Shally Awasthi, Rajiv
Awasthi* and RC Srivastav**
From the Department of
Pediatrics and Clinical Epidemiology Unit, King George’s Medical
College, Lucknow, Employees State Insurance Hospital, Sarojini Nagar,
Lucknow*, and Industrial Toxicology Research Center (ITRC), Lucknow**,
India.
Correspondence to: Dr.
Shally Awasthi, C-29, Chetan Vihar, Sector C, Aliganj, Lucknow (UP)
226 024, India. E-mail: [email protected]
Manuscript received:
June 8, 2001, Initial review completed: July 9, 2001;
Revision accepted: March
6, 2002.
The present study
was conducted to find the effect of maternal exposure to lead and
neonatal birth weight among women living in the urban slums of Lucknow
in a randomly selected cohort of 500 subjects. The mean blood lead
level in subjects was 14.34 ± 7.87 µg/dL. Babies born to women with
high blood lead levels (³ 30 µg/dL) weighed more ( P = 0.02), and
were less likely to be of low birth weight (Odd’s ratio 0.17; 95%
CI: 0.04 - 0.75; P = 0.02) when compared to babies born to mothers
with low blood lead (<30 µg/dL).
Key Words:
Birth weight, Maternal lead.
Metals pose a significant threat to
health through occupational and environmental exposure. Population is
exposed to lead via paints. cans, plumbing fixtures and leaded gasoline.
While exposure to lead has reduced through various regulatory actions in
the developed countries, it is still high in India and other developing
countries. In humans, the lead is absorbed into the blood plasma where
it equilibrates with the extra-cellular fluid and crosses the membranes
like the placenta and the blood brain barrier(1). Therefore the fetus is
exposed to maternal blood lead levels from the 12th week of
gestation(2-4). Fetal exposure to lead has been reported to be
associated with preterm delivery(5), abortions(6) and both reduction as
well as an increase in birth weight(5,7-8). Studies conducted in
pregnant women in Lucknow(9,10) have found high blood lead (PbB) levels
in them, probably due to exposure to fumes of leaded petrol(10). The
present study was conducted to find the effect of maternal exposure to
lead and neonatal birth weight among women living in the urban slums of
Lucknow. Our study hypothesis was that lead exposure would reduce birth
weight.
Subjects and Methods
This was a cohort study
in the urban anganwadi centers of Lucknow, North India. Sample size
calculations were based on a previous study done in Lucknow(9) where it
was observed that about 5% mothers are exposed to high lead levels of
³30 µg/dL. To calculate the relative risk of 2.5 for delivering a low
birth weight (LBW) neonate with an a of 0.05 (two-tailed) and a b
of 0.2 and assuming 10% abortion rate and 10% loss to follow-up, five
hundred women were to be recruited in the current study.
From Lucknow’s 203
slums, 70 were randomly selected and visited by a research assistant at
least twice in the same order from June 1994 through July 1995. An
informed and written consent was taken from all the participants. This
process continued till 500 subjects were enrolled. Potential subjects
were excluded if they declined to participate or if they indicated a
likelihood of moving out of the slum in the next six months.
The main study outcome
was birth weight. The secondary outcomes were abortions, gestational age
and still births. The expected date of delivery was noted and one or
more visits were made by the research assistant to determine the weight
of the neonate as soon as possible after birth and preferably within the
first 72 hours. Neonates were weighed in an infant weighing scale. The
minimum weight that could be measured with this scale was of 10 grams.
Gestational age of neonate at birth was calculated by subtracting the
date of birth from the date of the last menstrual period, for women who
knew this date. If the mother did not remember the exact date the events
calendar was used to facilitate recall and date of birth was noted
correct to the nearest week. For the purpose of analysis, pre-term
delivery was when the gestational age was <37 weeks(11) and LBW baby
was when the weight of the neonate was £ 2.5 Kg(11). The exposure of
interest was maternal blood lead levels.
For measurement of PbB, 5
mL of venous blood was taken after carefully cleaning the skin at the
venepuncture site. Analysis of blood lead was performed at the
laboratory of the Industrial Toxicology Research Centre (ITRC) in
Lucknow, India. Blood lead was analysed with graphic furnace atomic
absorption spectroscopy (GF - AAS; SpectrAA - 250 Plus. Varian, Palo
Alto, California). The means of four replicate analyses were used to
assess the concentration. The coefficient of variation of the four
analyses was < 2% for all samples.
