Abstract

Extensive data shows a direct link between low-level lead exposure during early development and deficits in neurobehavioral-cognitive performance evident late in childhood through adolescence. Our previous studies confirmed the transfer of lead from the mother to the fetus as well as the effect of low lead exposure on neuropsychological behavior in school children. Such results led us to design a longitudinal survey to evaluate the effect of prenatal and/or postnatal lead exposure on early cognitive development among selected group of children from birth to 2 years of age. During the first stage of this study (between March and July 2004), we measured lead levels in 653 umbilical cord blood samples taken from healthy Saudi mothers delivering at King Khalid Hospital, Al-Kharj. This gave a good opportunity to look at the prevalence of increased blood lead levels in umbilical cord blood and to identify risk factors for prenatal lead exposure. The mean cord lead levels were 2.21 ± 1.691 µg/dl in the range of 0.284–17.276 µg/dl. Only 1.23% of the newborns had blood lead levels >10 µg/dl, the Center for Disease Control level of concern. To investigate risk factors affecting cord blood lead levels, only subjects with lead levels above the 75th percentile (2.475 µg/dl) were selected in the multiple regression models. We observed that cord blood lead levels were significantly influenced by maternal age, the location of residence and intake of prenatal supplements. Controlling for newborn's head circumferences confounders, it was found that cord blood lead levels were significantly and negatively associated with newborn's head circumference (β = −0.158, p = 0.036). The negative association was seen between intake of prenatal supplements and cord blood lead levels emphasizing the role of prenatal supplementations during pregnancy. The significant reductions in newborns, head circumferences due to lead exposure may have serious implications for their future performance and achievement. This study reveals that even at low prenatal lead exposure, all possible measures to inspect lead sources in our environment and reduce lead exposure should be taken.

Introduction

Pregnancy is a period of high susceptibility to the effects of lead for both the mother and the embryo or fetus. The reasons are that: First, lead exposure may result from endogenous sources such as lead in the maternal skeletal system or exogenous sources such as diet and the environment. More than 90% of lead is stored in the bone, while the reminder is found in the blood and soft tissues [1]. Lead in the bone is not inert, however, it may become bioavailable when the bone tissue undergoes mineralization and resorption during certain physiological processes such as pregnancy and lactation [2, 3]. The increase in maternal calcium requirement is accompanied by release of lead into blood circulation, which in turn, poses a significant fetal exposure to lead with health consequences such as low birth weight, pre-term birth and mental retardation [4–6]. High intake of calcium decreases bone lead mobilization [7]. Chaung et al. [8] suggested that measuring maternal bone and blood lead levels could be important tools to assess fetal lead exposure. It has been recommended that calcium intake during the latter half of pregnancy may prevent bone demineralization [9]. Second, pregnancy induces a physiological anemia, which in turn decreases iron levels, resulting in increased absorption of lead [10]. Third, lead crosses the placenta during pregnancy and has been associated with intrauterine death, prematurity and low birth weight [11]. Durska et al. [12] estimated the transplacental gradient for lead to be 78.5%. Many studies found good correlations between lead concentrations in maternal and cord blood that range from 0.41 to 0.88 [13–18]. We do know that lead is cumulative and it was found in the fetal brain as early as the end of the first trimester (13 weeks) [19], with a similar rate of increase in brain size and lead content throughout pregnancy. A number of recent studies have revealed that blood lead levels lower than 10 µg/dl, the Centre of Diease Control (CDC) level of concern [20] can be associated with growth and developmental delay in children exposed to lead in utero and/or during early childhood [21–24]. Based on results of many studies, Gilbert and Weiss [25] emphasized lowering CDC's level of concern from 10 µg/dl to 2 µg/dl in order to ensure that children are protected from the detrimental neurobehavioral effects of lead.

