds ratios and their 95% confidence intervals were calculated. The significance of the associations between consanguinity and adverse pregnancy outcomes were adjusted for possible predictors using binary logistic regression. Factors that were significantly associated with each selected outcome in the univariate analysis were entered in the regression equation. A variable was entered into the model if the probability of its score statistic was less than the entry value of 0.05, and was removed if the probability was greater than the removal value of 0.1. All variables that remained significant in the multivariate analysis constituted the reference model. Consanguinity was assessed by what it added to the equation of the reference model at its point of entry. This was repeated for each outcome variable. A P-value of less than 0.05 was considered statistically significant.

Results

Participants’ Characteristics

A total of 3,269 women (14–49 years) with a mean age of 27.2 (SD 6.6) years were included. About 49% of women had consanguineous marriages. Their socio-demographic, obstetric and other relevant characteristics are shown in Table 1.
Table 1

Participants’ socio-demographic and obstetric characteristics

Variable

N (%)

Age (year)

    ≥40

161 (4.9)

    35–39

318 (9.7)

    21–34

2449 (74.9)

    <20

341 (10.4)

Income (JD)

    <200

1532 (46.9)

    ≥200

1737 (53.1)

Employment

    Employed

508 (15.5)

    Unemployed

2761 (84.5)

Residency

    City

1866 (57.1)

    Village

1403 (42.9)

Education Level

    High school or less

1918 (58.7)

    More than high school

1351 (41.3)

Consanguinity

    Yes

1603 (49.0)

    No

1666 (51.0)

Smoking

365 (11.2)

Gravidity

    1

1117 (34.2)

    2–3

966 (29.6)

    >3

1186 (36.3)

Parity

    0

935 (28.6)

    1–2

1149 (35.1)

    >2

1185 (36.2)

Onset of 1st antenatal visit

    1st trimester

1852 (65.7)

    2nd trimester

1258 (38.5)

    3rd trimester

159 (4.9)

Medical problems during pregnancy

370 (11.3)

Adverse Pregnancy Outcomes

Of the total 3,269 pregnant women, 16% delivered preterm (27% were medically indicated and the remaining were spontaneous), 11.9% gave birth to a low birth weight baby, 24.3% delivered by Caesarean section, and 11.9% had complications during delivery. There were 60 cases of congenital anomalies and these were mainly congenital heart defects, skeletal deformities or syndromic patterns, and were mostly autosomal recessive patterns. Of the total births (51.7% boys and 48.3% girls), 11.7% were admitted to NICU, 4.5% needed treatment by antibiotics and 0.3% underwent surgical interventions (Table 2). The distribution of selected common adverse pregnancy outcomes including stillbirths, low birth weight, preterm delivery, and congenital malformations according to socio-demographic, obstetric, and relevant characteristics are shown in Table 3.
Table 2

Pregnancy outcomes of 3,269 women in the north of Jordan

Variable

N (%)

Gender

    Male

1546 (51.7)

    Female

1147 (48.3)

Preterm delivery

524 (16.0)

Low birth weight delivery

365 (11.9)

Infant admission to neonatal intensive care unit

292 (11.7)

Treatment by antibiotics

112 (4.5)

Surgical intervention

8 (0.3)

Mode of delivery

    Normal

2449 (74.9)

    Caesarian section

795 (24.3)

    Vacuum or forceps

25 (0.8)

Fetal presentation

    Cephalic

3024 (92.5)

    Breech

217 (6.6)

    Other

28 (0.8)

Any complication during delivery

357 (11.9)

Congenital anomalies

60 (1.8)

Stillbirths

41 (1.3)

Table 3

Adverse pregnancy outcomes according to socio-demographic and obstetric characteristic

Variable

Stillbirths

LBW

Preterm delivery

Congenital malformations

Age (year)

    ≥40

4 (3.1)*

22 (17.3)

54 (33.5)*

24 (27.9)*

    35–39

8 (2.9)

24 (8.7)

68 (21.4)

7 (3)

    21–34

28 (1.2)

