doi:10.1136/oem.2003.012492 

Occup. Environ. Med. 2005;62;263-269 

 

P J Parsons and W Rogan 

E W Harville, I Hertz-Picciotto, M Schramm, M Watt-Morse, K Chantala, J Osterloh,

 

and cord blood lead

Factors influencing the difference between maternal

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ORIGINAL ARTICLE

Factors influencing the difference between maternal and

cord blood lead

E W Harville, I Hertz-Picciotto, M Schramm, M Watt-Morse, K Chantala, J Osterloh, P J Parsons,

W Rogan

...............................................................................................................................

See end of article for

authors’ affiliations

.......................

Correspondence to:

Dr E W Harville, CB

#7435, Department of

Epidemiology, University

of North Carolina–Chapel

Hill, Chapel Hill, NC

27599-7435, USA;

ewh@unc.edu

Accepted1December2004

.......................

Occup Environ Med 2005;62:263–269. doi: 10.1136/oem.2003.012492

Aims: To determine the factors that affect why some infants receive higher exposures relative to the

mother’s body burden than do others.

Methods: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at MageeWomens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead

determination. The difference between cord and maternal blood lead concentration (PbB) and a

dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative

transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium

nutrition, and physical activity.

Results: Higher blood pressure was associated with relatively greater cord compared with maternal PbB,

as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord

relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium

consumption.

Conclusion: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to

mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at

reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard.

E

xposure to lead causes developmental problems.

Although postnatal and childhood exposure can have

effects at low concentrations,1 children who have been

exposed to lead in utero may also suffer from deficits in

development (such as intelligence, information processing,

memory, and verbal skills),2–7 growth,8 9 and behaviour.10 11

Because lead is incorporated into the bone matrix where it is

retained for decades,12 13 prenatal exposure to lead also

contributes to an earlier and cumulatively greater body

burden.14 15

Maternal and infant blood lead levels (PbB) are highly

correlated across a wide range of exposure levels,16–18 so the

most obvious sources of variation in fetal lead dose are those

that affect the maternal PbB. Some sources of infant PbB

reflect direct maternal exposure, such as occupational lead

exposure, exposure to lead paint, or use of lead glazed

ceramics.19 Since cigarette smoke contains lead,20 21 smoking

and passive smoking could fall into this category as well.22

Other factors associated with infant PbB may reflect a

lifestyle associated with increased environmental exposure to

lead. Maternal coffee consumption and alcohol use,22 23

higher blood pressure,24 25 and seasonal patterns26–28 are such

variables.

For over 30 years, it has been recognised that lead freely

crosses the placenta via diffusion.29 30 It has generally been

assumed that there is no general enhancement or barrier to

transfer.31 However, factors besides the maternal lead

exposure and PbB also appear to affect the concentration in

fetal blood. Although maternal PbB is on average about 30%

higher than the infant’s, in most studies approximately one

quarter of the infants have PbB higher than their mothers.32–36

Rothenberg and coworkers reported that drinking milk

rarely, higher maternal age and parity, and caesarean section

delivery predicted increased cord lead after controlling for

maternal PbB.37 38 Sikorski et al found higher maternal-fetal

ratios in rural subjects, and a correlation between maternal:

fetal lead ratio and maternal:fetal iron and zinc ratios.39

Given inter-individual variability in maternal:cord PbB, we

hypothesised that there might be modifiable factors that

contribute to passage of lead to the fetus and that

identification of such factors could suggest ways to reduce

the burden of lead in newborns beyond what is achieved by

reducing maternal lead exposure. For this reason, we

examined variables that might influence the amount of lead

that an infant receives during gestation relative to maternal

burden.

MATERIALS AND METHODS

Subjects

During 1992–95, women were recruited for a longitudinal

study of lead, calcium, and blood pressure during pregnancy.40 Women were eligible to participate if they were in

prenatal care before week 12, planned to deliver at MageeWomens Hospital, had single gestations, spoke English, were

over 18, were white or African-American, and did not have

chronic diseases. A total of 498 women were part of the initial

cohort; 24 delivered elsewhere and 44 miscarried. Whole

blood samples were collected from the women at up to five

points during pregnancy and at delivery. Because of budget

constraints, it was only possible to assay one sample per

trimester for some women: 345 had at least one lead

measurement taken, and of these, 229 had PbB determination on their blood sample collected at delivery. A total of 162

infants had cord blood lead determined, leading to 159 pairs

with lead measurements available for this analysis (fig 1).