As in other developing countries, use of lead has increased in everyday life in Saudi Arabia, particularly over the last 20 years. The pollution of air, soil and water, which undoubtedly accompanies industrial developments, is one of the problems introduced by economic progress and industrialization. As a result, low-dose lead toxicity may be anticipated in the population. The traditional sources of lead described in the West include air, water, soil, paints and food [20]. Other unusual sources have been shown to participate in lead toxicity such as the use of Kohl and various traditional remedies [26]. Results from a previous study revealed high prevalence of lead exposure among Saudi children (23%) due to the use of traditional cosmetics and remedies [27]. A cross-sectional study was conducted to examine the relationship between lead exposure and adverse neurodevelopmental effects [28]. Neuropsychological and behavioral impairment was seen in the first and second grade Saudi school children at blood lead levels between 9.02 and 27.36 μg/dl. Such effect could be due to prenatal and/or postnatal exposure. Our earlier pilot study [29] clearly showed that Saudi newborn babies were prenataly exposed to lead. An excellent correlation (r = 0.83, p < 0.0001) between the maternal and the cord blood lead levels and a weak but significant relationship between maternal blood lead concentrations and birth weight of newborns were found (r = −0.27, p < 0.05). Considering possible consequences of prenatal and/or postnatal lead exposure on childhood mental development, we felt that there is a necessity to conduct further research in order to determine the magnitude of the effects of early lead exposure (i.e. prenatal) on cognitive development. A longitudinal epidemiological survey was designed to evaluate the effect of prenatal and postnatal lead exposure as measured by blood lead concentration on early cognitive development among selected group of children from birth to 2 years of age. Umbilical cord blood lead levels were used as an index of prenatal exposure. Repeated measures of blood lead levels and cognitive development scores as measured by Bayley Scales for Infant Development were then obtained every 6 months until 24 months of age. In this article, we looked at the prevalence of increased blood lead levels in umbilical cord blood and identified risk factors for prenatal lead exposure.

Materials and Methods

All Saudi pregnant women who attended King Khalid Hospital, Al-Kharj for newborn delivery between March and July 2004 were considered the source population of this study. A 10 ml umbilical cord blood was collected from total of 653 healthy mothers age 17–46 years. All mothers were resident of Al-Kharj area. Each participant signed an informed consent form. This research project was evaluated and approved by both the Research Basic Committee and the Research Ethic Committee of King Faisal Specialist Hospital and Research Centre. Information on estimated gestational age, based on date of last menstrual period, and characteristics of the birth and newborn were extracted from the medical records. Trained nurse took demographic, socio-economic, environmental and health information from each participant. Exclusion criteria included health condition such as Down's syndrome, retinoblastoma, cleft palate or a problem likely to require hospitalization beyond 3 weeks of age such as respiratory distress syndrome or gestational age less than 34 weeks.

Blood lead measurements

Umbilical cord blood samples were collected in vacutainer tubes containing 10.5 mg of K3-EDTA (tripotassium-ethylene diaminetetraacetic acid) as anticoagulant and stored at 4°C until analysis. All blood sample analyses were analyzed for lead using a Varian AA-280 Zeeman Atomic Absorption Spectrophotometer, coupled to GTA-120 (Varian Techtron PTY. Ltd, Australia). Lead analysis was performed at a wavelength of 283.3 nm with a 0.5 nm slit width and 10 mA lamp current. The gas flow was varied from 0 to 0.3 l min−1. The gas used was argon except in steps four and five where 0.1 l min−1 compressed air was introduced in order to facilitate ashing of the organic matrix. Background correction was used.

One volume of whole blood (usually 100 µl) was mixed with a two volumes of aqueous 2% (v/v) Triton X-100 solution in an Eppendrof microcentrifuge tube and vortexed for 30 s. Then centrifuged at 10 000 r.p.m. for 4 min. The clear supernatant was transferred to the vial. Total volume dispensed was 6 µl, which included 3 µl of NH4H2PO4 modifier (1% w/v). Quadruplicate determinations were made on all samples. Detection limit (DL) of lead in this study was 0.657 µg/dl.

Calibration standards were prepared daily using a manual standard addition procedure recommended by Brodie and Routh [30]. Fresh venous blood samples (obtained from the hospital blood bank) were divided into six equal portions. Known amounts of aqueous lead solution were added to these to give final concentrations in the range of 0.625–10.0 μg/dl for lead. There was a good linear relation between absorbance and standard concentration of lead up to 10.0 µg/dl with an overall correlation coefficient of 0.9993 ± 0.0007 for a total of 46 runs.