247 (12)

332 (13.6)

26 (1.3)

    <20

1 (0.3)

36 (11.9)

70 (20.5)

3 (1.2)

BMI

    <18.5

0 (0)

8 (29.6)*

11 (28.9)

0 (0.0)

    18.5–24.99

11 (1.5)

73 (9.9)

127 (15.4)

0 (0.0)

    ≥25

21 (1.5)

174 (12.1)

235 (15.2)

32 (2.7)

    ≥30

9 (1.1)

101 (12.8)

151 (17.7)

28 (4.1)*

Income (JD)

    <200

8 (0.6)*

137 (9.8)*

228 (14.9)

12 (1)*

    ≥200

33 (2.1)

219 (13.7)

296 (17)

48 (3.8)

Employment

    Employed

7 (1.6)

47 (10.6)

122 (24)*

10 (26)

    Unemployed

34 (1.3)

309 (12.1)

402 (14.6)

50 (2.3)

Residence area

    City

20 (1.2)

233 (13.6)*

303 (16.2)

38 (2.6)

    Village

21 (1.6)

123 (9.7)

221 (15.8)

22 (2.1)

Education level

    <high school

24 (3)

108 (11.7)*

153 (15.3)*

24 (3)*

    high school

8 (1)

81 (9.3)

103 (11.2)

8 (1)

    >high school

23 (1.9)

167 (13.9)

268 (19.8)

28 (3)

Consanguinity

    Yes

23 (1.6)

198 (13.9)*

319 (19.9)*

49 (4.1)*

    No

18 (1.1)

158 (10.1)

205 (12.3)

11 (0.8)

Smoking

    Yes

2 (0.6)

88 (27.3)*

89 (24.4)*

11 (4)

    No

39 (1.5)

268 (10)

435 (15)

49 (2.2)

Gravidity

    1

8 (0.8)

142 (13.4)

161 (14.4)*

21 (2.5)*

    2 or 3

16 (1.8)

93 (10.3)

133 (13.8)

4 (0.5)

    >3

17 (1.7)

121 (11.8)

230 (19.4)

35 (4.0)

Parity

    0

8 (0.9)

126 (14.4)*

157 (16.8)

23 (3.3)*

    1 or 2

11 (1)

98 (9.3)

174 (15.1)

4 (0.4)

    >2

22 (2.1)

132 (12.4)

193 (16.3)

33 (3.6)

Medical problems

    Yes

7 (2.3)

54 (17.5)*

99 (26.8)*

11 (4.1)

    No

34 (1.3)

302 (11.2)

425 (14.7)

49 (2.2)

P-value < 0.05; LBW, low birth weight

Consanguinity and Adverse Pregnancy Outcomes

Low birth weight delivery (13.9% vs. 10.1%), preterm delivery (19.9% vs. 12.3%), and births with congenital anomalies (4.1% vs. 0.8%) were significantly more prevalent among consanguineous marriages compared with non-consanguineous marriages. Further analysis of adverse pregnancy outcomes according to the degree of consanguinity (first or second cousins and distant relatives) showed no significant difference among various degrees of consanguinity and therefore consanguineous marriages were pooled together.

In the multivariate analysis, consanguinity was significantly associated with preterm delivery and congenital malformations (Table 4). After adjusting for age, body mass index, occupation, education, smoking, gravidity, parity, medical problems during pregnancy, and family history of premature deliveries, consanguinity was significantly associated with preterm delivery (OR = 1.5, 95% CI 1.2,1.9). The odds ratio for congenital anomalies at birth after adjusting for age, height, parity, medical problems during pregnancy, family history of low birth weight and onset of 1st antenatal visit for consanguineous marriages was 6.5 (95% CI 2.8, 15.3) compared with non-consanguineous marriages.
Table 4

Multivariate analysis of the association between consanguinity and adverse pregnancy outcome

Adverse pregnancy outcomes (dependent variables)

Univariate

Multivariate

OR (95% CI)e

P-value

OR (95% CI)