Protocols used in this study were approved by the

Institutional Review Boards of Magee-Womens Hospital

and the University of North Carolina School of Public

Abbreviations: AAS, atomic absorption spectroscopy; ALA-D, daminolevulinic acid dehydratase; BMI, body mass index; CLIA, Clinical

Laboratory Improvement Amendment of 1988; Hb, haemoglobin; PbB,

blood lead concentration; RBC, red blood cell

263

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Health. Written informed consent was obtained from all

subjects.

Lead determination

The protocol for blood drawing and lead measurement has

been previously described.40 The University of California San

Francisco–San Francisco General Hospital Metals Laboratory

analysed samples concurrently with the study data collection,

using electrothermal atomic absorption spectroscopy (AAS)

with continuum background correction. Interassay precision

had a coefficient of variation of 6% at 2 mg/dl. In 1998 the

Lead Poisoning/Trace Elements Laboratory at the New York

State Department of Health analysed blood samples that had

been frozen, using electrothermal atomisation AAS with

Zeeman background correction.41 This method is transferable

to a continuum based AAS instrumentation.42 Intermediate

precision estimates using New York State’s RM 028 (6.7 mg/

dl) are 0.2 mg/dl by the continuum correction method and

0.1 mg/dl by Zeeman corrected AAS.41 At a detection limit of

0.75 for Zeeman AAS and 0.50 for continuum AAS, the

precision is approximately 0.25 and 0.17 mg/dl, similar to that

reported at 6.7 mg/dl.

Several comparisons were made to determine the acceptability of values measured years after blood collection. First,

both laboratories participated satisfactorily in Clinical

Laboratory Improvement Amendment (CLIA) approved

proficiency testing programmes for blood lead using similar

analytical methodologies. Twenty specimens were analysed

by both laboratories, and of these, 80% were within 1 mg/dl,

with the remainder split between specimens that were higher

in the concurrent analysis and those higher in the later

determination. Second, we recently replicated our published

analyses40 of the maternal determinants of blood lead

concentration (PbB) and found that the regression models

showed the same variables to be predictive regardless of

whether the lead determinations were conducted concurrently or later. Third, the findings in the present examination

of cord versus maternal blood lead were unchanged by

inclusion or exclusion of the later assays. Therefore, we

included them in the analyses presented.

Of the 159 pairs with information on both maternal and

cord lead, 141 PbB determinations were completed concurrently with specimen collection (1992–95) and 18 in 1998. In

106 cases, the maternal blood draw was performed during

labour, and in 53 cases, after delivery. PbB was expressed in

mg of lead per dl of whole blood.

Data collection

Trained staff interviewed the women face-to-face twice

during their pregnancies, once shortly after enrolment (mean

week of gestation: 14, range 8–18), and once late in the

pregnancy (mean week: 36, range 31–41). Women were

questioned about their medical, occupational, and lifestyle

characteristics. Calcium intake was assessed through a

modified Block food frequency questionnaire,43 which

included the foods that account for most of the calcium

consumed in the typical US diet,44 as well as questions on

antacid, supplement, and vitamin use. Dietary calcium was

calculated using the Block DIETSYS software version 3.0,45

and the Physician’s Desk Reference provided estimates for

calcium from antacids and supplements.46 Blood pressure

was taken by study personnel according to the protocol of the

ARIC (Atherosclerosis Risk in Communities) study.47 Medical

records were abstracted for details of medications used;

prenatal, labour, and delivery histories; and information

about the infant.

Predictor variables

Certain factors were considered as possible sources of

variation in the difference between maternal and fetal PbB,

based on previous literature on humans and animals

(table 1). Since blood flow and blood pressure have been

linked to lead in humans and guinea pigs,48 we evaluated

systolic and diastolic blood pressure and self-reported

hypertension among the variables that we screened.

Because the blood-bone lead equilibrium changes during

Policy implications

N These findings give additional support to efforts to

control blood pressure (particularly in those over 30

years of age), encourage iron supplementation when

appropriate, and reduce alcohol consumption during

pregnancy.

N Interventions to reduce prenatal exposure to lead can

target not only overall maternal exposure, but also

modifiable factors that influence transfer from the

mother to the fetus.