A quality assurance program was incorporated to check the accuracy of blood lead measurements and to evaluate the performance of the method. Two sets of blood controls with known lead concentrations determined by a reference laboratory were obtained from Kaulson Laboratories (CONTOX Heavy Metal Blood Control-A, W. Caldwell, NJ, USA) to verify the accuracy of the method. There was an excellent agreement between the experimental and the certified recommended values for both sets of blood controls. The values found for level I and II for 27 runs were 19.736 ± 3.338 and 44.006 ± 9.328 μg/dl, respectively, while the recommended values for lead were 14.0–22.0 and 39.0–51.0 μg/dl, respectively. The accuracy of the method was also determined by measuring the recovery of lead added to blood samples. These spiked blood samples were run 12 times with the test samples using the same analytical procedure. The analytical recovery of blood samples spiked with 5.0, 10.0 and 20.0 μg/dl lead were 102.413 ± 6.038, 96.488 ± 6.666 and 96.233 ± 7.86%, respectively. This was thought to be satisfactory.

Data management and statistical analysis

A Scientific Information Received (SIR), computer database application was developed for the entry of these data for all subjects. Values in the text are means ± SD. To obtain approximately gaussian distributions, we had logarithmic transformed the measurements of blood lead levels. The effects of various confounding variables on cord blood lead levels were tested using ANOVA, Student's t-test and Pearson's product–moment correlation matrix. Multiple linear regression models using backward procedure were constructed in order to identify potential predictors of the status of lead levels in cord blood after controlling for a number of confounding variables. Statistical parameters presented are β (standardized regression coefficient) and R2 (coefficient of multiple determination).

Variables can be either quantitative or qualitative. Dummy variables can take only certain fixed values, with no intermediate values in between. They were used to quantify the qualitative variable for regression analysis such as location of residence. Each dummy variable can take only the values 1 or 0. The location of residence reflects the district that our participants come from. Due to the limited sample size in some of the districts, we had to classify our participants into nine districts: Saudi, Khalidia, Delam, Faisalia, Nahda, Shana, Aziziah, Zahir and others. Others include districts with sample size less than 20. Location of residence was quantified by eight dummy variables. When we use dummy coding, one of the groups becomes the reference group and all of the other groups are compared to it. The lowest value category was used as a reference group.

All the analyses were performed using SPSS version 10.0 (Chicago, IL). A p < 0.05 was considered significant.

Results

The blood lead concentration in 653 cord blood samples was 2.210 ± 1.691 μg/dl in the range of 0.284–17.276 µg/dl. As shown in Fig. 1, the distribution of blood lead data is positively skewed (skewness = 4.506). Therefore, all measurements were subjected to log transformation to obtain an approximate normality of their distribution. The distribution of our participants by their location of residence is shown in Fig. 2. About 15.2% of the participants live in Saudi district, 13.2% in Khalidia, 7.8% in Delam, 5.7% from Faisalia, 5.2% in Nahda, 3.8% in Aziziah, 3.5% in Shana, 3.4% in Zahir and the remaining 42.3% in other districts of Al-Kharj. None of the mothers were induced. Of the newborns, three had respiratory distress and one had malfunction. None had jaundice and neonatal infection. The condition of umbilical cord was normal in 99.7% of the newborns. Only two newborns had prolapsed and knot umbilical cord. Clearly many factors may affect the levels of lead in the blood.

Fig. 1.

The distribution of 653 cord blood lead data.

Fig. 1.

The distribution of 653 cord blood lead data.

Fig. 2.

The cord blood lead levels (µg/dl) classified by the location of residence. Error bars show mean ± SD.

Fig. 2.

The cord blood lead levels (µg/dl) classified by the location of residence. Error bars show mean ± SD.