P-value

Stillbirthsa

1.4 (0.8, 2.6)

0.272

1.2 (0.6, 2.3)

0.635

Low birth weightb

1.4 (1.2, 1.8)

0.001

1.1 (0.9, 1.4)

0.407

Preterm deliveryc

1.8 (1.5, 2.1)

<0.001

1.5 (1.2, 1.9)

0.001

Congenital malformationsd

5.1 (2.7, 9.9)

<0.001

6.5 (2.8, 15.3)

<0.001

aAdjusted for age, BMI, income, family history of low birth weight, congenital anomalies, and medical problems during pregnancy

bAdjusted for age, BMI, income, residency, smoking, parity, family history of low birth weight, preterm delivery, congenital anomalies and medical problems during pregnancy

cAdjusted for age, BMI, occupation, education, smoking, gravidity, parity, congenital anomalies, medical problems during pregnancy, and family history of premature babies

dAdjusted for age, BMI, parity, medical problems during pregnancy, family history of low birth weight and onset of 1st antenatal visit

eOR, odds ratio

CI, confidence interval

Discussion

The rate of consanguineous marriage in this study was 49%. This is similar to that reported in previous studies from Jordan and most Arab and Muslim countries [57]. This reflects no change in habitations in spite of modernization.

The results of this study confirmed a significant association between consanguinity and congenital malformation (OR = 6.5). This finding is in agreement with the findings of other studies [10, 27]. Shafi et al. found that there was a significant association between children born of consanguineous marriages and the risk of associated malformations (P = 0.001). Consanguinity was present in 74% of children with associated anomalies as compared to 40% of children with no associated anomalies [27]. In another study, Yunis et al. [10] reported that consanguinity remained significantly associated with an increased risk of congenital heart disease (CHD) after controlling for confounders. Babies born to first cousin marriages had more than twice the risk of CHD diagnosed at birth as compared to those born to unrelated parents. Those born to distant relatives had 1.8 times higher risk.

In our study, preterm delivery was significantly associated with consanguineous marriages too. This finding is supported by the finding reported by Al-Eissa and Ba′Aqeel [18]. Awareness of such a risk factor is essential in planning public education programs and in considering appropriate care options for women at a potentially higher risk for preterm delivery [19].

We found no association between low birth weight delivery and consanguinity. This finding disagrees with other reports in the literature. Mumtaz et al. found that consanguinity was associated with a decrease in birth weight for gestational age by 1.8%. They reported that the largest effect on fetal growth was seen with lower parity and smoking during pregnancy [8]. Jaber et al. [17] compared babies of consanguineous and non-consanguineous marriages and found no differences in their anthropometric features, except for a lower birth weight in the consanguineous group.

There was no evidence to support the association between stillbirth and consanguinity. This finding disagrees with other studies. In one study from Jordan [14], Koury and Massad showed that consanguineous marriages produced a significantly higher number of stillbirths, and that prematurity was not affected by consanguinity. However, in their study, they included patients with twin pregnancies, and this may explain the differences with our results. Kulkarni et al. [28] found that stillbirth and congenital malformation rates were significantly higher in offspring born to mothers of consanguineous than non-consanguineous marriages, while Nath et al. [29] revealed no significant effect of consanguinity on the number of stillbirths. In the latter study the sample size was not sufficiently large to study the effect of consanguinity on the stillbirth rate.

One of the limitations of this study is the fact that some of the variables were self reported by the participants and could not be validated. Another possible explanation for our results (especially low birth weight) could be residual confounding effect although it has been adjusted for all possible factors.

In conclusion, this study supports the association between consanguinity and some adverse pregnancy outcomes. This study has shown that consanguineous marriage is an important social and health problem which should be addressed by an intensive health education campaign, particularly in areas with high rates of consanguineous marriage. Furthermore, awareness of the risks of consanguineous marriages in pregnancy may greatly help care providers to counsel patients properly and to plan their care effectively in order to reduce or prevent these adverse pregnancy outcomes.

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© Springer Science+Business Media, LLC 2008