498 women

in initial cohort

229 motherinfant pairs with

delivery sample

345 women with

at least one PbB

measurement

753 women 

agreed to

participate

183 ineligible

44 miscarried

1 sample unmeasurable

85 with no PbB measurement

116 with no delivery

PbB measurement

2 infants with no corresponding

maternal sample

67 mothers with no corresponding

cord sample

72 randomised out

24 delivered elsewhere

160 motherinfant pairs with

delivery blood

samples

159 pairs with

both maternal

and cord

measurement

Figure 1 Creation of a cohort among Pittsburgh, PA women seeking

prenatal care at Magee-Womens Hospital, 1992–95. PbB, blood lead.

Main messages

N Higher blood pressure in some groups and alcohol

consumption were associated with more lead in cord

blood relative to maternal blood lead.

N Higher haemoglobin and sickle cell trait were associated with reduced lead in cord blood relative to

maternal blood lead.

N No associations were seen with calcium intake,

physical activity, or smoking.

264 Harville, Hertz-Picciotto, Schramm, et al

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pregnancy, calcium (which may affect the release of lead

from bone40 49), haemoglobin (Hb), and sickle cell trait were

examined. Reproductive history, medication use, and infection could also have effects on the structure or blood flow of

the placenta.50 Because fetal stress has been associated with

increased relative lead burden,51 we looked at factors such as

birth weight and Apgar score. Finally, factors that might

reflect the measurement and sample properties were examined, such as delayed versus concurrent lead analysis and

time of maternal blood draw relative to delivery.

To represent variability in amount of lead transferred, the

difference between cord and maternal whole PbB concentration, as well as a dichotomous indicator of whether the cord

PbB was higher/not higher than maternal PbB, were the

outcomes for this study. The ratio of maternal to cord PbB

was also examined.

Statistical analysis

To determine comparability across three groups of subjects,

analysis of variance was performed. The three groups were:

those without a cord PbB, those for whom PbB was measured

a few years after data collection, and those with cord PbB

determination performed concurrently with data collection.

Initially, to reduce a large list of candidate predictors of

potential maternal-fetal transfer, bivariate associations were

examined for each variable and outcome; variables that were

significant at a = 0.20 or OR greater than 2 were included in

subsequent linear and logistic models. All variables that

passed this initial bivariate screen were then included in

multiple linear (for the difference) and logistic (for the

dichotomous outcome) models, in which variables were

eliminated that satisfied a criterion of p . 0.20. In the next

step, some variables that were not predictive of the outcome

at a = 0.20 were reintroduced to examine as potential

confounding: race, age, parity, and smoking. In most cases,

inclusion of these variables did not change the effect

estimates in the multivariable models, so they were not

included in the final model.52 Finally, variables that were

predictive of the cord-maternal PbB difference were entered

in the logistic model, and vice versa. Interactions with age

and weight gain were examined as well.

A number of sensitivity analyses were performed. Because

the samples analysed later may have been compromised, we

report models with and without those observations. The

extent of the effect of missing data was assessed using

multiple imputation with SAS’s PROC MI and PROC

MIANALYZE. Sickle cell trait, weight gain, and alcohol use

later in pregnancy were each missing for some observations,

and the imputation model contained those variables as well

as race, age, pre-pregnancy body mass index (BMI),

education, smoking status, alcohol use at other times, and

the other variables in the prediction model. As additional

sensitivity analyses, the models were fit using only the

measurements that could be considered to be more robust:

those maternal and cord samples with PbB above 1 mg/dl and

the maternal specimens collected before delivery.

RESULTS

Mean maternal PbB at delivery was 1.93 mg/dl, with a range

of 0.55–4.70 mg/dl; mean cord lead was 1.64 mg/dl, with a

range of 0.05–3.95 mg/dl. The Pearson correlation coefficient

between maternal and cord PbB was r = 0.79. On average,

cord PbB was lower than maternal PbB by 0.30 mg/dl (95% CI

20.38 to 20.21 mg/dl), with a range of 21.93 to 1.20; 45 of

the pairs (28%) had the cord blood value higher than the

mother’s PbB.

The women included in this analysis differed in some ways

from those in the overall parent study: they were more likely

to be white, nulliparous, and higher income than those

lacking a cord measurement (table 2). Although the samples

analysed for lead at a later time point were chosen randomly,

the women differed in some respects from those for whom

PbB was measured concurrently with data collection: they

were more likely to be white and older, and their babies were

of lower birth weight.