Table 1 shows the descriptive characteristics of the continuous variables. The mean age at delivery was 28.46 ± 6.020 years. Only one (0.15%) newborn had head circumference <30 cm, three (0.61%) were small (birth weight ≤2 kg), one (0.15%) were very small (birth weight <1.5 kg) and eight (1.23%) had cord blood lead above the blood lead threshold health concern ≥10 µg/dl that was defined by the CDC (1990). The Pearson correlation coefficients (r) between log-transformed cord blood lead levels and a number of continuous variables such as maternal age, parity, number of gestational weeks, head circumference, apgar score after 1 min, apgar score after 5 min and Body Mass Index (BMI) were calculated. Only maternal age and parity were positively correlated with cord blood lead levels (r = 0.103, p = 0.008) and (r = 0.081, p = 0.039), respectively. The mean of lead levels in cord samples according to various risk factors is shown in Table 2. When one-way analysis of variance or Student's t-test were applied, only mothers who took prenatal supplements had significantly lower cord blood lead levels than those who did not (p = 0.012).

Table 1

Description of the measured continuous variables

Variable n Mean ± SD Median Range 
Blood lead levels (μg/dl) 653 2.21 ± 1.691 1.818 0.284–17.276 
Age of mothers (years) 653 28.46 ± 6.020 27.0 17–46 
Gestational age (weeks) 525 39.72 ± 1.855 39.86 34–45 
Birth weight (kg) 653 3.204 ± 0.484 3.2 1.15–5.15 
Birth height (cm) 653 50.35 ± 2.378 50.0 35–58 
BMI (kg/m2653 12.583 ± 1.278 12.572 8.68–17.6 
Newborn's head circumference (cm) 653 34.27 ± 1.475 34.0 28–43 
Apgar score after 1 min 653 7.58 ± 0.976 8.0 1–8 
Apgar score after 5 min 653 8.82 ± 0.546 9.0 4–9 
Total number of pregnancies 653 4.38 ± 3.237 4.0 1–19 
Parity 653 2.98 ± 2.855 2.0 0–13 
Variable n Mean ± SD Median Range 
Blood lead levels (μg/dl) 653 2.21 ± 1.691 1.818 0.284–17.276 
Age of mothers (years) 653 28.46 ± 6.020 27.0 17–46 
Gestational age (weeks) 525 39.72 ± 1.855 39.86 34–45 
Birth weight (kg) 653 3.204 ± 0.484 3.2 1.15–5.15 
Birth height (cm) 653 50.35 ± 2.378 50.0 35–58 
BMI (kg/m2653 12.583 ± 1.278 12.572 8.68–17.6 
Newborn's head circumference (cm) 653 34.27 ± 1.475 34.0 28–43 
Apgar score after 1 min 653 7.58 ± 0.976 8.0 1–8 
Apgar score after 5 min 653 8.82 ± 0.546 9.0 4–9 
Total number of pregnancies 653 4.38 ± 3.237 4.0 1–19 
Parity 653 2.98 ± 2.855 2.0 0–13 
Table 2

Mean blood lead levels in cord samples (µg/dl) according to participant characteristics