Information was collected
on other potential lead exposures, including source of drinking water,
use of surma, and lead paints at home, and residence in the
congested inner city with heavy stop-and-go vehicular traffic. Data was
collected on the potential confounders like, maternal age, parity and
date of the last menstrual period, correct to the nearest week, and
maternal nutritional status, as estimated by measuring the weight in
kilograms and hemoglobin in g/dL.
For analysis, maternal PbB were
categorized into 2 categories using PbB level of 30 µg/dL as cut-off as
it was two standard deviations above the mean PbB found in
Lucknow(9,10). Thus category 1 included women with PbB levels up to 29.9
µg/dL and category 2 had PbB ³30 µg/dL. Univariate distribution of
the potential confounders and main outcome variable (neonatal weight)
and secondary outcomes was studied across both
categories. Student’s t
test was used for continuous and chi square test for categorical
variables. Unconditional logistic regression to find the effect of PbB
on neonatal weight, controlling for sex and gestational age, and any
other variables that were either univariately associated with neonatal
weight or were not equally distributed in the two lead exposure
categories and/or were clinically meaningful. The software package used
was EPI 2000(12).
Results
An average of 7.2
pregnant women was enrolled per slum from 70 randomly selected slums.
None of the pregnant women refused to participate. 51.4% of the slums
were categorized as inner city slums. Of the 500 women enrolled, 40 (8%)
were in the first, 305 (61%) in the second and 155 (31%) in the third
trimester. 34.6% of the subjects reported the use of surma, a
cosmetic applied to the eyes, 75.2% reported the use of lead pipes for
water and 25.6% reported the presence of lead paints in their homes.
The mean maternal
hemoglobin level was 10.5 ± 1.14 g/dL and mean PbB was 14.34 ± 7.87
µg/dL. Maternal PbB was similar across in the first, second and third
trimesters of pregnancy being 14.6 ± 7.9 µg/dL, 14.5 ± 8.0 µg/dL and
14.1 ± 7.6 µg/dL, respectively. The mean PbB in women living in the
inner city (n = 197) was the highest being 15.7 ± 8.2 µg/dL as
compared to those living near industrial area with potential lead
emission (n = 94) in whom it was 13.6 ± 6.4 µg/dL, industrial
area without potential lead emission (n = 64) 12.9 ± 7.1 µg/dL
and near highways (n = 145) 13.6 ± 8.4 µg/dL (P value, analysis
of variance = 0.02). No association was found between the reported use
of either surma or lead piped water supply or lead paints at home
and maternal PbB.
Of the 500 women
enrolled, 2% (n = 10) had first and second trimester abortion. Of
the remaining 490 pregnant women, 2.45% (n = 12) had still
births. Only 5.5% of the deliveries were institutional, the rest were at
home. Of the 478 babies born alive, three (0.6%) were dead before the
officer could weigh them. Neonatal weight could be assessed for 475
babies and within 72 hours of birth in 393 babies (82.6%). There was no
correlation between the post-natal day of outcome assessment and
neonatal weight.
Mean neonatal weight was
2.65 Kg (SD:0.27) and mean postnatal age of weight assessment was 3.5
days (SD: 2.7). Females weighed less than the males at birth (2.61 Kg
(SD:0.26) versus 2.68 kg (SD: 0.27); P Value = 0.008). Mean gestational
age of babies who were weighed was 40.3 weeks (SD: 1.9). Overall there
were 14 (2.9%) preterm babies, 2.7% and 8.3% in category 1 and category
2, respectively (P value; Fisher’s exact = 0.15).
The primary and secondary
outcomes of pregnancy and the number of babies who died before the
weight could be measured in the both PbB categories is shown in Table
1. Weight of babies born to mothers with PbB ³30 µg/dL was higher
when compared to the other category (Table I). The crude relative
risk of low birth weight with PbB level in category 2 was 0.73 (95% CI:
0.63 - 0.83; 2-tailed P value with Yates’ correction = 0.02).
Adjusted odd’s ratio
for low birth weight in neonates in Category 2 women was 0.17 (95% CI:
0.04 - 0.75; P value of 0.02), controlling for maternal age, weight,
height, hemoglobin level, parity, and neonatal gender, in unconditional
logistic regression model.