Bivariate analysis indicated a number of factors associated

with maternal-fetal PbB difference (table 1), but in multivariate modelling, the strongest associations were seen with

medical factors (table 3). Maternal Hb and sickle cell trait

were associated with reduced fetal lead relative to maternal

lead. Compared with the 25th centile of maternal Hb, the

75th centile was associated with 1.32 mg/dl lower cord

relative to maternal blood lead. Children born to women

with sickle cell trait had on average 0.8 mg/dl relatively lower

lead. There was a significant interaction between age and

blood pressure as well as weight gain and blood pressure:

among mothers aged 30 years or over, or those who had

gained more weight during pregnancy, a higher blood

pressure was associated with a relatively greater lead

concentration in the cord blood. The findings were

unchanged when analysis was limited to the specimens

analysed concurrently with data collection (table 3).

Table 1 Factors found, in a bivariate screen, to be

associated with cord blood lead relative to maternal

blood lead in a cohort of 159 Pittsburgh, PA women,

1992–95

Associated*

Difference Binary`

Demographic

Black race neg 0

Highest income category 0 neg

Separated marital status pos pos

Educational disadvantage 0 neg

Lifestyle

Alcohol pos pos

Coffee/tea drinks per month 0 neg

Passive smoking pos 0

Milk while adolescent neg 0

Medical/obstetric

5 minute Apgar score pos 0

Baby to intensive care unit neg 0

Number of abortions pos 0

Number of miscarriages neg 0

Chlamydia pos 0

Trichomonas neg 0

Sexually transmitted disease pos 0

Genitourinary infection neg neg

Cold medicines neg 0

Augmented labour neg neg

Systolic blood pressure pos pos

Diastolic blood pressure 0 pos

Weight gain pos 0

BMI 0 pos

Haemoglobin neg neg

Factors affecting blood lead measurement

Blood specimen measured later pos pos

*The following variables were not associated with either the difference or

the ratio: age; calcium consumed during the pregnancy; calcium intake

from milk; milk intake as a child; physical exertion at home or work;

infant weight, length, or head circumference; parity; use of nausea

medications; complications of labour and delivery; gestational age at

birth; paternal exposure to lead; time between blood draw and birth.

Variables associated with difference between maternal and cord PbB at

p = 0.20 or showing a difference .0.1. pos indicates association with a

higher lead level of cord blood, relative to maternal; neg indicates

association with lower lead level of cord blood; 0 indicates no

association.

`Variables associated with binary outcome at p = 0.20 or OR .2. pos

indicates increased odds of higher lead level of cord blood, relative to

maternal; neg indicates association with lower lead level of cord blood;

0 indicates no association.

Maternal-fetal lead transfer 265

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Similar factors were significant in the logistic model

(table 4), although all the women with sickle cell trait

(n = 5) had maternal lead higher than their infant, so this

variable could not be included. The logistic model also

showed increased odds of the cord PbB being higher than the

maternal PbB for infants delivered by caesarean section. Both

the blood pressure and caesarean section associations were

attenuated when the samples analysed later were omitted.

A few non-medical variables were associated with the

outcome. Alcohol consumption in the second and third

trimesters was associated with an OR of 7.7 (95% CI 2.4 to

24.4) for higher cord than maternal PbB; no association was

seen for first trimester alcohol consumption. Children born in

the winter had relatively higher cord PbB than maternal

(season was not associated with the timing of lead

determination).

Calcium intake and physical exertion were not associated

with differences between maternal and cord PbB (table 1).

Those with greater fetal PbB relative to maternal PbB did not

differ with regard to race, parity, or smoking, nor did these

variables confound any of the results.

Use of the ratio of maternal/cord PbB as an outcome

measure yielded results similar to those of the difference

between maternal and cord PbB (data not shown). Data were

missing for 10 (6%) of the observations on at least one of the

following: sickle cell trait, weight gain, alcohol use. For

models of the cord-maternal difference in PbB, multiple

imputation gave essentially identical beta estimates as

models based on only the complete observations, except for

Hb, which increased from 21.18 to 21.04 mg/dl; standard

errors and p values were similarly close. Restriction of the

analysis to those measurements greater than 1 mg/dl changed

the beta estimates only in the second decimal place.

Restriction of the model to those samples taken before

delivery strengthened the sickle cell and delivery in winter

associations (for the difference, from 20.76 to 20.94 and

from 0.12 to 0.26, respectively; all other variables changed by

less than 0.06).