Variables n Mean ± SD Range p 
Gender     
    Male 337 2.188 ± 1.686 0.509–17.276 0.818 
    Female 316 2.234 ± 1.699 0.284–17.233  
Prenatal illnesses     
    Yes 48 2.126 ± 1.279 0.911–8.480 0.920 
    No 605 2.217 ± 1.720 0.284–17.276  
Prenatal supplements     
    Yes 576 2.120 ± 1.490 0.480–17.233 0.012 
    No 77 2.888 ± 2.684 0.284–17.276  
Location of residence     
    Saudi district 99 2.187 ± 1.339 0.662–7.984 0.096 
    Khailida district 86 1.994 ± 0.882 0.551–5.12  
    Delam district 51 1.777 ± 0.904 0.662–5.398  
    Faisaliah district 37 2.430 ± 2.184 0.545–12.425  
    Nahda district 34 1.675 ± 0.673 0.629–3.229  
    Shana district 25 2.797 ± 3.025 0.284–14.475  
    Aziziah district 23 1.953 ± 0.998 0.509–5.207  
    Zahir district 22 2.157 ± 0.756 0.654–3.457  
    Other districts 276 2.375 ± 1.999 0.296–17.276  
Mode of delivery     
    Vaginal 577 2.222 ± 1.719 0.284–17.276 0.800 
    Caesarean section 76 2.120 ± 1.470 0.662–10.101  
Variables n Mean ± SD Range p 
Gender     
    Male 337 2.188 ± 1.686 0.509–17.276 0.818 
    Female 316 2.234 ± 1.699 0.284–17.233  
Prenatal illnesses     
    Yes 48 2.126 ± 1.279 0.911–8.480 0.920 
    No 605 2.217 ± 1.720 0.284–17.276  
Prenatal supplements     
    Yes 576 2.120 ± 1.490 0.480–17.233 0.012 
    No 77 2.888 ± 2.684 0.284–17.276  
Location of residence     
    Saudi district 99 2.187 ± 1.339 0.662–7.984 0.096 
    Khailida district 86 1.994 ± 0.882 0.551–5.12  
    Delam district 51 1.777 ± 0.904 0.662–5.398  
    Faisaliah district 37 2.430 ± 2.184 0.545–12.425  
    Nahda district 34 1.675 ± 0.673 0.629–3.229  
    Shana district 25 2.797 ± 3.025 0.284–14.475  
    Aziziah district 23 1.953 ± 0.998 0.509–5.207  
    Zahir district 22 2.157 ± 0.756 0.654–3.457  
    Other districts 276 2.375 ± 1.999 0.296–17.276  
Mode of delivery     
    Vaginal 577 2.222 ± 1.719 0.284–17.276 0.800 
    Caesarean section 76 2.120 ± 1.470 0.662–10.101  

Above the 75th percentile of cord blood lead data, we looked at the relationships between cord blood lead levels and various continuous variables, it seems only newborn's head circumference was negatively correlated with blood lead levels (r = −0.16, p = 0.042). For categorical variables, significance differences in the blood lead levels were seen with respect to prenatal supplements (p = 0.029) and location of residence (p = 0.037). We used multiple regressions modeling to check the lead effect and other confounding variables on head circumference. Potential confounders were selected for inclusion in the multiple regression model were those who exhibited significant associations with either blood lead levels such as prenatal supplements and location of residence or head circumference such as the number of gestational weeks and BMI on subset of newborns with blood lead levels above the 75th percentile. With the backward elimination procedure, the only significant predictors of head circumference were blood lead levels, BMI and the number of gestational weeks. The model explained 30.1% of the variance (R2) observed (overall regression: F = 19.207, p = 0) as shown in Table 3. Another multivariate linear regression model was constructed, with backward elimination procedure including maternal age, parity, prenatal supplements and location of residence as independent variables and blood lead levels above the 75th percentile as the dependent variable. After elimination of the non-significant variables, the final regression model of the blood lead levels included location of residence (Shana and other districts), maternal age and taking prenatal supplements as shown in Table 4. However, only 7.2% of the variance in blood lead levels was explained by the variables in this model (Overall regression: F = 4.147, p = 0.003).

Table 3

The remained predicator variables of head circumference (cm) on subset of newborns with blood lead levels (µg/dl) above the 75th percentile after backward elimination in a multiple linear regression model

Predictor variables β (SE) T p 
Log-transformed blood lead levels (µg/dl) −0.158 (0.718) −2.125 0.036 
BMI 0.347 (0.094) 4.317 0.0 
Number of gestational weeks 0.306 (0.07) 3.799 0.0 
Predictor variables β (SE) T p 
Log-transformed blood lead levels (µg/dl) −0.158 (0.718) −2.125 0.036 
BMI 0.347 (0.094) 4.317 0.0 
Number of gestational weeks 0.306 (0.07) 3.799 0.0 
Table 4

The remained predicated variables of log-transformed blood lead levels (µg/dl) above the 75th percentile after backward elimination in a multiple linear regression model

Predictor variables β (SE) T P 
Mothers taking prenatal supplements (Yes vs. No) −0.156 (0.034) −2.044 0.043 
Location of residence: Mothers living in Shana districta 0.207 (0.069) 2.66 0.009 
Location of residence: Mothers living in other districtsa 0.136 (0.028) 1.759 0.081 
Maternal age (years) 0.133 (0.002) 1.756 0.081 
Predictor variables β (SE) T P 
Mothers taking prenatal supplements (Yes vs. No) −0.156 (0.034) −2.044 0.043 
Location of residence: Mothers living in Shana districta 0.207 (0.069) 2.66 0.009 
Location of residence: Mothers living in other districtsa 0.136 (0.028) 1.759 0.081 
Maternal age (years) 0.133 (0.002) 1.756 0.081 

aReference category: Nahda district.