Discussion
Lead exposure during pregnancy can lead
to abortion(6), fetal malformation, and
Table I__ Distribution of Outcome of Pregnancy and Neonatal Characteristics among
Women in Different Blood Lead Categories
|
Blood
Lead Categories
|
|
Upto 29.9 µg/dL
(n = 452)
|
³30 µg/dL
(n = 24)
|
P Value
|
Mean (SD)
|
Birth weight (kg)
|
2.64 (0.27)
|
2.79(0.32)
|
0.008
|
Gestational age (weeks)
|
40.34 (1.6)
|
39.96 (1.7)
|
0.2
|
Number (%)
|
Low birth weight
|
151 (33.5)
|
2 (8.3)
|
0.02
|
Abortions
|
9 (1.99)
|
1 (4.2)
|
0.5
|
Still births
|
11 (2.37)
|
1 (4.2)
|
0.6
|
change in neonatal birth
weight and gestational age(5,7-8,13-15). In the current study it was
observed that neonates born to women with PbB level ³30 µg/dL had a
reduced risk of being LBW (adjusted odd’s ratio 0.17; 95% CI: 0.04 -
0.75: P value 0.02) after controlling for gestational age. Neonatal
birth weight is affected by fetal, maternal and environmental
characterstics(16). Some of these factors have been controlling for in
the logistic regression analysis but many others could not be studied.
There are conflicting reports on effect of fetal lead exposure and birth
weight. Certain workers have reported an increase in birth weight(7,8)
while others have reported either no effect or decrease(2,6-7,13-15).
Lead reaches the body
through food, water and air by ingestion as well as inhalation(1).
Approximately 5-10% of ingested inorganic lead is absorbed but majority
is excreted in the urine. Lead absorption increases with diets rich in
fat and low in calcium, magnesium, iron, zinc and copper(1,16). Since
diet of Indian families of low socio-economic status have the above
characteristics it can partly explain higher mean PbB in our cohort as
compared to the West. In addition, organic lead exposure due to fumes
from unleaded petrol results in further elevation of PbB due to
absorption through the respiratory passage. In the current study, women
living in the inner cities, thus, have statistically higher mean PbB as
compared to others.
In state of calcium
deficiency during pregnancy, calcium is mobilized from the bone and
there is concomitant mobilization of lead and thus elevation of PbB in
women who have high bone lead stores(1). In the newborn PbB levels are
almost equal to the maternal PbB level(17). Thus, it is hypothesized
that women with better compensatory mechanism in face of calcium
deficiency state during pregnancy will have babies with higher birth
weight and also higher PbB levels primarily due to mobilization from the
bone. Therefore, elevated PbB may just be a confounding factor in such
cases. Neurobehavioral assessment of children who have been exposed to
high PbB levels in the fetal period is also needed, the exposure has
been reported to alter it(18-21).
It is concluded that pregnant women in
urban slums of Lucknow have elevated PbB levels. Levels ³30 µg/dL have
been associated with lower risk of LBW babies in the current study.
Since elevated PbB levels appear to be a confounder in the assessment of
association with LBW, further studies are recommended to assess
causality as well as to establish safe PbB level during pregnancy for
optimal fetal, neonatal and neuro-developmental outcomes.
Contributors:
SA is responsible for study design, supervision of data collection, data
analysis and manuscript writing. RA has provided assistance in
supervision of data collection, data analysis and manuscript writing.
RCS is responsible for laboratory analysis of lead levels and provided
assistance in data interpretation and manuscript writing. SA shall be
the guarantor for the paper.
Funding: This
work was supported by a grant from the Environmental and Occupational
Health Initiative of the International Clinical Epidemiology Network (INCLEN),
from the Rockefeller Foundation.
Competing interests:
None stated.
|
Key
Messages |
• High blood lead
(PbB) levels exist in women living in urban slums of Lucknow,
North India, more so among the residents of inner city.
• Babies born to women with high PbB levels ( ³30 µg/dL)
weighed more and were less likely to be of low birth weight when
compared to babies born to mothers with low PbB (<30 µg/dL)
• Further research is needed to
assess association, along with causality, of high maternal PbB
with higher neonatal birth weight and to assess its long term
effect on fetal development.
|