DISCUSSION

This analysis looked at factors that might influence the dose

of lead an infant receives, relative to maternal PbB. The

results suggest that alcohol use late in pregnancy, maternal

Hb during pregnancy, and blood pressure may explain some

of the variability in cord PbB beyond that explained by the

mother’s lead level.

Rothenberg’s group has studied the same issue in a more

highly lead exposed population than ours.37 38 They found a

decreased maternal/cord ratio associated with high blood

pressure, caesarean delivery, parity, and increasing maternal

Table 2 Characteristics of a cohort of Pittsburgh, PA pregnant women, 1992–95

Both maternal and

cord blood

measurements, samples

analysed shortly after

delivery (n = 140)

Both maternal and

cord blood

measurements,

samples analysed

later (n = 19)

Maternal lead

measurement at

delivery, no cord

blood (n = 67)

n (%) n (%) n (%) p*

Race

Black 64 (46) 6 (32) 38 (58)

White 74 (54) 13 (68) 27 (42) 0.08

Age (y)

18–20 42 (30) 3 (16) 9 (13)

21–25 53 (38) 9 (47) 32 (48)

26–30 30 (21) 1 (5) 13 (19)

.30 15 (11) 6 (32) 13 (19) 0.02

Parity

0 62 (44) 9 (47) 19 (28)

1 46 (33) 4 (21) 22 (33)

2+ 32 (23) 6 (32) 26 (39) 0.09

Annual income category`

,$10000 56 (46) 4 (24) 36 (59)

$10–$15000 25 (21) 3 (18) 5 (8.2)

$15–$25000 19 (16) 5 (29) 12 (20)

.$25000 21 (17) 5 (29) 8 (13) 0.08

Smoking, interview 1 or 2

Non-smoker 89 (64) 12 (63) 43 (64)

Smoker 51 (36) 7 (37) 24 (36) 1.00

Mean calcium intake

.1200 mg/day 87 (62) 12 (63) 42 (63)

,1200 mg/day 53 (38) 7 (37) 25 (37) 0.99

Treated for anaemia1

Yes 36 (26) 4 (22) 15 (23) 0.87

No 104 (74) 14 (78) 51 (77)

Mean maternal lead at

delivery (SD) 1.96 (0.84) 1.73 (0.97) 2.10 (0.98) 0.27

Mean cord blood lead (SD) 1.65 (0.76) 1.57 (0.79) 0.69

Mean birth weight in grams

(SD) 3309 (491) 2890 (373) 3165 (664) 0.00

Mean haemoglobin in

g/100 ml (SD) 12.1 (0.84) 12.2 (0.67) 12.0 (0.77) 0.69

Mean systolic blood

pressure throughout

pregnancy in mmHg (SD) 112 (7.6) 110 (5.9) 112 (7.1) 0.75

*Two sided, x2 test for categorical variables, ANOVA for continuous variables.

Four women missing or other race.

`Missing data on 27 women.

1Missing data on 2 women.

266 Harville, Hertz-Picciotto, Schramm, et al

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age, and increased maternal/cord ratio with daily milk

drinking and previous premature birth (Rothenberg et al,

personal communication). We also found a relatively higher

fetal PbB with increased blood pressure (among women over

30 years and with increasing weight gain), even though

women with underlying hypertension were excluded from

our study. Although the mechanism for the effect of blood

pressure is not clear, lead has been associated with blood

pressure in adults in several studies.53 54 Unlike previous

studies, which have focused on lead as a predictor of

cardiovascular health outcomes, in this study we were

interested in the potential effects of blood pressure on lead

levels as the outcome. Our results differ from those of

Rothenberg et al with respect to caesarean section and parity.

We saw no association with calcium intake, unlike

Rothenberg and despite a previous article associating higher

maternal PbB with lower calcium.40 It is possible that the

effects of these factors are only apparent at high levels of

exposure, or the methods of analysis gave rise to divergent

findings (the structure of the statistical models is different).

One of the strongest associations in our data was with

alcohol consumption reported at the second (late pregnancy)

interview: higher alcohol use was associated with a greater

cord PbB relative to maternal PbB. Alcohol has been shown to

potentiate the effects of lead and to cause increased

absorption by various organs in rats.55 Our results are

consistent with the analyses of Ernhart and colleagues23

and Rabinowitz,22 but not with that of Rothenberg and

colleagues.38 We do not know if the levels of alcohol

consumption differed in the Mexico City women as compared

with our study cohort.