Discussion

Cord blood lead level was measured as an index of prenatal lead exposure. In this study, lead was detected in all cord blood samples confirming its placental transfer and leading to an early fetal lead burden. None of the studied mothers was occupationally exposed to lead and their exposure therefore probably resulted from the general environment. Lead concentrations in umbilical cord blood were found to be 2.21 ± 1.691 µg/dl in the range of 0.284–17.276 µg/dl. Compared to the cord blood lead levels in other countries that are shown in Table 5, our data was higher than those reported in Canada-Montreal (1.7 µg/dl) [32]; Greece (1.29 µg/dl) [40]; Sweden (1.12 µg/dl) [43]; Turkey (1.65 µg/dl) [45] and (1.69 µg/dl) [46]; and USA (1.6 µg/dl) [47] and (1.64 µg/dl) [48]. In comparison to the mean of cord blood lead levels (4.14 ± 1.81 μg/dl) reported by Al-Saleh et al. [29], it seems that there is a 50% decrease in the blood lead levels, which could be related to the use of lead-free gasoline that has been introduced in the Saudi market since 2001. According to the CDC [20], the upper limit of tolerable blood lead levels for children should be <10 µg/dl. Among all participants, 1.23% exceeded 10 μg/dl blood lead levels. However, the mean cord blood lead level (2.21 µg/dl) was about one-fourth the CDC cutoff level, but the highest value (17.284 µg/dl) was approximately twice the CDC cutoff. One cannot dismiss its potential impact on pregnancy outcome or cognitive development afterwards.

Table 5

Reported values for cord blood lead (µg/dl)

Country Blood lead levels No. References 
Albani 8.9 (4.9–20.0) 151 [31
Canada (Montereal) 1.7b 160 [32
Canada-Arctic 2.8 (0.21–15.5) 402 [33
Canada-Quebec 3.934b (0.21–27.122) 475 [34
China 6.90 165 [35
China-Shanghai 9.2b (8.86–9.54) 348 [36
China 6.9b (1.25–18.5) 89 [37
China 5.31 ± 2.79b 100 [38
France 2.32 1021 [39
Greece 1.29 ± 0.36 50 [40
Greece 13.1 ± 3.7 47 [13
India 5.15 ± 12.65 176 [23
Iran 4.30 ± 2.49 31 [41
Mexico 10.4 ± 6.2 1404 [16
Mexico 6.7 ± 3.4 (1.2–21.6) 197 [6
Mexico 5.49 ± 3.43 583 [42
Mexico 6.2 ± 3.38 (0.9–20.0) 83 [22
Mexico 6.8 ± 3.8 329 [5
Poland 2.14 83 [12
Saudi Arabia 4.14 ± 1.81 126 [29
Sweden 1.118a (0.089–12.215) 101 [43
Taiwan 2.35 ± 1.12 184 [44
Turkey 1.69 ± 0.91 104 [45
Turkey 1.65 ± 1.4 143 [46
USA-New York 1.6 ± 1.78b 220 [47
USA-Pittesburg 1.64 ± 0.76 (0.05–3.95) 140 [48
Saudi Arabia, Al-Kharj 2.21 ± 1.691 653 This study 
Country Blood lead levels No. References 
Albani 8.9 (4.9–20.0) 151 [31
Canada (Montereal) 1.7b 160 [32
Canada-Arctic 2.8 (0.21–15.5) 402 [33
Canada-Quebec 3.934b (0.21–27.122) 475 [34
China 6.90 165 [35
China-Shanghai 9.2b (8.86–9.54) 348 [36
China 6.9b (1.25–18.5) 89 [37
China 5.31 ± 2.79b 100 [38
France 2.32 1021 [39
Greece 1.29 ± 0.36 50 [40
Greece 13.1 ± 3.7 47 [13
India 5.15 ± 12.65 176 [23
Iran 4.30 ± 2.49 31 [41
Mexico 10.4 ± 6.2 1404 [16
Mexico 6.7 ± 3.4 (1.2–21.6) 197 [6
Mexico 5.49 ± 3.43 583 [42
Mexico 6.2 ± 3.38 (0.9–20.0) 83 [22
Mexico 6.8 ± 3.8 329 [5
Poland 2.14 83 [12
Saudi Arabia 4.14 ± 1.81 126 [29
Sweden 1.118a (0.089–12.215) 101 [43
Taiwan 2.35 ± 1.12 184 [44
Turkey 1.69 ± 0.91 104 [45
Turkey 1.65 ± 1.4 143 [46
USA-New York 1.6 ± 1.78b 220 [47
USA-Pittesburg 1.64 ± 0.76 (0.05–3.95) 140 [48
Saudi Arabia, Al-Kharj 2.21 ± 1.691 653 This study 