We also saw an association with Hb, which may change the

proportions of bound lead versus free plasma lead or correct

for haemodilution. Similarly, sickle cell trait appears to

reduce cord PbB, perhaps due to a different affinity for lead of

sickle red blood cells, as compared with normal red blood

cells (RBCs).56 57

Strengths of our study include detailed measurement of a

large number of covariates and prospective measurements.

Sensitivity analyses indicated the results were robust. For

instance, at low levels of lead small measurement errors

could have a large impact, but restriction of the model to only

those women with lead higher than 1 mg/dl did not change

the conclusions. Likewise, blood loss at delivery, fluid

replacement, and stress conditions could affect maternal

and fetal PbB concentrations, but restriction to the maternal

blood samples taken before delivery did not change the

overall conclusions. With regard to haemodilution, we

Table 3 Results of multiple linear regression models predicting the difference between cord and maternal blood lead in a

cohort of Pittsburgh, PA pregnant women, 1992–95

All samples (n = 159)

All samples analysed shortly

after delivery (n = 131)

b 95% CI b 95% CI

Sample analysed in second batch 0.20 20.03 to 0.44

Blood pressure, centred, per 10 mm Hg 20.06 20.20 to 0.08 Blood pressure, centred, per 10 mm Hg 20.06 20.20 to 0.08

Mean Hb, per 1 g/100 ml 20.12 20.22 to 20.02 Mean Hb, per 1 g/100 ml 20.12 20.22 to 20.02

Alcohol, 2nd interview, yes/no 0.36 0.14 to 0.58 Alcohol, 2nd interview, yes/no 0.33 0.10 to 0.55

Sickle cell trait 20.76 21.21 to 20.32 Sickle cell trait 20.74 21.17 to 20.30

Previous miscarriage 20.20 20.39 to 20.01 Previous miscarriage 20.23 20.43 to 20.03

Delivery in winter 0.12 20.05 to 0.29 Delivery in winter 0.10 20.08 to 20.28

Mother .30 y 20.22 20.44 to 0.00 Mother .30 y 20.08 20.32 to 0.16

Weight gain .40 lb 0.01 20.16 to 0.19 Weight gain .40 lb 0.02 20.17 to 0.20

Blood pressure 6 mother’s age .30 0.36 0.09 to 0.62 Blood pressure 6mother’s age .30 0.35 0.07 to 0.64

Blood pressure 6 weight gain 0.26 0.04 to 0.47 Blood pressure 6weight gain 0.28 0.05 to 0.50

Positive association indicates increased relative amount of lead transferred.

Table 4 Models of dichotomous (cord higher/not higher than maternal)

b 95% CI OR 95% CI

All samples (n = 157)

Sample analysed in second batch 1.63 0.35 to 2.91 5.11 1.42 to 18.33

Blood pressure, centred, per 10 mm Hg 0.40 20.19 to 0.99

Mean Hb, per g/100 ml 20.61 21.14 to 20.08 0.55 0.32 to 0.93

Alcohol, 2nd interview, yes/no 2.04 0.88 to 3.19 7.67 2.41 to 24.38

Caesarean section 21.25 23.04 to 0.55 0.29 0.05 to 1.73

Previous miscarriage 20.82 22.08 to 0.43 0.44 0.13 to 1.54

Previous abortion 0.78 20.21 to 1.77 2.18 0.81 to 5.89

Delivery in winter 0.79 20.10 to 1.69 2.21 0.91 to 5.40

Mother .30 y 22.09 24.10 to 20.08

Blood pressure 6 mother’s age .30 4.02 0.75 to 7.29

All samples analysed shortly after delivery (n = 138)

Blood pressure, centred, per 10 mm Hg 0.43 20.17 to 1.03

Mean Hb, per g/100 ml 20.58 21.12 to 20.04 0.56 0.33 to 0.96

Alcohol, 2nd interview, yes/no 1.92 0.76 to 3.09 6.84 2.13 to 21.92

Caesarean section 20.88 22.69 to 0.93 0.42 0.07 to 2.54

Previous miscarriage 20.84 22.19 to 0.52 0.43 0.11 to 1.68

Previous abortion 0.62 20.43 to 1.67 1.85 0.65 to 5.29

Delivery in winter 0.66 20.30 to 1.61 1.93 0.74 to 5.01

Mother .30 y 21.17 23.19 to 0.85

Blood pressure 6 mother’s age .30 2.66 20.12 to 5.43

Positive association increased odds of having cord PbB higher than maternal.

Maternal-fetal lead transfer 267

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controlled for Hb, and also note that adjustment for weight

gain as a continuous or categorical variable did not modify

the other results. Some data were missing, but imputation

showed they had little effect. The examination of a large

number of variables could have created spurious chance

associations, but the similarity of effects estimated in three

forms (linear difference, logistic, and exponential model of

the ratio [not shown]) as well as their confirmation in other

studies, argue that this is not the case. The lead measurements were not all analysed at the same lab, and some

(40/451, 9%) of the stored samples that were not analysed

had small clots, leading us to suspect the validity of those

measurements. However, the effect estimates were not

confounded by timing or location of laboratory analysis.

Thus, the consistency of findings throughout these sensitivity

analyses strengthens confidence in the associations.

The study population was predominantly young, low

income, and urban, and was balanced between white and

African-American women; the exclusion of women who were

not in prenatal care by week 13 may limit generalisability.

Women who had both cord and maternal lead measurements

at delivery were different from other women in the broader

study; they were of lower parity, higher income, and their

babies were of higher birth weight. It is difficult to determine

whether these differences are important or not. Labour

progresses more rapidly for women of higher parity and

delivery is quicker for low birth weight infants, who also have

more complications. Therefore, lack of a cord blood sample

could simply be a marker for either a quick delivery or a

complicated birth, when the nurses might not have had time

to collect the specimen.

Lead transfer has a greater potential impact in more highly

exposed populations; our cohort had a low mean level, as is

currently common in the USA (mean lead for this study

<2 mg/dl, US mean for ages 20–49 = 2.1 mg/dl58). Despite the

low concentrations, known risk factors for increased lead

were easily identified, as we reported in previous work,40

indicating a high signal:noise ratio in the lead determinations. The consistency for many of our findings with other

studies of more highly exposed populations provides reassurance that the associations are not artefacts. Also, the

maternal-cord PbB association has been shown to be linear

across a wide range of levels.16

Future studies should seek more refined methods of

measuring placental transfer; differences between maternal

and cord PbB are only partial measures of transfer. Any factor

that caused changes in the maternal plasma-RBC-bone

equilibrium or in excretion, resorption, or accumulation of

lead in the fetus, or that affected placental transfer per se,

could alter the difference between maternal and cord PbB.

We had measurements in whole blood; plasma blood

lead may be more predictive of cord blood lead.59 The

d-aminolevulinic acid dehydratase (ALA-D) genotype may

influence lead susceptibility,60 and ALA-D activity is higher in

cord than maternal blood.61 Also, knowledge of both the total

Hb and the percentage of fetal versus adult Hb in the cord

blood would have been valuable, since fetal Hb has a higher

affinity for lead than does adult Hb62 and its proportion of the

total varies across newborns. Notably, sudden infant death

syndrome has been linked both to lead,63 as well as the

percent adult haemoglobin in the newborn.64

In conclusion, this analysis suggests that sickle cell trait,

alcohol use, and maternal blood pressure and haemoglobin,

among other factors, influence lead transfer to the fetus. If

corroborated, these findings could give additional impetus to

efforts to control blood pressure (particularly in those over 30

years of age), encourage iron supplementation when appropriate, and reduce alcohol consumption during pregnancy.

While the best way to reduce prenatal transmission is to

reduce maternal exposure to lead, future research should also

focus on how we can mitigate lead’s effects on development

by reducing transfer to the infant.

ACKNOWLEDGEMENTS

This work was supported by grant R01-ES05738 from the National

Institute of Environmental Health Sciences.

Emily Harville is a Howard Hughes Medical Institute Predoctoral

Fellow.

Authors’ affiliations

.....................

E W Harville, I Hertz-Picciotto, Department of Epidemiology, University

of North Carolina–Chapel Hill, USA

K Chantala, Carolina Population Center, University of North Carolina–

Chapel Hill, USA

M Schramm, M Watt-Morse, Department of Obstetrics and Gynecology,

Magee-Womens Hospital, USA

J Osterloh, Department of Laboratory Medicine, University of California

at San Francisco, USA

P J Parsons, Wadsworth Center, New York State Department of Health,

USA

W Rogan, Epidemiology Branch, National Institute of Environmental

Health Sciences, USA

Competing interests: none declared

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