aMedian; bGeometric mean.

Even though the cord blood lead levels are low in the present study, its variation was found to be significantly associated with newborn's head circumference when we examined cord blood lead levels above 75th percentiles. This indicates that lead might have influence on growth in children even at very low exposure levels. Many studies reported reduction in head circumference of children with low lead exposure [36, 44, 49–53]. The effects of lead on head circumference may reflect disruption of early brain growth [52] and raises concerns about the potential effects of increased lead exposure resulting from maternal bone lead mobilization on the developing fetus.

Above the 75th percentile of cord blood lead levels, mother's age, taking prenatal supplements and location of residence (mothers living in Sahna and other districts) were also significant predicators of cord blood lead levels. The observation that cord blood lead levels were significantly higher in mothers living in Shana and other districts than reference group (Nahda, lowest cord blood lead levels) suggesting that these women were exposed to an environmental lead source unique to these locations. As we know that sources of lead are diverse and are from both natural and anthropogenic origins. No data are available on environmental lead contamination in Al-Kharj area. During the past few decades, Al-Kharj has grown from a small farming and trading village into a modern town of about 250 000 inhabitants. Its proximity to the capital ‘Riyadh’; 50 miles to the south, and its abundant water resources has attracted large investment in agriculture; in particular. In addition to this important economic role; its military role as a military air base has enhanced its development. These drastic changes might have an important impact on Al-Kharj's environment. Apart from the usual sources of lead exposure such as air, water, paint, soil and food, other less well-recognized sources have been identified. The use of traditional cosmetics and remedies; such as Kohl is still popular; especially, among women in Saudi Arabia [26, 54] where a number of lead poisoning cases were reported [55, 56]. Jones et al. [57] referred to number of unusual sources of lead exposure that can be a threat to health.

Our results confirm the previously reported findings that maternal age could be an important determinant of cord blood lead levels [9, 58]. It suggests that older women had higher bone lead burden that was accumulated over the years of their lives. It also suggests that even in the case of no lead exposure, lead can remain a significant threat to the fetus of pregnant women because bone lead has a half-life of years to decades. Interventions to reduce early lead exposures must be highly considered. This highlights the need to take prenatal supplements to reduce the exposure to previously accumulated lead. In our study, 88.2% of the women were taking supplements during pregnancy as part of their routine prenatal care. This might have contributed to low lead body burden, which has been suggested by many studies [7, 59, 60].

Regardless of the small proportion of newborns with ‘high’ cord blood lead levels in Al-Kharj, this study suggests that in utero lead exposure may be more of a widespread problem in the area and might cause adverse effects even at very low exposure levels on the growth and development in young children. If the CDC adopts Gilbert and Weiss [25] recommendation to reduce the blood lead level of concern from 10 to 2 µg/dl as the level of concern, 49.2% of the newborns in this study had blood lead levels in the range of 2.00–17.276 µg/dl.

Even at low prenatal lead exposure, all possible measures to inspect lead sources in our environment and reduce lead exposure should be taken.

Acknowledgements

The investigators would like to thank the Prince Salman Centre for Disability Research for funding this study 02-R-0028-NE-02-EP-1.

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